Background. Medical grade Calcium Sulphate can be used as a delivery vehicle for antibiotics. We use these for treating patients with established osteomyelitis, but also use it prophylactic for contaminated war injuries, to fill voids in bone with osteo conductve filler that delivers local antibiotics, and can integrate with bone. Although antibiotic loaded calcium sulphate is increasingly used, there is little data to demonstrate that systemic levels generated by local release of antibiotics are safe. For this reason, we routinely assay systemic levels of antibiotics. Objectives. To determine if systemic toxicity occurs after the use of antibiotic loaded calcium sulphate in the treatment of bone and soft tissue infection. Material and Method. Bone cavities and soft tissue dead spaces were aggressively debrided, lavaged and packed with Calcium Sulphate (10–40 cc) loaded with Vancomycin (1–4 g) and Gentamicin (240–960 mg). Post-operatively serial assays of Vancomycin and Gentamicin levels 1 hour after surgery then daily for three days. Renal function was also measured. Results. In patients with normal renal function. : The systemic levels were either un-measurable at the first assay, or below the acceptable trough level (Mean 2.4 and 1.8 for Vancomycin and Gentamycin respectively). They had measurable systemic levels at the third assay . In patients with renal dysfunction. : Systemic levels were in the therapeutic range determined for systemically administered antibiotics, but these levels remained high and did not decrease until patients had undergone their routine dialysis. Conclusions. In patients treated with antibiotic loaded Calcium Sulphate: Antibiotic assays are not necessary in patients who have normal renal function. Patients with impaired renal function should have:. Use lower doses of antibiotics. Should undergo assays routinely. Ensure dialysis after surgery. If they remain high, the antibiotic loaded calcium sulphate could be removed

The aim was to report operative complications, radiographic and patient-reported outcomes following lateral tibial plateau fracture fixation augmented with calcium phosphate cement (CPC). From 2007–2018, 187 patients (median age 57yrs [range 22–88], 63% female [n=118/187]) with a Schatzker II/III fracture were retrospectively identified. There were 103 (55%) ORIF and 84 (45%) percutaneous fixation procedures. Complications and radiographic outcomes were determined from outpatient records and radiographs. Long-term follow-up was via telephone interview. At a median of 6 months (range 0.1–138) postoperatively, complications included superficial peroneal nerve injury (0.5%, n=1/187), infection (6.4%, n=12/187), prominent metalwork (10.2%, n=19/187) and post-traumatic osteoarthritis (PTOA; 5.3%, n=10/187). The median postoperative medial proximal tibial angle was 89o (range 82–107) and posterior proximal tibial angle 82o (range 45–95). Three patients (1.6%) underwent debridement for infection and 27 (14.4%) required metalwork removal. Seven patients (4.2%) underwent total knee replacement for PTOA. Sixty percent of available patients (n=97/163) completed telephone follow-up at a median of 6yrs (range 1–13). The median Oxford Knee Score was 42 (range 3–48), Knee injury and Osteoarthritis Outcome Score 88 (range 10–100), EuroQol 5-Dimension score 0.812 (range −0.349–1.000) and Visual Analogue Scale 75 (range 10–100). There were no significant differences between ORIF and percutaneous fixation in patient-reported outcome (all p>0.05). Fixation augmented with CPC is safe and effective for lateral tibial plateau fractures, with a low complication rate and good long-term knee function and health-related quality of life. Percutaneous fixation offers a viable alternative to ORIF with no detriment to patient-reported outcome

