We developed a novel silorane-based biomaterial (SBB) for use as an orthopedic cement. SBB is comprised of non-toxic silicon-based monomers, undergoes non-exothermic polymerization, and has weight-bearing strength required of orthopedic cements. We sought to compare the antibiotic release kinetics of this new cement to that of commercially available PMMA bone cement. We also evaluated each material's inherent propensity to support the attachment of bacteria under both static and dynamic conditions. One gram of either rifampin or vancomycin was added to 40g batches of PMMA and SBB. Pellets were individually soaked in PBS. Eluate was collected and tested daily for 14 days using HPLC. Compressive strength and modulus were tested over 21 days. Bioassays were used to confirm the bioactivity of the antibiotics eluted. We measured the growth and maturation of staphylococcus aureus (SA) biofilm on the surface of both PMMA and SBB disks over the course of 72 hours in a static well plate and in a dynamic biofilm reactor (CDC Biofilm Reactor). N=4 at 24, 48, and 72 hours. A luminescent strain of SA (Xen 29) was employed allowing imaging of bacteria on the discs. SBB eluted higher concentrations of vancomycin than did PMMA over the course of 14 days (p<0.001). A significant 55.1% greater day 1 elution was observed from SBB. Silorane cement was able to deliver rifampin in clinically favorable concentrations over 14 days. On the contrary, PMMA was unable to deliver rifampin past day 1. The incorporation of rifampin into PMMA severely reduced its mechanical strength (p<0.001) and modulus (p<0.001). Surface bacterial radiance of PMMA specimens was significantly greater than that of SBB specimens at all time points (p<0.05). The novel silorane-based cement demonstrated superior antibiotic release and, even without antibiotic incorporation, demonstrated an innate inhabitation to bacterial attachment and biofilm

Aims. Poly(methyl methacrylate) (PMMA)-based bone cements are the industry standard in orthopaedics. PMMA cement has inherent disadvantages, which has led to the development and evaluation of a novel silorane-based biomaterial (SBB) for use as an orthopaedic cement. In this study we test both elution and mechanical properties of both PMMA and SBB, with and without antibiotic loading. Methods. For each cement (PMMA or SBB), three formulations were prepared (rifampin-added, vancomycin-added, and control) and made into pellets (6 mm × 12 mm) for testing. Antibiotic elution into phosphate-buffered saline was measured over 14 days. Compressive strength and modulus of all cement pellets were tested over 14 days. Results. The SBB cement was able to deliver rifampin over 14 days, while PMMA was unable to do so. SBB released more vancomycin overall than did PMMA. The mechanical properties of PMMA were significantly reduced upon rifampin incorporation, while there was no effect to the SBB cement. Vancomycin incorporation had no effect on the strength of either cement. Conclusion. SBB was found to be superior in terms of rifampin and vancomycin elution. Additionally, the incorporation of these antibiotics into SBB did not reduce the strength of the resultant SBB cement composite whereas rifampin substantially attenuates the strength of PMMA. Thus, SBB emerges as a potential weight-bearing alternative to PMMA for the local delivery of antibiotics. Cite this article: Bone Joint Res 2021;10(4):277–284

Introduction Polymethylmethacrylate (PMMA) has been widely used in orthopaedic procedures for fixation of joint replacements or enhancing the fixation of implants. However, the use of PMMA has been associated with cardiovascular deterioration and even death. More recently, PMMA has also been used for augmenting osteoporotic vertebral bodies which have fractured or are at risk of fracture. The main complication is PMMA leakage into adjacent structures. Transient hypotension and fatal fat embolism (FE) have also been reported. The pathomechanism of cardiovascular deterioration after the injection of PMMA (i.e. FE) remains a highly controversial subject. The exact role of PMMA in the development of FE remains unclear. The aim of the present study was to elucidate the acute effects of injecting PMMA compared with bone wax into vertebral bodies on the cardiovascular system using an established animal model for vertebroplasty (VP) (Aebli, N, et al. Spine. 2002). Methods In 8 skeletally mature mixed-bred ewes (2–4 years) 6.0ml PMMA (CMW3-Depuy) or bone wax (Bone Wax, Ethicon) were injected unilaterally, through an open approach into the L1 & L2 pedicles. Blood pressure, heart rate, and cardiac output were measured. Results The major difference between the cardiovascular response of the PMMA and that of the bone wax group was the recovery in Pulmonary Artery Pressure (PAP) and Pulmonary Vascular Resistance (PVR). Three minutes post-injection, PAP had fully recovered to baseline values in the wax group. However in the PMMA group, PAP had only recovered by 52% after 3 min and fully recovered after 10 min. Discussion The augmentation of vertebral bodies resulted in transient cardiovascular changes regardless of the material used. However, the recovery of PAP and PVR values took significantly longer with the PMMA group. The peak response was a result of pulmonary vasoconstriction triggered by a reflex reaction to the embolisation of bone marrow particles or by vasoactive cytokines. The peak response was therefore mainly associated with the increase in intraosseous pressure during the augmentation causing release of bone marrow contents into the and not the cement monomer. The cement monomer however plays a role in the cardiovascular complications during FE. The delayed recovery of PAP and PVR in the PMMA group may be due to a vasoconstriction effect of the cement monomer on the pulmonary vascular system. Potentially serious cardiovascular complications may occur during VP regardless of the material used. The injection of PMMA may cause prolonged pulmonary hypertension during vertebro- and also arthroplasty. Continuous invasive cardiovascular monitoring may be required in patients with impaired cardiovascular and pulmonary function

Thermal damage to bone related to the exothermic polymerisation of bone cement (PMMA) remains a concern. A series of studies were conducted to examine PMMA bone interface during cemented arthroplasty. In vitro and in vivo temperature distributions were performed in the laboratory and human and animal surgery. In vivo (10 patients) measurements of cement temperature during cementing of BHR femoral prosthesis using thermocouples. Intra-operative measurement of cement temperature in BHR in the presence of femoral head cysts was examined in patients. The BHR femoral heads were sectioned to assess cement mantle as well as position of thermocouples. An additional study was performed in sheep with PMMA implanted into cancellous defects. Thermocouples were used to monitor temperature in the cement as well as adjacent bone. Histology and CT was used to assess any thermal damage. The exothermic reaction of PMMA during polymerization does indeed result in an increase in temperature at the interface with bone. The in vivo study recorded a maximum temperature of 49.12C for approximately three minutes in the cancellous bone underneath the BHR prosthesis. This exposure is probably not sufficient to cause significant injury to the femoral head. The maximum temperature of the cement on the surface of the bone was 54.12C, whereas the maximum recorded in the cement in the mixing bowl was 110.2C. In the presence of artificial cysts within the bone, however, temperatures generated within the larger cysts, and even at the bone-cement interface of these cysts, reached levels greater than those previously shown to be harmful to bone. This occurred in one case even in the 1 cc cyst. Routine histology revealed a fibrous layer at the cement bone interface in the sheep study. Fluorescent microscopy demonstrated bone label uptake adjacent to the defect site. Histology did not reveal thermal necrosis in the defects in terms of bony necrosis. CT data was used to measure the amount of PMMA placed into each defect. This analysis revealed a range of volumes that did not seem to influence the histology. The heat of cement polymerisation in resurfacing as performed in our study is not sufficient to cause necrosis. This may reflect the ability of the body to rapidly conduct heat away by acting as a heat sink. The temperature-conducting properties of the metal prosthesis are also likely to be important

Introduction. Temporary use of antibiotic-impregnated polymethylmethacrylate (PMMA) bone cement spacers in two-stage revisions is considered to be standard of care for patients with a chronic infection of a joint replacement. Spacers should be wear resistant and load-bearing to avoid prolonged immobilisation of the patient and to reduce morbidity. Most cement spacers contain barium sulphate or zirconium dioxide as radio-opaque substrate. Both are quite hard materials that may negatively influence the wear behaviour of the spacer. Calcium carbonate is another radio-opaque substrate with lower hardness potentially increasing the wear resistance of the spacer materials. The purpose of the study was to compare a prototype PMMA knee spacer (calcium carbonate loaded) with a commercially available spacer (containing barium sulphate) regarding the wear performance and particle release in a knee wear simulator. Material and Methods. Spacer K (TECRES, Italy) was used as barium sulphate (10%) containing spacer material. A prototype material (Heraeaus Medical, Germany) with 15% calcium carbonate was compared. Both were gentamicin impregnated, ready-made for clinical application (preformed) and consist of a tibial and a femoral component. Force-controlled simulation was carried out on an AMTI knee simulator. The test parameters were in accordance to ISO 14243–1 with a 50% reduced axial force (partial weight bearing). Tests were carried out at 37 °C in closed chambers filled with calf serum. Tests were run for 500,000 cycles at a frequency of 1 Hz. For wear analysis, gravimetric wear measurements according to ISO 14243–2 and wear particle analysis according to ASTM F1877–05 were performed. Results. Fig. 1 presents the results of the gravimetric wear measurements. For the Spacer K cement a mean articular wear mass of 375.53±161.22 mg was determined after 500.000 cycles (femoral components: 149.55±17.30 mg, tibial components: 225.98±153.01 mg). The prototype cement showed lower mean total wear of 136.32±37.58 mg (femoral components: 74.32±33.83 mg, tibial components: 61.99±15.74 mg). However, a statistically significant lower wear rate was only seen for the femoral components (p=0,027). In Fig. 2 isolated PMMA wear particles are shown and the morphological characteristics are given in Tab. 1. Discussion and conclusion. The prototype material showed better wear performance in terms of gravimetric wear and particle release. Thus calcium carbonate seems to be a promising material as radio-opaque substrate in PMMA spacers. Nevertheless, the wear amount released from both spacer materials is much higher as compared to conventional total knee replacements with polyethylene inserts. In this context biological reactions against PMMA particles and an increased release of cytokines have been reported in vitro [1] and furthermore, the promotion of osteolysis has been shown in vivo in the presence of PMMA particles [2]. As a clinical consequence we suggest excessive debridement during removal of the cement spacer components to reduce the risk of third body wear for the final joint replacement. Beside the wear performance further studies are essential to prove the mechanical stability and the antibiotic release kinetics for the prototype cement

Introduction and Aims: Polymethylmethacrylate (PMMA) has been widely used in orthopaedic surgery including more recently vertebroplasty. The reported rate of complications following vertebroplasty is low and mainly related to PMMA leakage. The aim of this study was to elucidate the acute cardiovascular effects of PMMA or bone wax in a vertebroplasty animal model. Method: Eight skeletally mature sheep were used and PMMA or bone wax were injected unilaterally into L1 and L2 at 10-minute intervals. Arterial, central venous, pulmonary artery and left ventricular pressures were recorded using Statham pressure transducers and Swan Ganz catheters were used for monitoring cardiac output. Results: Augmentation resulted in a two-phase response regardless of which material was used. First the mean arterial blood pressures started to drop after approximately two seconds. Secondly the pulmonary artery pressure and central venous pressure increased after approximately 11 seconds, whereas cardiac output and left ventricular pressure decreased. There was no significant change in heart rate for both groups. There was a significant difference (p< 0.05) in the pulmonary artery pressure values in the PMMA group compared to the basal values at one, three and five minutes, whereas in the wax group the pulmonary artery pressure recovered within three minutes. Conclusion: Augmentation resulted in a two-phase cardiovascular response regardless of which material was used. Peak responses were similar for both groups, but pulmonary artery pressure and cardiac output recovered quicker in the wax group. The late recovery of pulmonary artery pressure and cardiac output in the PMMA group may be due to a vasoconstriction effect of the cement monomer

Aims: PMMA is currently used as grouting agent of arthroprostheses and for filling of bone cavities after bone curettage. It is moreover used as a carrier of antibiotics in the local treatment of bone infections and it has been proposed as a carrier of antiblastic drugs in the local treatment of bone metastases. The aim of this study is to analyse the biological properties and compressive strenght of PMMA-Methotrexate mixture to be used for the local treatment of bone metastases. Methods: Cylinders of PMMA containing Methotrexate in different concentrations were manufactured according to ASTM F-451. Cylinders of PMMA were used as control. The porosity of the cylinders was characterised by SEM. Drug elution rate in saline solution was measured by HPLC. The biological activity of Methotrexate was analysed on human breast cancer cells using MTT test at different time (from 5 minutes to 30 days). Compressive tests was performed in conformity to ASTM F-451 on PMMA- Methotrexate samples and control as-made and after 30 days of aging in saline. Results: SEM analysis showed the presence of granules of Methotrexate on the surface of as-made cylinders that can be readily released from PMMA cylinders. The release occurred in large amount within 24 hours after immersion. We observed a relative release rate is more sustained in samples containing the drug in lower concentration. Also the biological activity was time dependent: cell death decreased progressively from 60% at 24 hours to 10% at 30 days. Compressive tests showed no statistical differences between PMMA cylinders containing Methotrexate and controls before and after aging in saline. Conclusions: The results show that PMMA-Metho-trexate may be considered an interesting option in the treatment of bone metastases because cement allows mechanical resistance after bone curettage or resection and Methotrexate improves locally anticancer activity

The pathogenesis of aseptic loosening of total joint prostheses is not clearly understood. Two features are associated with loosened prostheses, namely, particulate debris and movement of the implant. While numerous studies have evaluated the cellular response to particulate biomaterials, few have investigated the influence of movement of the implant on the biological response to particles. Our aim was therefore to test the hypothesis that excessive mechanical stimulation of the periprosthetic tissues induces an inflammatory response and that the addition of particulate biomaterials intensifies this. We allocated 66 adult Beagle dogs to four groups as follows: stable implants with (I) and without (II) particulate polymethylmethacrylate (PMMA) and moving implants with (III) and without (IV) particulate PMMA. They were then evaluated at 2, 4, 6, 12 and 24 weeks. The stable implants were well tolerated and a thin, fibrous membrane of connective tissue was observed. There was evidence of positive staining in some cells for interleukin-6 (IL-6). Addition of particulate PMMA around the stable implants resulted in an increase in the fibroblastic response and positive staining for IL-6 and tumour necrosis factor-alpha (TNF-α). By contrast, movement of the implant resulted in an immediate inflammatory response characterised by large numbers of histiocytes and cytokine staining for IL-1ß, TNF-α and IL-6. Introduction of particulate PMMA aggravated this response. Animals with particulate PMMA and movement of the implant have an intense inflammatory response associated with accelerated bone loss. Our results indicate that the initiation of the inflammatory response to biomaterial particles was much slower than that to gross mechanical instability. Furthermore, when there was both particulate debris and movement, there was an amplification of the adverse tissue response as evidenced by the presence of osteolysis and increases in the presence of inflammatory cells and their associated cytokines

Antibiotic-loaded PMMA spacers are used with increased frequency in two-stage revision arthroplasty. The release of aminoglycosides and vancomycin, the most commonly used antibiotics, is prompt, and concentrations are inhibitory. The release kinetic from PMMA bone cement shows a biphasic profile, consisting in an initially high and rapid drug release followed by a slower but sustained phase. However, this general profile of drug release kinetics from PMMA spacers in vitro may have great variability in terms of drug amount, modality, and duration of elution. Initial drug concentration, cement surface area and porosity are essential and well-known factors in determining the drug release. Moreover, viscosity, vacuum-preparation and the different technical characteristics of commercially available spacers are additional factors of variability. Industrial preformed spacers are considered superior to custom-made devices because of uniform mixing and standardized procedures. Spacers produced by different manufacturers vary in their mechanical properties and antibiotic elution characteristics. Small changes in the formulation of a bone cement can also affect these properties. Similar bone cements produced by various brands release different amount of drugs. Gentamicin diffuses from Palacos in a larger amount and for a longer period than from Simplex and CMV. Spacers produced in France (Synicem™) and in Argentina (Subiton™) elute less total amount of gentamicin than those produced in Italy (Spacer G™) and show a delayed peak drug release. The low initial release of antibiotic can contribute to unsatisfactory antimicrobial effect and to the risk of selection of resistant bacteria. Some spacers release gentamicin for longtime (months), while others release antibiotic for only two weeks. In the last years an evolution of PMMA spacers production occurred and modifications in the polimerization process of cement can increase cement porosity and antibiotic elution from spacers. The current commercial preformed spacers for 10 days elution (Spacer G™, prepared with Cemex HP) release more gentamicin (34.1 mg) than previous models, which were prepared with Cemex SP (16.4 mg). Furthermore, they maintain a high elution rate (1.4–1.6 mg/day after one month). The combination of Gentamicin and Vancomycin mantains an elution pharmacokinetic profile that is superimposable to that of Gentamicin and Vancomycin alone, with synergistic effects against multiresistant bacteria in prosthetic infection site. In conclusion, the antibiotic release from PMMA spacers of various brands is not equivalent. The old elution data are no longer valid for new preparations. Consequently, this additional factor of variability should be considered in clinical practice and literature data utilisation

Introduction. Antibiotic loaded polymethyle methacrylate spacers are commonly used in the management of septic hip replacements. Aim. The aim of this study was to determine wear patterns on the articulating surfaces of these spacers, as well as to determine the extent of PMMA particulate debris generation. Method. We took tissue specimens around the acetabulae in 12 cases at the time of the second stage procedure for septic total hip revisions. These were subjected to histological analysis to determine the extent of PMMA particulate debris contamination. We also performed a basic explant retrieval analysis of the articulating surfaces of the PMMA spacers to determine any specific wear patterns. Results. We found numerous PMMA particles in the acetabular soft tissues biopsied. The particle concentration was highest in the area of the acetabular fovea. We could also demonstrate specific wear patterns on the spacers that could be correlated with the generally mismatched articulating couple between the spacer and the bony acetabulum. We could also demonstrate some boney destruction present in the acetabulum with long-term spacer use. Conclusions. We concluded that significant amounts of PMMA particulate debris are generated by these articulating antibiotic spacers. The total volume of this debris may be determined by specific wear patterns on the spacers’ surfaces. We recommend a thorough debridement to decrease the PMMA particle load generated. Consideration in respect of the bearing surface implanted after the explantation of the PMMA spacer should take into account the effect of the debris on the bearing surfaces. We also make recommendations in respect of the design of these PMMA spacers

Two-stage exchange revision is the gold standard in treating an infected total hip arthroplasty. The new emerging gold standard appears to be using an antibiotic impregnated spacer made from polymethylmeta-crylate (PMMA) bone cement between two stages. However, a consensus has not been reached on the antibiotic to use in the cement and its dose. Vancomycin an aminoglycoside is widely used for this purpose in the PMMA cement in doses such as 3 to 9 gr per 40 gr polymer powder. The purpose of this study was to see if Vancomycin is as effective in safer low doses of 1 gr per 40 gr polymer powder.Between 1997 and 2002, twenty-six patients were treated for an infected hip arthroplasty with a two-stage exchange arthroplasty using a Vancomycin impregnated polymethylmetacrylate (PMMA) bone cement spacer. During the first stage all prosthetic material was removed and after debridement, irrigation an articulating spacer was made from PMMA cement (Surgical Simplex, Howmedica, Rutherford, NJ, USA). One gram of Vancomycin HCl (Vancomycin, Eli Lilly, USA) powder was added to each 40 gr polymer powder prior to curing the cement. After the first stage parenteral antibiotics were administered for six weeks. When erythrocyte sedimentation rate and the CRP returned to a normal level, the patient underwent the second stage were a cementless prosthesis was inserted. Intra-operative cultures and frozen sections obtained during the second stage were negative in all patients indicating successful treatment of the infection. Mean follow up after the second stage was 36 (range 24 to 74) months. Two patients had a reinfection after four months. These two patients were infected with gram-negative micro-organisms. This gave us a 92 percent infection eradication rate at 3 years. None of the patients suffered from Vancomycin related side effects.In this study we used a lower dose (1 gr per 40 gr polymer powder) of Vancomycin in the PMMA spacer instead of the commonly used 3 to 9 gr per 40 gr polymer powder. The reason for this was our concerns for nephrotoxicity and allergic reactions frequently associated with use of Vancomycin. Antibiotics are used in cement spacers as a disinfecting agent and sterilizer of dead spaces. As Vancomycin is highly effective when used in PMMA due to its elution dynamics and thermostability we believed it would be effective even in low doses. In all patients the infection appeared to be cured after the first stage. This was demonstrated with negative intraoperative cultures and frozen sections. However, we had two reinfections in patients that initially were infected with gram-negative organism, which Vancomycin is not as effective. Despite this we were able to sterilize the infected hip with a low dose approach in the first stage. Vancomycin is effective in low dose when used in PMMA cement spacers for infected total hip arthroplasties. This approach will decrease potential serious side effects of Vancomycin

