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The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 632 - 638
1 Jun 2024
Hart CM Kelley BV Mamouei Z Turkmani A Ralston M Arnold M Bernthal NM Sassoon AA

Aims. Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods. A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 10. 5. colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results. The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log. 10. (95%) and 1.5-log. 10. (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 10. 3. vs 7.0 × 10. 4. ; p = 0.022; 3.6 × 10. 3. vs 1.0 × 10. 5. ; p = 0.007, respectively) at POD 21. There was a significant 1.6-log. 10. (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 10. 0. vs 4.7 × 10. 1. , respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion. In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections. Cite this article: Bone Joint J 2024;106-B(6):632–638


Bone & Joint Research
Vol. 11, Issue 11 | Pages 835 - 842
17 Nov 2022
Wiesli MG Livio F Achermann Y Gautier E Wahl P

Aims. There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO. 4. ) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO. 4. applied locally to treat ODAI. Methods. A total of 30 operations with ceftriaxone-loaded CaSO. 4. had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results. A total of 37 wound fluid concentrations from 16 operations performed in 14 patients were collected. The ceftriaxone concentrations remained approximately within a range of 100 to 200 mg/l up to three weeks. The median concentration was 108.9 mg/l (interquartile range 98.8 to 142.5) within the first ten days. No systemic adverse reactions were observed. Conclusion. Our study highlights new clinical data of locally administered ceftriaxone with CaSO. 4. as carrier material. The near-constant release of ceftriaxone from CaSO. 4. observed in vitro could be confirmed in vivo. The concentrations remained below known local toxicity thresholds. Cite this article: Bone Joint Res 2022;11(11):835–842


Bone & Joint Research
Vol. 7, Issue 10 | Pages 570 - 579
1 Oct 2018
Kallala R Harris WE Ibrahim M Dipane M McPherson E

Aims. Calcium sulphate has traditionally been used as a filler of dead space arising during surgery. Various complications have been described following the use of Stimulan bio-absorbable calcium sulphate beads. This study is a prospective observational study to assess the safety profile of these beads when used in revision arthroplasty, comparing the complication rates with those reported in the literature. Methods. A total of 755 patients who underwent 456 revision total knee arthroplasties (TKA) and 299 revision total hip arthroplasties (THA), with a mean follow-up of 35 months (0 to 78) were included in the study. Results. A total of 32 patients (4.2%) had wound drainage, and this was higher with higher bead volumes and in McPherson grade C patients. There was also a significantly higher bead volume in the 41 patients who developed hypercalcaemia, two of which were symptomatic (p < 0.0001). A total of 13 patients (1.7%) had heterotopic ossification (HO). There was no statistically significant relationship between the development of HO and bead volume (p > 0.05). Conclusion. The strength of this study lies in the large number of patients and the detailed data collection, making it the most comprehensive report available in the literature on the use of calcium sulphate-based bone substitutes. Cite this article: R. Kallala, W. Edwin Harris, M. Ibrahim, M. Dipane, E. McPherson. Use of Stimulan absorbable calcium sulphate beads in revision lower limb arthroplasty: Safety profile and complication rates. Bone Joint Res 2018;7:570–579. DOI: 10.1302/2046-3758.710.BJR-2017-0319.R1


Bone & Joint Research
Vol. 8, Issue 2 | Pages 65 - 72
1 Feb 2019
Cowie RM Aiken SS Cooper JJ Jennings LM

Objectives. Bone void fillers are increasingly being used for dead space management in arthroplasty revision surgery. The aim of this study was to investigate the influence of calcium sulphate bone void filler (CS-BVF) on the damage and wear of total knee arthroplasty using experimental wear simulation. Methods. A total of 18 fixed-bearing U2 total knee arthroplasty system implants (United Orthopedic Corp., Hsinchu, Taiwan) were used. Implants challenged with CS-BVF were compared with new implants (negative controls) and those intentionally scratched with a diamond stylus (positive controls) representative of severe surface damage (n = 6 for each experimental group). Three million cycles (MC) of experimental simulation were carried out to simulate a walking gait cycle. Wear of the ultra-high-molecular-weight polyethylene (UHMWPE) tibial inserts was measured gravimetrically, and damage to articulating surfaces was assessed using profilometry. Results. There was no significant difference (p  >  0.05) between the wear rate of implants challenged with CS-BVF (3.3 mm. 3. /MC (95% confidence interval (CI) 1.8 to 4.8)) and the wear rate of those not challenged (2.8 mm. 3. /MC (95% CI 1.3 to 4.3)). However, scratching the cobalt-chrome (CoCr) significantly (p < 0.001) increased the wear rate (20.6 mm. 3. /MC (95% CI 15.5 to 25.7)). The mean surface roughness of implants challenged with CS-BVF was equivalent to negative controls both after damage simulation (p = 0.98) and at the conclusion of the study (p = 0.28). Conclusion. When used close to articulating surfaces, a low-hardness, high-purity CS-BVF had no influence on wear. When trapped between the articulating surfaces of a total knee arthroplasty, CS-BVF did not scratch the surface of CoCr femoral components, nor did it increase the wear of UHMWPE tibial inserts compared with undamaged negative controls. Cite this article: R. M. Cowie, S. S. Aiken, J. J. Cooper, L. M. Jennings. The influence of a calcium sulphate bone void filler on the third-body damage and polyethylene wear of total knee arthroplasty. Bone Joint Res 2019;8:65–72. DOI: 10.1302/2046-3758.82.BJR-2018-0146.R1


Bone & Joint Research
Vol. 5, Issue 10 | Pages 500 - 511
1 Oct 2016
Raina DB Gupta A Petersen MM Hettwer W McNally M Tägil M Zheng M Kumar A Lidgren L

Objectives. We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. Materials and Methods. We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy. Results. C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (. sd. ) 0.8) and BMP-7 (50.6 ng/mg, . sd. 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage. Conclusion. Extra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation. Cite this article: D. B. Raina, A. Gupta, M. M. Petersen, W. Hettwer, M. McNally, M. Tägil, M-H. Zheng, A. Kumar, L. Lidgren. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial. Bone Joint Res 2016;5:500–511. DOI: 10.1302/2046-3758.510.BJR-2016-0133.R1


The Bone & Joint Journal
Vol. 97-B, Issue 9 | Pages 1237 - 1241
1 Sep 2015
Kallala R Haddad FS

