Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics. Cite this article: Bone Joint J 2021;103-B(2):234–244

Aims. The value of core decompression (CD) in the treatment of osteonecrosis of the femoral head (ONFH) remains controversial. We conducted a systematic review and meta-analysis to evaluate whether CD combined with other treatments could improve the clinical and radiological outcomes of ONFH patients compared with CD alone. Methods. We searched the PubMed, Embase, Web of Science, and Cochrane Library databases until June 2020. All randomized controlled trials (RCTs) and clinical controlled trials (CCTs) comparing CD alone and CD combined with other measures (CD + cell therapy, CD + bone grafting, CD + porous tantalum rod, etc.) for the treatment of ONFH were considered eligible for inclusion. The primary outcomes of interest were Harris Hip Score (HHS), ONFH stage progression, structural failure (collapse) of the femoral head, and conversion to total hip arthroplasty (THA). The pooled data were analyzed using Review Manager 5.3 software. Results. A total of 20 studies with 2,123 hips were included (CD alone = 768, CD combined with other treatments = 1,355). The combination of CD with other therapeutic interventions resulted in a higher HHS (mean difference (MD) = 6.46, 95% confidence interval (CI) = 2.10 to 10.83, p = 0.004) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (MD = −10.92, 95% CI = -21.41 to -4.03, p = 0.040) and a lower visual analogue scale (VAS) score (MD = −0.99, 95% CI = -1.56 to -0.42, p < 0.001) than CD alone. For the rates of disease stage progression, 91 (20%) progressed in the intervention group compared to 146 (36%) in the control group (odds ratio (OR) = 0.32, 95% CI = 0.16 to 0.64, p = 0.001). In addition, the intervention group had a more significant advantage in delaying femoral head progression to the collapsed stage (OR = 0.32, 95% CI = 0.17 to 0.61, p < 0.001) and reducing the odds of conversion to THA (OR = 0.35, 95% CI = 0.23 to 0.55, p < 0.001) compared to the control group. There were no serious adverse events in either group. Subgroup analysis showed that the addition of cell therapy significantly improved clinical and radiological outcomes compared to CD alone, and this approach appeared to be more effective than other therapies, particularly in precollapse (stage I to II) ONFH patients. Conclusion. There was marked heterogeneity in the studies. There is a trend towards improved clinical outcomes with the addition of stem cell therapy to CD. Cite this article: Bone Joint Res 2021;10(7):445–458

Aims. Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS. Methods. A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis. Results. Overall, 123 patients with 127 spinal metastases from NSCLC who underwent decompression surgery followed by postoperative systemic therapy were included. A total of 43 lesions were treated with stereotactic body radiotherapy (SBRT) after surgery and 84 lesions were not. Survival rate at one, two, and three years was 83.4%, 58.9%, and 48.2%, respectively, and LC rate was 87.8%, 78.8%, and 78.8%, respectively. Histological type was the only significant associated factor for both LC (p = 0.007) and OS (p < 0.001). Treatment with targeted therapy was significantly associated with longer survival (p = 0.039). The risk factors associated with worse survival were abnormal laboratory data (p = 0.021), lesions located in the thoracic spine (p = 0.047), and lumbar spine (p = 0.044). This study also revealed that postoperative radiotherapy had little effect in improving OS or LC. Conclusion. Tumour histological type was significantly associated with the prognosis in spinal NSCLC metastasis patients. In the presence of post-surgical systemic therapy, radiotherapy appeared to be less effective in improving LC, OS, or quality of life in spinal NSCLC metastasis patients. Cite this article: Bone Jt Open 2024;5(4):350–360