Study Design: Comparative, prospective follow-up study. Objective: Comparison of outcome between patients treated with Percutaneous VertebroPlasty (PVP) using low viscosity PolyMethylMetAcrylate (PMMA) bone cement and patients treated with PVP using medium viscosity PMMA bone cement. Summary of background data. Viscosity is the characterizing parameter of PMMA bone cement, currently the standard augmentation material in PVP, and influences interdigitation and cement distribution inside the vertebral body, injected volume and extravasation, thereby affecting the clinical outcome of PVP. In PVP, low, medium and high viscosity PMMA bone cements are used interchangeably. However, effect of viscosity of cement on clinical outcome in patients with Osteoporotic Vertebral Compression Fractures (OVCFs) has not yet been explicit subject of investigation. Methods: Follow-up was conducted using a 0–10 Pain Intensity Numerical Rating Scale (PI-NRS) and the Short Form 36 (SF-36) Quality of Life (QoL) questionnaire before PVP and at 7 days (PI-NRS only), 1 month, 3 months and 12 months after PVP. Cement leakage was analyzed on direct post-operative CT-scanning. Injected cement volume was measured using a calibrated DICOM-viewer and the degree of interdigitation was assessed. At six and 52 weeks and at suspicion, patients were analyzed for the incidence of new fractures. Results: Thirty consecutive patients received PVP using low viscosity PMMA bone cement (OsteoPal-V. ®. ) for 62 OVCFs, followed by 34 patients who received PVP using medium viscosity PMMA bone cement (Disc-O-Tech. ®. ) for 67 OVCFs. Baseline characteristics were comparable between groups. Viscosity qualification was stated by the manufacturer. results regarding PI-NRS and SF-36 were comparable between both groups. Postoperative comparison of injected cement volume, degree of interdigitation, proportion of bipedicular procedures, incidence of new vertebral fractures and complications revealed no substantial differences between both groups. In the low viscosity group a significantly greater proportion of vertebrae showed cement extravastion (81,0% versus 71,6%, p = 0,029). Multiple logistic analysis revealed no definitive predictive factors for the occurrence of cement leakage (yes/ no) (Odds Ratio [95% CI], P):. Severity (acc to Genant et al): 1.82 [0,69 – 4.89], 0.229. Fracture Type (Genant et al): 1.22 [0.64 – 2.32], 0.550. Injected Volume: 0.98 [0.76 – 1.27], 0.875. Spinal Region: 0.87 [0.48 – 1.55], 0.628. Cement Viscosity: 0.42 [0.16 – 1.10], 0.076. Conclusion: No major differences in clinical outcome after PVP in OVCFs using low and medium viscosity PMMA bone cement were found. Viscosity of PMMA bone cement is likely to influence cement extravastion, although this could not be confirmed

Introduction: Patients with spinal metastases often have patterns of disease requiring both an anterior and posterior surgical decompression and stabilisation. Subtotal spondylectomy and circumferential stabilisation can be safely performed via a single posterior transpedicular approach. Polymethyl-methacrylate bone cement (PMMA) has been widely used in spinal column reconstruction with mixed results. PMMA is a potential means for local drug delivery in the prevention of locally recurrent disease. The biomechanical characteristics of anterior reconstruction using PMMA have not been adequately evaluated. Purpose: To evaluate the stability of an anterior cement construct following total spondylectomy and to compare this reconstruction against alternative stabilisation techniques. Methods: Ten fresh-frozen human cadaveric spines (T9-L3) were used. After intact analysis, a total spondylectomy was performed at T12. Three potential reconstruction techniques were tested for their ability to restore stiffness to the specimen: (1) multi-level posterior pedicle screw instrumentation from T10-L2 {MP1} [Depuy Acromed], (2) anterior instrumentation [ATL Z-plate II™, Medtronic, Sofamor Danek Instruments] and rib graft at T11-L1 with multi-level posterior instrumentation from T10-L2 {AMPI}, and (3) anterior cement [Simplex P] and pins construct (T12) with multi-level posterior instrumentation from T10-L2 {CMPI}. Each of the three potential reconstruction techniques was tested on each specimen in random order. Non-destructive testing was performed under load control. The specimen was positioned vertically for axial compression and torsion testing, and horizontal for flexion/extension and lateral bending tests. A customised jig was manufactured for this latter purpose. Results: Only circumferential stabilisation techniques (AMPI, CMPI) restored stiffness to a level equivalent or higher to that of the intact spine in all loading modes (p< 0.05). CMPI provided more stability to the specimen than AMPI in compression and flexion testing (p< 0.05). Posterior instrumentation alone (MPI) did not restore stiffness to the intact level in compression and flexion testing (p< 0.005). Conclusions: Circumferential reconstruction using an anterior cement construct provides equal or more stability than the intact spine in all testing modes. Posterior stabilisation alone is an inadequate method of reconstruction following total spondylectomy. PMMA has the advantage over traditional anterior reconstruction techniques in that it can be inserted using a single posterior approach and offers the potential value of local drug delivery

Purpose: This study investigates the synergistic use of fusidic acid with vancomycin, and linezolid in poly-methylmethacrylate (PMMA) cement for the treatment of orthopedic MRSA and MRSE infections. Alone, Vancomycin is typically eluted in limited quantities from cement. The purpose of this study was to. combine FA and Vancomycin, and Linezolid alone in PMMA cement and characterize antibiotic elution, and. to improve drug release using polyethylene glycol (PEG) and NaCl in PMMA cement. Method: Standardized 1g pellets of Palacos cement were manufactured containing Vancomycin and FA or Linezolid at increasing concentrations in three batches: without additive, with increasing concentrations of PEG, and with increasing concentrations of NaCl. The pellets were incubated in phosphate buffered saline and sampled at regular intervals. Drug analysis was performed with high pressure liquid chromatograpy. Results: Total drug release at 2.5% loading of Vancomycin alone was 0.84% and of FA was 2.35%. Linezolid showed comparable release profiles. Vancomycin and FA combined yeilded Vancomycin release of 6.2% and FA of 8.4%. The addition of 30% PEG increased release of Vancomycin and Fusidic Acid by six-fold. The addition of 18% NaCl increased total Vancomycin release by 11-fold but had no effect on FA release. Conclusion: Linezolid, Vancomycin and FA can be combined in PMMA and have favorable release profiles. The addition of PEG and NaCl dramatically increases the release of antibiotics, with the exception of FA and NaCl. These strategies may be useful in the management of MRSA/MRSE infections

Introduction: morcelized defatted bone-Bank graft (MOD-B) has been employed in 249 patients for different diseases in Rizzoli Institute from 1998 to 2002. 82 hip revisions, 51 spine fusions, 50 osteolitic bone cavities, 47 non-unions). Good results obtained with MOD-B have been the reason for different researches of his properties like an antibiotic carrier and, in the same time, a particular new bone graft. Material and Methods:. MOD-B with antibiotic powder and PMMA Cylinders (A-MB-C) have been placed in saline solution and plasma for 4 weeks, compared with cylinders made with PMMA and antibiotic. The mechanical resistance of A-MB-C to compressive test has been performed subsequently. About biocompatibility, A-MB-C were implanted in sheep’s Ilium. After 3 moths an histologic evaluation has been performed. Results:. The MOD-B + antibiotic + PMMA have released the higher quantity of antibiotic for all the 4 weeks. The A-MB-C resistance has been of 13.6 MPa, the same resistance of cancellous bone in the man’s femur. The histological result with a fluoroscopic microscope has been an osteogenesis in the full section of the cylinders. Conclusions: morcelized defatted bone-Bank graft is an important opportunity to restore bone loss lesions but, with a septic situation, it is not so easy obtain good results. A very important goal would be to have a graft with good antibiotic deliver system, good mechanical compressive strength and the potential capacity to become new living bone

Pain is the main symptom of acetabular osteolysis and is frequently associated with pathologic fractures. Surgical procedures requiring an aggressive approach, and as a consequence high morbidity, are rarely indicated. The minimally invasive approach may be effective in treating tumours and is capable of reducing the mechanical pain. PMMA has been widely used in neoplastic and spinal surgery as a bone filler because of its mechanical and biologic behaviours. Recently percutaneous injection of PMMA was proposed for the treatment of neoplastic acetabular osteolysis. The technique was tested in four patients affected by secondary ostheolytic lesions. The patients were evaluated clinically (HHS, Womac, SF-12) and radiographically (X-ray and CT) at 18 months. All the patients demonstrated a durable and significant improvement in terms of pain and restoration of function. The radiographic examinations (X-ray and CT) confirm these results. Complications (temporary increase in pain and fever) were only observed in one patient. The preliminary results demonstrate the reliability and effectiveness of this procedure. Clinical results showed a significant reduction in pain and the capability of restoring function. The indications can be extended also to the acetabular lesion at a distance from the weight-bearing zone, reducing pain and the risk of pathologic fractures. The technique was demonstrated to be effective and showed only minor and self-resolving complications. It is useful in patients in whom major surgery is contraindicated and clinical improvement is necessary to improve the quality of life

The use of PMMA cement vertebroplasty for the treatment of severe disabling focal back pain as a result of osteoporotic compression fractures is well established. However clinical experience of this treatment is limited in New Zealand. This study reports a technique and indications for this treatment and early clinical results. A prospective study of eight cases of severe disabling focal back pain due to osteoporotic compression fractures was undertaken. These were treated with percutaneous transpedicle vertebroplasty. The patient’s pain was assessed before and after the treatment using a visual analogue pain scale. All eight patients reported an improvement in pain immediately and at one month following the procedure. A sustained improvement in pain followed the vertebroplasty. This is consistent with other case reports in the literature although in this study the response appears to be less dramatic than that reported in other series

Introduction. Radio-opaque additives for Orthopaedic Bone Cement, like BaSO4 or ZrO2, are now routinely used because of the valuable help in identifying cement location around an implant on the x-ray films. A new bone cement formulation was devised with the aim to improve the reparative response of bone tissue surrounding a cemented implant, soon after the operation: a 6% NaF 6% BaSO4 preparation “Fluoride Bone Cement©” (Tecres, I) was tested in-vivo versus a 9% BaSO4 preparation “CemexRX©” (Tecres, I). NaF stimulating action towards bone repair is prompt by the formation of fluoroapatite and the stimulation of osteoblast differentiation. NaF-added cement acts like a “drug-release device” for fluoride ions.

Materials & Methods. Eighteen outbred male New Zealand White rabbits of approximately 3,2 kg of weight have been used. They were divided into six groups of three units. Gropus A1, A2, A3 were implanted with cement without fluoride “CemexRX©” while groups B1, B2, B3 had “Fluoride Bone Cement©”. Retrieval occurred after 17 days (A1, B1); 33 days (A2, B2); 60 days (A3, B3). The surgical implantation site selected was the distal femural canal (meta-epiphyseal region). The canal in the right femur was filled with cement while the canal in the left femur was used as a surgical control (“sham” operation). Sections of 100 micron of thickness were taken by a rotating diamond-saw microtome (Leitz Wetzlar) and analyzed by polarized light and ultra-violet fluorescence microscopy (Nikon Miscroscope). One hundred and twenty sections were obtained for each femur.

Results. Calcein green fluorescent labelling showed that no real endosteal osteogenic response was evidenced the day after surgery, for both cement preparations, while periosteal response was normal. This was the consequence of the biological insult of the intramedullary polymerization of the cement. Xylenol orange showed that all the contra-lateral femurs (“sham”) had a normal endosteal and periosteal osteogenesis at all times. Both cement preparations continued to show a limited end-osteal response after 17 days and a slow recovery after 33 days, with better pictures in favour of NaF cement. After 60 days recovery in endosteal osteogenesis was adequate but, again, NaF cement showed the highst number of good pictures.

Conclusions. Adding NaF promoted the better recovery in endosteal osteogenic response observed in comparison with NaF-free cement. To differentiate the biological response it was essential to compare a high number of sections (120) in comparable locations, in a contralateral “sham” operated control in the very same animal. This procedure, costly and demanding, seems to be a right methodological approach.

Aims

Two-stage exchange revision total hip arthroplasty (THA) performed in case of periprosthetic joint infection (PJI) has been considered for many years as being the gold standard for the treatment of chronic infection. However, over the past decade, there have been concerns about its safety and its effectiveness. The purposes of our study were to investigate our practice, collecting the overall spacer complications, and then to analyze their risk factors.

Knee sepsis following TKR can have devastating consequences for patient as well as surgeon. A two stage revision is a well accepted technique in TKR sepsis with the introduction of a temporary antibiotic cement spacer being the most popular procedure although irrigation techniques are popular in SA.

From a total of 111 revisions TKR from my practice 26 (23%) were 2 stage revisions for joint sepsis following TKR. 3 cases were early, 10 intermediate and 13 late onset sepsis cases. Most common organism was S. Aureus (7/26) and S. Epidermidis (7/26) although numerous other organisms were seen.

In all cases a two stage revision with a Palacos R cements spacer plus parenteral antibiotics were used. Prosthesis used for revision was primary knee prosthesis in 8 cases and revision (stemmed) prosthesis in 18 cases. Follow up range from 13 years to 6 months (average 6.8 years) with only one case of recurrent sepsis (3.8%) which went on to an arthrodesis. Time from debridement and spacer placement to revision TKR varied from 3 weeks to 10 months (average 2.1 months).

This paper shows that meticulous debridement followed by standard antibiotic cement spacer technique with additional parenteral antibiotics is indeed the gold standard approach without necessitating additional irrigation techniques.

To evaluate and compare the stability of an anterior cement construct following total spondylectomy for meta-static disease against alternative stabilization techniques.

After intact analysis of ten cadaveric spines (T9–L3), a T12 spondylectomy was performed. Three reconstruction techniques were tested for their ability to restore stiffness to the specimen using non-destructive tests:

1) multilevel posterior pedicle screw instrumentation (PPSI) from T10–L2 {MPI}, 2) anterior instrumentation from T11–L1 with PPSI {AMPI}, and 3) anterior cement and pins construct (T12) with PPSI {CMPI}.

Circumferential stabilization {AMPI, CMPI} restored stiffness to a level of the intact spine. CMPI provided more stability to the specimen than AMPI. MPI alone did not restore stiffness to the intact level.

Circumferential reconstruction using an anterior cement construct following total spondylectomy is biomechanically superior to posterior stabilisation alone.

Introduction: In two-stage revision of an infected total hip replacement a preformed temporary antibiotic-loaded polymethylmethacrylate spacer may be required in order to allow weightbearing and joint motion while ensuring antibiotic local release.

Methods: 29 patients with infected hips were treated by a two-stage procedure including removal of prosthesis and implantation of a spacer. The device comprised a stem with 3 available head sizes pre-coated by bone cement supplemented with gentamicin (2.5% w/w) and vancomycin (2.5% w/w). Joint motion and weight-bearing were allowed when the bone stock ensured an adequate stability to the spacer. Systemic antibiotics were administered for 8 weeks. The spacer remained in situ for an average of 155 (range 70–272) days. Reimplantation was performed when recovery of clinical and serological signs of infection was obtained. Patients’ evaluation included clinical assessment (HHS), standard x-ray and laboratory parameters.

Results: mean follow-up was 52 months (range 36–100). Healing of the infection was obtained in 27/29 cases (93.1%). 5 patients required resection-arthroplasty (2 persistent infections, 2 inadequate bone stock, 1 recurrent infection). In 4 cases the spacer dislocated, being treated by non-surgical reduction. The reimplanted patients (24) showed no clinical or laboratory signs of infection recurrence, with a mean HHS score of 79 (range 53 to 100); no radiographic signs of loosening were observed.

Discussion: the use of a preformed antibiotic-loaded spacer in two-stage revisions, allowing a local antibiotic release together with some degree of joint motion, appears to enhance infection’s treatment improving patients’ quality of life and functional recovery.

We retrospectively compared the outcome after the treatment of giant cell tumours of bone either with curettage alone or with adjuvant cementation. Between 1975 and 2008, 330 patients with a giant cell tumour were treated primarily by intralesional curettage, with 84 (25%) receiving adjuvant bone cement in the cavity. The local recurrence rate for curettage alone was 29.7% (73 of 246) compared with 14.3% (12 of 84) for curettage and cementation (p = 0.001). On multivariate analysis both the stage of disease and use of cement were independent significant factors associated with local recurrence. The use of cement was associated with a higher risk of the subsequent need for joint replacement. In patients without local recurrence, 18.1% (13 of 72) of those with cement needed a subsequent joint replacement compared to 2.3% (4 of 173) of those without cement (p = 0.001). In patients who developed local recurrence, 75.0% (9 of 12) of those with previous cementation required a joint replacement, compared with 45.2% (33 of 73) of those without cement (p = 0.044).

The augmentation of fixation with bone cement is increasingly being used in the treatment of severe osteoporotic fractures. We investigated the influence of bone quality on the mechanics of augmentation of plate fixation in a distal femoral fracture model (AO 33 A3 type). Eight osteoporotic and eight non-osteoporotic femoral models were randomly assigned to either an augmented or a non-augmented group. Fixation was performed using a locking compression plate. In the augmented group additionally 1 ml of bone cement was injected into the screw hole before insertion of the screw. Biomechanical testing was performed in axial sinusoidal loading. Augmentation significantly reduced the cut-out distance in the osteoporotic models by about 67% (non-augmented mean 0.30 mm (sd 0.08) vs augmented 0.13 mm (sd 0.06); p = 0.017). There was no statistical reduction in this distance following augmentation in the non-osteoporotic models (non-augmented mean 0.15 mm (sd 0.02) vs augmented 0.15 mm (sd 0.07); p = 0.915). In the osteoporotic models, augmentation significantly increased stability (p = 0.017).

Cite this article: Bone Joint J 2013;95-B:1406–9.

Background: Polymethylmethacrylate (PMMA) is a potent stimulant of inflammatory response. This study investigated the role of Prostaglandin E2 (PGE2), Platelet activating factor (PAF) and histamine and their specific antagonists in bone changes.

Materials: 120 white-male-wistar rats were divided into ten groups. Using sterile technique, a 2mm drill hole was made in the tibia 1cm distal to the knee joint bilaterally. The left tibia was filled with Simplex particulate cement polymer (PMMA) and the right tibia was used as control. The first nine groups respectively received terfenadine 1mg/kg, 10mg/kg and 25mg/kg, alprazolam 0.08mg/kg, 0.32mg/kg and 0.64mg/kg, and naproxen 1mg/kg, 5mg/kg and 25mg/kg; however, the tenth group received no drug and served as control. The animals were killed after 16 weeks and implant areas were harvested aseptically and studied by one pathologist.

Results: Our study revealed that the cellular reaction in the left side was statistically more than the right one in all cases (p< 0.05). Also, a significant decrease in histiocytes and giant cells was seen just in those groups that had received 10mg/kg and 25mg/kg of terfenadine, 0.32mg/kg and 0.64mg/kg of alprazolam and 5mg/kg and 25mg/kg of naproxen (P< 0.05) while administration of 1mg/kg naproxen resulted in significant decrease only in giant cells (P< 0.05) but not in histiocytes.

Discussion: Previous studies have suggested that particulate debris, PGE2 production and inflammatory response are associated with arthroplasty loosening. This experiment has demonstrated that the increased cellular reaction by the membrane surrounding particulate cement polymer can be suppressed by administration of PGE2, PAF and histamine specific inhibitors. The use of these agents may be indicated in retarding the bone loss associated with early prosthetic loosening.

Local antimicrobial therapy is an integral aspect of treating orthopaedic device related infection (ODRI), which is conventionally administered via polymethylmethacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibioticloaded hydrogel in a single- stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in. sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture negative. Antibiotic delivery via hydrogel resulted in 10–100 times greater local concentrations for the first 2–3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use

Osteosarcoma and other types of bone cancers often require bone resection, and backfill with cement. A novel silorane-based cement without PMMA's drawbacks, previously developed for dental applications, has been reformulated for orthopedic use. The aim of this study is to assess each cement's ability to elute doxorubicin, maintain its potency, and maintain suitable weight-bearing strength. The silorane-based epoxy cement was synthesized using a platinum-based Lamoreaux's catalyst. Four groups of cement were prepared. Two PMMA groups, one without any additives, one with 200 mg of doxorubicin. Two silorane groups: one without any additive, one with doxorubicin, added so that the w% of drug into both cements were equal. Pellets 6 × 12 mm were used for testing (ASTM F451). n=10. Ten pellets from each group were kept dry. All others were placed into tubes containing 2.5 mL of PBS and stored at 37 °C. Elution from doxorubicin-containing groups were collected every day for 7 days, with daily PBS changeout. Antibiotic concentrations were determined via HPLC. Compressive strength and compressive modulus of all groups were determined for unsoaked specimens, and those soaked for 7 and 14 days. MTT assays were done using an MG63 osteosarcoma cell line. Both cements were able to elute doxorubicin over 7 days in clinically-favorable quantities. For PMMA samples, the incorporation of doxorubicin was shown to significantly affect the compressive strength and modulus of the samples (p<0.01). Incorporation of doxorubicin into silorane had no significant effect on either (p>.05). MTT assays indicated that doxorubicin incorporated into the silorane cement maintained its effectiveness whereas that into PMMA did not. At the dosing used, both cements remained above the 70 MPa. Both PMMA and silorane-based cements can deliver doxorubicin. Doxorubicin, however, interacts chemically with PMMA, inhibiting polymerization and lowering the chemotherapeutic's effectiveness

Polymethylmethacrylate (PMMA) bone cement is strong in compression, however it tends to fail under torsion. Sufficient pressurisation and subsequent interdigitation between cement and bone are critical for the mechanical interlock of cemented orthopaedic implants, and an irregular surface on the acetabular cup is necessary for reasonable fixation at the cup-cement interface. There is limited literature investigating discrepancies in the failure mechanisms of cemented all-polyethylene acetabular cups with and without cement spacers, under torsional loading. In vitro experimental comparison of three groups of polyethylene acetabular prosthesis (PAP) cemented into prepared sawbone hemipelvises:. * PAP without PMMA spacers maintaining an equal cement mantle circumferentially. (Group 1 n=3). * PAP without PMMA spacers cemented deliberately ‘bottoming-out’ the implant within the acetabulum. (Group 2 n=3). * PAP with PMMA spacers. (Group 3 n=3). The constructs were tested to torstional failure on a custom designed setup, and statistical analysis done by a one-way ANOVA and Tukey-Welsh test. Group 3 demonstrated superior torsional resistance with a statistically significant torque of 145Nm (SD±12Nm) at failure, compared to group 2 (109Nm, SD±7Nm) and group 1 (99Nm, SD±8Nm). Group 3 experienced failure predominantly at the bone-cement interface, in contrast, Groups 1 and 2 exhibited failure predominantly at the cup-cement interface. There was no significant difference between Group 1 and 2. Qualitative analysis of the failure mode indicates the efficient redistribution of stress throughout the cement mantle, consistent with the greater uniformity of cement. PMMA spacers increase the resistance to torsional failure at the implant-cement interface. Acetabular components without spacers (Groups 1 and 2) failed at the implant-cement interface before the cement-bone interface, at a statistically significantly lower level of torque to failure. Although the PMMA spacers may reduce cement interdigitation at the cement-bone interface the torsional forces required to fail are likely supraphysiological