Periprosthetic joint infection (PJI) is a devastating complication for patients and results in greatly increased costs of care for both healthcare providers and patients. More than 15 500 revision hip and knee procedures were recorded in England, Wales and Northern Ireland in 2013, with infection accounting for 13% of revision hip and 23% of revision knee procedures. We report our experience of using antibiotic eluting absorbable calcium sulphate beads in 15 patients (eight men and seven women with a mean age of 64.8 years; 41 to 83) as part of a treatment protocol for PJI in revision arthroplasty. . The mean follow-up was 16 months (12 to 22). We report the outcomes and complications, highlighting the risk of hypercalcaemia which occurred in three patients. We recommend that serum levels of calcium be routinely sought following the implantation of absorbable calcium sulphate beads in orthopaedic surgery. Cite this article: Bone Joint J 2015;97-B:1237–41


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 10 | Pages 1382 - 1386
1 Oct 2007
Bajada S Harrison PE Ashton BA Cassar-Pullicino VN Ashammakhi N Richardson JB

Successful healing of a nine-year tibial nonunion resistant to six previous surgical procedures was achieved by tissue engineering. We used autologous bone marrow stromal cells (BMSCs) expanded to 5 × 10. 6. cells after three weeks’ tissue culture. Calcium sulphate (CaSO. 4. ) in pellet form was combined with these cells at operation. The nonunion was clinically and radiologically healed two months after implantation. This is the description of on healing of a long-standing tibial nonunion by tissue engineering. The successful combination of BMSCs and CaSO. 4. has not to our knowledge been reported in a clinical setting


The Bone & Joint Journal
Vol. 99-B, Issue 11 | Pages 1537 - 1544
1 Nov 2017
Wahl P Guidi M Benninger E Rönn K Gautier E Buclin T Magnin J Livio F

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


Bone & Joint Open
Vol. 4, Issue 7 | Pages 516 - 522
10 Jul 2023
Mereddy P Nallamilli SR Gowda VP Kasha S Godey SK Nallamilli RR GPRK R Meda VGR

Aims. Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections. Methods. Between January 2019 and December 2022, 106 patients with bone and joint infections were treated by five surgeons in five hospitals. Surgical debridement and calcium sulphate bead insertion was performed for local elution of antibiotics in high concentration. In all, 100 patients were available for follow-up at regular intervals. Choice of antibiotic was tailor made for each patient in consultation with microbiologist based on the organism grown on culture and the sensitivity. In majority of our cases, we used a combination of vancomycin and culture sensitive heat stable antibiotic after a thorough debridement of the site. Primary wound closure was achieved in 99 patients and a split skin graft closure was done in one patient. Mean follow-up was 20 months (12 to 30). Results. Overall, six out of 106 patients (5.6%) presented with sepsis and poorly controlled comorbid conditions, and died in the hospital within few days of index surgery. Out of the remaining 100 patients, control of infection was achieved in 95 patients (95%). Persistence of infection was noted in five (5%) patients. Out of these 95 patients that had good control of infection, four patients (4.2%) with gap nonunion needed Masquelet procedure to achieve union. Conclusion. Our multicentre experience confirmed that surgical debridement along with calcium sulphate bead insertion was effective in treating bone and joint infections without any side effects and complications. Cite this article: Bone Jt Open 2023;4(7):516–522


Bone & Joint Research
Vol. 12, Issue 7 | Pages 412 - 422
4 Jul 2023
Ferguson J Bourget-Murray J Hotchen AJ Stubbs D McNally M

Aims. Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up. Methods. A total of 179 patients received preformed calcium sulphate pellets containing 4% tobramycin (Group OT), and 180 patients had an injectable calcium sulphate/nanocrystalline hydroxyapatite ceramic containing gentamicin (Group CG). Outcome measures were infection recurrence, wound leakage, and subsequent fracture involving the treated segment. Bone-void filling was assessed radiologically at a minimum of six months post-surgery. Results. The median follow-up was 4.6 years (interquartile range (IQR) 3.2 to 5.4; range 1.3 to 10.5) in Group OT compared to 4.9 years (IQR 2.1 to 6.0; range 1.0 to 8.3) in Group CG. The groups had similar defect sizes following excision (both mean 10.9 cm. 3. (1 to 30)). Infection recurrence was higher in Group OT (20/179 (11.2%) vs 8/180 (4.4%), p = 0.019) than Group CG, as was early wound leakage (33/179 (18.4%) vs 18/180 (10.0%), p = 0.024) and subsequent fracture (11/179 (6.1%) vs 1.7% (3/180), p = 0.032). Group OT cases had an odds ratio 2.9-times higher of developing any one of these complications, compared to Group CG (95% confidence interval 1.74 to 4.81, p < 0.001). The mean bone-void healing in Group CG was better than in Group OT, in those with ≥ six-month radiological follow-up (73.9% vs 40.0%, p < 0.001). Conclusion. Local antibiotic carrier choice affects outcome in chronic osteomyelitis surgery. A biphasic injectable carrier with a slower dissolution time was associated with better radiological and clinical outcomes compared to a preformed calcium sulphate pellet carrier. Cite this article: Bone Joint Res 2023;12(7):412–422


The Bone & Joint Journal
Vol. 96-B, Issue 6 | Pages 829 - 836
1 Jun 2014
Ferguson JY Dudareva M Riley ND Stubbs D Atkins BL McNally MA

We report our experience using a biodegradable calcium sulphate antibiotic carrier containing tobramycin in the surgical management of patients with chronic osteomyelitis. The patients were reviewed to determine the rate of recurrent infection, the filling of bony defects, and any problems with wound healing. A total of 193 patients (195 cases) with a mean age of 46.1 years (16.1 to 82.0) underwent surgery. According to the Cierny–Mader classification of osteomyelitis there were 12 type I, 1 type II, 144 type III and 38 type IV cases. The mean follow-up was 3.7 years (1.3 to 7.1) with recurrent infection occurring in 18 cases (9.2%) at a mean of 10.3 months post-operatively (1 to 25.0). After further treatment the infection resolved in 191 cases (97.9%). Prolonged wound ooze (longer than two weeks post-operatively) occurred in 30 cases (15.4%) in which there were no recurrent infection. Radiographic assessment at final follow-up showed no filling of the defect with bone in 67 (36.6%), partial filling in 108 (59.0%) and complete filling in eight (4.4%). A fracture occurred in nine (4.6%) of the treated osteomyelitic segments at a mean of 1.9 years (0.4 to 4.9) after operation.

We conclude that Osteoset T is helpful in the management of patients with chronic osteomyelitis, but the filling of the defect in bone is variable. Prolonged wound ooze is usually self-limiting and not associated with recurrent infection.