Magnesium calcium alloys are promising candidates for an application as biodegradable osteosynthesis implants [1,2]. As the success of most internal fracture fixation techniques relies on safe anchorage of bone screws, there is necessity to investigate the holding power of biodegradable magnesium calcium alloy screws. Therefore, the aim of the present study was to compare the holding power of magnesium calcium alloy screws and commonly used surgical steel screws, as a control, by pull-out testing. Magnesium calcium alloy screws with 0.8wt% calcium (MgCa0.8) and conventional surgical steel screws (S316L) of identical geometries (major diameter 4mm, core diameter 3mm, thread pitch 1mm) were implanted into both tibiae of 40 rabbits. The screws were placed into the lateral tibial cortex just proximal of the fibula insertion and tightened with a manual torque gauge (15cNm). For intended pull-out tests a 1.5mm thick silicone washer served as spacer between bone and screw head. Six animals with MgCa0.8 and four animals with S316L were followed up for 2, 4, 6 and 8 weeks, respectively. Thereafter the rabbits were sacrificed. Both tibiae were explanted, adherent soft tissue and new bone was carefully dissected around the screw head. Pull-out tests were carried out with an MTS 858 MiniBionix at a rate of 0.1mm/sec until failure of the screw or the bone. For each trial the maximum pull-out force [N] was determined. Statistical analysis was performed (ANOVA, Student's t-test). Both implant materials were tolerated well. Radiographically, new bone was detected at the implantation site of MgCa0.8 and S316L, which was carefully removed to perform pull-out trials. Furthermore, periimplant accumulations of gas were radiographically detected in MgCa0.8. The pull-out force of MgCa0.8 and S316L did not significantly differ (p = 0.121) after two weeks. From 6 weeks on the pull-out force of MgCa0.8 decreased resulting in significantly lower pull-out values after 8 weeks. Contrary, S316L pull-out force increased throughout the follow up. Thus, S316L showed significantly higher pull-out values than MgCa0.8 after 4, 6 and 8 weeks (p<0.001). MgCa0.8 showed good biocompatibility and pull-out values comparable to S316L in the first weeks of implantation. Thus, its application as biodegradable osteosynthesis implant is conceivable. Further studies are necessary to investigate whether the reduced holding power of MgCa0.8 is sufficient for secure fracture fixation. In addition, not only solitary screws, but also screw-plate-combinations should be examined over a longer time period. Acknowledgements. The study is part of the collaborative research centre 599 funded by the German Research Foundation

Introduction. Calcium sulphate is a resorbable void filler that can be used for local antibiotic delivery. Results from clinical studies on chronic osteomyelitis thus treated with local vancomycin have already been published. Despite significant exposure to this drug, there are no pharmacokinetic studies published so far. Based on observations in our patients, a model predicting vancomycin serum and wound fluid levels and toxicity potential is presented. Methods. Following implantation of Osteoset® added with vancomycin, serum and wound fluid concentrations of this antibiotic have been monitored systematically. The pharmacokinetic analysis was performed using a non-linear mixed-effects model based on a one-compartment model with first-degree absorption. Results. Data from 43 patients treated between October 2006 and August 2010 were analysed. Serum concentrations remained far below the usually accepted trough levels of 10 mg/L, and were still acceptable in two cases of post-operative renal failure. Wound fluid concentrations around 1,000 mg/l were observed for the first 7–10 days, and remained above usual minimal inhibitory concentrations for approximately a month. Discussion and Conclusion. This is the first pharmacokinetic exploration of calcium sulphate added with vancomycin for local antibiotic therapy. The systemic exposure to vancomycin is low and appears safe even after implantation of up to 6 g vancomycin, except in case of markedly impaired renal function. Wound fluid concentrations of vancomycin appear extremely interesting for further studies

A total of 63 women who had an operation for a fracture of the hip was randomly allocated to one year of treatment either with anabolic steroids, vitamin D and calcium (anabolic group) or with calcium only (control group). The thigh muscle volume was measured by quantitative CT. The bone mineral density of the hip, femur and tibia was assessed by quantitative CT and dual-energy x-ray absorptiometry and of the heel by quantitative ultrasound. Quantitative CT showed that the anabolic group did not lose muscle volume during the first 12 months whereas the control group did (p< 0.01). There was less bone loss in the proximal tibia in the anabolic group than in the control group. The speed of gait and the Harris hip score were significantly better in the anabolic group after six and 12 months. Anabolic steroids, even in this moderate dose, given in combination with vitamin D and calcium had a beneficial effect on muscle volume, bone mineral density and clinical function in this group of elderly women