Great strides have been made in the early detection and treatment of cancer which is resulting in improved survivability and more Canadians living with cancer. Approximately 80% of primary breast, lung, and prostate cancers metastasize to the spine. Poly-methyl methacrylate (PMMA) bone cement is one of the most commonly used bone substitutes in spine surgery. In clinical practice it can be loaded with various drugs, such as antibiotics or chemotheraputic drugs, as a means of local drug delivery. However, studies have shown that drugs loaded into PMMA cement tend to release in small bursts in the first 48–72 hours, and the remaining drug is trapped without any significant release over time. The objective of this study is to develop a nanoparticle-functionalized PMMA cement for use as a sustained doxorubicin delivery device. We hypothesize that PMMA cement containing mesoporous silica nanoparticles will release more doxorubicin than regular PMMA. High viscosity SmartSet ™ PMMA cement by DePuy Synthes was used in this study. The experimental group consisted of 3 replicates each containing 0.24 g of mesoporous silica nanoparticles, 1.76 g of cement powder, 1ml of liquid cement monomer and 1 mg of doxorubicin. The control group consisted 3 replicates each containing 2.0 g of cement powder, 1ml of liquid cement monomer and 1 mg of doxorubicin. The experimental group contained an average of 8.18 ± 0.008 % (W/W) mesoporous silica nanoparticles. Each replicate was casted into a cylindrical block and incubated in a PBS solution which was changed at predetermined intervals for 45 days. The concentration of eluted doxorubicin in each solution was measured using a florescent plate reader. The mechanical properties of cement were assessed by unconfined compression testing. The effect of the doxorubicin released from cement on prostate and breast tumor cell metabolic activity was assessed using the Alamar Blue test. After 45 days the experimental group released 3.24 ± 0.25 % of the initially loaded doxorubicin which was more than the 2.12 ± 0.005% released by the control group (p 0.03). There was no statistically significant difference in Young's elasticity modulus between groups (p 0.53). Nanoparticle functionalized PMMA suppressed the metabolic activity of prostate cancer by more than 50 percent but did not reach statistical significance. Nanoparticle functionalized PMMA suppressed the metabolic activity of breast cancer cells by 69 % (p < 0.05). Nanoparticle-functionalized PMMA cement can release up to 1.53 times more doxorubicin than the standard PMMA. The use of mesoporous silica nanoparticles to improve drug release from PMMA cement shows promise. In the future, in vivo experiments are required to test the efficacy of released doxorubicin on tumor cell growth

Treatment of bone infection often includes a burdensome two-stage revision. After debridement, contaminated implants are removed and replaced with a non-absorbable cement spacer loaded with antibiotics. Weeks later, the spacer is exchanged with a bone graft aiding bone healing. However, even with this two-stage approach infection persists. In this study, we investigated whether a novel 3D-printed, antibiotic-loaded, osteoinductive calcium phosphate scaffold (CPS) is effective in single-stage revision of an infected non-union with segmental bone loss in rabbits. A 5 mm defect was created in the radius of female New Zealand White rabbits. The bone fragment was replaced, stabilized with cerclage wire and inoculated with Staphylococcus aureus (MSSA). After 4 weeks, the infected bone fragment was removed, the site debrided and a spacer implanted. Depending on group allocation, rabbits received: 1) PMMA spacer with gentamycin; 2) CPS loaded with rifampin and vancomycin and 3) Non-loaded CPS. These groups received systemic cefazolin for 4 weeks after revision. Group 4 received a loaded CPS without any adjunctive systemic therapy (n=12 group1-3, n=11 group 4). All animals were euthanized 8 weeks after revision and assessed by quantitative bacteriology or histology. Covariance analysis (ANCOVA) and multiple regression were performed. All animals were culture positive at revision surgery. Half of the animals in all groups had eliminated the infection by end of study. In a historical control group with empty defect and no systemic antibiotic treatment, all animals were infected at euthanasia. There was no significant difference in CFU counts between groups at euthanasia. Our results show that treating an osteomyelitis with segmental bone loss either with CPS or PMMA has a similar cure rate of infection. However, by not requiring a second surgery, the use of CPS may offer advantages over non-resorbable equivalents such as PMMA

Residual tumor cells left in the bone defect after malignant bone tumor resection can result in local tumor recurrence and high mortality. Therefore, ideal bone filling materials should not only aid bone reconstruction or regeneration, but also exert local chemotherapeutic efficacy. However, common bone substitutes used in clinics are barely studied in research for local delivery of chemotherapeutic drugs. Here, we aimed to use facile manufacturing methods to render polymethylmethacrylate (PMMA) cement and ceramic granules suitable for local delivery of cisplatin to limit bone tumor recurrence. Porosity was introduced into PMMA cement by adding 1-4% carboxymethylcellulose (CMC) containing cisplatin, and chemotherapeutic activity was rendered to two types of granules via adsorption. Then, mechanical properties, porosity, morphology, drug release kinetics, ex vivo reconstructive properties of porous PMMA and in vitro anti-cancer efficacy against osteosarcoma cells were assessed. Morphologies, molecular structures, drug release profiles and in vitro cytostatic effects of two different drug-loaded granules on the proliferation of metastatic bone tumor cells were investigated. The mechanical strengths of PMMA-based cements were sufficient for tibia reconstruction at CMC contents lower than 4% (≤3%). The concentrations of released cisplatin (12.1% and 16.6% from PMMA with 3% and 4% CMC, respectively) were sufficient for killing of osteosarcoma cells, and the fraction of dead cells increased to 91.3% within 7 days. Functionalized xenogeneic granules released 29.5% of cisplatin, but synthetic CaP granules only released 1.4% of cisplatin over 28 days. The immobilized and released cisplatin retained its anti-cancer efficacy and showed dose-dependent cytostatic effects on the viability of metastatic bone tumor cells. Bone substitutes can be rendered therapeutically active for anticancer efficacy by functionalization with cisplatin. As such, our data suggest that multi-functional PMMA-based cements and cisplatin-loaded granules represent viable treatment options for filling bone defects after bone tumor resection

Introduction. The medical field has long held largely anecdotal beliefs that polymethyl methacrylate (PMMA) vapors are dangerous to a growing fetus, and as such, women who are pregnant should avoid exposure. This study investigates the perceptions of female orthopedic surgeons regarding PMMA cement exposure during pregnancy, and if it influences 1) currently held beliefs / practices and 2) clinical and career choices. Methods. A 23-question survey was distributed via e-mail to active members of the Ruth Jackson Orthopaedic Society and a private social media group for women in orthopedics. Questions included demographics, current usage of PMMA, previous exposure during pregnancy and/or breastfeeding, and beliefs regarding current or future willingness of exposure. Additionally, questions were asked regarding PMMA training and whether beliefs influenced specialty choices. Results. There were 278 survey responses received, of which 256 met inclusion criteria. 73% currently utilize PMMA in training/practice, and >90% of survey respondents reported awareness of risks surrounding PMMA in pregnancy. PMMA training was found to have a weak positive correlation with those who remained in the room while pregnant. 43.6% would leave the room in the future if PMMA were being used while they were pregnant, with 26.2% leaving if they were breastfeeding. 24.9% would leave if they were the primary surgeon on the case, and 8.4% admitted that PMMA exposure during pregnancy factored into which subspecialty they chose. Conclusion. This survey demonstrates a lack of consensus amongst female orthopedic surgeons regarding the risks posed by remaining in a room during pregnancy and breastfeeding while PMMA is used. Despite 90% of respondents claiming awareness of the risks of PMMA, beliefs and education practices should be examined to determine if they match the available literature. It is plausible that beliefs regarding this exposure are deterring individuals from pursuing specialties where PMMA is used regularly. For any tables or figures, please contact the authors directly

In chronically infected fracture non-unions, treatment requires extensive debridement to remove necrotic and infected bone, often resulting in large defects requiring elaborate and prolonged bone reconstruction. One approach includes the induced membrane technique (IMT), although the differences in outcome between infected and non-infectious aetiologies remain unclear. Here we present a new rabbit humerus model for IMT secondary to infection, and, furthermore, we compare bone healing in rabbits with a chronically infected non-union compared to non-infected equivalents. A 5 mm defect was created in the humerus and filled with a polymethylmethacrylate (PMMA) spacer or left empty (n=6 per group). After 3 weeks, the PMMA spacer was replaced with a beta-tricalcium phosphate (chronOs, Synthes) scaffold, which was placed within the induced membrane and observed for a further 10 weeks. The same protocol was followed for the infected group, except that four week prior to treatment, the wound was inoculated with Staphylococcus aureus (4×10. 6. CFU/animal) and the PMMA spacer was loaded with gentamicin, and systemic therapy was applied for 4 weeks prior to chronOs application. All the animals from the infected group were culture positive during the first revision surgery (mean 3×10. 5. CFU/animal, n= 12), while at the second revision, after antibiotic therapy, all the animals were culture negative. The differences in bone healing between the non-infected and infected groups were evaluated by radiography and histology. The initially infected animals showed impaired bone healing at euthanasia, and some remnants of bacteria in histology. The non-infected animals reached bone bridging in both empty and chronOs conditions. We developed a preclinical in vivo model to investigate how bacterial infection influence bone healing in large defects with the future aim to explore new treatment concepts of infected non-union

Aims. The aim of this study was to determine if the local delivery of vancomycin and tobramycin in primary total knee arthroplasty (TKA) can achieve intra-articular concentrations exceeding the minimum inhibitory concentration thresholds for bacteria causing acute prosthetic joint infection (PJI). Methods. Using a retrospective single-institution database of all primary TKAs performed between January 1 2014 and May 7 2019, we identified patients with acute PJI that were managed surgically within 90 days of the initial procedure. The organisms from positive cultures obtained at the time of revision were tested for susceptibility to gentamicin, tobramycin, and vancomycin. A prospective study was then performed to determine the intra-articular antibiotic concentration on postoperative day one after primary TKA using one of five local antibiotic delivery strategies with tobramycin and/or vancomycin mixed into the polymethylmethacrylate (PMMA) or vancomycin powder. Results. A total of 19 patients with acute PJI after TKA were identified and 29 unique bacterial isolates were recovered. The mean time to revision was 37 days (6 to 84). Nine isolates (31%) were resistant to gentamicin, ten (34%) were resistant to tobramycin, and seven (24%) were resistant to vancomycin. Excluding one Fusobacterium nucleatum, which was resistant to all three antibiotics, all isolates resistant to tobramycin or gentamicin were susceptible to vancomycin and vice versa. Overall, 2.4 g of tobramycin hand-mixed into 80 g of PMMA and 1 g of intra-articular vancomycin powder consistently achieved concentrations above the minimum inhibitory concentrations of susceptible organisms. Conclusion. One-third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides commonly mixed into PMMA, and one-quarter were resistant to vancomycin. With one exception, all bacteria resistant to tobramycin were susceptible to vancomycin and vice versa. Based on these results, the optimal cover for organisms causing most cases of acute PJI after TKA can be achieved with a combination of tobramycin mixed in antibiotic cement, and vancomycin powder. Cite this article: Bone Joint J 2020;102-B(6 Supple A):163–169

Introduction. Degeneration of the cervical spine can lead to neurological symptoms that require surgical intervention. Often, an anterior cervical discectomy (ACD) with fusion is performed with interposition of a cage. However, a cage substantially increases health care costs. The polymer polymethylmethacrylate (PMMA) is an alternative to cages, associated with lower costs. The reported high-occurrence of non-fusion with PMMA is often seen as a drawback, but evidence for a correlation between radiological fusion and clinical outcome is absent. To investigate if the lower rate of fusion with PMMA has negative effects on long-term clinical outcome, we assessed the clinical results of ACD with PMMA as a intervertebral spacer with a 5–10 year follow-up. Methods. A retrospective cohort study among all patients who underwent a mono-level ACD with PMMA for degenerative cervical disease, between 2007–2012, was performed. Patients filled out an online questionnaire, developed to assess clinical long-term outcome, complications and re-operation rates. The primary outcome measure was the Neck Disability Index (NDI), secondary outcome measures were re-operation and complication rates. Results. Of 196 eligible patients, 90 patients were assessed (response rate 53%). The average NDI score at follow-up (mean 7.5 years) was 19.0 points ± 18.0 points. Complications occurred in 10% and re-operation in 8.8%. Conclusion. This study provides evidence of good long-term clinical results of ACD with PMMA, as the results were similar with long-term outcomes of ACD with a cage as spacer. Therefore, the results of this study may suggest that the use of PMMA is an lower-cost alternative. No conflicts of interests. No funding obtained

Objectives. Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study. Methods. A total of 12 patients with prosthetic hip infections were included for a three-stage revision procedure. All patients received either a gentamicin-PMMA spacer (80 g to 160 g PMMA depending on hip joint dimension) with additional loading of 1% (w/w) of microsilver (0.8 g to 1.6 g per spacer) at surgery 1 followed by a gentamicin-PMMA spacer without microsilver at surgery 2 or vice versa. Implantation of the revision prosthesis was carried out at surgery 3. Results. In total, 11 of the 12 patients completed the study. No argyria or considerable differences in laboratory parameters were detected. Silver blood concentrations were below or around the detection limit of 1 ppb in ten of the 11 patients. A maximum of 5.6 ppb at 48 hours after implantation of the silver spacer, which is below the recommended maximum level of 10 ppb, was found in one patient. No silver was detected in the urine. Drainage fluids showed concentrations between 16.1 ppb and 23.3 ppb at 12 hours after implantation of the silver spacers, and between 16.8 ppb to 25.1 ppb at 48 hours after implantation. Pathohistological assessment of the periprosthetic membrane did not reveal any differences between the two groups. Conclusion. Microsilver-loaded gentamicin-PMMA spacers showed good biocompatibility and the broad antimicrobial activity warrants further clinical research to assess its effectivity in reducing infection rates in prosthetic joint infection. Cite this article: V. Alt, M. Rupp, K. Lemberger, T. Bechert, T. Konradt, P. Steinrücke, R. Schnettler, S. Söder, R. Ascherl. Safety assessment of microsilver-loaded poly(methyl methacrylate) (PMMA) cement spacers in patients with prosthetic hip infections: Results of a prospective cohort study. Bone Joint Res 2019;8:387–396. DOI: 10.1302/2046-3758.88.BJR-2018-0270.R1

Abstract. Objectives. The principle of osteoporotic vertebral compression fracture (OVCF) is fixing instability, providing anterior support, and decompression. Contraindication for vertebroplasty is anterior or posterior wall fracture. The study objectives was to evaluate the efficacy and safety of vertebroplasty with short segmented PMMA cement augmented pedicle screws for OVCF with posterior/anterior wall fracture patients. Methods. A retrospective study of 24 patients of DGOU type-4 (vertebra plana) OVCF with posterior/anterior wall fracture, were treated by vertebroplasty and short segment PMMA cement augmented pedicle screws fixation. Radiological parameters (kyphosis angle and compression ratio) and clinical parameters Visual analogue scale (VAS) and Oswestry disability index (ODI) were analysed. Results. A significant improvement was noted in VAS (preoperative, 7.90 ±0.60; final follow-up 2.90 ± 0.54) and ODI (77.10 ± 6.96 to 21.30 ± 6.70), (P < 0.05). Neurological improvement was noted in all patients. Kyphosis corrected significantly from preoperative 23.20±5.90 to 5.30±1.40 postoperative with 5% (3.30± 2.95) loss of correction at final follow-up. Anterior vertebral height restored significantly from 55.80±11.9% t0 87.6±13.1% postoperative with 4.5±4.0% loss at final follow-up. One case had cement leakage was found, but the patient is asymptomatic. No implant-related complication was seen. No iatrogenic dural or nerve injury. Conclusions. Treatment with vertebroplasty with cement augmented screw fixation and direct decompression is a great option in treating such a complex situation in fragile age with fragile bones because It provides anterior support with cementing that avoids corpectomy. Short segment fixation has less stress risers at the junctional area

Objectives. The objective of this study was to characterize the effect of rifampin incorporation into poly(methyl methacrylate) (PMMA) bone cement. While incompatibilities between the two materials have been previously noted, we sought to identify and quantify the cause of rifampin’s effects, including alterations in curing properties, mechanical strength, and residual monomer content. Methods. Four cement groups were prepared using commercial PMMA bone cement: a control; one with 1 g of rifampin; and one each with equimolar amounts of ascorbic acid or hydroquinone relative to the amount of rifampin added. The handling properties, setting time, exothermic output, and monomer loss were measured throughout curing. The mechanical strength of each group was tested over 14 days. A radical scavenging assay was used to assess the scavenging abilities of rifampin and its individual moieties. Results. Compared with control, the rifampin-incorporated cement had a prolonged setting time and a reduction in exothermic output during polymerization. The rifampin cement showed significantly reduced strength and was below the orthopaedic weight-bearing threshold of 70 MPa. Based on the radical scavenging assay and strength tests, the hydroquinone structure within rifampin was identified as the polymerization inhibitor. Conclusion. The incorporation of rifampin into PMMA bone cement interferes with the cement’s radical polymerization. This interference is due to the hydroquinone moiety within rifampin. This combination alters the cement’s handling and curing properties, and lowers the strength below the threshold for weight-bearing applications. Additionally, the incomplete polymerization leads to increased toxic monomer output, which discourages its use even in non-weight-bearing applications. Cite this article: G. A. Funk, E. M. Menuey, K. A. Cole, T. P. Schuman, K. V. Kilway, T. E. McIff. Radical scavenging of poly(methyl methacrylate) bone cement by rifampin and clinically relevant properties of the rifampin-loaded cement. Bone Joint Res 2019;8:81–89. DOI: 10.1302/2046-3758.82.BJR-2018-0170.R2

Aim. The preparation of antibiotic-containing polymethyl methacrylate (PMMA), as spacers generates a high polymerization heat, which may affect their antibiotic activity; it is desirable to use bone cement with a low polymerization heat. Calcium phosphate cement (CPC) does not generate heat on polymerization, and comparative elution testings are reported that vancomycin (VCM)-containing CPC (VCM-CPC) exceeded the antibiotic elution volume and period of PMMA (VCM-PMMA). Although CPC alone is a weak of mechanical property spacer, the double-layered, PMMA-covered CPC spacer has been created and clinically used in our hospital. In this study, we prepared the double-layered spacers: CPC covered with PMMA and we evaluated its elution concentration, antimicrobial activity and antibacterial capability. Method. We prepared spherical, double-layered, PMMA-coated (CPC+PMMA; 24 g CPC coated with 16 g PMMA and 2 g VCM) and PMMA alone (40 g PMMA with 2 g VCM) spacers (5 each). In order to facilitate VCM elution from the central CPC, we drilled multiple holes into the CPC from the spacer surface. Each spacer was immersed in phosphate buffer (1.5 mL/g of the spacer), and the solvent was changed daily. VCM concentrations were measured on days 1, 3, 7, 14, 28, 56, and 84. Antimicrobial activity against MRSA and MSSA was evaluated by the broth microdilution method. After measuring all the concentration, the spacers were compressed at 5 mm/min and the maximum compressive load up to destruction was measured. Results. The VCM concentration of the CPC+PMMA spacer exceeded that of the PMMA spacer at all-time points; in particular, it was approximately 7.3 times (109.30 vs. 15.03 μg/mL) and approximately 9.1 times (54.47 vs. 6.50 μg/mL) greater on days 14 and 28, respectively. Using the broth microdilution method, we found that the CPC+PMMA spacer had higher antimicrobial activity than the PMMA model. On day 56, the PMMA spacer lost the capability to inhibit bacterial growth, but the CPC+PMMA spacer maintained this ability. The average maximum compressive load for the CPC+PMMA was 7.28 kN, and that of PMMA was 16.21 kN. Conclusions. The CPC+PMMA spacer was superior to PMMA alone in VCM elution volume and duration, so CP- C+PMMA may be effective for the treatment of MRSA and MSSA infection. The double-layered, antibiotic-loaded cement spacer may maintain antibacterial capability and sufficient strength

Aim. We aimed to compare the in vitro antibacterial activity of Bioactive Glass (BAG) S53P4, which is a compound showing local antibacterial activity, to that of antibiotic-loaded polymethylmethacrylate (PMMA) against multidrug resistant bacteria from osteomyelitis (OM) and prosthetic joint infection (PJI) isolates. Method. We studied convenience samples of multidrug resistant (MDR) microorganisms obtained from patients presenting OM and prosthetic joint infection (PJI). Mixtures containing tryptic soy broth (TSB) and inert glass beads (2mm), BAG-S53P4 granules (0.5–0.8mm and <45 mm) and Gentamicin or Vancomycin-loaded PMMA beads were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MR-CoNS), Pseudomonas aeruginosa or Klebsiella pneumoniae isolates. Glass beads (2.0mm) were used as a control. Antibacterial activity was evaluated by means of time-kill curve, through seeding the strains on blood agar plates, and subsequently performing colony counts after 24, 48, 72, 96, 120 and 168 hours of incubation. Differences between groups were evaluated by means of two-way analysis of variance (ANOVA) and Bonferroni's t test. Results. Inhibition of bacterial growth started soon after 48 hours of incubation, reached zero CFU/ml between 120 and 168 hours of incubation for both antibiotic-loaded PMMA and BAG S53P4 groups, in comparison with inert glass (p< 0.05). No difference regarding time-kill curves between antibiotic-loaded PMMA and BAG S53P4 was observed. Moreover, despite no difference was observed between both Vancomycin - or Gentamicin-loaded PMMA and BAG groups, there was statistical difference between the effectiveness of all treatments (BAG included) against gram-positive cocci and gram-negative bacilli, the latter of which requiring longer time frames for the cultures to yield no bacterial growth. Conclusions. BAG S53P4 presented antibacterial properties as much as antibiotic-loaded PMMA for MDR bacteria producing OM and PJI, although presenting differences between its effectiveness against different bacterial groups