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293

Aims. A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process. Methods. A total of 16 adult male Wistar rats were randomly divided into two groups (n = eight each): Group 1 was given a combination of Tenfovir 30 mg, Lamivudine 30 mg, and Efavirenz 60 mg per day orally, whereas Group 2 was used as a control. After one week of medication preload, all rats underwent a standardized surgical procedure of mid-shaft tibial osteotomy fixed by intramedullary nail with no gap at the fracture site. Progress in fracture healing was monitored regularly for eight weeks. Further evaluations were carried out after euthanasia by micro-CT, mechanically and histologically. Two blinded orthopaedic surgeons used the Radiological Union Scoring system for the Tibia (RUST) to determine fracture healing. Results. The fracture healing process was different between the two groups at week 4 after surgery; only two out of eight rats showed full healing in Group 1 (ART-treated), while seven out of eight rats had bone union in Group 2 (control) (p = 0.040). However, at week eight postoperatively, there was no statistical difference in bone healing; seven out of eight progressed to full union in both groups. Conclusion. This study demonstrated that combination ART resulted in delayed fracture healing at week 4 after surgery in rats, but did not result in the development of nonunion. Cite this article: Bone Joint Res 2022;11(8):585–593

Stem cells are defined by their potential for self-renewal and the ability to differentiate into numerous cell types, including cartilage and bone cells. Although basic laboratory studies demonstrate that cell therapies have strong potential for improvement in tissue healing and regeneration, there is little evidence in the scientific literature for many of the available cell formulations that are currently offered to patients. Numerous commercial entities and ‘regenerative medicine centres’ have aggressively marketed unproven cell therapies for a wide range of medical conditions, leading to sometimes indiscriminate use of these treatments, which has added to the confusion and unpredictable outcomes. The significant variability and heterogeneity in cell formulations between different individuals makes it difficult to draw conclusions about efficacy. The ‘minimally manipulated’ preparations derived from bone marrow and adipose tissue that are currently used differ substantially from cells that are processed and prepared under defined laboratory protocols. The term ‘stem cells’ should be reserved for laboratory-purified, culture-expanded cells. The number of cells in uncultured preparations that meet these defined criteria is estimated to be approximately one in 10 000 to 20 000 (0.005% to 0.01%) in native bone marrow and 1 in 2000 in adipose tissue. It is clear that more refined definitions of stem cells are required, as the lumping together of widely diverse progenitor cell types under the umbrella term ‘mesenchymal stem cells’ has created confusion among scientists, clinicians, regulators, and our patients. Validated methods need to be developed to measure and characterize the ‘critical quality attributes’ and biological activity of a specific cell formulation. It is certain that ‘one size does not fit all’ – different cell formulations, dosing schedules, and culturing parameters will likely be required based on the tissue being treated and the desired biological target. As an alternative to the use of exogenous cells, in the future we may be able to stimulate the intrinsic vascular stem cell niche that is known to exist in many tissues. The tremendous potential of cell therapy will only be realized with further basic, translational, and clinical research. Cite this article: Bone Joint J 2019;101-B:361–364

Aims. Currently, periprosthetic fractures are excluded from the American Society for Bone and Mineral Research (ASBMR) definition of atypical femoral fracture (AFFs). This study aims to report on a series of periprosthetic femoral fractures (PFFs) that otherwise meet the criteria for AFFs. Secondary aims were to identify predictors of periprosthetic atypical femoral fractures (PAFFs) and quantify the complications of treatment. Patients and Methods. This was a retrospective case control study of consecutive patients with periprosthetic femoral fractures between 2007 and 2017. Two observers identified 16 PAFF cases (mean age 73.9 years (44 to 88), 14 female patients) and 17 typical periprosthetic fractures in patients on bisphosphonate therapy as controls (mean age 80.7 years (60 to 86, 13 female patients). Univariate and multivariate analysis was performed to identify predictors of PAFF. Management and complications were recorded. Results. Interobserver agreement for the PAFF classification was excellent (kappa = 0.944; p < 0.001). On univariate analysis compared with controls, patients with PAFFs had higher mean body mass indices (28.6 kg/m. 2. (. sd. 8.9) vs 21.5 kg/m. 2. (. sd. 3.3); p = 0.009), longer durations of bisphosphonate therapy (median 5.5 years (IQR 3.2 to 10.6) vs 2.4 years (IQR 1.0 to 6.4); p = 0.04), and were less likely to be on alendronate (50% vs 94%; p = 0.02) with an indication of secondary osteoporosis (19% vs 0%; p = 0.049). Duration of bisphosphonate therapy was an independent predictor of PAFF on multivariate analysis (R. 2. = 0.733; p = 0.05). Following primary fracture management, complication rates were higher in PAFFs (9/16, 56%) than controls (5/17, 29%; p = 0.178) with a relative risk of any complication following PAFF of 1.71 (95% confidence interval (CI) 0.77 to 3.8) and of reoperation 2.56 (95% CI 1.3 to 5.2). Conclusion. AFFs do occur in association with prostheses. Longer duration of bisphosphonate therapy is an independent predictor of PAFF. Complication rates are higher following PAFFs compared with typical PFFs, particularly of reoperation and infection. Cite this article: Bone Joint J 2019;101-B:1285–1291