Cite this article: Bone Joint J 2014; 96-B:829–36


The Bone & Joint Journal
Vol. 98-B, Issue 9 | Pages 1289 - 1296
1 Sep 2016
McNally MA Ferguson JY Lau ACK Diefenbeck M Scarborough M Ramsden AJ Atkins BL

Aims

Chronic osteomyelitis may recur if dead space management, after excision of infected bone, is inadequate. This study describes the results of a strategy for the management of deep bone infection and evaluates a new antibiotic-loaded biocomposite in the eradication of infection from bone defects.

Patients and Methods

We report a prospective study of 100 patients with chronic osteomyelitis, in 105 bones. Osteomyelitis followed injury or surgery in 81 patients. Nine had concomitant septic arthritis. 80 patients had comorbidities (Cierny-Mader (C-M) Class B hosts). Ten had infected nonunions.

All patients were treated by a multidisciplinary team with a single-stage protocol including debridement, multiple sampling, culture-specific systemic antibiotics, stabilisation, dead space filling with the biocomposite and primary skin closure.


The Bone & Joint Journal
Vol. 104-B, Issue 5 | Pages 575 - 580
2 May 2022
Hamad C Chowdhry M Sindeldecker D Bernthal NM Stoodley P McPherson EJ

Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI. Cite this article: Bone Joint J 2022;104-B(5):575–580


Bone & Joint Open
Vol. 3, Issue 12 | Pages 991 - 997
23 Dec 2022
McPherson EJ Stavrakis AI Chowdhry M Curtin NL Dipane MV Crawford BM

Aims

Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects.

Methods

We performed a retrospective review at a single institution of patients undergoing revision THA by a single surgeon. We identified 49 consecutive patients with large acetabular defects where the biphasic BGS was applied, with no other products added to the BGS. After placement of metallic acetabular implants, the BGS was injected into the remaining bone defects surrounding the new implants. Patients were followed and monitored for functional outcome scores, implant fixation, radiological graft site remodelling, and revision failures.


Bone & Joint Research
Vol. 11, Issue 11 | Pages 787 - 802
1 Nov 2022
Sebastian S Tandberg F Liu Y Raina DB Tägil M Collin M Lidgren L

Aims. There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). Methods. The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. Results. Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. Conclusion. Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections. Cite this article: Bone Joint Res 2022;11(11):787–802


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 8 | Pages 1102 - 1104
1 Aug 2006
Wenke JC Owens BD Svoboda SJ Brooks DE

The aim of this study was to determine the effectiveness of antibiotic-impregnated implants in the prevention of bone infection. We used a model of contaminated fracture in goats to evaluate four treatment groups: no treatment, hand-made tobramycin-impregnated polymethylmethacrylate beads, commercially-available tobramycin-impregnated calcium sulphate pellets and commercially-available tobramycin-impregnated polymethylmethacrylate beads. Three weeks after intraosseous inoculation with streptomycin-resistant Staphylococcus aureus tissue cultures showed no evidence of infection in any of the antibiotic-treated groups. All of the cultures were positive in the untreated group. These results show that effective local antibiotic delivery can be obtained with both commercially-available products and with hand-made polymethylmethacrylate beads. The calcium sulphate pellets have the advantage of being bioabsorbable, thereby obviating the need for a second procedure to remove them


Bone & Joint Research
Vol. 8, Issue 2 | Pages 49 - 54
1 Feb 2019
Stravinskas M Nilsson M Vitkauskiene A Tarasevicius S Lidgren L

Objectives. The aim of this study was to analyze drain fluid, blood, and urine simultaneously to follow the long-term release of vancomycin from a biphasic ceramic carrier in major hip surgery. Our hypothesis was that there would be high local vancomycin concentrations during the first week with safe low systemic trough levels and a complete antibiotic release during the first month. Methods. Nine patients (six female, three male; mean age 75.3 years (sd 12.3; 44 to 84)) with trochanteric hip fractures had internal fixations. An injectable ceramic bone substitute, with hydroxyapatite in a calcium sulphate matrix, containing 66 mg of vancomycin per millilitre, was inserted to augment the fixation. The vancomycin elution was followed by simultaneously collecting drain fluid, blood, and urine. Results. The antibiotic concentration in the drain reached a peak during the first six hours post-surgery (mean 966.1 mg/l), which decreased linearly to a mean value of 88.3 mg/l at 2.5 days. In the urine, the vancomycin concentration reached 99.8 mg/l during the first two days, followed by a logarithmic decrease over the next two weeks to reach 0 mg/l at 20 days. The systemic concentration of vancomycin measured in blood serum was low and decreased linearly from 2.17 mg/l at one hour post-surgery to 0 mg/l at four days postoperatively. Conclusion. This is the first long-term pharmacokinetic study that reports vancomycin release from a biphasic injectable ceramic bone substitute. The study shows initial high targeted local vancomycin levels, sustained and complete release at three weeks, and systemic concentrations well below toxic levels. The plain ceramic bone substitute has been proven to regenerate bone but should also be useful in preventing bone infection. Cite this article: M. Stravinskas, M. Nilsson, A. Vitkauskiene, S. Tarasevicius, L. Lidgren. Vancomycin elution from a biphasic ceramic bone substitute. Bone Joint Res 2019;8:49–54. DOI: 10.1302/2046-3758.82.BJR-2018-0174.R2


The Bone & Joint Journal
Vol. 98-B, Issue 1_Supple_A | Pages 6 - 9
1 Jan 2016
Fillingham Y Jacobs J

The continual cycle of bone formation and resorption is carried out by osteoblasts, osteocytes, and osteoclasts under the direction of the bone-signaling pathway. In certain situations the host cycle of bone repair is insufficient and requires the assistance of bone grafts and their substitutes. The fundamental properties of a bone graft are osteoconduction, osteoinduction, osteogenesis, and structural support. Options for bone grafting include autogenous and allograft bone and the various isolated or combined substitutes of calcium sulphate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. Not all bone grafts will have the same properties. As a result, understanding the requirements of the clinical situation and specific properties of the various types of bone grafts is necessary to identify the ideal graft. We present a review of the bone repair process and properties of bone grafts and their substitutes to help guide the clinician in the decision making process. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):6–9


Bone & Joint Research
Vol. 5, Issue 9 | Pages 427 - 435
1 Sep 2016
Stravinskas M Horstmann P Ferguson J Hettwer W Nilsson M Tarasevicius S Petersen MM McNally MA Lidgren L