INTRODUCTION. Autologous bone grafts are considered gold standard in the repair of bone defects. However they are limited in supply and are associated with donor site morbidity. This has led to the development of synthetic bone graft substitute (BGS) materials, many of which have been reported as being osteoinductive. The structure of the BGS is important and bone formation has been observed in scaffolds with a macroporous morphology. Smaller pores termed ‘strut porosity’ may also be important for osteoinduction. The aim of this study was to compare the osteoinductive ability of one silicate-substituted calcium phosphate (SiCaP) with differing strut porosities in an ectopic ovine model. Our hypothesis was that SiCaP with greater strut porosity would be more osteoinductive. METHODS. The osteoinduction of SiCaP BGS with two different strut porosities (AF and AF++) was investigated. The materials had an identical chemical composition and morphological structure but differing strut porosity (AF=22.5%, AF++=47%). Implants were inserted into the paraspinal muscles in skeletally mature sheep. Procedures were carried out in compliance with UK Home Office regulations. There were 12 implants in each group. Implants remained in vivo for 8 and 12 weeks and on retrieval were prepared for undecalcified histology. Sections were stained and examined using light microscopy. A line intersection method was used to quantify bone, implant and implant surface/bone contact within seven random regions of interest along each implant. A Mann-Whitney U test was used for statistical analysis where p values < 0.05 were considered significant. RESULTS. Bone formation was observed to be greater in the AF++ group at 8 (AF=0.2%+/−0.15; AF++=0.44%+/−0.12) and significantly higher at 12 weeks (AF=1.33% +/−0.84; AF++=6.17%+/−1.51) (p=0.04). Significantly higher implant surface/bone contact was observed in the AF++ group at 8 (AF=0.67%+/−0.52; AF++=3.30%+/−1.17) (p=0.04) and 12 weeks (AF=3.06%+/−1.89; AF++=21.82%+/−5.59) (p=0.01). The % implant measured was less in the AF++ group at 8 (AF=39.06%+/−1.26; AF++=33.09%+/−2.14) and 12 weeks (AF=36.05% +/−3.55; AF++=30.60%+/−2.29) but this was not significant. Histology revealed bone formation within BGS strut pores measuring < 50um. Endochondral and intramembranous ossification were also observed in both groups. DISCUSSION. The results indicate that higher strut porosity promotes greater osteoinduction in SiCaP materials. This could be attributed to the micropores providing a greater surface area for the action of growth factors and osteoblasts leading to the formation of bone at an earlier time point. Endochondral ossification was an unusual finding as this is usually associated with bone formation secondary to Bone Morphogenetic proteins (BMPs). This suggests that the osteoinductive mechanisms by SiCaP may involve cytokines such as BMPs

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

Aims. Bone health assessment and the prescription of medication for secondary fracture prevention have become an integral part of the acute management of patients with hip fracture. However, there is little evidence regarding compliance with prescription guidelines and subsequent adherence to medication in this patient group. Patients and Methods. The World Hip Trauma Evaluation (WHiTE) is a multicentre, prospective cohort of hip fracture patients in NHS hospitals in England and Wales. Patients aged 60 years and older who received operative treatment for a hip fracture were eligible for inclusion in WHiTE. The prescription of bone protection medications was recorded from participants’ discharge summaries, and participant-reported use of bone protection medications was recorded at 120 days following surgery. Results. Of 5456 recruited patients with baseline data, 2853 patients (52%) were prescribed bone protection medication at discharge, of which oral bisphosphonates were the most common, 4109 patients (75%) were prescribed vitamin D or calcium, and 606 patients (11%) were not prescribed anything. Of those prescribed a bone protection medication, only 932 patients (33%) reported still taking their medication 120 days later. Conclusion. These data provide a reference for current prescription and adherence rates. Adherence with oral medication remains poor in patients with hip fracture. Cite this article: Bone Joint J 2019;101-B:1402–1407

Aims. The use of local antibiotic carriers in the treatment of chronic osteomyelitis is an important adjunct in dead space management. We present the outcomes of two different biodegradable antibiotic carriers used in the management of chronic osteomyelitis. Method. A single centre series between 2006–2017. The initial cohort (2006–2010) of 137 cases, Group A, had Osteoset® T (calcium sulphate carrier containing tobramycin). The second cohort (2013–1017) of 160 cases, group B, had CeramentTM G (biphasic calcium sulphate, nano-crystalline hydroxyapatite carrier containing gentamicin). Only Cierny-Mader Grade III and IV cases were included with a minimum six-month radiographic follow-up. Infection recurrence rate, wound leakage, subsequent fracture involving the treated segment, and radiographic void filling were assessed at a minimum of 6 months following surgery. Results. Mean follow-up in Group A was 2.5 yrs (0.5–10.5) and in Group B it was 1.4 yrs (0.6–4.7). Group A had a significantly higher rate of infection recurrence (16/137 (11.7%) Vs. 7/160 (4.4%) p=0.0278), wound leakage (26/137 (19.0%) Vs. 16/160 (10.0%) p=0.0304) and subsequent fracture rate (11/137 (8.0%) Vs. 3/160 (1.9%) p=0.0143) compared to Group B. Average time to recurrence was 1.07 years (0.1–2.6) in Group A and 1.02 (0.2–2.1) in Group B. The mean bone void healing in Group B was significantly better than Group A (73.2% Vs. 40.0%, p <0.00001). Conclusions. Cerament™ G has significantly better bone healing compared to a calcium sulphate carrier and was associated with a lower rate of recurrent infection, wound leakage and subsequent fracture risk