Objectives. The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. Methods. Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student t-test (two tailed; p < 0.05 was considered significant). Results. Average PMMA spacer in vivo time was 11.9 weeks (six to 18). Trabecular bone was present in 33.3% of the biomembrane specimens; bone presence did not correlate with spacer duration. Biomembrane morphology showed high vascularity and collagen content and positive staining for the key bone forming regulators, bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2). Positive differentiation of cultured biomembrane cells for osteogenesis was found in cells from patients with PMMA present for six to 17 weeks. Stem cell differentiation showed greater variability in pluripotency for osteogenic potential (70.0%) compared with chondrogenic or adipogenic potentials (100% and 90.0%, respectively). Significant upregulation of BMP2 and 6, numerous collagens, and bone gla protein was present in biomembrane compared with the cultured cell line. Biomembranes with longer resident PMMA spacer duration (vs those with shorter residence) showed significant upregulation of bone-related, stem cell, and vascular-related genes. Conclusion. The biomembrane technique is gaining favour in the management of complicated bone defects. Novel data on biological mechanisms provide improved understanding of the biomembrane’s osteogenic potential and molecular properties. Cite this article: Dr H. E. Gruber. Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects. Bone Joint Res 2016;5:106–115. DOI: 10.1302/2046-3758.54.2000483

Introduction. The management of open long bone fractures is well described and has been standardised through a number of well-established guidelines. However, there is no consensus regarding the application of local antibiotics into the open fracture site as a means of reducing infection rates. Materials & Methods. A systematic review and meta-analysis were undertaken as per PRISMA guidelines. PROSPERO Registration CRD42022323545. PubMed, EMBASE, Scopus and CENTRAL were the databases assessed. The Newcastle Ottawa Scale and the Rob 2 Tool were used to assess bias. A qualitative synthesis of all included studies and meta-analysis of suitable subgroups was undertaken. Results. In total, 12 studies (11 observational, 1 RCT) assessing 2431 open fractures were included for analysis. All compared the addition of a local antibiotic therapy to a standard treatment versus the standard treatment alone. The methods of delivery were vancomycin powder (4 papers), tobramycin polymethylmethacrylate beads (4 papers), gentamicin coated intramedullary (IM) nails (2 papers), gentamicin injections (1 paper) and antibiotic released IM core cement (1 paper). The addition of vancomycin powder did not decrease infection rates in comparison to intravenous antibiotics alone (OR 1.3, 95% CI (0.75 – 2.26)). Antibiotic coated IM Nails appear to have an association with lower infection rates than standard IM Nails. PMMA antibiotics have shown varied results in reducing infection rates depending on the individual studies. Conclusions. There are numerous methods available to deliver antibiotics locally to an open fracture site. Further high-quality research is required to provide a definitive conclusion on their efficacy irrespective of delivery method

The burden of periprosthetic joint infection (PJI) continues to rise and the management of this dreaded complication continues to pose challenges to the orthopaedic community. Dr Buchholz from the Endo Klinik has been credited for reporting the initial observation that addition of antibiotic to polymethylmethacrylate (PMMA) cement lead to better ability to deliver higher concentrations of antibiotic to the joint milieu and avoid administration of high doses of systemic antibiotics with potential for systemic toxicity. Addition of antibiotics to PMMA cement has continued to be an important aspect of managing patients with chronic PJI. The rationale for this practice is that higher doses of local antibiotics can be reached without placing the patients at risk of systemic toxicity. Whether a one-stage or a two-stage exchange arthroplasty is being performed, antibiotics that can withstand the exothermic reaction of PMMA and are able to elude from cement are added at various doses to the PMMA for later delivery. Although this practice continues to be almost universal, there are a few unknowns. First of all, a recent study raised a valid question regarding this practice. Though intuitively logical, addition of antibiotics to PMMA spacers has not been scrutinised by any level 1 study and hence one is not able to prove that this practice does indeed accomplish its intended objectives of reducing recurrence or persistence of infection. Orthopaedic community is advised to seek avenues to generate this much-needed evidence. The other main unknown is how much, and in some instances which antibiotic, needs to be added to the PMMA cement. Some authorities have declared that antibiotics can be added at high doses, with an average total dose of 10.5 g of vancomycin (range, 3–16 g) and 12.5 g of gentamicin (range, 3.6–19.2 g) in one study, to PMMA cement without the fear of systemic toxicity. In recent years, renal toxicity and other systemic adverse effects have been attributed to addition of high doses of antibiotics to cement. I have personally witnessed such adverse reactions in a few patients. Although initially I was inclined to “blame” the concurrent administration of systemic antibiotics for the renal toxicity that patients developed following insertion of spacer, selective nephrotoxicity (i.e. reaction to aminoglycoside that was only present in the spacer and not systemically administered) and resolution of the nephrotoxicity upon removal of antibiotic spacer, convinced me that our nephrology colleagues have a valid reason to be concerned about addition of high doses of antibiotics to PMMA spacers. What has become clear is that high viscosity cements containing MA-MMA copolymers have been shown to have better antibiotic elution profiles than other PMMA formulations. So when fashioning a spacer in the operating room the surgeon needs to be aware of the differences in elution profile of antibiotics from PMMA and individualise the dose of antibiotics being added to spacer based on the type and viscosity of cement being used and the renal status of the patient. Thus, systemic toxicity caused by addition of antibiotics to cement spacer appears to be a real issue in some circumstances and this needs to be born in mind when managing patients with PJI. There are numerous other issues related to the use of antibiotic cement spacers. In the hip, the lack of adequate offset and limited portfolio of products result in laxity in the soft tissue and subsequent dislocation of the hip. In addition, the dose and type of antibiotic in the premanufactured spacers, at least in the US, are inadequate to lead to a substantial delivery of antibiotics in the local tissues. Because of these issues, I prefer to fabricate “customised” spacers for each patient that I operate on

The enhancement of current bone cement properties is a challenging issue that has been the focus of much research. Developing bone composites with high level of cytocompatibility, mechanical and antibacterial properties is a challenging task. We overcome this challenge by designing a nanocomposite that contain two-dimensional (2D) nanosheets. To develop our novel bone cement nanocomposite, 2D nanosheets were synthesized, mixed in different ratios, and then added to the PMMA matrix. The results reveal that the incorporation of 2D nanosheets into the PMMA matrix leads to increase in the antibacterial properties of the bone cement composite against E. coli bacteria. In addition, the 2D nanosheets improve the compression strength of the bone cement nanocomposite significantly. We also show that nanosheets increased the bioactivity of the bone cements. Finally, MTT assay results indicate that PMMA as a control sample has the lowest cytocompatibility, however, our novel nanocomposites have the highest amount of cytocompatibility. Thus, the current study suggests that 2D nanosheets are potential filler components for the next generation of PMMA bone cement nanocomposites. The findings of this work reveal that the excellent performance of the proposed bone composite can result in a paradigm shift in design of state-of-the art bone cement composites

A spine compression fracture is a very common form of fracture in elderly with osteoporosis. Injection of polymethyl methacrylate (PMMA) to fracture sites is a minimally invasive surgical treatment, but PMMA has considerable clinical risks. We develop a novel type thermoplastic injectable bone substitute contains the proprietary composites of synthetic ceramic bone substitute and absorbable thermoplastic polymer. We used thermoplastic biocompatible polymers Polycaproactone (PCL) to encapsulate calcium-based bone substitutes hydroxyapatite (Ca10(PO4)6(OH)2, HA) and tricalcium phosphate (TCP) to form a biodegradable injectable bone composite material. The space occupation ration PCL:HA/TCP is 1:9. After heating process, it can be injected to fracture site by specific instrument and then self-setting to immediate reinforce the vertebral body. The thermoplastic injection bone substitute can obtain good injection properties after being heated by a heater at 90˚C for three minutes, and has good anti-washout property when injected into normal saline at 37˚C. After three minutes, solidification is achieved. Mechanical properties were assessed using the material compression test system and the mechanical support close to the vertebral spongy bone. In vitro cytotoxicity MTT assay (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was performed and no cell cytotoxicity was observed. In vivo study with three New Zealand rabbits was performed, well bone growth into bone substitute was observed and can maintain good mechanical support after three months implantation. The novel type thermoplastic injection bone substitute can achieve (a) adequate injectability and viscosity without the risk of cement leakage; (b) adequate mechanical strength for immediate reinforcement and prevent adjacent fracture; (c) adequate porosity for new bone ingrowth; (e) biodegradability. It could be developed as a new option for treating vertebral compression fractures

Multiple studies have established an inverse relationship between ambient theatre temperatures and polymethyl methacrylate (PMMA) cement setting times. It is also known that allowing cement to equilibrate to ambient theatre temperatures restores expected setting characteristics. One overlooked entity is the transport and storage conditions of cement. This is important in tropical regions, where extreme temperature and humidity may cause rapid cement setting times, resulting in potentially significant intra-operative complications. This study investigated the relationship between extreme transport and storage conditions of Antibiotic Simplex cement (Stryker), and the effect on setting times at Cairns Hospital, Far North Queensland, Australia. Fifty units of cement were divided evenly into a control arm and four experimental arms. The experimental arms were designed to mimic potential transport and storage conditions. They included seven days of storage in a medication fridge, on the hospital loading dock, in a cane shed, and in a Toyota Landcruiser parked outdoors during January 2022. Humidity and temperature readings were recorded. The samples in each group were evenly distributed to equilibrate to theatre conditions for 1 hour and 24 hours. Setting time was recorded when a no. 15 scalpel blade was unable to mark the surface. All three ‘hot’ exposures setting times were significantly faster for both 1 hour (ρ=0.001) and 24 hours (ρ=0.024) equilibration times. The difference in setting times for the ‘cold’ exposure was not significant for either equilibration times (ρ=1). To our knowledge, this is the first study investigating cement setting times in tropical climates. Further studies are required to address the effect of these conditions on biomechanical strength of PMMA cement. We conclude that extreme heat and humidity during transport and storage have a statistically significant effect on cement setting times

Majority of osteoporosis related fractures are treated surgically using metallic fixation devices. Anchorage of fixation devices is sometimes challenging due to poor osteoporotic bone quality that can lead to failure of the fracture fixation. Using a rat osteoporosis model, we employed neutron tomography and histology to study the biological effects of implant augmentation using an isothermally setting calcium sulphate/hydroxyapatite (CaS/HA) biomaterial with synthetic HA particles as recruiting moiety for systemically administered bisphosphonates. Using an osteoporotic sawbones model, we then provide a standardized method for the delivery of the CaS/HA biomaterial at the bone-implant interface for improved mechanical anchorage of a lag-screw commonly used for hip fracture fixation. As a proof-of-concept, the method was then verified in donated femoral heads and in patients with osteoporosis undergoing hip fracture fixation. We show that placing HA particles around a stainless-steel screw in-vivo, systemically administered bisphosphonates could be targeted towards the implant, yielding significantly higher peri-implant bone formation compared to un-augmented controls. In the sawbones model, CaS/HA based lag-screw augmentation led to significant increase (up to 4 times) in peak extraction force with CaS/HA performing at par with PMMA. Micro-CT imaging of the CaS/HA augmented lag-screws in cadaver femoral heads verified that the entire length of the lag-screw threads and the surrounding bone was covered with the CaS/HA material. X-ray images from fracture fixation surgery indicated that the CaS/HA material could be applied at the lag-screw-bone interface without exerting any additional pressure or risk of venous vascular leakage.: We present a new method for augmentation of lag-screws in fragile bone. It is envisaged that this methodcould potentially reduce the risk of fracture fixation failure especially when HA seeking “bone active” drugs are used systemically

Objectives. Understanding lumbar facet joint involvement and biomechanical changes post spinal fusion is limited. This study aimed to establish an in vitro model assessing mechanical effects of fusion on human lumbar facet joints, employing synchronized motion, pressure, and stiffness analysis. Methods and Results. Seven human lumbar spinal units (age 54 to 92, ethics 15/YH/0096) underwent fusion via a partial nucleotomy model mimicking a lateral cage approach with PMMA cement injection. Mechanical testing pre and post-fusion included measuring compressive displacement and load, local motion capture, and pressure mapping at the facet joints. pQCT imaging (82 microns isotropic) was carried out at each stage to assess the integrity of the vertebral endplates and quantify the amount of cement injected. Before fusion, relative facet joint displacement (6.5 ± 4.1 mm) at maximum load (1.1 kN) exceeded crosshead displacement (3.9 ± 1.5 mm), with loads transferred across both facet joints. After fusion, facet displacement (2.0 ± 1.2 mm) reduced compared to pre-fusion, as was the crosshead displacement (2.2 ± 0.6 mm). Post-fusion loads (71.4 ± 73.2 N) transferred were reduced compared to pre-fusion levels (194.5 ± 125.4 N). Analysis of CT images showed no endplate damage post-fusion, whilst the IVD tissue: cement volume ratio did not correlate with the post-fusion behaviour of the specimens. Conclusion. An in vitro model showed significant facet movement reduction with stand-alone interbody cage placement. This technique identifies changes in facet movement post-fusion, potentially contributing to subsequent spinal degeneration, highlighting its utility in biomechanical assessment. Conflicts of interest. None. Sources of funding. This work was funded by EPSRC, under grant EP/W015617/1

Objectives. Investigate the incorporation of an antibiotic in bone cement using liposomes (a drug delivery system) with the potential to promote osseointegration at the bone cement interface whilst maintaining antibiotic elution, anti-microbiological efficacy and cement mechanical properties. Prosthetic joint infection and aseptic loosening are associated with significant morbidity. Antibiotic loaded bone cement is commonly used and successfully reduces infection rates; however, there is increasing resistance to the commonly used gentamicin. Previous studies have shown gentamicin incorporated into bone cement using liposomes can maintain the cement's mechanical properties and improve antibiotic elution. The phospholipid phosphatidyl-l-serine has been postulated to encourage surface osteoblast attachment and in a liposome could improve osseointegration, thereby reducing aseptic loosening. Preliminary clinical isolate testing showed excellent antimicrobial action with amoxicillin therefore the study aims were to test amoxicillin incorporated into bone cement using liposomes containing phosphatidyl-l-serine in terms of antibiotic elution, microbiological profile and mechanical properties. Methods. Amoxicillin was encapsulated within 100nm liposomes containing phosphatidyl-L-serine and added to PMMA bone cement (Palacos R (Heraeus Medical, Newbury, UK)). Mechanical testing was performed according to Acrylic Cement standards (ISO BS 5833:2002). Elution testing was carried out along with microbiological testing utilising clinical isolates. Results. Liposomal encapsulated amoxicillin PMMA bone cement exceeded minimum ISO BS 5833:2002 standards, had better elution at 12.9% when compared with plain amoxicillin (p=0.036 at 48 hours) or commercial gentamicin cement (Palacos R+G, Heraeus Medical, Newbury, UK – previous studies showed 6% elution over the same time period). Amoxicillin showed superior antimicrobial action when compared with gentamicin of the same concentration. However, liposomal encapsulated amoxicillin in solution and liposomal encapsulated amoxicillin in PMMA were both less effective than free amoxicillin in bacterial growth inhibition. The liposomal amoxicillin also seemed to decrease the cement setting time. Conclusions. Phosphatidyl-l-serine containing liposomes maintained the cement's mechanical properties and seemed to have better antibiotic elution, however, had less effective antibacterial action than plain amoxicillin. This difference in antibacterial action requires further investigation along with investigation of osteoblast attachment to phosphatidyl-l-serine containing liposomes within cement. Plain amoxicillin, for those not penicillin allergic, seems to be a credible alternative to gentamicin for incorporation in PMMA bone cement. It has shown superior antibacterial action, which may improve infection rates, whilst maintaining the cement's mechanical properties

Aims. Tissue responses to debris formed by abrasion of polymethylmethacrylate (PMMA) spacers at two-stage revision arthroplasty for prosthetic joint infection are not well described. We hypothesised that PMMA debris induces immunomodulation in periprosthetic tissues. Patients and Methods. Samples of tissue were taken during 35 two-stage revision arthroplasties (nine total hip and 26 total knee arthroplasties) in patients whose mean age was 67 years (44 to 85). Fourier transform infrared microscopy was used to confirm the presence of PMMA particles. Histomorphometry was performed using Sudan Red and Haematoxylin-Eosin staining. CD-68, CD-20, CD-11(c), CD-3 and IL-17 antibodies were used to immunophenotype the inflammatory cells. All slides were scored semi-quantitatively using the modified Willert scoring system. Results. The mean CD-68 scores did not show any significant change during the six weeks between the stages. Perivascular and diffuse scores showed significant difference in CD-3, CD-20, CD-11(c) and IL-17. At the time of re-implantation, a shift in the pattern of the expression of dendritic cells towards a perivascular arrangement and towards the periphery of PMMA particles was observed. Positive microbiological cultures were found at the time of re-implantation in three patients. Five further revisions were required for other reasons. Conclusion. Our results represent a biological reaction of the synovial tissues to spacers with a less diffuse expression of dendritic cells and an increased expression of perivascular lymphocytes. The use of spacers in two-stage revision for infection probably induces an immunomodulation of synovial tissues. Cite this article: Bone Joint J 2016;98-B:1062–8

Intro. Calcium sulphate (CS) is a recent alternative for antibiotic elution in infected bones and joints. The purpose of this study is to evaluate the use of antibiotic impregnated calcium sulphate (AICS) beads in the management of infected tibia and femur, with regards to patient outcomes and complication rates (including reinfection rate, remission rate and union rate). Methods. Searches of AMED, CINAHL, EMBASE, EMCARE, Medline, PubMed and Google Scholar were conducted in June 2020, with the mesh terms: “Calcium sulphate beads” or “Calcium sulfate beads” or “antibiotic beads” or “Stimulan” AND “Bone infection” or “Osteomyelitis” or “Debridement” AND “Tibia” or “Femur”. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of interventions (ROBINS-i) tool, and quality assessed via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. Results. Out of 105 relevant papers, 11 met the inclusion criteria for data extraction. Total infection recurrence rate was 6.8% (range 3.2 – 11.9%, n = 295), which was significantly lower (p < 0.001) than that of polymethylmethacrylate (PMMA; 19.6%, n = 163). Complication rates varied. The main issue regarding AICS use was wound drainage (7.9 – 33.3%), which was considerably higher in studies involving treatment of the tibia only. Studies using PMMA did not experience this issue, but there were a few incidences of superficial pin tract infection following surgery. Conclusions. AICS was consistently effective at infection eradication, despite variation in causative organism and location of bead placement. Additionally, PMMA has many inconvenient properties. AICS is therefore an attractive alternative as an adjunct in treatment of infected tibia and femur. Wound drainage rate varied and was higher in studies regarding tibial cases alone

Abstract. Objectives. While spinal fusion is known to be associated with adjacent disc degeneration, little is known on the role of the facet joints in the process, and whether their altered biomechanics following fusion plays a role in further spinal degeneration. This work aimed to develop a model and method to sequentially measure the effects of spinal fusion on lumbar facet joints through synchronisation of both motion analysis, pressure mapping and mechanical analysis. Methods. Parallel measurements of mature ovine lumbar facet joints (∼8yr old, n=3) were carried out using synchronised load and displacement measurements, motion capture during loading and pressure mapping of the joint spaces during loading. Functional units were prepared and cemented in PMMA endcaps. Displacement-controlled compression measurements were carried out using a materials testing machine (3365, Instron, USA) at 1 mm/min up to 950 N with the samples in a neutral position, while motion capture of the facet joints during compression was carried out using orthogonal HD webcams (Logitech, Switzerland) to measure the displacement of key facet joint features. The pressure mapping of load transfer during displacement was carried out using a flexible pressure sensor (6900 series, Tekscan, USA). Each sample was imaged at an isotropic resolution of 82 microns using a μCT scanner (XtremeCT, Scanco, Switzerland) to quantify the curvature within the facet joints. Results. Relative facet joint displacement under load, in a neutral position, showed more displacement (2.36 ±1.68 mm) compared to the cross-head when under compression (2.06 ±1.19 mm). Motion capture indicated the relative displacement of the facet joints was more posterior with some lateral motion. For five of the six facet joints, pressure measurement was possible only on 24±7 % of the surface due to the large change in curvature. Partially measured loads through the facets was 10.5 ±1.1 N. Conclusions. The relative displacement of the lumbar facet joints compared to the crosshead displacement was consistent with previous studies of cervical facet joints, despite the differences in anatomical geometry between cervical and lumbar joints. The difficulties in accurately measuring the load transfer through the facet joints was due to the age of the tissue and the degree of curvature of the facet joints. Synchronisation of the biomechanical data will provide a setup to assess the effect of interventions such as spinal fusion, with curvature-related issues unlikely to occur in human spines. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Spinal surgery deals with the treatment of different pathological conditions of the spine such as tumors, deformities, degenerative disease, infections and traumas. Research in the field of vertebral surgery can be divided into two main areas: 1) research lines transversal to the different branches; 2) specific research lines for the different branches. The transversal lines of research are represented by strategies for the reduction of complications, by the development of minimally invasive surgical techniques, by the development of surgical navigation systems and by the development of increasingly reliable systems for the control of intra-operative monitoring. Instead, specific lines of research are developed within the different branches. In the field of oncological pathology, the current research concerns the development of in vitro models for the study of metastases and research for the study of targeted treatment methods such as electrochemotherapy and mesenchymal stem cells for the treatment of aneurysmal bone cysts. Research in the field of spinal deformities is focused on the development of increasingly minimally invasive methods and systems which, combined with appropriate pharmacological treatments, help reduce trauma, stress and post-operative pain. Scaffolds based on blood clots are also being developed to promote vertebral fusion, a fundamental requirement for improving the outcome of vertebral arthrodesis performed for the treatment of degenerative disc disease. To improve the management and the medical and surgical treatment of vertebral infections, research has focused on the definition of multidisciplinary strategies aimed at identifying the best possible treatment path. Thus, flow-charts have been created which allow to manage the patient suffering from vertebral infection. In addition, dedicated silver-coated surgical instrumentation and bone substitutes have been developed that simultaneously guarantee mechanical stability and reduce the risk of further local infection. In the field of vertebral traumatology, the most recent research studies have focused on the development of methods for the biostimulation of the bone growth in order to obtain, when possible, healing without surgery. Methods have also been developed that allow the minimally invasive percutaneous treatment of fractures by means of vertebral augmentation with PMMA, or more recently with the use of silicone which from a biomechanical point of view has an elastic modulus more similar to that of bone. It is clear that scientific research has changed clinical practice both in terms of medical and surgical management of patients with spinal pathologies. The results obtained stimulate the basic research to achieve even more. For this reason, new lines of research have been undertaken which, in the oncology field, aim at developing increasingly specific therapies against target receptors. Research efforts are also being multiplied to achieve regeneration of the degenerated intervertebral disc and to develop implants with characteristics increasingly similar to those of bone in order to improve mechanical stability and durability over time. Photodynamic therapies are being developed for the treatment of infections in order to reduce the use of antibiotic therapies. Finally, innovative lines of research are being launched to treat and regenerate damaged nerve structures with the goal, still far from today, of making patients with spinal cord injuries to walk