Aims. Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. Methods. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated. Results. The viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 μg/ml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer. Conclusion. AO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The reduction in tumour volume by AO-RDT was also confirmed in vivo. Cite this article: Bone Joint Res 2022;11(10):715–722

Aims. The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells. Methods. HIPGEN is a multicentre, multinational, randomized, double-blind, placebo-controlled trial. A total of 240 patients aged 60 to 90 years with low-energy femoral neck fractures (FNF) will be allocated to two arms and receive an intramuscular injection of either 150 × 10. 6. PLX-PAD cells or placebo into the medial gluteal muscle after direct lateral implantation of total or hemi hip arthroplasty. Patients will be followed for two years. The primary endpoint is the Short Physical Performance Battery (SPPB) at week 26. Secondary and exploratory endpoints include morphological parameters (lean body mass), functional parameters (abduction and handgrip strength, symmetry in gait, weightbearing), all-cause mortality rate and patient-reported outcome measures (Lower Limb Measure, EuroQol five-dimension questionnaire). Immunological biomarker and in vitro studies will be performed to analyze the PLX-PAD mechanism of action. A sample size of 240 subjects was calculated providing 88% power for the detection of a 1 SPPB point treatment effect for a two-sided test with an α level of 5%. Conclusion. The HIPGEN study assesses the efficacy, safety, and tolerability of intramuscular PLX-PAD administration for the treatment of muscle injury following arthroplasty for hip fracture. It is the first phase III study to investigate the effect of an allogeneic cell therapy on improved mobilization after hip fracture, an aspect which is in sore need of addressing for the improvement in standard of care treatment for patients with FNF. Cite this article: Bone Jt Open 2022;3(4):340–347

Osteoarthritis (OA) is an important cause of pain, disability and economic loss in humans, and is similarly important in the horse. Recent knowledge on post-traumatic OA has suggested opportunities for early intervention, but it is difficult to identify the appropriate time of these interventions. The horse provides two useful mechanisms to answer these questions: 1) extensive experience with clinical OA in horses; and 2) use of a consistently predictable model of OA that can help study early pathobiological events, define targets for therapeutic intervention and then test these putative therapies. This paper summarises the syndromes of clinical OA in horses including pathogenesis, diagnosis and treatment, and details controlled studies of various treatment options using an equine model of clinical OA

Aims. High-energy injuries can result in multiple complications, the most prevalent being infection. Vancomycin powder has been used with increasing frequency in orthopaedic trauma given its success in reducing infection following spine surgery. Additionally, large, traumatic injuries require wound coverage and management by dressings such as negative pressure wound therapy (NPWT). NPWT has been shown to decrease the ability of antibiotic cement beads to reduce infection, but its effect on antibiotic powder is not known. The goal of this study was to determine if NPWT reduces the efficacy of topically applied antibiotic powder. Methods. Complex musculoskeletal wounds were created in goats and inoculated with a strain of Staphylococcus aureus modified to emit light. Six hours after contaminating the wounds, imaging, irrigation, and debridement and treatment application were performed. Animals received either vancomycin powder with a wound pouch dressing or vancomycin powder with NPWT. Results. There were no differences in eradication of bacteria when vancomycin powder was used in combination with NPWT (4.5% of baseline) compared to vancomycin powder with a wound pouch dressing (1.7% of baseline) (p = 0.986), even though approximately 50% of the vancomycin was recovered in the NPWT exudate canister. Conclusion. The antimicrobial efficacy of the vancomycin powder was not diminished by the application of NPWT. These topical and locally applied therapies are potentially effective tools that can provide quick, simple treatments to prevent infection while providing coverage. By reducing the occurrence of infection, the recovery is shortened, leading to an overall improvement in quality of life. Cite this article: Bone Joint Res 2021;10(2):149–155