Aims

Frailty greatly increases the risk of adverse outcome of trauma in older people. Frailty detection tools appear to be unsuitable for use in traumatically injured older patients. We therefore aimed to develop a method for detecting frailty in older people sustaining trauma using routinely collected clinical data.

Aims

To investigate health-related quality of life (HRQoL) of older adults (aged ≥ 60 years) after tibial plateau fracture (TPF) compared to preinjury and population matched values, and what aspects of treatment were most important to patients.

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

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.

Early mortality in patients with hip fractures due to bony metastases is unknown. The aim was to quantify 30 and 90-day mortality in patients with metastatic hip fractures and identify markers associated with early death. Consecutive patients referred to orthopaedics with a metastatic proximal femoral fracture/impending fracture over a six-year period were compared to a matched control group of non-malignant hip fractures. Minimum follow-up was 1 year and data was analysed using the student´s t-test (significance p<0.05). From Jan 2010-Dec 2015, 163 patients were referred with metastatic proximal femoral lesions. 90-day mortality was three times higher than controls (44% 71/163 vs. 12% 4/33, p<0.01). Mean time from referral to surgery was longer in impending versus completed fractures (11 and 4 days respectively, p<0.05). Multiple biochemical markers were associated with early mortality in the metastatic group. Patients who died early were more likely to demonstrate low haemoglobin and albumin, and high c-reactive protein, platelets, urea, alkaline phosphatase and calcium (p<0.05). Several biochemical markers associated with early mortality reached clinical and statistical significance. These markers were combined into a score out of 7 and indicated a higher early mortality in metastatic patients compared to controls. Patients with a score of 5–6/7 were 31 times more likely to die within 90 days versus controls. This scoring system could be utilised to predict early mortality and guide management. The average delay to surgery of 4 days (completed) and 11 days (impending fractures) identifies a window to intervene and correct these abnormalities to improve survival

Introduction. Anatomical reduction of articular fragments in tibial plateau fractures often leads to a void and there is a need to fill dead space and support the articular fragment. MIIG X3 is marketed as high strength injectable graft, which resorbs and remodels fast. Efficacy and complications related to the use of this bone graft substitute were evaluated in this study. Methods. Between January 2012 and December 2016 we injected calcium sulphate (MIIGX3) in 50 out of 126 consecutive complete articular (AO type C3) tibial plateau fractures that were stabilised with Ilizarov ring fixator. Postoperative CT scans after weight bearing and sequential radiographs were evaluated for union, graft resorption and subsidence. IOWA functional outcome score and complications were recorded. Results. The median age was 52 (Range 17–87) years. Post-operative CT scans showed leak of the graft into the joint in 11 patients and around the proximal tibiofibular joint in 2 patients but this disappeared spontaneously in all patients. Average time for graft resorption was 3.1 months. Union occurred in all patients. Minor subsidence was noted in almost half of these patients. There was no significant difference in IOWA knee score between those with or without MIIGX3 at final follow up. (p value > 0.05). Conclusion. MIIGX3 is effective as a void filler providing articular support, eradicating dead space and potentially reducing the risk of infection. Leak in the joint or soft tissue resorbed spontaneously in all cases without complications or need for surgical removal. Its use may also be associated with lack of significant late subsidence