Polymethylmethacetate (PMMA) is a bone cement used in over 725,000 primary hip arthroplasties in 2018. Cement integrity is affected by external factors, including temperature, mixing technique and moisture uptake, which can influence cement microstructure. Changes in the cement microstructure may ultimately threaten the survivorship of the implant. The introduction of enhanced recovery and various local anaesthetic infiltration techniques have been adopted in an attempt to facilitate early mobilisation and reduce length of stay. Our study aims to investigate if the mechanical properties of PMMA are altered with exposure to Ropivacaine LA. Cements were cured in three separate states (air, serum and serum with LA) and the mechanical properties tested at 24 hours and 28 days. Using Refobacin bone cement provided by ZimmerBIOMET, cylindrical molds (12×6mm) were constructed with a split-mold. The LA used was 2mg/ml Ropivacaine hydrochloride solution. Using pilot data, this study was powered to 80% and a sample size of 10 per group (n=60) was calculated. Cement samples were subjected to compressive loading using a universal testing apparatus (Zwick/Roell). Yield-strength and modulus values were extracted from the respective stress versus strain curves. Significant differences were determined by one-way anova for each time point, and Bonferroni post-hoc testing to determine significance between actual groups. At 24-hours there were no significant differences in strength or modulus between groups. At 28-day strength and modulus increased in all groups. Compared to the air group, both serum and LA groups show a significant decrease in compressive strength. The modulus for the LA group is significantly less stiff compared to the air group. The results suggest that the initial exposure to LA has a significant impact on the physical properties of the PMMA. We propose increased awareness of the potential effects this may have on the longevity and survivorship of cemented implants

Abstract. Objective. Open fracture management in the United Kingdom and several other countries is guided by the British Orthopaedic Association's Standards for Trauma Number 4 (BOAST-4). This is updated periodically and is based on the best available evidence at the time. The aim of this study is to evaluate the evidence base forming this guidance and to highlight new developments since the last version in 2017. Methods. Searches have been performed using the PubMed, Embase and Medline databases for time periods a) before December 31, 2017 and from 01/01/2018–01/02/2021. Results have been summarised and discussed. Results. Several contentious issues remain within the 2017 guideline. Antibiotic guidance, the use of antibiotic impregnated PMMA beads and intramedullary devices, irrigation in the emergency department, time to theatre and the use of negative pressure dressings and guidance regarding the management of paediatric injuries have all demonstrated no clear consensus. Conclusion. The advent of the BOAST-4 guideline has been of huge benefit, however the refinement and improvement of this work remains ongoing. There remains a need for further study into these contentious issues previously listed

Objectives. Third-body wear is believed to be one trigger for adverse results with metal-on-metal (MOM) bearings. Impingement and subluxation may release metal particles from MOM replacements. We therefore challenged MOM bearings with relevant debris types of cobalt–chrome alloy (CoCr), titanium alloy (Ti6Al4V) and polymethylmethacrylate bone cement (PMMA). Methods. Cement flakes (PMMA), CoCr and Ti6Al4V particles (size range 5 µm to 400 µm) were run in a MOM wear simulation. Debris allotments (5 mg) were inserted at ten intervals during the five million cycle (5 Mc) test. . Results. In a clean test phase (0 Mc to 0.8 Mc), lubricants retained their yellow colour. Addition of metal particles at 0.8 Mc turned lubricants black within the first hour of the test and remained so for the duration, while PMMA particles did not change the colour of the lubricant. Rates of wear with PMMA, CoCr and Ti6Al4V debris averaged 0.3 mm. 3. /Mc, 4.1Â mm. 3. /Mc and 6.4 mm. 3. /Mc, respectively. . Conclusions. Metal particles turned simulator lubricants black with rates of wear of MOM bearings an order of magnitude higher than with control PMMA particles. This appeared to model the findings of black, periarticular joint tissues and high CoCr wear in failed MOM replacements. The amount of wear debris produced during a 500 000-cycle interval of gait was 30 to 50 times greater than the weight of triggering particle allotment, indicating that MOM bearings were extremely sensitive to third-body wear. Cite this article: Bone Joint Res 2015;4:29–37

Introduction. Over 40-years the dominant form of implant fixation has been bone cement (PMMA). However the presence of circulating PMMA debris represents a 3rd-body wear mechanism for metal-on-polyethylene (MPE). Wear studies using PMMA slurries represent tests of clinical relevance (Table 1). Cup designs now use many varieties of highly-crosslinked polyethylene (HXPE) of improved wear resistance. However there appears to be no adverse wear studies of vitamin-E blended cups.1–4 The addition of vitamin E as an anti-oxidant is the currently preferred method to preserve mechanical properties and ageing resistance of HXPE. Therefore the present study examined the response of vitamin-E blended liners to PMMA abrasion combined with CoCr and ceramic heads. The hip simulator wear study was run in two phases to compare wear with, (i) clean lubricants and (ii) PMMA slurries. Methods. The vitamin-e blended polyethylene liners (HXe+) were provided by DJO Surgical (Austin, TX) with 40mm CoCr and ceramic femoral heads (Biolox-delta). Polyethylene liners were run in standard “Inverted” test. (Table 1) All cups were run in ‘clean’ serum lubricant for 6-million load cycles (6Mc)5 and in a debris slurry (PMMA: 5mg/ml concentration) for 2Mc.4 A commercial bone cement powder was used as “abrasive” (Biomet, Warsaw, IN). PMMA slurries were added at test intervals 6, 6.5, 7 and 7.5Mc.4 Wear was assessed gravimetrically and characterized by linear regression. Bearing roughness was analyzed by interferometry and SEM. Results. The acetabular cups showed low wear-rates to 6Mc duration with both ceramic and CoCr heads (Fig. 1). The debris slurries created much higher wear-rates, whereas control liners continued as before (Table 2). Discussion. This is the 1st study of vitamin-E blended polyethylene under 3rd-body wear conditions. With clean lubricant conditions, CPE combination wore approximately 50% less than MPE combination. Under abrasive lubricant conditions, CPE and MPE combinations wore at approximately same rate but more than an order of magnitude greater than the clean test phase. This was typical of such PMMA abrasion tests (Table 1). However there are no guidelines as to optimal choice of particulate type, morphology, dosage, frequency of injection or duration of test intervals (Table 1). The production of particulates in vivo is an unpredictable phenomenon and consequently laboratory simulation is fraught with uncertainties.6 On completion of the abrasive challenge (6–8Mc duration), our study will continue under clean conditions to 10Mc to define the important recovery phase of the vitamin-E blended polyethylene.3

Two-stage exchange revision total hip arthroplasty performed in case of infection has been considered during many years the gold standard for treatment of chronic infection. Nevertheless, during the last decade, concerns have risen regarding its safety and its efficiency. The purpose of our study was to, first investigate the spacer complications, then to analyze their risks factors. We retrospectively included 125 patients with chronic hip periprosthetic joint infection who underwent a two stage exchange revision arthroplasty performed between January 2013 and December 2019. All spacer complications were systematically collected and risk factors were analyzed. Statistical evaluation were performed using the Student and Mann-Whitney tests. Our study confirms the hypothesis of a high-risk strategy with 42% of patients who had a mechanical spacer failure and a 20% recurrence of infection during the average two years period of follow-up. We found a high rate of spacer migration (23%) and a low rate of spacer fracture (8%) compared to literature. The most important finding was that the majority of spacer complications and failures were found in a population with high medical comorbidities as highlighted by the ASA, Charlson and Lee score associations, as well as with the cardiac, pulmonary, kidney or hepatic chronic conditions. This study showed that a two-stage hip exchange revision is a high-risk procedure regarding complications and mechanical failures of PMMA spacers. In patients with high medical comorbidities, other strategies may be considered and interdisciplinary cooperation with other facilities are needed to identify and control each risk factor

Abstract. Objectives. To evaluate the safety and efficacy of vertebroplasty with short segmented cement augmented pedicle screws fixation for severe osteoporotic vertebral compression fractures (OVCF) with posterior/anterior wall fractured patients. Methods. A retrospective study of 24 patients of DGOU type-4 (vertebra plana) OVCF with posterior/anterior wall fracture, were treated by vertebroplasty and short segment PMMA cement augmented pedicle screws fixation. Radiological parameters (kyphosis angle and compression ratio) and clinical parameters Visual analogue scale (VAS) and Oswestry disability index (ODI) were analysed. Results. A significant improvement was noted in VAS (preoperative, 7.90 ± 0.60; final follow-up 2.90 ± 0.54) and ODI (77.10 ± 6.96 to 21.30 ± 6.70), (P < 0.05). Neurological improvement was noted in all patients. Kyphosis corrected significantly from preoperative 23.20 ± 5.90 to 5.30 ± 1.40 postoperative with 5% (3.30 ± 2.95) loss of correction at final follow-up. Anterior vertebral height restored significantly from 55.80 ± 11.9% to 87.6 ± 13.1% postoperative with 4.5 ± 4.0% loss at final follow-up. One case had cement leakage was found, but the patient is asymptomatic. No implant-related complication was seen. No iatrogenic dural or nerve injury. Conclusions. Treatment with vertebroplasty with cement augmented screw fixation and direct decompression is a great option in treating such a complex situation in fragile age with fragile bones because. Vertebroplasty is viable option for restoring vertebral anterior column in patients who are considered as contraindications for vertebroplasty, like DGOU-4. It provides anterior support avoiding corpectomy, minimise blood loss and also duration of surgery. Addition of short segment fixation gives adequate support with less stress risers at the junctional area

Aim. To improve the challenging treatment of periprosthetic joint infections (PJI), researchers are constantly developing new handling methods and strategies. In patients with PJI after total knee arthroplasty (TKA) and severe local or systemic comorbidities, a two-stage exchange using a temporary antibiotic loaded PMMA-spacer is considered gold standard. This method has undisputed advantages, however, the increased risk of biofilm formation on the spacer surface, bone defects and soft tissue contractions after a six-week spacer interval are severe limitations. Our hypothesis is that a vacuum sealed foam in combination with constant instillation of an antiseptic fluid can address these drawbacks due to a significantly reduced spacer interval. Method. A pilot study was conducted in five PJI cases after TKA with severe comorbidities and/or multiple previous operations to evaluate the feasibility and safety of the proposed method. In the first step, surgical treatment included the explantation of the prosthesis, debridement, and the implantation of the VeraFlo-Dressing foam. The foam is connected to the VAC-Instill-Device via an inflow and an outflow tube. The surgical site is sealed airtight with the VAC-film. During the next 5 days, an antiseptic fluid (Lavasorb® or Taurolidine®) is instilled in a 30-minute interval using the VAC-Instill-Device. The limb is immobilized (no flexion in the knee joint, no weight bearing) for five days. Following that, the second operation is performed in which the VAC-VeraFlo. TM. -Therapy System is explanted and the revision TKA is implanted after debridement of the joint. Results. No serious adverse event occurred during the VAC-Instill spacer treatment. The TKA revision was performed after a mean of 5.4 ± 1.9 days. Mean patient age was 71±6 years with a mean of 6 previous PJI surgeries. Host classification according to McPherson was I/B/3, III/B/3 and III/C/3 in three cases. Out of the five cases included, four were successfully treated and remained infect free to date (mean 14.2 ± 12 months; germs: methicillin-resistant s. aureus, e. coli, staph. lugdunensis and one culture neg.). One case with candida infection of a total femur prosthesis had to be treated with an enucleation of the hip due to rising inflammation parameters and signs of sepsis 7 days after VAC-Instill implantation. Conclusions. The presented data on the VAC-Instill spacer method in septic two-stage revision TKA show promising results regarding feasibility and safety. A prospective randomized controlled examination is in progress to evaluate the possible advantages over a two-stage approach using a standard PMMA spacer

INTRODUCTION. Joint replacement is one of the most common orthopaedic procedures, with over 2 million surgeries performed each year across the globe. Loss of implant fixation, or aseptic loosening, is the leading cause of revision following primary joint replacement, accounting for ∼25% of all revision cases [1]. However, diagnosis of aseptic loosening and its underlying causes remain challenging due to the low sensitivity and specificity of plain radiographs. To address this, we propose a novel approach inspired by [2] involving the use of a self-sensing bone cement (by imparting strain-dependent electrical conductivity or piezoresistivity) combined with electrical impedance tomography (EIT). Piezoresistivity is imparted to cement via incorporation of micro/nanoscale conductive fillers. Therefore mechanical effects such as loosening and cracks will manifest as a conductivity change of the cement. This work explores if EIT is able to detect strains and cracks within the bone cement volume. METHODS. Experiments were designed to determine whether EIT combined with piezoresistive cement can be used to detect strains and cracks (Fig. 1). The setup consists of a tank filled with water, 16 electrodes, sample, a loading machine (MTS), and an EIT system. To develop the piezoresistive bone cement, microscale carbon fibers were used with varying CF/PMMA volumetric ratios (VR) from VR = 0.25% to 3.0%. Three conical samples were made to model a loading condition similar to knee implants (Fig. 1). The samples were compressed while the conductivity map of the tank was measured with the EIT system. RESULTS. Figure 2 shows the conductivity of the piezoresistive bone cement with respect to the CF/PMMA VR, the percolation happens at VR = 1.0% and the maximum gradient occurs at VR = 1.5%. Three conical samples were built and experimented to examine the hypothesis. The samples were loaded from F = 0 to F = 4000 N for the strain measurement and then loaded until the first crack initiates. Figure 3 (a) and (b) show the conductivity difference map measured by EIT for strain measurement and crack detection respectively. It can be seen in Fig. 3(a) that due to the shear stresses within the bone cement the conductivity of the sample decreases under compression. At the crack initiation the conductivity of the samples increases significantly (Fig. 3(b)). Figure 3(c) shows evolution of sample conductivity difference measured by EIT as a function of the applied load, VR = 1.5% shows the largest sensitivity. DISCUSSION. The results validate our hypothesis; both cracks and strains resulted in electrical conductivity changes measurable by EIT. While these initial results are encouraging, the approach must be validated via testing of surrogate and cadaver bones in an EIT phantom. If successful, this approach could for the first time provide means of in-vivo studying of aseptic loosening, leading to a paradigm shift in the understanding of this important clinical problem. For any figures or tables, please contact the authors directly

BACKGROUND. This scientific work is a non-interventional, experimental and prospective comparative study of two very high-viscosity PMMA bone cements: DePuy CMW 2G and Palacos® fast R+G. Reference product: Palacos® R+G. Fast-setting PMMA bone cements are used in the endoprothetics of the patella and knee (in Australia) and are also used to cement an artificial acetabulum (in the UK). Are there any differences regarding the characteristics of the two fast-setting PMMA bone cements?. MATERIALS AND METHODS. All cements were mixed as specified by the manufacturer and analysed on the following parameters: handling properties (mixing, waiting, working and hardening phase), powder/liquid-ratio, mechanical properties (ISO 5833:2002 and DIN 53435), fatigue strength (ISO 16402) and elution profile. All tests were done in an acclimatised laboratory with temperatures set at 23.5°C ± 0.5°C and a humidity of >40%. Of two batch numbers, 11 units of each bone cement were tested. RESULTS AND DISCUSSION. The handling properties of the two tested PMMA bone cements Palacos® fast R+G and CMW 2G are highly similar (n=12). CMW 2G reaches the mixing and waiting phase approximately 20s later than Palacos® fast R+G. Palacos® fast R+G has a similar working, but a shorter hardening phase than CMW 2G. In addition, working with Palacos® fast R+G was advantageous due to its green dye. Palacos® fast R+G has a higher powder/liquid-ratio of 2.550. Due to the higher powder percentage, the cement has a shorter mixing and waiting phase than CMW 2G with a ratio of 2:1. Both analysed bone cements fulfil the quasi-static properties of ISO 5833:2002 and DIN 53435. Palacos® fast R+G was far superior in its ISO compressive strength (MPa) shown through one-way analysis of variance (ANOVA) (p<0.01) and independent two sample t-test (p<0.01) at 0.05 level of significance (n=20)(Fig. 1). CMW 2G has a higher quasi-static ISO bending strength (MPa) than Palacos® fast R+G, but the same test shows a much higher fatigue strength (ISO 16402) of Palacos® fast R+G (n=5) (Fig. 2). Palacos® R+G and Palacos® fast R+G show a similar elution profile (n=3), whereas CMW 2G shows a much lower antibiotic elution over time. CMW 2G releases approximately 1/3 of gentamicin per mould body after 24h. After day 3 and 5, CMW 2G has a significantly lower gentamicin release than Palacos® fast R+G (Fig. 3). Palacos® fast R+G has a higher gentamicin release, due to its hydrophilic polymer basis, which is identical to Palacos® R+G. CMW 2G contains pure PMMA and is therefore more hydrophobic than the other two tested cements. CONCLUSION. Handling with Palacos® fast R+G was advantageous due to its green dye. Because of the shorter handling phases of Palacos® fast R+G, it is superior as it minimises the length of surgeries. Mechanical properties according (ISO 5833:2002 and DIN 53435) were comparable. Palacos® fast R+G has a statistically significant higher ISO compressive strength (MPa). Palacos® fast R+G also showed higher fatigue strength (ISO 16402). Palacos® fast R+G was far superior in matters of gentamicin release over time

Introduction. Polymethylmethacrylate(PMMA) bone cement has been used in joint reconstruction surgery and recently introduced for treatment of osteoporotic vertebral compression fracture. However, the use of PMMA bone cement in vertebroplasty leads to extensive bone stiffening and high rate of adjacent vertebrae fracture. Aim. The purpose of this study was to investigate the properties of PMMA bone cement augmented with collagen and assess its characteristics and relevance for the reduction of complication rate associated with vertebroplasty. Methods. Bone cement was produced using 2 types of PMMA based bone cement. Augmented groups were prepared using 40g of bone cement with 1% of rat tail liquid collagen. Mixing was conducted in controlled laboratory environment and at room temperature. The working and setting time and the mechanical properties were determined in accordance to ASTM standards for acrylic cements. The effect of ageing in simulated body fluid(SBF) on mechanical properties of these cements and the microstructure were studied. Results. Addition of collagen to bone cement has shown no marked effect on the working and setting time and produces bone cement with good injectability. The compressive strength is not affected but the modulus shows the material is less brittle than PMMA. Conclusion. Addition of liquid collagen to PMMA based bone cement does not necessarily compromise the properties of the cements and produce cement with good injectability and less brittle than PMMA based bone cement alone. However, bone cement augmented with different concentration of collagen need to be studied further in order to assess its clinical relevance especially in vertebroplasty