Objectives. Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. Materials and Methods. We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis. Results. The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). Conclusions. This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials. Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. Bone Joint Res 2016;5:427–435. DOI: 10.1302/2046-3758.59.BJR-2016-0108.R1


Bone & Joint Research
Vol. 3, Issue 7 | Pages 223 - 229
1 Jul 2014
Fleiter N Walter G Bösebeck H Vogt S Büchner H Hirschberger W Hoffmann R

Objective . A clinical investigation into a new bone void filler is giving first data on systemic and local exposure to the anti-infective substance after implantation. Method . A total of 20 patients with post-traumatic/post-operative bone infections were enrolled in this open-label, prospective study. After radical surgical debridement, the bone cavity was filled with this material. The 21-day hospitalisation phase included determination of gentamicin concentrations in plasma, urine and wound exudate, assessment of wound healing, infection parameters, implant resorption, laboratory parameters, and adverse event monitoring. The follow-up period was six months. . Results . Systemic exposure to gentamicin after implantation was very low as local gentamicin concentrations were measured in wound exudate after six to ten hours. There were no signs of infectious complication throughout the clinical phase. Four patients had recurrent infections several weeks to months after implantation. The outcome was deemed successful by remission of infection in 16 (80%) of these problematic long-term treated patients. Safety laboratory measurements did not indicate nephrotoxic or hepatotoxic effects. . Conclusions . Local application of calcium sulphate/carbonate bone void filler comprising gentamicin revealed sufficient active local levels of the antibiotic by simultaneous significant low systemic exposure in patients with mostly chronic osteomyelitis/osteitis. The material was safe and well tolerated. Cite this article: Bone Joint Res 2014;3:223–9


The Bone & Joint Journal
Vol. 96-B, Issue 6 | Pages 845 - 850
1 Jun 2014
Romanò CL Logoluso N Meani E Romanò D De Vecchi E Vassena C Drago L

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed. . In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups. After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate. Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes. Cite this article: Bone Joint J 2014; 96-B:845–50


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 1 | Pages 120 - 125
1 Jan 2004
Nilsson M Wang J Wielanek L Tanner KE Lidgren L

An injectable material consisting of calcium sulphate mixed with hydroxyapatite was investigated as a possible alternative to autograft in the restoration of bone defects. The material was studied both in vitro in simulated body fluid (SBF) and in vivo when implanted in rat muscles and into the proximal tibiae of rabbits. Variation in the strength and weight of the material during ageing in SBF was measured. Tissue response, material resorption and bone ingrowth were studied in the animal models. A good tissue response was observed in both the rat muscles and rabbit tibiae without inflammatory reactions or the presence of fibrous tissue. Ageing in SBF showed that during the first week carbonated hydroxyapatite precipitated on the surfaces of the material and this may enhance bone ingrowth


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1095 - 1100
1 Sep 2022
McNally MA Ferguson JY Scarborough M Ramsden A Stubbs DA Atkins BL

Aims

Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier.

Methods

A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4).


The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 646 - 655
1 Jul 2024
Longo UG Gulotta LV De Salvatore S Lalli A Bandini B Giannarelli D Denaro V

Aims

Proximal humeral fractures are the third most common fracture among the elderly. Complications associated with fixation include screw perforation, varus collapse, and avascular necrosis of the humeral head. To address these challenges, various augmentation techniques to increase medial column support have been developed. There are currently no recent studies that definitively establish the superiority of augmented fixation over non-augmented implants in the surgical treatment of proximal humeral fractures. The aim of this systematic review and meta-analysis was to compare the outcomes of patients who underwent locking-plate fixation with cement augmentation or bone-graft augmentation versus those who underwent locking-plate fixation without augmentation for proximal humeral fractures.

Methods

The search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Articles involving patients with complex proximal humeral fractures treated using open reduction with locking-plate fixation, with or without augmentation, were considered. A meta-analysis of comparative studies comparing locking-plate fixation with cement augmentation or with bone-graft augmentation versus locking-plate fixation without augmentation was performed.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 546 - 558
12 Sep 2023
Shen J Wei Z Wang S Wang X Lin W Liu L Wang G

Aims

This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes.

Methods

A comprehensive search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases between 1 January 2000 and 31 October 2021. Studies with a minimum sample size of five patients with infected bone defects treated with the induced membrane technique were included. Factors associated with nonunion, infection recurrence, and additional procedures were identified using logistic regression analysis on individual patient data.


Bone & Joint Open
Vol. 4, Issue 8 | Pages 643 - 651
24 Aug 2023
Langit MB Tay KS Al-Omar HK Barlow G Bates J Chuo CB Muir R Sharma H

Aims

The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit.

Methods

We analyzed the retrospective record review from 2014 to 2020 of patients with long bone COM. All were managed by multidisciplinary infection team (MDT) protocol. Adequate debridement was employed for all cases, and no case of wide resection was included.


The Bone & Joint Journal
Vol. 103-B, Issue 10 | Pages 1611 - 1618
1 Oct 2021
Kavarthapu V Budair B

Aims

In our unit, we adopt a two-stage surgical reconstruction approach using internal fixation for the management of infected Charcot foot deformity. We evaluate our experience with this functional limb salvage method.

Methods

We conducted a retrospective analysis of prospectively collected data of all patients with infected Charcot foot deformity who underwent two-stage reconstruction with internal fixation between July 2011 and November 2019, with a minimum of 12 months’ follow-up.


Bone & Joint Research
Vol. 10, Issue 3 | Pages 218 - 225
1 Mar 2021
Wiesli MG Kaiser J Gautier E Wick P Maniura-Weber K Rottmar M Wahl P

Aims

In orthopaedic and trauma surgery, implant-associated infections are increasingly treated with local application of antibiotics, which allows a high local drug concentration to be reached without eliciting systematic adverse effects. While ceftriaxone is a widely used antibiotic agent that has been shown to be effective against musculoskeletal infections, high local concentrations may harm the surrounding tissue. This study investigates the acute and subacute cytotoxicity of increasing ceftriaxone concentrations as well as their influence on the osteogenic differentiation of human bone progenitor cells.

Methods

Human preosteoblasts were cultured in presence of different concentrations of ceftriaxone for up to 28 days and potential cytotoxic effects, cell death, metabolic activity, cell proliferation, and osteogenic differentiation were studied.


Aims

Our objective was to conduct a systematic review and meta-analysis, to establish whether differences arise in clinical outcomes between autologous and synthetic bone grafts in the operative management of tibial plateau fractures.