Aim. Previous studies of primary internal fixation of infected non-unions have reported high failure rates. Local antibiotic carriers and coatings have been advocated to reduce infection around implants and allow bone healing. We evaluated the effect of a calcium sulphate/hydroxyapatite antibiotic-loaded composite on bone healing and the eradication of infection in combination with internal fixation. Method. Twelve cases of established infected non-union, with segmental bone loss of up to 1cm were treated using a multidisciplinary protocol. This included; excision, deep sampling, stabilisation, local and systemic antibiotics, and soft-tissue closure. We treated 5 femurs, 4 humeri, 1 tibia and 2 periarticular non-unions at the ankle. Mean age was 59.8 years (34–75) and 9 patients had systemic co-morbidities (C-M Type B hosts). 9 patients had single stage surgery, with 5 IM Nails and 4 plates. Three patients had planned second stage internal fixation after external fixation to correct deformity. Staph. aureus was the commonest pathogen (5 cases) with polymicrobial infection in 3 cases. Results. All 12 patients were infection-free at a mean follow-up of 23 months (range 13–34 months). Union was achieved in 11/12 (92%) with the primary surgery alone. The single failure was the tibial case, who remains with an infection-free, stiff non-union. Conclusion. This protocol offered good results, mainly with a single stage treatment. Primary internal fixation was possible in 9 cases, without recurrent infection. The combination of excision of infected dead bone and a high level of local antibiotics above the Minimum Inhibitory Concentration and Minimum Biofilm Eradication Concentration levels for common bacteria, allowed a high success rate in these difficult cases

Aims

The incidence of atypical femoral fractures (AFFs) continues to increase. However, there are currently few long-term studies on the complications of AFFs and factors affecting them. Therefore, we attempted to investigate the outcomes, complications, and risk factors for complication through mid-term follow-up of more than three years.

Background:. – A multidisciplinary approach is essential to treat chronic osteomyelitis. Surgical debridement of macroscopic infection precedes targeted antibiotics to eradicate microscopic infection. This study analyses early results of our single-stage protocol for chronic osteomyelitis using antibiotic-impregnated calcium sulphate beads (Stimulan). Methods:. – We retrospectively analysed patients with primary or secondary chronic osteomyelitis treated with Stimulan. Patients with incomplete metal-work removal or follow up less than 3 months were excluded. Our study focused on 15 patients (10 male) with an average age of 40.5 years (16–73 years), average follow up of 10.6 months (3 – 21 months). There were 12 cases of secondary osteomyelitis (3 primary). Majority of cases involved the tibia, femur or humerus. Following debridement Stimulan mixed with Vancomycin and/or tobramycin was placed to obliterate dead space and deliver local antibiotics. Intravenous antibiotics, typically piperacillin/tazobactam and/or teicoplanin, were administered post-operatively until tissue culture results were known – rationalised long term antibiotic regimen followed thereafter. Results:. – Staphylococcus aureus was the commonest organism. Follow up monitoring indicated absorption of Stimulan typically by 3 months and no evidence of recurrence based on clinical, radiographic and biochemical parameters. Conclusion:. – Single stage osteomyelitis treatment with Stimulan shows early promising results, is cost effective and decreases the morbidity of further surgery

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Patients who sustain neck of femur fractures are at high risk of malnutrition. Our intention was to assess to what extent malnutrition was associated with worse patient outcomes.

Introduction. The concept of “bone graft expanders” has been popularised to increase the volume and biological activity of the implanted Material. HYPOTHESIS. Orthoss® granules support exogenously seeded MSCs and attract neighbouring host MSCs. Methods. In 3-D cultures’ Orthoss® granules were seeded with 2×10. 5. bone marrow MSCs/granule and maintained in MSC expansion or differentiation media for 21 days. In homing experiments’ bone autografts were placed in close proximity to Orthoss®. Scaffold colonisation and MSC differentiation were assessed by confocal microscopy’ standard electron microscopy’ and energy-dispersive X-ray spectroscopy. Results. Long-term incubation of MSC/scaffold resulted in formation of multiple cell-matrix layers lining the scaffold pores as well as outer surfaces. MSC differentiation to osteoblasts was evident as strong deposition of Calcium and Phosphorus was detected in both MSC expansion and osteogenic conditions. Cell egress experiments demonstrated the migration of cells from neighbouring autografts and their attachment and re-settlement on Orthoss®. Discussion & Conclusions. Orthoss® scaffolds support MSC attachment’ growth and osteogenic differentiation whereas resident bone subpopulations can rapidly migrate towards’ attach’ and expand on them. These results indicate that Orthoss® can serve as a graft expander for repairing large bone defects in trauma patients