Is is believed that 3rd-body wear of polyethylene, be it from particles of bone, bone-cement (PMMA), or metal, is an unavoidable risk in total hip arthroplasty (THA). Simulator studies have demonstrated that wear in conventional polyethylene (CXPE) and highly crosslinked polyethylene (HXPE) cups increased 6 and 20-fold respectively when challenged by circulating 3. rd. -body PMMA particulates. There was no corresponding change in head roughness, i.e. the PMMA did not roughen CoCr surfaces. Many contemporary cup designs now use the vitamin-E process combined with higher crosslinking dosage (VEPE). However, little if anything is known about the VEPE debris. Therefore in this study we analyzed the morphology of VEPE particles from cups that had been run in, a) standard simulator test mode and b) adverse PMMA debris-challenge mode. The aim of this study was to determine how a clinically relevant challenge, such as addition of PMMA particles affected the wear debris. This had not been attempted previously due to contamination polyethylene by PMMA debris. The hypotheses were that, a) during the ‘clean’ test, VEPE would yield smaller debris of standard globular shape compared to controls (XPE) and b) in adverse PMMA challenge mode, VEPE debris size would increase and become more flake-like. The XPE and vitamin-E blended cups (VEPE) cups were gamma-irradiated at 7.5 Mrad and 15 Mrad, respectively. Cups were run Inverted and mated with ceramic femoral heads of diameter 44 mm (Biolox-delta, Ceramtec). The three test phases included; ‘clean’ for 6 million cycles (6 Mc), abrasive slurry 6–8 Mc (concentration 10g/L), and ‘clean’ 8–10 Mc. The debris was isolated using standard procedure for ‘clean’ tests and a modified procedure for the abrasive slurries. Particles were imaged using SEM and the micrographs analyzed (Image J). Approximately 600 particles were analyzed from each sample (4.5 Mc and 8 Mc) and morphology defined via aspect ratio (AR), equivalent circular diameter (ECD), and circular shape factor (CSF). The clean test revealed slight differences in shape factors for XPE and VEPE (AR, CSF within 30%: p <0.0001) but none with regard to size (p > 0.9999). The median ECD for both XPE and VEPE was approximately 0.55 μm. The abrasive test revealed a statistical difference (p < 0.0001) in shape compared to the clean test, but varied less than 25%. The greater change in debris morphology between the abrasive test and clean test was size, which increased 3.6 fold for VEPE particles (ECD = 2.0 μm) and 4.3 fold for XPE particles (ECD = 2.3 μm). It was determined that addition of vitamin E to the PE did not change the size, but did change the shape of PE debris particles up to 30%. This study was the first to isolate debris particles during an abrasive slurry test and determine morphology under such conditions. Debris particles formed in abrasive conditions were found to be 4-fold larger in diameter, suggesting a larger volume of shreds in comparison to the mostly submicron population observed under standard testing conditions. Figure 1: Boxplot of equivalent circular diameter values. Figure 2: Boxplot of aspect ratio values. Figure 3: Boxplot of circular shape factor values

Introduction and Aims: The scientific ‘need’ for porosity reduction of polymethylmethacrylate (PMMA) bone cement due to the influence of PMMA porosity with respect to femoral stem subsidence in total hip arthroplasty (THA) is not well understood. Therefore, we investigated the influence of bone cement porosity upon subsidence in physiologically simulated THA models. Method: Twelve Exeter femoral components were implanted into mechanical analog femora – six with PMMA mixed under vacuum-mixed (VM) conditions (0.26 atms.), the others with PMMA under atmospheric (AM) conditions. Each specimen was subjected to cyclic loading in an MTS from 0.2 kN to 2.0 kN at 2Hz for at least two million cycles. Specimens were subjected to 0.5 hrs ‘on’ (3600 cycles), and 0.5 hrs ‘off’, where ‘off’ represents no cyclic loading but a static rest period at 0.1 kN. Radiographs were acquired during the testing regime. Femurs were sectioned and PMMA porosity determined; subsidence was measured from radiographs. Results: Even though stem subsidence was greater in AM PMMA than in the VM PMMA, implant subsidence in our study between air and vacuum mixed was not significantly different (p> 0.05), nor was total percent porosity (p> 0.05). Evaluating porosity regardless of mixing method, distal porosity correlated with subsidence. The rates of stem subsidence were influenced by PMMA porosity near the distal tip (r = 0.62). Specifically, during the first six months at level 0 (distal tip), increased porosity correlated with increased subsidence. After the initial six months, this correlation (level 0) ceased. The stems with the greatest distal tip porosity were the first stems to fail (range 16 to 20 months, average 18 months). Conclusion: We concluded, air or vacuum mixed cement does not alter porosity, but subsidence is related to the level of porosity located about the distal stem. Exeter subsidence depends upon PMMA porosity and pore location in this model

Introduction: By compromising bone structure, peri-prosthetic osteolysis may increase the risk of fracture and/or aseptic loosening of components leading to revision surgery. Our purpose was to develop a reproducible rabbit model of periprosthetic osteolysis and observe the effects of implant type and fixation on the latency to onset and size of the osteolytic lesions. Methods: Thirty-seven New Zealand White rabbits (71 knees) underwent knee arthrotomy and placement of cylindrical intramedullary stainless steel or polymethylmethacrylate (PMMA) implants. Each knee contained both a metallic and PMMA implant in either the femur or tibia that communicated with a common synovial space. A suspension of polyethylene particles (size < 4.5 um and concentration of 1-5 x 106 particles/ul) was injected into each knee at two-week intervals for ten weeks to induce osteolysis. Serial radiographs were taken at 4, 8, 14, 18, and 22 weeks postoperatively to document the progression of osteolysis. Statistical analysis was performed utilizing a two-tailed, unpaired t-test and a Mantel-Cox test with the level of significance set a p < 0.05. Results: Radiographic analysis revealed that 96.9% of the stainless steel implants had evidence of osteolysis by 22 weeks compared to 22.9% of the PMMA implants (p< 0.001). The earliest onset of lesions in the metal implant group occurred at four weeks compared to 14 weeks in the PMMA group. We also found the area and volume of the osteolytic lesions to be significantly larger in the metal implants when compared to the implants composed of PMMA (p < 0.01). Conclusions: Onset of osteolysis around metal implants occurred in a significantly shorter period of time and more frequently when compared to implants composed of PMMA. Also, the area and volume of the osteolytic lesions around the metal implants was found to be significantly larger than those of the PMMA. We concluded that relative material effects on osteoclast induced bone resorption and differences in ease of transport of particulate debris along metallic compared to PMMA surfaces may account for observed differences in frequency and severity of osteolytic lesions

Introduction: We developed a signal inducing bone cement for surgical interventions under MR guidance. This cement is based on conventional polymethylmeth-acrylate (PMMA), which is mixed with 0.9% saline solution and a contrast agent (CA), or with a hydroxyapatite based bone-filler (Ostim. ®. , aap Biomaterials, Germany). This signal inducing cement should allow bone filling procedures, like vertebro- and kyphoplasty, under MR guidance in an open Highfield MR Scanner. As we added the signal inducing substances (saline solution, CA, bone substitute) to the PMMA, we changed the biomechanical properties of the cement. The purpose of this study was to evaluate the biomechanical properties of the signal inducing bone cement for vertebroplasty in a spine model. Materials/Methods: We placed cadaveric vertebral bodies (n=18, of 4 lumbar spines) between the crosshead and baseplate of a universal testing machine (Zwick. ®. , Germany) and compressed to failure. Then, we injected cements into the broken vertebral bodies through a transpedicular approach on both sides, under image intensifier control. The so treated vertebral bodies were then tested again in the testing machine. We injected three cements: a conventional PMMA cement (BonOs. ®. , aap Biomaterials, Germany, 12g PMMA, 5 ml MMA), an NaCl-cement compound (3 ml 0.9% saline solution, 12g PMMA, 5 ml MMA) and a bone substitute-cement compound (3 ml Ostim. ®. , 12g PMMA, 5 ml MMA). As the CA amount is negligible (< 9μl), it was neglected for these tests. Each cement type was injected in 6 vertebral bodies. We defined the initial strength (N) of the vertebral bodies as the load at failure, and the strength after treatment as the maximum load, which occurred within the first 6 mm of compression. Results: The initial strength of the vertebral bodies (n=18) was 4179 N (SD 497 N). The strength after treatment was 7433 N (SD 503 N) for the conventional cements (n=6), 5900 N (SD 376) for the NaCl-cements (n=6), and 7000 N (SD 413 N) for the Ostim. ®. -cements (n=6). Discussion: Although the PMMA cement is weakened by dilution with the signal inducing substances (saline solution, CA, bone substitute), the MRI-cements restored the initial strength of the vertebral bodies. The results suggest that these MRI-cements meet the biomechanical requirements for vertebroplasty, and can be used for MRI guided vertebroplasty

We aimed to determine the optimal method of inserting a screw into polymethylmethacrylate (PMMA) cement to enhance fixation. We performed six groups of ten axial pull-out tests with two sizes of screw (3.5 and 4.5 mm AO cortical) and three methods of insertion. Screws were placed into 'fluid' PMMA, into 'solid' PMMA by drilling and tapping, or into 'curing' PMMA with quarter-revolution turns every 30 seconds until the PMMA had hardened. After full hardening, we measured the maximum load to failure for each screw-PMMA construct. We found no significant difference in the pull-out strengths between screw sizes or between screws placed in fluid or solid PMMA. Screws placed in curing PMMA were significantly weaker: the relative strengths of solid, fluid and curing groups were 100%, 97% and 71%, respectively. We recommend the use of either solid or fluid insertion according to the circumstances and the preference of the surgeon

Recent clinical data suggest improvement in the fixation of tibia trays for total knee arthroplasty when the trays are additive manufactured with highly porous bone ingrowth structures. Currently, press-fit TKA is less common than press-fit THA. This is partly because the loads on the relatively flat, porous, bony apposition area of a tibial tray are more demanding than those same porous materials surrounding a hip stem. Even the most advanced additive manufactured (AM) highly porous structures have bone ingrowth limitations clinically as aseptic loosening still remains more common in press-fit TKA vs. THA implants. Osseointegration and antibacterial properties have been shown in vitro and in vivo to improve when implants have modified surfaces that have biomimetic nanostructures designed to mimic and interact with biological structures on the nano-scale. Pre-clinical evaluations show that TiO. 2. nanotubes (TNT), produced by anodization, on Ti6Al4V surfaces positively enhance the rate at which osseointegration occurs and TNT nano-texturization enhances the antibacterial properties of the implant surface. 2. In this in vivo sheep study, identical Direct Metal laser Sintered (DMLS) highly porous Ti6Al4V specimens with and without TNT surface treatment are compared to sintered bead specimens with plasma sprayed hydroxyapatite-coated surface treatment. Identical DMLS specimens made from CoCrMo were also implanted in sheep tibia bi-cortically (3 per tibia) and in the cancellous bone of the distal femur and proximal tibia (1 per site). Animals were injected with fluorochrome labels at weeks 1, 2 and 3 after surgery to assess the rate of bone integration. The cortical specimens were mechanically tested and processed for PMMA histology and histomorphometry after 4 or 12 weeks. The cancellous samples were also processed for PMMA histology and histomorphometry. The three types of bone labels were visualized under UV light to examine the rate of new bony integration. At 4 weeks, a 42% increase in average pull-out shear strength between nanotube treated specimens and non-nanotube treated specimens was shown. A 21% increase in average pull-out shear strength between nanotube treated specimens and hydroxyapatite-coated specimens was shown. At 12 weeks, all specimens had statistically similar pull-out values. Bone labels demonstrated new bone formation into the porous domains on the materials as early as 2 weeks. A separate in vivo study on 8 rabbits infected with methicillin-resistant Staphylococcus aureus showed bacterial colonization reduction on the surface of the implants treated with TNT. In vitro and in vivo evidence suggests that nanoscale surfaces have an antibacterial effect due to surface energy changes that reduce the ability of bacteria to adhere. These in vivo studies show that TNT on highly porous AM specimens made from Ti6Al4V enhances new bone integration and also reduce microbial attachment

Aim: To investigate the possibility of using polymethylmethacrylate (PMMA) bone cement as a delivery vehicle for anti-tumour chemotherapy. Methods: Doxorubicin was incorporated into PMMA pellets and incubated in physiological medium at 37°C. Release of Doxorubicin from the pellets continued for eight weeks as demonstrated by high performance liquid chromatography (HPLC). Doxorubicin-containing pellets were incubated with sarcoma cultures at 37°C for 24 hours. A significantly higher cell death rate(as measured by flow cytometry) was seen in the plates exposed to Doxorubicin compared to those exposed only to plain PMMA, indicating that the Doxorubicin released from the cement pellets retained its cytotoxic capability. PMMA-Doxorubicin cement pellets were implanted in rat tibiae and the animals killed at intervals over three weeks. HPLC analysis showed that this technique produced high concentrations of Doxorubicin adjacent to the implant but negligible systemic levels(heart, kidney, lung, liver). Four groups of rats had sarcomas established in their tibiae and then treated either by excision of tumour and Doxorubicin/PMMA implantation, excision and plain PMMA implantation, excision only or no treatment. The animals were then observed for tumour regrowth. A survival advantage was demonstrated for those animals treated by tumour excision and Doxorubicin/PMMA implantation. Conclusion: These experiments demonstrate that PMMA is an effective medium for the delivery of cytotoxic chemotherapy. This method has scope for early translation to the human situation

Introduction and Objective. The continued effectiveness of antibiotic loaded bone cements is threatened by antibiotic resistance. The common antiseptic, chlorhexidine (CHX), is a potential alternative to antibiotics in bone cements, but conventional salts are highly soluble, causing burst release and rapid decline to subinhibitory local CHX concentrations. Here, chlorhexidine triphosphate (CHX-TP), a low solubility CHX salt, is investigated as an alternative antimicrobial in PMMA bone cements. The aim was to assess duration of antimicrobial release and antimicrobial efficacy, along with handling, setting and mechanical properties of CHX-TP loaded cements, compared with an existing cement formulation containing gentamicin. Materials and Methods. Palacos R (Heraeus Medical, Newbury, UK) with 0, 1, 4, 7 and 12% CHX-TP (w/w) cements were prepared by combining solid CHX-TP with Palacos R components, and compared with Palacos R+G. All cements were prepared without vacuum and under ISO 5833:2002 conditions. Cements were tested under ISO 5833:2002 for compressive and bending properties, setting time, maximum temperature and doughing time. Antimicrobial release from the cements into deionised water was studied and antimicrobial efficacy of unaged and aged cements against Staphylococcus aureus (ATCC 29213) was assessed using a disc diffusion assay. Results. Compressive strength of CHX-TP loaded cements was not significantly different to Palacos R or Palacos R+G (p > 0.05, all exceeding ISO 5833:2002 minimum of 70 MPa). Mean bending strength was significantly lower with CHX-TP loading (p < 0.05) than bending strength of Palacos R and Palacos R+G, though all bending moduli exceeded the ISO 5833:2002 minimum (1800 MPa). All cements studied were within the ISO 5833:2002 limits for setting time (3 to 15 min), doughing time (≤ 5 min) and maximum temperature (90 . o. C). Mean doughing time for Palacos R, Palacos R+G and Palacos R + 12 % CHX-TP respectively: 52.5 s, 45 s and 45 s. Mean setting time and mean maximum temperature for Palacos R, Palacos R+G and Palacos R + 1, 4, 7 and 12% CHX-TP respectively: 11.00 min (73 . o. C), 11.25 min (72 . o. C), 12.25 min (66 . o. C), 10.50 min (70 . o. C), 10.00 min (70 . o. C), 10.75 min (62 . o. C). Sustained CHX release into deionised water was observed from all Palacos R + CHX-TP cements. Duration varied according to CHX-TP dosing and diminished over time, although to an extent that itself varied with dosing. 1 % CHX-TP ceased releasing CHX at 6.9 weeks; 4 % CHX-TP ceased at 67.7 weeks; 7 % and 12 % CHX-TP were ongoing at 75.5 weeks. Palacos R+G cements ceased releasing detectable levels of gentamicin after 14.4 weeks. Palacos R+G and Palacos R + CHX-TP cement discs showed efficacy against S. aureus (ATCC 29213) when applied as prepared (unaged) to S. aureus bacterial lawns in disc diffusion assays, with CHX-TP cements showing dose dependency. Zone of inhibition (ZOI) size was significantly reduced for Palacos R+G cements and Palacos R + 1% CHX-TP cements after 1 week and 6 weeks aging, compared to ZOI from unaged cements (p < 0.05). ZOI size produced by Palacos R + 4, 7, and 12 % CHX-TP cements did not decline significantly after 6 weeks aging (p > 0.05). Conclusions. CHX-TP can be incorporated into the Palacos R cement matrix up to 12% w/w without deterioration of compressive strength, bending modulus, doughing time, setting time or maximum temperature. Bending strength was significantly reduced at all CHX-TP loadings studied. Palacos R + 4, 7 and 12% CHX-TP cements provided sustained CHX release, exceeding the duration of gentamicin release from Palacos R+G, and showed sustained efficacy against S. Aureus after 6 weeks aging, which was not achieved by Palacos R+G cements

Introduction: Osteoneocrosis of the femoral head (ONFH) is difficult to treat as collapse frequently occurs after core decompression. This may be due to the failure to provide structural support during revascularization and healing after core decompression. Cement (PMMA) packing for giant cell tumors of bone has been shown to provide adequate support of the subchondral bone. This study was undertaken to determine whether or not the addition of PMMA packing provides any benefit to the outcome of core decompression for ONFH. Secondary objectives were to assess various factors for prognostic significance. Materials and Methods: A prospective, randomized trial of core decompression ± cement (PMMA) packing for ARCO stage I or II ONFH was conducted. Outcome measures were: radiographic (XR) progression, conversion to hip arthroplasty (THA), WOMAC, SF 36, and Harris Hip scores (HHS). Survivorship analysis using Kaplan-Meier estimates was performed. Results: The time to XR progression at 3 years for the core vs. core + PMMA cohorts was 42 ± 11 mo vs. 45 ± 12 mo, p=0.68, respectively. The time to THA at 3 yrs for the core vs. core± PMMA groups was 42 ± 11 mo vs. 67 ± 12 mo, p=0.17, respectively. Comparing pre vs.1 year postoperative WOMAC scores, for the core + PMMA group, there were statistically significant improvements in pain (p=0.082), stiffness (p=0.03), physical function (p= 0.05) and total score (p=0.03) whereas for the core decompression group, there was no significant difference noted among the same domains (p=0.06, 0.25, 0.74, 0.88) respectively. The SF 36 role physical domain score was higher for the core + PMMA group at 1 year (p=0.07) and 15 mos (p=0.09) but was no different at 3 yrs (p=85). For the physical function and bodily physical domains, there was no difference at any time point. The factors of smoking (y/n) p=0.003, location (central/ medial/lateral) p=0.03, per cent femoral head involvement (< 15, 15–30, > 30%) p=0.05, age (< 40, ≥40 yrs), and necrotic arc (< 40, ≥40) p=0.005, were significant predictors for XR progression on univariate analysis but upon Cox multivariate regression, only age (p=0.09), smoking (p=0.07), and necrotic arc (p=0.04) remained independently, statistically significant. Discussion: The addition of PMMA packing to core decompression for pre-collapse ONFH (ARCO I/II) does not improve the outcome of treatment as measured by XR progression and conversion to THA. There is a benefit to PMMA packing for pain relief at 12–15 mos. as measured by the mean WOMAC, HHS and SF 36/role physical scores but this benefit ceases at 3 years after treatment. Age ≥40 years, smoking, and necrotic arc ≥40 are all predictive of eventual progression of disease on XR

Proponents of the biological theory of aseptic loosening have in recent years tended to concentrate on the production and distribution of particulate ultra-high-molecular-weight polyethylene (UHMWPE) debris around the potential joint space. However, mechanical loading of cemented implants with the differing elastic moduli of metal stems, polymethylmethacrylate (PMMA) cement and bone can result in relative micromotion, implying the potential for production of metal and PMMA particles from the stem-cement interface by fretting wear. In order to investigate the production and biological reactivity of debris from this interface, PMMA and metal particulate debris was produced by sliding wear of PMMA pins containing barium sulphate and zirconium dioxide against a Vaquasheened stainless steel counterface. This debris was characterised by SEM, energy-dispersive analysis by X-ray (EDAX) and image analysis, then added to cell cultures of a human monocytic cell line, U937, and stimulation of pro-osteolytic cytokines measured by ELISA. Large quantities of PMMA cement debris were generated by the sliding wear of PMMA pins against Vaquasheened stainless steel plates in the method developed for this study. Both cements stimulated the release of pro-osteolytic TNFα from the U937 monocytic cell line, in a dose-dependent fashion. There was a trend towards greater TNFα release with Palacos cement than CMW cement at the same dose. Palacos particles also caused significant release of IL-6, another pro-osteolytic cytokine, while CMW did not. The particulate cement debris produced did not stimulate the release of GM-CSF or IL1β from the U937 cells. These results may explain the cytokine pathway responsible for bone resorption caused by particulate PMMA debris. Radio-opaque additives are of value in surgical practice and clinical studies to quantify the relevance of these in vitro findings are required before the use of cement containing radio-opacifier is constrained

Interbody fusion aims to treat painful disc disease by demobilising the spinal segment through the use of an interbody fusion device (IFD). Diminished contact area at the endplate interface raises the risk of device subsidence, particularly in osteoporosis patients. The aim of the study was to ascertain whether vertebral body (VB) cement augmentation would reduce IFD subsidence following dynamic loading. Twenty-four human two-vertebra motion segments (T6–T11) were implanted with an IFD and distributed into three groups; a control with no cement augmentation; a second with PMMA augmentation; and a third group with calcium phosphate (CP) cement augmentation. Dynamic cyclic compression was applied at 1Hz for 24 hours in a specimen specific manner. Subsidence magnitude was calculated from pre and post-test micro-CT scans. The inferior VB analysis showed significantly increased subsidence in the control group (5.0±3.7mm) over both PMMA (1.6±1.5mm, p=.034) and CP (1.0±1.1mm, p=.010) cohorts. Subsidence in the superior VB to the index level showed no significant differences (control 1.6±3.0mm, PMMA 2.1±1.5mm, CP 2.2±1.2mm, p=.811). In the control group, the majority of subsidence occurred in the lower VB with the upper VB displaying little or no subsidence, which reflects the weaker nature of the superior endplate. Subsidence was significantly reduced in the lower VB when both levels were reinforced regardless of cement type. Both PMMA and CP cement augmentation significantly affected IFD subsidence by increasing VB strength within the motion segment, indicating that this may be a useful method for widening indications for surgical interventions in osteoporotic patients