Methods

A structured search of MEDLINE, EMBASE, the online archives of Bone & Joint Publishing, and CENTRAL databases from inception until 28 July 2021 was performed. Randomized, controlled, clinical trials that compared autologous and synthetic bone grafts in tibial plateau fractures were included. Preclinical studies, clinical studies in paediatric patients, pathological fractures, fracture nonunion, or chondral defects were excluded. Outcome data were assessed using the Risk of Bias 2 (ROB2) framework and synthesized in random-effect meta-analysis. The Preferred Reported Items for Systematic Review and Meta-Analyses guidance was followed throughout.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 709 - 718
1 Oct 2020
Raina DB Liu Y Jacobson OLP Tanner KE Tägil M Lidgren L

Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health.

Cite this article: Bone Joint Res 2020;9(10):709–718.


Bone & Joint Research
Vol. 9, Issue 7 | Pages 394 - 401
1 Jul 2020
Blirup-Plum SA Bjarnsholt T Jensen HE Kragh KN Aalbæk B Gottlieb H Bue M Jensen LK

Aims

CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e. without additional systemic antimicrobial therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model.

Methods

Osteomyelitis was induced in nine pigs by inoculation of 104 colony-forming units (CFUs) of Staphylococcus aureus into a drill hole in the right tibia. After one week, the pigs were allocated into three groups. Group A (n = 3) received no treatment during the study period (19 days). Groups B (n = 3) and C (n = 3) received limited or extensive debridement seven days postinoculation, respectively, followed by injection of CERAMENT|G into the bone voids. The pigs were euthanized ten (Group C) and 12 (Group B) days after the intervention.


Bone & Joint 360
Vol. 9, Issue 6 | Pages 22 - 27
1 Dec 2020


The Bone & Joint Journal
Vol. 100-B, Issue 11 | Pages 1409 - 1415
1 Nov 2018
Marson BA Deshmukh SR Grindlay DJC Ollivere BJ Scammell BE

Aims

Local antibiotics are used in the surgical management of foot infection in diabetic patients. This systematic review analyzes the available evidence of the use of local antibiotic delivery systems as an adjunct to surgery.

Materials and Methods

Databases were searched to identify eligible studies and 13 were identified for inclusion.


The Bone & Joint Journal
Vol. 102-B, Issue 11 | Pages 1587 - 1596
1 Nov 2020
Hotchen AJ Dudareva M Corrigan RA Ferguson JY McNally MA

Aims

This study presents patient-reported quality of life (QoL) over the first year following surgical debridement of long bone osteomyelitis. It assesses the bone involvement, antimicrobial options, coverage of soft tissues, and host status (BACH) classification as a prognostic tool and its ability to stratify cases into ‘uncomplicated’ or ‘complex’.

Methods

Patients with long-bone osteomyelitis were identified prospectively between June 2010 and October 2015. All patients underwent surgical debridement in a single-staged procedure at a specialist bone infection unit. Self-reported QoL was assessed prospectively using the three-level EuroQol five-dimension questionnaire (EQ-5D-3L) index score and visual analogue scale (EQ-VAS) at five postoperative time-points (baseline, 14 days, 42 days, 120 days, and 365 days). BACH classification was applied retrospectively by two clinicians blinded to outcome.


The Bone & Joint Journal
Vol. 102-B, Issue 12 | Pages 1723 - 1734
1 Dec 2020
Fung B Hoit G Schemitsch E Godbout C Nauth A

Aims

The purpose of this study was to: review the efficacy of the induced membrane technique (IMT), also known as the Masquelet technique; and investigate the relationship between patient factors and technique variations on the outcomes of the IMT.

Methods

A systematic search was performed in CINAHL, The Cochrane Library, Embase, Ovid MEDLINE, and PubMed. We included articles from 1 January 1980 to 30 September 2019. Studies with a minimum sample size of five cases, where the IMT was performed primarily in adult patients (≥ 18 years old), in a long bone were included. Multivariate regression models were performed on patient-level data to determine variables associated with nonunion, postoperative infection, and the need for additional procedures.


Bone & Joint Research
Vol. 7, Issue 10 | Pages 548 - 560
1 Oct 2018
Qayoom I Raina DB Širka A Tarasevičius Š Tägil M Kumar A Lidgren L

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions.

Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.


Bone & Joint Research
Vol. 6, Issue 7 | Pages 423 - 432
1 Jul 2017
van der Stok J Hartholt KA Schoenmakers DAL Arts JJC

Objectives

The aim of this systematic literature review was to assess the clinical level of evidence of commercially available demineralised bone matrix (DBM) products for their use in trauma and orthopaedic related surgery.

Methods

A total of 17 DBM products were used as search terms in two available databases: Embase and PubMed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. All articles that reported the clinical use of a DBM-product in trauma and orthopaedic related surgery were included.


The Bone & Joint Journal
Vol. 95-B, Issue 5 | Pages 583 - 597
1 May 2013
Kurien T Pearson RG Scammell BE

We reviewed 59 bone graft substitutes marketed by 17 companies currently available for implantation in the United Kingdom, with the aim of assessing the peer-reviewed literature to facilitate informed decision-making regarding their use in clinical practice. After critical analysis of the literature, only 22 products (37%) had any clinical data. Norian SRS (Synthes), Vitoss (Orthovita), Cortoss (Orthovita) and Alpha-BSM (Etex) had Level I evidence. We question the need for so many different products, especially with limited published clinical evidence for their efficacy, and conclude that there is a considerable need for further prospective randomised trials to facilitate informed decision-making with regard to the use of current and future bone graft substitutes in clinical practice.

Cite this article: Bone Joint J 2013;95-B:583–97.


Bone & Joint Research
Vol. 8, Issue 2 | Pages 81 - 89
1 Feb 2019
Funk GA Menuey EM Cole KA Schuman TP Kilway KV McIff TE

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.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 8 | Pages 1106 - 1109
1 Aug 2009
Branstetter JG Jackson SR Haggard WO Richelsoph KC Wenke JC

We used a goat model of a contaminated musculoskeletal defect to determine the effectiveness of rapidly-resorbing calcium-sulphate pellets containing amikacin to reduce the local bacterial count. Our findings showed that this treatment eradicated the bacteria quickly, performed as well as standard polymethylmethacrylate mixed with an antibiotic and had many advantages over the latter. The pellets were prepared before surgery and absorbed completely. They released all of the antibiotic and did not require a subsequent operation for their removal. Our study indicated that locally administered antibiotics reduced bacteria within the wound rapidly. This method of treatment may have an important role in decreasing the rate of infection in contaminated wounds.