Aims. It has been generally accepted that open fractures require early skeletal stabilization and soft-tissue reconstruction. Traditionally, a standard gauze dressing was applied to open wounds. There has been a recent shift in this paradigm towards negative pressure wound therapy (NPWT). The aim of this study was to compare the clinical outcomes in patients with open tibial fractures receiving standard dressing versus NPWT. Methods. This multicentre randomized controlled trial was approved by the ethical review board of a public sector tertiary care institute. Wounds were graded using Gustilo-Anderson (GA) classification, and patients with GA-II to III-C were included in the study. To be eligible, the patient had to present within 72 hours of the injury. The primary outcome of the study was patient-reported Disability Rating Index (DRI) at 12 months. Secondary outcomes included quality of life assessment using 12-Item Short-Form Health Survey questionnaire (SF-12), wound infection rates at six weeks and nonunion rates at 12 months. Logistic regression analysis and independent-samples t-test were applied for secondary outcomes. Analyses of primary and secondary outcomes were performed using SPSS v. 22.0.1 and p-values of < 0.05 were considered significant. Results. A total of 486 patients were randomized between January 2016 and December 2018. Overall 206 (49.04%) patients underwent NPWT, while 214 (50.95%) patients were allocated to the standard dressing group. There was no statistically significant difference in DRI at 12 months between NPWT and standard dressing groups (mean difference 0.5; 95% confidence interval (CI) -0.08 to 1.1; p = 0.581). Regarding SF-12 scores at 12 months follow-up, there was no significant difference at any point from injury until 12 months (mean difference 1.4; 95% CI 0.7 to 1.9; p = 0.781). The 30-day deep infection rate was slightly higher in the standard gauze dressing group. The non-union odds were also comparable (odds ratio (OR) 0.90, 95% CI 0.56 to 1.45; p = 0.685). Conclusion. Our study concludes that NPWT therapy does not confer benefit over standard dressing technique for open fractures. The DRI, SF-12 scores, wound infection, and nonunion rates were analogous in both study groups. We suggest surgeons continue to use cheaper and more readily available standard dressings. Cite this article: Bone Joint J 2020;102-B(7):912–917

Aims. Rotator cuff (RC) tears are common musculoskeletal injuries which often require surgical intervention. Noninvasive pulsed electromagnetic field (PEMF) devices have been approved for treatment of long-bone fracture nonunions and as an adjunct to lumbar and cervical spine fusion surgery. This study aimed to assess the effect of continuous PEMF on postoperative RC healing in a rat RC repair model. Methods. A total of 30 Wistar rats underwent acute bilateral supraspinatus tear and repair. A miniaturized electromagnetic device (MED) was implanted at the right shoulder and generated focused PEMF therapy. The animals’ left shoulders served as controls. Biomechanical, histological, and bone properties were assessed at three and six weeks. Results. Extension of the tendon from preload to the maximum load to failure was significantly better in the PEMF-treated shoulders at three weeks compared to controls (p = 0.038). The percentage strain was significantly higher in the PEMF group at both timepoints (p = 0.037). Collagen organization was significantly better (p = 0.034) as was tissue mineral density in the PEMF-treated group at three weeks (p = 0.028). Tendon immunohistochemistry revealed a prominent increase in type I collagen at the repair site at three weeks following continuous PEMF treatment compared with controls. None of the other tested parameters differed between the groups. Conclusion. MED-generated PEMF may enhance early postoperative tendon-to-bone healing in an acute rat supraspinatus detachment and repair model. Superior biomechanical elasticity parameters together with better collagen organization suggest improved RC healing. Cite this article: Bone Joint Res 2021;10(5):298–306