Introduction Reported clinical results suggest that vertebroplasty is a safe and effective technique for providing pain relief. However, information about the long-term effect of PMMA on the adjacent intervertebral discs and the augmented bone is lacking. Adjacent intervertebral discs may be at higher risk of degeneration due to nutritional constraints. Bone loss in augmented vertebrae may occur due to mechanical stress-shielding or toxicological effects. The aim of the present study was therefore to investigate the effect of PMMA augmentation on intervertebral disc and bone tissue after 6 and 12 months, using an animal model. Methods In 12 skeletally mature sheep, 2.0ml PMMA (Simplex P) was injected into three lumbar vertebrae (approved by Animal Ethics Committee). Two injection holes were drilled into the middle of three vertebrae at a distance of 5.0mm from the cranial and caudal endplate and 1.0ml PMMA was injected into each hole. Four weeks before euthanasia, animals received an injection of tetracycline for bone labeling. Postmortem, T1- and T2-weighted sagittal and axial MR images were taken prior to fixation in 80% ethanol. Spines were cut into specimens containing one intervertebral disc and half of the two adjacent vertebrae. The discs which were two levels above the first augmented vertebra served as controls. Microsections were stained with H& E, Goldner, Alcian blue-PAS and Safranin O. MRI signal intensity and morphology of discs were evaluated qualitatively. Histomorphological analysis of discs and endplates was conducted using published criteria [. 1. ]. Presence of bone remodeling, fibrous tissue and foreign body reaction in the vertebrae was also recorded. Results There was no distinguishable loss of MRI signal intensity in the discs in between augmented vertebrae. Cement injection resulted in blocking 50–75% of the endplate lengths. Most discs that were in between augmented vertebrae showed signs of degeneration (chondrocyte proliferation, necrosis) after 6 (80%) and 12 months (88%). Inflammatory reaction to PMMA was observed in some specimens (approximately 25%). Cement had been covered with fibrous tissue in all augmented vertebrae, but tetracycline labeling revealed new bone formation in the vicinity of PMMA. Discussion Augmentation of three adjacent vertebrae initiated degenerative changes of intervertebral discs in between two augmented vertebrae. This is in contrast to previous animal studies [. 2. ] where no degenerative changes after cementing endplates were observed. Current investigations were performed with the specific aim to block the endplates. Clinically, endplates may not get blocked as effectively. On the other hand, discs in older patients are nutritionally constrained due to end-plate calcification and even partial blockage may lead to degenerative changes as documented presently. The risk of degenerative changes of intervertebral discs should be considered in patients undergoing vertebroplasty

Being commonly missed in the clinical practice, Lisfranc injuries can lead to arthritis and long-term complications. There are controversial opinions about the contribution of the main stabilizers of the joint. Moreover, the role of the ligament that connects the medial cuneiform (MC) and the third metatarsal (MT3) is not well investigated. The aim of this study was to investigate the influence of different Lisfranc ligament injuries on CT findings under two specified loads. Sixteen fresh-frozen human cadaveric lower limbs were embedded in PMMA at mid-shaft of the tibia and placed in a weight-bearing radiolucent frame for CT scanning. All intact specimens were initially scanned under 7.5 kg and 70 kg loads in neutral foot position. A dorsal approach was then used for sequential ligaments cutting: first – the dorsal and the (Lisfranc) interosseous ligaments; second – the plantar ligament between the MC and MT3; third – the plantar Lisfranc ligament between the MC and the MT2. All feet were rescanned after each cutting step under the two loads. The average distances between MT1 and MT2 in the intact feet under 7.5 kg and 70 kg loads were 0.77 mm and 0.82 mm, whereas between MC and MT2 they were 0.61 mm and 0.80 mm, without any signs of misalignment or dorsal displacement of MT2. A slight increase in the distances MT1-MT2 (0.89 mm; 0.97 mm) and MC-MT2 (0.97 mm; 1.13 mm) was observed after the first disruption of the dorsal and the interosseous ligaments under 7.5 kg and 70 kg loads. A further increase in MT1-MT2 and MC-MT2 distances was registered after the second disruption of the ligament between MC and MT3. The largest distances MT1-MT2 (1.5 mm; 1.95 mm) and MC-MT2 (1.74 mm; 2.35 mm) were measured after the final plantar Lisfranc ligament cut under the two loads. In contrast to the previous two the previous two cuts, misalignment and dorsal displacement of 1.25 mm were seen at this final disrupted stage. The minimal pathological increase in the distances MT1-MT2 and MC-MT2 is an important indicator for ligamentous Lisfranc injury. Dorsal displacement and misalignment of the second metatarsal in the CT scans identify severe ligamentous Lisfranc injury. The plantar Lisfranc ligament between the medial cuneiform and the second metatarsal seems to be the strongest stabilizer of the Lisfranc joint. Partial lesion of the Lisfranc ligaments requires high clinical suspicion as it can be easily missed

In the 1960's Sir John Charnley introduced to clinical practice his low friction arthroplasty with a highly polished cemented femoral stem. The satisfactory long term results of this and other cemented stems support the use of polymethylmethacrylate (PMMA) for fixation. The constituents of PMMA remain virtually unchanged since the 1960s. However, in the last three decades, advances in the understanding of cement fixation, mixing techniques, application, pressurization, stem materials and design provided further improvements to the clinical results. The beneficial changes in cementing technique include femoral preparation to diminish interface bleeding, pulsatile lavage, reduced cement porosity by vacuum mixing, the use of a cement restrictor, pre-heating of the stem and polymer, retrograde canal filling and pressurization with a cement gun, stem centralization and stem geometries that increase the intramedullary pressure and penetration of PMMA into the cancellous structure of bone. Some other changes in cementing technique proved to be detrimental and were abandoned, such as the use of Boneloc cement that polymerised at a low temperature, and roughening and pre-coating of the stem surface. In the last two decades there has been a tendency towards an increased use of cementless femoral fixation for primary hip arthroplasty. The shift in the type of fixation followed the consistent, durable fixation obtained with uncemented acetabular cups, ease of implantation and the poor results of cemented femoral fixation of rough and pre-coated stems. Unlike cementless femoral fixation, modern cemented femoral fixation has numerous advantages: it is versatile, durable and can be used regardless of the diagnosis, proximal femoral geometry, natural neck version, and bone quality. It can be used in combination with antibiotics in patients with a history or predisposition for infection. Intra-operative femoral fractures are rare. However, the risk may be increased in collarless polished tapered stems. Post-operative thigh pain is extremely rare. Survivorship has not been surpassed by uncemented femoral fixation and it continues to be my preferred form of fixation. However, heavy, young, male patients may exhibit a slightly higher aseptic loosening rate

Aims. Calcium sulphate (CaSO. 4. ) is a resorbable material that can be used simultaneously as filler of a dead space and as a carrier for the local application of antibiotics. Our aim was to describe the systemic exposure and the wound fluid concentrations of vancomycin in patients treated with vancomycin-loaded CaSO. 4. as an adjunct to the routine therapy of bone and joint infections. Patients and Methods. A total of 680 post-operative blood and 233 wound fluid samples were available for analysis from 94 implantations performed in 87 patients for various infective indications. Up to 6 g of vancomycin were used. Non-compartmental pharmacokinetic analysis was performed on the data from 37 patients treated for an infection of the hip. Results. The overall systemic exposure remained within a safe range, even in patients with post-operative renal failure, none requiring removal of the pellets. Local concentrations were approximately ten times higher than with polymethylmethacrylate (PMMA) as a carrier, but remained below reported cell toxicity thresholds. Decreasing concentrations in wound fluid were observed over several weeks, but remained above the common minimum inhibitory concentrations for Staphylococcus up to three months post-operatively. . Conclusion. This study provides the first pharmacokinetic description of the local application of vancomycin with CaSO. 4. as a carrier, documenting slow release, systemic safety and a release profile far more interesting than from PMMA. In particular, considering in vitro data, concentrations of vancomycin active against staphylococcal biofilm were seen for several weeks. Cite this article: Bone Joint J 2017;99-B:1537–44

The aim of the present study was to assess the antibiofilm activity of daptomycin- and vancomycin-loaded poly(methyl methacrylate) (PMMA) and PMMA-Eudragit RL100 (EUD) microparticles against mature biofilms of polysaccharide intercellular adhesin-positive S. epidermidis. The effect of plain, daptomycin- and vancomycin-loaded PMMA and PMMA-EUD microparticles on S. epidermidis biofilms was assessed by isothermal microcalorimetry (IMC) and fluorescence in situ hybridization (FISH). Biofilms were grown for 48h onto poly-urethane pieces of fixed dimensions. Each sample was washed with PBS in order to remove planktonic bacteria and incubated for 24h with different concentrations of acrylic microparticles (20–1.25 mg/mL). The minimal biofilm inhibitory concentration (MBIC) of the antibiotic-loaded particles was defined as the lowest concentration of particles that was able to prevent heat flow associated to the recovery of the biofilms. After incubation with the microparticles, sessile cocci were hybridized with the pan-bacterial EUB338-FITC and the staphylococci-specific STAPHY-FICT probes and stained with DAPI. Biofilm structure and metabolic state were characterized by fluorescence microscopy. According to the IMC results, plain PMMA-particles showed no effect on S. epidermidis biofilms, whereas PMMA-EUD-microparticles negatively influenced the recovery of the biofilm probably due to the highly positive charge of these particles. The MBIC of daptomycin-loaded PMMA-microparticles was 20 mg/mL, whereas vancomycin-loaded PMMA microparticles were not able to inhibit biofilm recovery. Adding EUD to the formulation reduced the MBIC of daptomycin-loaded microparticles to 1.25 mg/mL, corresponding to a 16-fold reduction. Regarding the vancomycin-loaded microparticles, EUD caused a further decrease of their antibiofilm activity. The FISH micrographs corroborated the IMC results and provided additional insights on the antibiofilm effect of these carriers. According to FISH, daptomycin-loaded PMMA-EUD microparticles were responsible for the most pronounced reduction in biofilm mass. In addition, FISH showed that both PMMA and PMMA-EUD microparticles were able to attach to the biofilms. Adding EUD to the formulations proved to be a powerful strategy to improve daptomycin-loaded microparticles antibiofilm activity. In addition, the combination of IMC and FISH was essential in order to fully assess the effect of polymeric microparticles on sessile S. epidermidis. Although the present study enabled gaining further insights on this subject, the nature of these interactions remains unclear. However, this may be a crucial aspect for the enhancement of antibiofilm activity of antibiotic-loaded polymeric microcarriers against mature biofilms. This work was supported by the Portuguese government (Fundação para a Ciência e a Tecnologia) and FEDER (grant SFRH/BD/69260/2010 and research project EXCL/CTM-NAN/0166/2012) and strategic project PEst-OE/SAU/UI4013/2011

Introduction: Vertebroplasty using polymethylmethacrylate (PMMA) is an established technique in the treatment of osteoporotic fractures of the vertebra. Complications of vertebroplasty associated with PMMA leakage can include damage to the spinal cord. Previous studies have sought to investigate thermal changes in the paravertebral region, but used smaller volumes of cement than are used clinically. 1. , or used in vitro experimental techniques. 2. We have designed an in vivo sheep model to investigate the thermal changes after injection of clinically relevant volumes of PMMA, and to measure change in cord function associated with PMMA extrusion. Methods: Five sheep were anaesthetised and 1.0ml of PMMA was injected into the spinal canal at the L1 level, with measurement of the temperature by thermocouple. The L2 to L5 vertebral bodies were then exposed and 9 thermocouples placed at points in and around the vertebra (superior and inferior endplate, disc above and below, central body, posterior wall, and spinal canal) to measure paravertebral temperature for a 10- minute period after injecting 6.0mls of PMMA. All animals were then humanely euthanased, and the T12 to L2 vertebrae harvested to examine the effect of temperature on the vertebral body and spinal cord using light microscopy. Results: The experiments showed significant increases in the paravertebral temperature, especially at the end-plates (mean temperature 51.7°C, mean increase in temperature +16°C). This is contrary to studies using small cement volumes or in vitro conditions. Intradiscal and posterior wall temperature did not significantly rise. Spinal canal temperature reached a mean 75.4°C in the presence of “extruded” cement. Microscopic examination showed thermal damage to the spinal cord. Discussion: The experiments indicate that neurological complications associated with vertebroplasty are likely to be thermally mediated, and that the analgesic effects of vertebroplasty are likely to be, at least in part, due to thermal damage to endplate neurological structures

Introduction. The role of porosity in the longevity of polymethylmethacrylate (PMMA) bone cement mantles remains unclear, although porosity reduction is probably desirable. It is not known whether pore patterns, pore distribution or pore morphology contribute to failure, since it is difficult to assess these features with traditional techniques. We used a novel microtomographic technique to quantitatively and qualitatively assess porosity in PMMA cements of differing viscosities to establish whether pore distribution can be effectively assessed and to document any differences in porosity (in both quantity, distribution and morphology). Each cement was also examined with and without the addition of vacuum, since this is thought to reduce porosity. Methods and materials. Four PMMA bone cements of different viscosities (three of the same brand and the fourth chosen due to its popularity) were prepared and moulded according to established protocols (ASTM F451-99a), with and without the addition of vacuum. 25 samples per group (200 total) were prepared and densities for each sample calculated using Archimedes' principle. Four samples per group (total 32) were randomly selected for further analysis. These samples underwent micro-computer tomography (micro-CT) at a magnification of 20× and slice thickness of 13.67μm and reconstructed images were analysed with in-house developed software to measure pore size and volume. Results were analysed and compared with the two-sample T-test assuming significance at P<0.05. Qualitative assessment of pore character and distribution was made using three dimensional (3D) reconstruction. Results. Densities and mean total pore volume showed an overall reduction in porosity with vacuum. Mean pore volume (MPV) was not significantly different between samples due to the huge range of pore sizes. Qualitative assessment revealed a striking, distinctive pore distribution between cements with an asymmetric distribution in the high viscosity group. Pore size was also qualitatively distinct between cement types and groups with and without vacuum. Conclusion. Micro-CT allows detailed in vitro quantitative and qualitative assessment of porosity in PMMA cement. Pore volume, architecture and volumetric distribution differ in cements of differing viscosity and with or without the application of vacuum. This effect is marked enough to allow distinction between cements based on their micro-CT appearances. Further study using this technique in combination with other methods (such as quantitative analysis of 3D pore distribution) may shed light on the failure mechanisms in PMMA cement mantles, particularly with regard to the role of pore orientation, distribution and size

Introduction Cement leakage into adjacent structures is the main complication during vertebroplasty. The majority of these leaks are asymptomatic, but pulmonary cement embolism has been reported to cause cardiovascular disturbances and even death (. 1. ,. 2. ). Furthermore, the use of calcium phosphate (CaP) cements for vertebroplasty may aggravate cardiovascular deterioration in the event of cement embolism by stimulating coagulation [3]. The cardiovascular effects of pulmonary cement embolism were investigated using an animal model. Methods In 18 skeletally mature sheep, 2.0ml cement was injected into the pulmonary trunk during general anaesthesia (approved by Animal Ethics Committee). Three different cements were used: 1) PMMA (Simplex P, Stryker); 2) PMMA with 10% hydroxyapatite (PMMA & HA) (Vertecem, Synthes); 3) Experimental injectable CaP cement (Synthes). The following cardiovascular parameters were recorded continuously (endpoint: 60min post-injection): arterial, central venous, pulmonary arterial pressures and cardiac output. Blood gases and coagulation parameters (antithrombin, D-dimer, prothrombin fragments I & II) were measured pre-injection, 10, 30 and 60min post-injection. Postmortem, lungs were removed intact and submitted to computer tomography (CT) imaging. Results There were no fatalities. After 1min, mean pulmonary arterial pressure had increased by 9%, 14% and 21% from pre-injection value in the PMMA, PMMA & HA and CaP group respectively. Differences in pulmonary arterial pressure between the three material groups were not statistically significant. Pulmonary arterial pressure stayed elevated for the duration of the experiment (i.e. 60min post-injection). There were no other significant changes in cardiovascular, blood gas or coagulation parameters from pre- to post-injection values. Three dimensional reconstructions of the CT images showed a tendency of the CaP cement to break up into multiple smaller pieces whereas the two other cements did not. Discussion Cement embolism led to mild pulmonary hypertension in all material groups. Present results are in contrast to earlier reports (pig model) of fulminant cardiovascular deterioration after CaP cement embolism (. 3. ). Present changes were not as severe and there was no evidence of thromboembolism. This discrepancy may have been due to differences in the cement formulations or the animal model. Pulmonary hypertension was more severe in the CaP cement group. This may have been due to the disintegration of the CaP cement resulting in blockage of more pulmonary vessels compared to the PMMA cements

Purpose: Osteolysis associated with periprosthetic loosening is generally associated with the presence of wear particle-associated macrophages which (i) release inflammatory cytokines (e.g. TNFα and IL-1α) and (ii) are capable of osteoclast differentiation and bone resorption. The recently identified molecule, RANKL (expressed on osteoblastic cells) has been shown to play a central role in the macrophage-osteoclast differentiation observed in aseptic loosening. However, as TNFα and IL-1α are abundant in periprosthetic tissues and have been shown to mediate wear particle (bone cement)-associated osteolysis in animal models, and as we have recently shown that TNFa can induce osteoclastogenesis in a manner independent of RANKL mechanism, the aim of the present study was to determine whether wear particles, in particular bone cement particles, can affect RANKL- and TNFα-induced osteoclast formation and bone resorption in vitro. Methods: Murine monocytes were cultured on glass coverslips and dentine slices with or without PMMA particles in presence of:- (i) macrophage colony stimulating factor (M-CSF) alone, (ii) M-CSF + soluble RANKL (iii) M-CSF + TNFα or (iv) M-CSF + TNFα + IL-1a. All cultures were maintained for 7–10 days after which the extent of osteoclast differentiation was determined by the expression of specific osteoclast markers including tartrate-resistant acid phosphatase (TRAP) on coverslips and evidence of lacunar resorption on dentine slices. Results: Extensive osteoclast formation and lacunar resorption was evident in monocyte cultures in the presence of soluble RANKL and M-CSF. Addition of PMMA in these cultures increased the extent of RANKL-induced lacunar resorption by about 2 fold. In the absence of soluble RANKL, but in the presence of TNFα (± IL-1α), murine monocytes were also capable of differentiating into active bone resorbing osteoclasts. Addition of PMMA particles to these cultures resulted in a marked increase in the TNFα-induced osteoclas-togenesis. It is worth noting that monocyte cultures containing M-CSF and PMMA particles only did not differentiate into bone resorbing osteoclasts. Conclusion: These results indicate that PMMA particles can activate both RANKL- and cytokine-induced osteoclast formation and osteolysis. Although, we had previously shown the existence of these two distinct cellular mechanisms in periprosthetic loosening, this is the first report in which wear particles have directly been shown to stimulate these cellular mechanisms independently. Our findings could provide possible therapeutic approaches to control the wear particle-associated early failure of joint replacements

Background: Bacteria form a biofilm on the surface of orthopaedic devices, causing persistent and infection. Little is known about biofilms formation on bone grafts and bone substitutes. We analyzed various representative materials regarding their propensity for biofilm formation caused by Staphylococcus aureus. Methods: As bone graft beta-tricalciumphosphate (b-TCP, CyclOsTM) and as bone substitute a tantalum metal mesh (trabecular metalTM) and PMMA (Pala-cosTM) were investigated. As test organism S. aureus (strain ATCC 29213) was used. Test materials were incubated with bacterial solution of 105 colony-forming units (cfu)/ml at 37°C for 24 h without shaking. After 24 h, the test materials were removed and washed 3 times in normal saline, followed by sonication in 50 ml Ringer solution at 40 kHz for 5 minutes. The resulting sonication fluid was plated in aliquots of 0.1 ml onto aerobe blood agar with 5% sheep blood and incubated at 37°C with 5% CO2 for 24 h. Then, bacterial counts were enumerated and expressed as cfu/ml. All experiments were performed in triplicate to calculate the mean ± standard deviation. The Wilcoxon test was used for statistical calculations. Results: The three investigated materials show a differing specific surface with b-TCB> trabecular metal> PMMA per mm2. S. aureus formed biofilm on all test materials as confirmed by quantitative culture after washing and sonication. The bacterial counts in sonication fluid (in cfu/ml) were higher in b-TCP (5.1 x 106 ± 0.6 x 106) and trabecular metal (3.7 x 106 ± 0.6 x 106) than in PMMA (3.9 x 104 ± 1.8 x 104), p< 0.05. Conclusion: Our results demonstrate that about 100-times more bacteria adhere on b-TCP and trabecular metal than on PMMA, reflecting the larger surface of b-TCP and trabecuar metal compared to the one of PMMA. This in-vitro data indicates that bone grafts are susceptible to infection. Further studies are needed to evaluate efficient approaches to prevent and treat infections associated with bone grafts and substitutes, including modification of the surface or antibacterial coating

INTRODUCTION. Surgical site infections (SSI) in orthopaedics are a major source of postoperative morbidity. Although perioperative antibiotic prophylaxis is a common practice, orthopaedic infections are still high in numbers, due to the increasing use of osteosynthesis material and implants. Implants are avascular and can be easily colonized with biofilm-producing germs. For both, effective prophylaxis and treatment of orthopaedic infections, the right choice of the antibiotics used, the mode of application (only systemic or systemic & local), the timing, dosage and the duration of antibiotics are of extremely high importance. Their inappropriate use does not only lead to failures in prevention or treatment of infections, but may also promote microbial resistance development and may cause serious side effects for the patients. SELECTION & USE OF ANTIBIOTICS. Prophylaxis. Broad-spectrum prophylactic antibiotics should help to eliminate the germs before they start to colonize the implant. For prophylactic purposes the recently published AAOS guidelines [1] recommend the use of cephalosporins, such as cefazolin or cefuroxim, administered within one hour prior to surgery. In cases of suspected beta-lactam allergy, clindamycin or vancomycin can be used. The latter one is also recommended in cases of MRSA colonisation. Due to extended infusion times, vancomycin should be started within two hours prior to incision. In cases of blood loss or long op duration, antibiotic administration must be repeated (e.g. cefazolin, every 2–5 hrs; vancomycin, every 6–12 hrs). There is no evidence of a benefit of continued antibiotic administration past 24 hrs of end of surgery [2]. Treatment. In cases of established infections, use of antibiotics is only considered as an adjuvant to surgical debridement. Typically, the choice of the appropriate antibiotic depends on the bacteria, its antibiotic sensitivity profile and the health state of the patient. A combination of rifampicin & a quinolone (or rifampicin & vancomycin in cases of MRSA) for at least 2 wks up to several months has shown good results [3]. In chronic infections with biofilm involvement, all foreign material must be removed and locally delivered antibiotics via e.g. PMMA as carrier (spacers, PMMA-chains) are of additional clinical benefit. ROLE OF LOCAL ANTIBIOTICS. There is general consensus that PMMA chains or PMMA spacers loaded with specific antibiotics support the eradication of bone and joint infections, because of the high local concentrations achieved. The exact treatment time is, however, variable, ranging from few weeks up to several months. Only small amounts of these local antibiotics are systemically detectable and do not represent a major risk for side effects. Still a matter of debate is the benefit of antibiotic impregnated PMMA for infection prophylaxis. Although common practice in Europe, its routine use in e.g. primary arthroplasty is still discussed in other world regions. Meanwhile, evidence accumulates that joint infection rates are, indeed, lower, if antibiotic loaded bone cement with high initial release rates is routinely used in arthroplasty. 4.