The Bone & Joint Journal
Vol. 96-B, Issue 11_Supple_A | Pages 70 - 72
1 Nov 2014
Callaghan JJ Liu SS Phruetthiphat O

A common situation presenting to the orthopaedic surgeon today is a worn acetabular liner with substantial acetabular and pelvic osteolysis. The surgeon has many options for dealing with osteolytic defects. These include allograft, calcium based substitutes, demineralised bone matrix, or combinations of these options with or without addition of platelet rich plasma. To date there are no clinical studies to determine the efficacy of using bone-stimulating materials in osteolytic defects at the time of revision surgery and there are surprisingly few studies demonstrating the clinical efficacy of these treatment options. Even when radiographs appear to demonstrate incorporation of graft material CT studies have shown that incorporation is incomplete. The surgeon, in choosing a graft material for a surgical procedure must take into account the efficacy, safety, cost and convenience of that material.

Cite this article: Bone Joint J 2014;96-B (11 Suppl A):70–2.


The Bone & Joint Journal
Vol. 97-B, Issue 6 | Pages 836 - 841
1 Jun 2015
Jónsson BY Mjöberg B

A total of 20 patients with a depressed fracture of the lateral tibial plateau (Schatzker II or III) who would undergo open reduction and internal fixation were randomised to have the metaphyseal void in the bone filled with either porous titanium granules or autograft bone. Radiographs were undertaken within one week, after six weeks, three months, six months, and after 12 months.

The primary outcome measure was recurrent depression of the joint surface: a secondary outcome was the duration of surgery.

The risk of recurrent depression of the joint surface was lower (p < 0.001) and the operating time less (p < 0.002) when titanium granules were used.

The indication is that it is therefore beneficial to use porous titanium granules than autograft bone to fill the void created by reducing a depressed fracture of the lateral tibial plateau. There is no donor site morbidity, the operating time is shorter and the risk of recurrent depression of the articular surface is less.

Cite this article: Bone Joint J 2015; 97-B:836–41


The Bone & Joint Journal
Vol. 98-B, Issue 8 | Pages 1126 - 1131
1 Aug 2016
Shiels SM Cobb RR Bedigrew KM Ritter G Kirk JF Kimbler A Finger Baker I Wenke JC

Aims

Demineralised bone matrix (DBM) is rarely used for the local delivery of prophylactic antibiotics. Our aim, in this study, was to show that a graft with a bioactive glass and DBM combination, which is currently available for clinical use, can be loaded with tobramycin and release levels of antibiotic greater than the minimum inhibitory concentration for Staphylococcus aureus without interfering with the bone healing properties of the graft, thus protecting the graft and surrounding tissues from infection.

Materials and Methods

Antibiotic was loaded into a graft and subsequently evaluated for drug elution kinetics and the inhibition of bacterial growth. A rat femoral condylar plug model was used to determine the effect of the graft, loaded with antibiotic, on bone healing.


Bone & Joint 360
Vol. 5, Issue 3 | Pages 2 - 6
1 Jun 2016
Raglan M Scammell B


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 2 | Pages 151 - 157
1 Feb 2011
El-Husseiny M Patel S MacFarlane RJ Haddad FS

Bacterial infection in orthopaedic surgery can be devastating, and is associated with significant morbidity and poor functional outcomes, which may be improved if high concentrations of antibiotics can be delivered locally over a prolonged period of time. The two most widely used methods of doing this involve antibiotic-loaded polymethylmethacrylate or collagen fleece. The former is not biodegradable and is a surface upon which secondary bacterial infection may occur. Consequently, it has to be removed once treatment has finished. The latter has been used successfully as an adjunct to systemic antibiotics, but cannot effect a sustained release that would allow it to be used on its own, thereby avoiding systemic toxicity.

This review explores the newer biodegradable carrier systems which are currently in the experimental phase of development and which may prove to be more effective in the treatment of osteomyelitis.


Bone & Joint Research
Vol. 7, Issue 5 | Pages 336 - 342
1 May 2018
Hotham WE Malviya A

This systematic review examines the current literature regarding surgical techniques for restoring articular cartilage in the hip, from the older microfracture techniques involving perforation to the subchondral bone, to adaptations of this technique using nanofractures and scaffolds. This review discusses the autologous and allograft transfer systems and the autologous matrix-induced chondrogenesis (AMIC) technique, as well as a summary of the previously discussed techniques, which could become common practice for restoring articular cartilage, thus reducing the need for total hip arthroplasty. Using the British Medical Journal Grading of Recommendations, Assessment, Development and Evaluation (BMJ GRADE) system and Grade system. Comparison of the studies discussed shows that microfracture has the greatest quantity and quality of research, whereas the newer AMIC technique requires more research, but shows promise.

Cite this article: W. E. Hotham, A. Malviya. A systematic review of surgical methods to restore articular cartilage in the hip. Bone Joint Res 2018;7:336–342. DOI: 10.1302/2046-3758.75.BJR-2017-0331.


Bone & Joint Research
Vol. 2, Issue 2 | Pages 41 - 50
1 Feb 2013
Cottrell JA Keshav V Mitchell A O’Connor JP

Objectives

Recent studies have shown that modulating inflammation-related lipid signalling after a bone fracture can accelerate healing in animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity during fracture healing increases cyclooxygenase-2 (COX-2) expression in the fracture callus, accelerates chondrogenesis and decreases healing time. In this study, we test the hypothesis that 5-LO inhibition will increase direct osteogenesis.

Methods

Bilateral, unicortical femoral defects were used in rats to measure the effects of local 5-LO inhibition on direct osteogenesis. The defect sites were filled with a polycaprolactone (PCL) scaffold containing 5-LO inhibitor (A-79175) at three dose levels, scaffold with drug carrier, or scaffold only. Drug release was assessed in vitro. Osteogenesis was assessed by micro-CT and histology at two endpoints of ten and 30 days.


The Bone & Joint Journal
Vol. 95-B, Issue 11 | Pages 1514 - 1520
1 Nov 2013
D’Agostino P Barbier O

The osteoinductive properties of demineralised bone matrix have been demonstrated in animal studies. However, its therapeutic efficacy has yet to be proven in humans. The clinical properties of AlloMatrix, an injectable calcium-based demineralised bone matrix allograft, were studied in a prospective randomised study of 50 patients with an isolated unstable distal radial fracture treated by reduction and Kirschner (K-) wire fixation. A total of 24 patients were randomised to the graft group (13 men and 11 women, mean age 42.3 years (20 to 62)) and 26 to the no graft group (8 men and 18 women, mean age 45.0 years (17 to 69)).