Aims. Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. Methods. For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. Results. Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. Conclusion. Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143–151

Objectives. Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis. Methods. We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value. Results. With respect to preventing new vertebral fractures (NVF), all ten drugs outperformed placebo, and etidronate proved to be the most effective treatment (OR 0.24, 95% CI 0.14 to 0.39). In addition, zoledronic acid and parathyroid hormone ranked higher compared with the other drugs. With respect to preventing clinical vertebral fractures (CVF), zoledronic acid proved to be the most effective drug (OR = 0.25, 95% CI 0.08 to 0.92), with denosumab as a desirable second option (OR = 0.48, 95% CI 0.22 to 0.96), when both were compared with placebo. As for adverse events (AE) and severe adverse events (SAE), no significant difference was observed. According to SUCRA, etidronate ranked first in preventing CVF; parathyroid hormone and zoledronic acid ranked highly in preventing NVF and CVF. Raloxifene was safe with a high rank in preventing AEs and SAEs though performed unsatisfactorily in efficacy. Conclusions. This study suggests that, taking efficacy and safety into account, parathyroid hormone and zoledronic acid had the highest probability of satisfactory performance in preventing osteoporotic fractures. Cite this article: G. Wang, L. Sui, P. Gai, G. Li, X. Qi, X. Jiang. The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment: Which therapies work best? a network meta-analysis. Bone Joint Res 2017;6:452–463. DOI: 10.1302/2046-3758.67.BJR-2016-0292.R1

Aims. To evaluate the impact of negative pressure wound therapy (NPWT) on the odds of having deep infections and health-related quality of life (HRQoL) following open fractures. Methods. Patients from the Fluid Lavage in Open Fracture Wounds (FLOW) trial with Gustilo-Anderson grade II or III open fractures within the lower limb were included in this secondary analysis. Using mixed effects logistic regression, we assessed the impact of NPWT on deep wound infection requiring surgical intervention within 12 months post-injury. Using multilevel model analyses, we evaluated the impact of NPWT on the Physical Component Summary (PCS) of the 12-Item Short-Form Health Survey (SF-12) at 12 months post-injury. Results. After applying inverse probability treatment weighting to adjust for the influence of injury characteristics on type of dressing used, 1,322 participants were assessed. The odds of developing a deep infection requiring operative management within 12 months of initial surgery was 4.52-times higher in patients who received NPWT compared to those who received a standard wound dressing (95% confidence interval (CI) 1.84 to 11.12; p = 0.001). Overall, 1,040 participants were included in our HRQoL analysis, and those treated with NPWT had statistically significantly lower mean SF-12 PCS post-fracture (p < 0.001). These differences did not reach the minimally important difference for the SF-12 PCS. Conclusion. Our analysis found that patients treated with NPWT had higher odds of developing a deep infection requiring operative management within 12 months post-fracture. Due to possible residual confounding with the worst cases being treated with NPWT, we are unable to determine if NPWT has a negative effect or is simply a marker of worse injuries or poor access to early soft-tissue coverage. Regardless, our results suggest that the use of this treatment requires further evaluation. Cite this article: Bone Jt Open 2022;3(3):189–195

We evaluated the long-term outcome of patients with an osteosarcoma who had undergone prior manipulative therapy, a popular treatment in Asia, and investigated its effects on several prognostic factors. Of the 134 patients in this study, 70 (52%) patients had manipulative therapy and 64 (48%) did not. The age, location, and size of tumour were not significantly different between the groups. The five-year overall survival rate was 58% and 92% in the groups with and without manipulative therapy (p = 0.004). Both the primary and overall rates of lung metastasis were significantly higher in the manipulative group (primary: 32% vs 3%, p = 0.003; overall lung metastasis rate: 51.4% vs 18.8%, p < 0.001). Patients who had manipulative therapy had higher local recurrence rates in comparison to patients who did not (29% vs 6%, p = 0.011). The prognosis for patients with osteosarcoma who had manipulative therapy was significantly poorer than those who had not. Manipulative therapy was an independent factor for survival. This form of therapy may serve as a mechanism to accelerate the spread of tumour cells, and therefore must be avoided in order to improve the outcome for patients with an osteosarcoma