Aims

We performed a systematic literature review to define features of patients, treatment, and biological behaviour of multicentric giant cell tumour (GCT) of bone.

Introduction. Pedicle screw pullout or loosening is increased in the osteoporotic spine. Recent studies showed a significant increase of pullout forces especially for PMMA-augmentation. With application of conventional viscosity PMMA the risk of cement extravasation is associated. This risk can be reduced by using radiofrequency-responsive, ultrahigh viscosity bone cement. Method. 11 fresh-frozen lumbar vertebral bodies (VB) from 5 cadavers were collected and freed from soft-tissue and ligaments. By DEXA scan (Siemens QDR 2000) 8 VB were identified as severely osteoporotic (BMD 0.8 g/cm3), 3 VB were above this level. Two screws (6×45 mm, WSI-Expertise Inject, Peter Brehm, Weisendorf, Germany) were placed in the pedicles. Through the right screw 3ml of radiofrequency-responsive bone cement (StabiliT® ER2 Bone Cement, DFine, Germany) were injected via hydraulic cement delivery system (StabiliT® Vertebral Augmentation System, DFine, Germany). As control group, left pedicle screws remained uncemented. After potting the whole VB in technical PMMA (Technovit 4004, Heraeus Kulzer, Germany) axial pullout test was performed by a material testing device (Zwick-Roell, Zmart-Pro, Ulm, Germany). Results. The mean BMD of all specimen was 0.771 g/cm3 (min./max. 0.615/1.116, SD ± 0.170). Due to the definition of osteoporosis 8 specimens had a BMD lower than 0.8 g/cm3 (mean 0.677, min./max. 0.615/0,730, SD ±0.045). The non-osteoporotic group consisted of 3 specimens with a mean BMD of 1.020 g/cm3 (min/max 0.928/1.116, SD ±0.094). Overall we observed an increase in the mean axial pullout strength of 284% when using cement augmentated screws (non-cemented 385 N vs. cemented 1029 N, p 0,001). In the osteoporotic group the mean pullout force of the non-cemented screws was 407 N vs. 1022 N for the cemented screws (p 0.001). Similarly the pullout force rose in the non-osteoporotic group from 325 N for the non-cemented screws to 1048 N for the cemented screws p 0,001). All surgical procedures could be performed without technical problems. Conclusion. This cadaver study demonstrates the efficacy and effectiveness of pedicle-screw augmentation with ultra-high viscosity cement. Pullout forces are significantly increased, especially in osteoporotic bone. No complications like clogged in cannulated pedicle-screws or extravasation of bone cement were observed. In daily clinical routine radiation exposure to operator during cement delivery is reduced due to remote-controlled, automated delivery of radiofrequency-responsive bone cement. Furthermore availability of longer time to work with the cement (up to 30 min) is achieved; hectically injection or multiple-cement-mixing is not necessary anymore. The WSI-Expertise cannulated pedicle screws can be inserted and also augmented in a minimal-invasive technique. The PMMA then is injected through an extension adapter. PMMA augmentation of pedicle screws is already well established in spine surgery. With the combination of radiofrequency-responsive, ultra-high viscosity bone cement and cannulated pedicle screws this established procedure could become more controlled and safer for both patient and physician

Systemic antibiotics reduce infection in open fractures. Local delivery of antibiotics can provide higher doses to wounds without toxic systemic effects. This study investigated the effect on infection of combining systemic with local antibiotics via polymethylmethacrylate (PMMA) beads or gel delivery. An established Staphylococcus aureus contaminated fracture model in rats was used. Wounds were debrided and irrigated six hours after contamination and animals assigned to one of three groups, all of which received systemic antibiotics. One group had local delivery via antibiotic gel, another PMMA beads and the control group received no local antibiotics. After two weeks, bacterial levels were quantified. . Combined local and systemic antibiotics were superior to systemic antibiotics alone at reducing the quantity of bacteria recoverable from each group (p = 0.002 for gel; p = 0.032 for beads). There was no difference in the bacterial counts between bead and gel delivery (p = 0.62). . These results suggest that local antibiotics augment the antimicrobial effect of systemic antibiotics. Although no significant difference was found between vehicles, gel delivery offers technical advantages with its biodegradable nature, ability to conform to wound shape and to deliver increased doses. Further study is required to see if the gel delivery system has a clinical role. Cite this article: Bone Joint J 2015;97-B:1423–7

Purpose: To investigate the effect of pressurizing vertebral bodies during vertebroplasty using different materials in the development of fat embolism (FE) and any associated cardiovascular changes. Polymethylmethacrylate (PMMA) is the material of choice for vertebroplasty (VP). However, PMMA has several disadvantages such as exothermic curing, uncertain long-term biomechanical effects and biocompatibility. As a result alternative materials are being developed to overcome these problems. In order to determine the role of PMMA in the generation of cardiovascular changes following vertebroplasty we compared injection of cement with wax in an animal model. Method: In twenty sheep, four vertebral bodies were augmented either with PMMA or bone wax. Heart rate, arterial, central venous and pulmonary artery pressure, cardiac output and blood gas values were recorded. At postmortem the lungs were subjected to histological evaluation. Results: The consecutive augmentation of four vertebral bodies with PMMA induced cumulative fat embolism causing significant deterioration of baseline mean arterial blood pressure (MABP) and blood gas values. Injection of bone wax resulted in similar cardiovascular changes and amount of intravascular fat in the lungs. Conclusion: In this animal model cardiovascular complications during multiple VP happen regardless of the augmentation material used. The deteriorating baseline MABP during VP is associated with the pressurization and displacement of bone marrow/fat into the circulation rather than caused by polymethylmethacrylate

Introduction. Looking for optimal solutions to wear risks evident in total hip arthroplasty (THA), silicon nitride ceramic bearings (Si. 3. N. 4. ) are noted for demanding high-temperature applications such as diesel engines and aerospace bearings. As high-strength ceramic for orthopedic applications, Si. 3. N. 4. offers improved fracture toughness and fracture strength over contemporary aluminas (Al. 2. O. 3. ). Our pilot studies of Si. 3. N. 4. in 28mm diameter THA showed promising results at ISTA meeting of 2007. 1. In this simulator study, we compared the wear resistance of 40mm to 28mm diameter Si. 3. N. 4. bearings. The 28mm and 40mm bearings (Fig. 1) were fabricated from Si. 3. N. 4. powder (Amedica Inc, Salt Lake City, UT). 1. Wear tests run were run at 3kN peak load in an orbital hip simulator (SWM, Monrovia, CA) and. The lubricant was standard bovine serum (Hyclone: diluted to 17 mg/ml protein concentration). Wear was measured by gravimetric method and wear-rates calculated by linear regression. SEM and interferometic microscopic was performed at 3.5-million cycles (3.5Mc) to 12Mc. The simulator was run to 3.5Mc duration with no consistent weight-loss trends. The bearings could show either small positive or negative weight fluctuations in an unpredictable manner (Fig. 2). Surface analysis showed protein layers up to 3μm thick, furrowed due to abrasion by small particles (Fig. 3). The low ceramic wear was camouflaged by protein contaminants alternatively forming and shedding. From 3.5 to 12.8Mc duration we experimented with various detergents and wash-procedures, all to no avail. Protein coatings were also more prevalent on 44 mm heads, likely due to frictional heating by the larger diameter effect. Selected heads were washed with a mild acid solution - the cumulative effect appeared to be removal of some protein layers, but not in a predictable manner. The Si. 3. N. 4. ceramic is used in demanding industrial applications and it is therefore unfortunate that we are yet not able to quantify the actual wear performance of Si. 3. N. 4. / Si. 3. N. 4. bearings (COC). The contaminating protein layers combined with low-wearing silicon nitride obscured the actual wear data. This has also been a problem in prior studies with alumina and zirconia bearings. Considerable challenges still stand in the way of the optimal biomaterials choices that will result in reduced risk of failure while providing extended lifetimes. Thus important issues remain unsolved and call for innovative solutions. Searching for a more effective ‘wear-measurement’ remedy, we noted that abrasive slurries of bone cement (PMMA) used in contemporary simulator studies were effective in promoting adverse wear in polyethylene bearings. These investigations also revealed that PMMA debris did not damage CoCr heads. 2,3. , alumina heads. 4,5. or diffusion-hardened zirconia heads (ZrDH). 6. We can therefore speculate at this ISTA meeting of 2014 that future ceramic wear tests should incorporate PMMA slurries. Here a new hypothesis can be formulated, that PMMA particulates will provide a continual and beneficial removal of contaminating proteins from the ceramic surfaces (see Fig. 3) and thereby aid definition of low-wearing COC bearings such as Si. 3. N. 4. . The application of non-oxide ceramics such as silicon nitride presented here may become a viable alternative for THA designs of next decade

To investigate the effect of pressurizing vertebral bodies during vertebroplasty using different materials in the development of fat embolism (FE) and any associated cardiovascular changes. Polymethylmethacrylate (PMMA) is the material of choice for vertebroplasty (VP). However, PMMA has several disadvantages such as exothermic curing, uncertain long-term biomechanical effects and biocompatibility. As a result alternative materials are being developed to overcome these problems. In order to determine the role of PMMA in the generation of cardiovascular changes following vertebroplasty we compared injection of cement with wax in an animal model. In twenty sheep, four vertebral bodies were augmented either with PMMA or bone wax. Heart rate, arterial, central venous and pulmonary artery pressure, cardiac output and blood gas values were recorded. At postmortem the lungs were subjected to histological evaluation. The consecutive augmentation of four vertebral bodies with PMMA induced cumulative fat embolism causing significant deterioration of baseline mean arterial blood pressure (MABP) and blood gas values. Injection of bone wax resulted in similar cardiovascular changes and amount of intravascular fat in the lungs. Conclusion: In this animal model cardiovascular complications during multiple VP happen regardless of the augmentation material used. The deteriorating baseline MABP during VP is associated with the pressurization and displacement of bone marrow/fat into the circulation rather than caused by polymethylmethacrylate

Particulate wear debris is associated with periprosthetic inflammation and loosening in total joint arthroplasty. We tested the effects of titanium alloy (Ti-alloy) and PMMA particles on monocyte/macrophage expression of the C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory protein-1 alpha (MIP-1α), and regulated upon activation normal T expressed and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed for expression of macrophage chemokines by immunohistochemistry. Chemokine expression in human monocytes/macrophages exposed to Ti-alloy and PMMA particles in vitro was determined by RT-PCR, ELISA and monocyte migration. We observed MCP-1 and MIP-1α expression in all tissue samples from failed arthroplasties. Ti-alloy and PMMA particles increased expression of MCP-1 and MIP-1α in macrophages in vitro in a dose- and time-dependent manner whereas RANTES was not detected. mRNA signal levels for MCP-1 and MIP-1α were also observed in cells after exposure to particles. Monocyte migration was stimulated by culture medium collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to MCP-1 and MIP-1α inhibited chemotactic activity of the culture medium samples. Release of C-C chemokines by macrophages in response to wear particles may contribute to chronic inflammation at the bone-implant interface in total joint arthroplasty

Since September 1999, a total of 45 senile patients with vertebral compression fractures have been randomly selected for this study. Three treatment modalities were performed including the medical treatment only(15; control group), PMMA cement(15; PMMA group) and HA cement(15; HA group) augmentation. The transpedicular injections of PMMA and HA cements were performed on the latter two groups respectively via posterior approach. For all these patients, the subjective feeling and physical performance were evaluated by questionnaire (Modified Oswestry Questionnaire). The preop and postop X-rays, CT, bone density and bone markers were performed regularly for comparison and analysis. In general, the subjective feeling and physical performance had at least one grade improvement. Even though the short-term results using questionnaire did not have significant differences among these three groups, many parameters did show the advantages of using cements. The back pain, self-esteem and quality of life resolved much earlier and persistent than that of control group. The non-progression in local kyphosis was also noted in the cement groups. In addition, there were no significant differences between PMMA and HA cement groups. Both could be regarded as effective and reliable. However, due to the unique biological properties, HA cement is more promising in the future management of osteoporotic fractures

Aseptic loosening has become the single most important long-term complication of total joint replacements. The pathophysiology of this loosening is multifactorial in origin ranging from mechanical wear, poor surgical technique, thermal damage and the inflammatory response to particulate wear debris. Cytokines are released in response to macrophage activation by particulate wear debris (PWD), the resultant inflammatory cascade stimulates osteoclastic resorption of bone. The failure of remodelling and repair mechanisms may be as a result of Osteonecrosis from cement (PMMA). Hypothesis: That PMMA increases Osteoblast susceptibility to necrosis and apoptosis following inflammatory challenge. Materials and Methods: Osteoblast cell cultures were grown on PMMA cement plates and assessed for apoptosis and necrosis by PI exclusion staining, morphological changes on light and electron microscopy and flow cytometry. Results: PMMA induced osteonecrosis is highest at 1 hour (34.45) in comparison to control levels (4.55). There is no significant change in Apoptosis at 24 hours. Culture of the Osteoblasts on cement and delayed stimulation with TNF-α causes increased Apoptosis and Necrosis. Conclusion: PMMA cement causes Osteoblast necrosis in the early stages of polymerisation, after 24 hours there is little increase in apoptosis/necrosis. However Osteoblasts that grow in contact with cement are more susceptible to apoptosis and necrosis following TNFα challenge. This may prove to be an important step in the pathogenesis of Aseptic loosening

A heavy infiltrate of foreign-body macrophages is commonly seen in the fibrous membrane which surrounds an aseptically loose cemented implant. This is in response to particles of polymethylmethacrylate (PMMA) bone cement and other biomaterials. We have previously shown that monocytes and macrophages responding to particles of bone cement are capable of differentiating into osteoclastic cells which resorb bone. To determine whether the radio-opaque additives barium sulphate (BaSO. 4. ) and zirconium dioxide (ZrO. 2. ) influence this process, particles of PMMA with and without these agents were added to mouse monocytes and cocultured with osteoblast-like cells on bone slices. Osteoclast differentiation, as shown by the presence of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and lacunar bone resorption, was observed in all cocultures. The addition of PMMA alone to these cocultures caused no increase in TRAP expression or bone resorption relative to control cocultures. Adding PMMA particles containing BaSO. 4. or ZrO. 2. , however, caused an increase in TRAP expression and a highly significant increase in bone resorption. Particles containing BaSO. 4. were associated with 50% more bone resorption than those containing ZrO. 2. . Our results suggest that radio-opaque agents in bone cement may contribute to the bone resorption of aseptic loosening by enhancing macrophage-osteoclast differentiation, and that PMMA containing is BaSO. 4. likely to be associated with more osteolysis than that containing ZrO. 2.

Introduction Vertebroplasty (VP), where vertebral bodies are injected with polymethylmethacrylate (PMMA) cement, is used to treat various spinal lesions. More recently VP has been used for augmenting osteoporotic vertebral bodies that have fractured or are at risk of fracture. Although the complication rate for VP is low, thermal damage caused by the exothermic curing of PMMA has been implicated. The aim of this series of experiments was to measure the temperatures reached during VP using a sheep model. The cement volume effect and inter cement differences were assessed. Spinal cord monitoring was undertaken to monitor spinal cord function during this procedure to validate this for clinical use. Methods In the in vivo experiment each of the lumbar vertebral bodies of 10 sheep were injected with one of two cements (Simplex & Vertebroplastic) and one of two volumes (3.0ml or 6.0ml). This was undertaken through an open approach in the lumbar vertebrae. While performing the in vivo experimental studies 6 of the sheep were concurrently monitored using epidural Motor Evoked Potentials (MEP’s). Results There was a significant increase in the temperature at the bone cement interface. The mean peak temperature at the bone-cement interface was 49.5 C (3.0ml Simplex); 61.47 C (6.0ml Simplex); 42.1 C (DePuy 3ml) and 47.2 (DePuy 6ml). Spinal cord monitoring showed that when PMMA was injected into the correct location within the vertebral body there was no change in amplitude of the evoked potentials. When significant leakage of PMMA occurred, there was a decrease in amplitude of MEP’s. Discussion In this sheep model, using cement volumes similar to those used in human clinical practice, we were able to monitor temperature changes within the vertebral body at the bone cement interface. The temperature of the bone cement interface reached temperatures that are known to cause tissue necrosis. Using epidural monitoring we were able to show that when PMMA is injected into the correct location within the vertebral body there is no change in amplitude of MEP’s

Aims

As an increasing number of female surgeons are choosing orthopaedics, it is important to recognize the impact of pregnancy within this cohort. The aim of this review was to examine common themes and data surrounding pregnancy, parenthood, and fertility within orthopaedics.

Aims

Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

Introduction. Vertebroplasty helps to restore mechanical function to a fractured vertebra. We investigated how the distribution of injected cement benefits both fractured and neighbouring vertebrae. Methods. Nine pairs of three-vertebra cadaver spine specimens (aged 67–90 yr) were compressed to induce fracture. One of each pair underwent vertebroplasty with PMMA, the other with a resin (Cortoss). Specimens were then creep-loaded at 1.0kN for 1hr. Before and after vertebroplasty, compressive stiffness was determined, and stress profilometry was performed by pulling a pressure-transducer through each disc whilst under 1.0kN load. Profiles indicated intradiscal pressure (IDP) and compressive load-bearing by the neural arch (F. N. ) at both disc levels. Micro-CT was used to quantify cement fill in the anterior and posterior halves of each augmented vertebral body, and also in the region immediately adjacent to the fractured endplate. Results. Fracture reduced stiffness and IDP, and increased F. N. Following vertebroplasty, anterior fill was greater for Cortoss (30%) than PMMA (17%) (P<0.01). With Cortoss, increased posterior fill was associated with a greater restoration of IDP in the adjacent disc (P<0.05). Furthermore, specimen stiffness increased in proportion to cement fill adjacent to the fractured end-plate. With PMMA, increased anterior fill caused a greater reduction in F. N. in the non-adjacent disc (P<0.05), whereas increased posterior fill and increased fill adjacent to the fracture caused a greater restoration of IDP in the adjacent disc (P<0.05). Conclusion. Cement distribution varied between the two cements. However, increased filling immediately adjacent to the fractured endplate was linked most consistently to improved mechanical function. Conflicts of Interest. None. Source of Funding. This work was funded by Action Medical Research. Vertebroplasty materials were provided by Stryker and by Orthovita. We can confirm that this abstract has not been published previously in whole or substantial part, and the findings have not been presented previously at a national meeting

To investigate whether restoration of mechanical function and spinal load-sharing following vertebroplasty depends upon cement distribution. Fifteen pairs of cadaver motion segments (51-91 yr) were loaded to induce fracture. One from each pair underwent vertebroplasty with PMMA, the other with a resin (Cortoss). Various mechanical parameters were measured before and after vertebroplasty. Micro-CT was used to determine volumetric cement fill, and plane radiographs (sagittal, frontal, and axial) to determine areal fill, for the whole vertebral body and for several specific regions. Correlations between volumetric fill and areal fill for the whole vertebral body, and between regional volumetric fill and changes in mechanical parameters following vertebroplasty, were assessed using linear regression. For Cortoss, areal and volumetric fills were significantly correlated (R=0.58-0.84) but cement distribution had no significant effect on any mechanical parameters following vertebroplasty. For PMMA, areal fills showed no correlation with volumetric fill, suggesting a non-uniform distribution of cement that influenced mechanical outcome. Increased filling of the vertebral body adjacent to the disc was associated with increased intradiscal pressure (R=0.56, p<0.05) in flexed posture, and reduced neural arch load bearing (F. N. ) in extended posture (R=0.76, p<0.01). Increased filling of the anterior vertebral body was associated with increased bending stiffness (R=0.55, p<0.05). Cortoss tends to spread evenly within the vertebral body, and its distribution has little influence on the mechanical outcome of vertebroplasty. PMMA spreads less evenly, and its mechanical benefits are increased when cement is concentrated in the anterior vertebral body and adjacent to the intervertebral disc