At one, three, six and nine weeks, and six and 12 months post-operatively, patients underwent radiological evaluation, assessments for range of movement, grip and pinch strength, and also completed the Disabilities of Arm, Shoulder and Hand questionnaire. At one and six weeks and one year post-operatively, bone mineral density evaluations of both wrists were performed.

No significant difference in wrist function and speed of recovery, rate of union, complications or bone mineral density was found between the two groups. The operating time was significantly higher in the graft group (p = 0.004). Radiologically, the reduction parameters remained similar in the two groups and all AlloMatrix extraosseous leakages disappeared after nine weeks.

This prospective randomised controlled trial did not demonstrate a beneficial effect of AlloMatrix demineralised bone matrix in the treatment of this category of distal radial fractures treated by K-wire fixation.

Cite this article: Bone Joint J 2013;95-B:1514–20.


The Bone & Joint Journal
Vol. 98-B, Issue 6 | Pages 834 - 839
1 Jun 2016
Wang S Ma H Lin C Chou P Liu C Yu W Chang M

Aim

Many aspects of the surgical treatment of patients with tuberculosis (TB) of the spine, including the use of instrumentation and the types of graft, remain controversial. Our aim was to report the outcome of a single-stage posterior procedure, with or without posterior decompression, in this group of patients.

Patients and Methods

Between 2001 and 2010, 51 patients with a mean age of 62.5 years (39 to 86) underwent long posterior instrumentation and short posterior or posterolateral fusion for TB of the thoracic and lumbar spines, followed by anti-TB chemotherapy for 12 months. No anterior debridement of the necrotic tissue was undertaken. Posterior decompression with laminectomy was carried out for the 30 patients with a neurological deficit.


Bone & Joint Research
Vol. 5, Issue 7 | Pages 287 - 293
1 Jul 2016
Ismail H Phedy P Kholinne E Djaja YP Kusnadi Y Merlina M Yulisa ND

Objectives

To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone.

Methods

Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm3 (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm3 HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment.


The Bone & Joint Journal
Vol. 97-B, Issue 10 | Pages 1423 - 1427
1 Oct 2015
Rand BCC Penn-Barwell JG Wenke JC

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.


The Bone & Joint Journal
Vol. 97-B, Issue 9 | Pages 1162 - 1169
1 Sep 2015
George DA Gant V Haddad FS

The number of arthroplasties being undertaken is expected to grow year on year, and periprosthetic joint infections will be an increasing socioeconomic burden. The challenge to prevent and eradicate these infections has resulted in the emergence of several new strategies, which are discussed in this review.

Cite this article: Bone Joint J 2015;97-B:1162–9.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 10 | Pages 1383 - 1387
1 Oct 2009
Yoo WJ Choi IH Cho T Chung CY Shin Y Shin SJ

We evaluated radiological hip remodelling after shelf acetabuloplasty and sought to identify prognostic factors in 25 patients with a mean age of 8.9 years (7.0 to 12.3) who had unilateral Perthes’ disease with reducible subluxation of the hip in the fragmentation stage.

At a mean follow-up of 6.7 years (3.2 to 9.0), satisfactory remodelling was observed in 18 hips (72%). The type of labrum in hip abduction, as determined by intra-operative dynamic arthrography, was found to be a statistically significant prognostic factor (p = 0.012).

Shelf acetabuloplasty as containment surgery seems to be best indicated for hips in which there is not marked collapse of the epiphysis and in which the extruded epiphyseal segment slips easily underneath the labrum on abduction, without imposing undue pressure on the lateral edge of the acetabulum.


Bone & Joint 360
Vol. 3, Issue 4 | Pages 33 - 35
1 Aug 2014

The August 2014 Research Roundup360 looks at: Antibiotic loaded ceramic of use in osteomyelitis; fibronectin implicated in cartilage degeneration; Zinc Chloride accelerates fracture healing in rats; advertisements and false claims; Net Promoter Score: substance or rhetoric?; aspirin for venous thromboembolism prophylaxis and dissection, stress and the soul.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 8 | Pages 1032 - 1038
1 Aug 2006
Hopgood P Kumar R Wood PLR

Between 1999 and 2005, 23 failed total ankle replacements were converted to arthrodeses. Three surgical techniques were used: tibiotalar arthrodesis with screw fixation, tibiotalocalcaneal arthrodesis with screw fixation, and tibiotalocalcaneal arthrodesis with an intramedullary nail. As experience was gained, the benefits and problems became apparent. Successful bony union was seen in 17 of the 23 ankles. The complication rate was higher in ankles where the loosening had caused extensive destruction of the body of the talus, usually in rheumatoid arthritis. In this situation we recommend tibiotalocalcaneal arthrodesis with an intramedullary nail. This technique can also be used when there is severe arthritic change in the subtalar joint. Arthrodesis of the tibiotalar joint alone using compression screws was generally possible in osteoarthritis because the destruction of the body of the talus was less extensive. Tibiotalocalcaneal arthrodesis fusion with compression screws has not been successful in our experience.


The Bone & Joint Journal
Vol. 96-B, Issue 6 | Pages 783 - 788
1 Jun 2014
Kanakaris N Gudipati S Tosounidis T Harwood P Britten S Giannoudis PV

Intramedullary infection in long bones represents a complex clinical challenge, with an increasing incidence due to the increasing use of intramedullary fixation. We report a prospective case series using an intramedullary reaming device, the Reamer–Irrigator–Aspirator (RIA) system, in association with antibiotic cement rods for the treatment of lower limb long bone infections. A total of 24 such patients, 16 men and eight women, with a mean age of 44.5 years (17 to 75), 14 with femoral and 10 with tibial infection, were treated in a staged manner over a period of 2.5 years in a single referral centre. Of these, 21 patients had had previous surgery, usually for fixation of a fracture (seven had sustained an open fracture originally and one had undergone fasciotomies). According to the Cierny–Mader classification system, 18 patients were classified as type 1A, four as 3A (discharging sinus tract), one as type 4A and one as type 1B. Staphylococcus species were isolated in 20 patients (83.3%). Local antibiotic delivery was used in the form of impregnated cement rods in 23 patients. These were removed at a mean of 2.6 months (1 to 5). Pathogen-specific antibiotics were administered systemically for a mean of six weeks (3 to 18). At a mean follow-up of 21 months (8 to 36), 23 patients (96%) had no evidence of recurrent infection. One underwent a planned trans-tibial amputation two weeks post-operatively due to peripheral vascular disease and chronic recalcitrant osteomyelitis of the tibia and foot. The combination of RIA reaming, the administration of systemic pathogen-specific antibiotics and local delivery using impregnated cement rods proved to be a safe and efficient form of treatment in these patients.

Cite this article: Bone Joint J 2014; 96-B:783–8.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 5 | Pages 565 - 576
1 May 2009
Getgood A Brooks R Fortier L Rushton N

Articular cartilage repair remains a challenge to surgeons and basic scientists. The field of tissue engineering allows the simultaneous use of material scaffolds, cells and signalling molecules to attempt to modulate the regenerative tissue. This review summarises the research that has been undertaken to date using this approach, with a particular emphasis on those techniques that have been introduced into clinical practice, via in vitro and preclinical studies.


Bone & Joint Research
Vol. 1, Issue 1 | Pages 1 - 7
1 Jan 2012
Rosenberg N Rosenberg O

Objectives

The need for bone tissue supplementation exists in a wide range of clinical conditions involving surgical reconstruction in limbs, the spine and skull. The bone supplementation materials currently used include autografts, allografts and inorganic matrix components; but these pose potentially serious side-effects. In particular the availability of the autografts is usually limited and their harvesting causes surgical morbidity. Therefore for the purpose of supplementation of autologous bone graft, we have developed a method for autologous extracorporeal bone generation.

Methods

Human osteoblast-like cells were seeded on porous granules of tricalcium phosphate and incubated in osteogenic media while exposed to mechanical stimulation by vibration in the infrasonic range of frequencies. The generated tissue was examined microscopically following haematoxylin eosin, trichrome and immunohistochemical staining.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 8 | Pages 1101 - 1106
1 Aug 2012
Jindal N Sankhala SS Bachhal V

The purpose of this study was to determine whether patients with a burst fracture of the thoracolumbar spine treated by short segment pedicle screw fixation fared better clinically and radiologically if the affected segment was fused at the same time. A total of 50 patients were enrolled in a prospective study and assigned to one of two groups. After the exclusion of three patients, there were 23 patients in the fusion group and 24 in the non-fusion group. Follow-up was at a mean of 23.9 months (18 to 30). Functional outcome was evaluated using the Greenough Low Back Outcome Score. Neurological function was graded using the American Spinal Injury Association Impairment Scale. Radiological outcome was assessed on the basis of the angle of kyphosis.

Peri-operative blood transfusion requirements and duration of surgery were significantly higher in the fusion group (p = 0.029 and p < 0.001, respectively). There were no clinical or radiological differences in outcome between the groups (all outcomes p > 0.05). The results of this study suggest that adjunctive fusion is unnecessary when managing patients with a burst fracture of the thoracolumbar spine with short segment pedicle screw fixation.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 4 | Pages 527 - 534
1 Apr 2010
Streubel PN Gardner MJ Morshed S Collinge CA Gallagher B Ricci WM

It is unclear whether there is a limit to the amount of distal bone required to support fixation of supracondylar periprosthetic femoral fractures. This retrospective multicentre study evaluated lateral locked plating of periprosthetic supracondylar femoral fractures and compared the results according to extension of the fracture distal with the proximal border of the femoral prosthetic component.

Between 1999 and 2008, 89 patients underwent lateral locked plating of a supracondylar periprosthetic femoral fracture, of whom 61 patients with a mean age of 72 years (42 to 96) comprising 53 women, were available after a minimum follow-up of six months or until fracture healing. Patients were grouped into those with fractures located proximally (28) and those with fractures that extended distal to the proximal border of the femoral component (33).

Delayed healing and nonunion occurred respectively in five (18%) and three (11%) of more proximal fractures, and in two (6%) and five (15%) of the fractures with distal extension (p = 0.23 for delayed healing; p = 0.72 for nonunion, Fisher’s exact test). Four construct failures (14%) occurred in more proximal fractures, and three (9%) in fractures with distal extension (p = 0.51). Of the two deep infections that occurred in each group, one resolved after surgical debridement and antibiotics, and one progressed to a nonunion.

Extreme distal periprosthetic supracondylar fractures of the femur are not a contra-indication to lateral locked plating. These fractures can be managed with internal fixation, with predictable results, similar to those seen in more proximal fractures.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 11 | Pages 1401 - 1406
1 Nov 2008
Patel A Calfee RP Plante M Fischer SA Arcand N Born C

Methicillin-resistant Staphylococcus aureus (MRSA) has become a ubiquitous bacterium in both the hospital and community setting. There are two major subclassifications of MRSA, community-acquired and healthcare-acquired, each with differing pathogenicity and management. MRSA is increasingly responsible for infections in otherwise healthy, active adults. Local outbreaks affect both professional and amateur athletes and there is increasing public awareness of the issue. Health-acquired MRSA has major cost and outcome implications for patients and hospitals. The increasing prevalence and severity of MRSA means that the orthopaedic community should have a basic knowledge of the bacterium, its presentation and options for treatment.

This paper examines the evolution of MRSA, analyses the spectrum of diseases produced by this bacterium and presents current prevention and treatment strategies for orthopaedic infections from MRSA.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 3 | Pages 421 - 425
1 Mar 2005
Blom AW Cunningham JL Hughes G Lawes TJ Smith N Blunn G Learmonth ID Goodship AE

This study investigates the use of porous biphasic ceramics as graft extenders in impaction grafting of the femur during revision hip surgery.

Impaction grafting of the femur was performed in four groups of sheep. Group one received pure allograft, group two 50% allograft and 50% BoneSave, group three 50% allograft and 50% BoneSave type 2 and group four 10% allograft and 90% BoneSave as the graft material. Function was assessed using an index of pre- and post-operative peak vertical ground reaction force ratios. Changes in bone mineral density were measured by dual energy X ray absorptiometry (DEXA) scanning. Loosening and subsidence were assessed radiographically and by histological examination of the explanted specimens.

There was no statistically significant difference between the four groups after 18 months of unrestricted functional loading for all outcome measures.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 5 | Pages 574 - 580
1 May 2007
Delloye C Cornu O Druez V Barbier O

Bone allografts can be used in any kind of surgery involving bone from minor defects to major bone loss after tumour resection. This review describes the various types of bone grafts and the current knowledge on bone allografts, from procurement and preparation to implantation. The surgical conditions for optimising the incorporation of bone are outlined, and surgeon expectations from a bone allograft discussed.