Aims. To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs). Methods. This is a retrospective cohort study of patients with GCT who presented between January 2011 and July 2017. Intralesional curettage was performed and patients treated from 2015 to 2017 also received denosumab therapy. The patients were divided into three groups: Cohort 1: control group (n = 36); cohort 2: adjuvant denosumab group (n = 9); and cohort 3: neo- and adjuvant-denosumab group (n = 17). Results. There were 68 patients within the study period. Six patients were lost to follow-up. The mean follow-up was 47.7 months (SD 23.2). Preoperative denosumab was found to reduce intraoperative haemorrhage and was associated with shorter operating time for tumour volume > 200 cm. 3. A total of 17 patients (27.4%) developed local recurrence. The locoregional control rate was 77.8% (7/9) and 87.5% (14/16) respectively for cohorts 2 and 3, in comparison to 66.7% (24/36) of the control group. The recurrence-free survival (RFS) rate was significantly higher for adjuvant denosumab group versus those without adjuvant denosumab during the first two years: 100% vs 83.8% at one year and 95.0% vs 70.3% at two years. No significant difference was found for the three-year RFS rate. Conclusion. Preoperative denosumab therapy was found to reduce intraoperative haemorrhage and was associated with shorter operating times. Adjuvant denosumab was useful to prevent early recurrence during the first two years after surgery. Cite this article: Bone Joint J 2020;102-B(2):177–185

Aims. The primary objective of this study was to compare the postoperative infection rate between negative pressure wound therapy (NPWT) and conventional dressings for closed incisions following soft-tissue sarcoma (STS) surgery. Secondary objectives were to compare rates of adverse wound events and functional scores. Methods. In this prospective, single-centre, randomized controlled trial (RCT), patients were randomized to either NPWT or conventional sterile occlusive dressings. A total of 17 patients, with a mean age of 54 years (21 to 81), were successfully recruited and none were lost to follow-up. Wound reviews were undertaken to identify any surgical site infection (SSI) or adverse wound events within 30 days. The Toronto Extremity Salvage Score (TESS) and Musculoskeletal Tumor Society (MSTS) score were recorded as patient-reported outcome measures (PROMs). Results. There were two out of seven patients in the control group (28.6%), and two out of ten patients in the intervention group (20%) who were diagnosed with a SSI (p > 0.999), while one additional adverse wound event was identified in the control group (p = 0.593). No significant differences in PROMs were identified between the groups at either 30 days (TESS, p = 0.987; MSTS, p = 0.951) or six-month (TESS, p = 0.400) follow-up. However, neoadjuvant radiotherapy was significantly associated with a SSI within 30 days of surgery, across all patients (p = 0.029). The mean preoperative modified Glasgow Prognostic Score (mGPS) was also significantly higher among patients who developed a postoperative adverse wound event (p = 0.028), including a SSI (p = 0.008), across both groups. Conclusion. This is the first RCT comparing NPWT with conventional dressings following musculoskeletal tumour surgery. Postoperative wound complications are common in this group of patients and we observed an overall SSI rate of 23.5%. We propose proceeding to a multicentre trial, which will help more clearly define the role of closed incision NPWT in STS surgery. Cite this article: Bone Jt Open 2021;2(12):1049–1056

Objectives. Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls. Methods. Trabecular bone from hip fracture patients treated with BP (n = 10) was compared with naïve fractured (n = 14) and non-fractured controls (n = 6). Trabecular cores were synchrotron scanned and micro-CT scanned for microstructural analysis, including quantification of bone volume fraction, microarchitecture and microcracks. The specimens were then mechanically tested in compression. Results. BP bone was 28% lower in strength than untreated hip fracture bone, and 48% lower in strength than non-fractured control bone (4.6 MPa vs 6.4 MPa vs 8.9 MPa). BP-treated bone had 24% more microcracks than naïve fractured bone and 51% more than non-fractured control (8.12/cm. 2. vs 6.55/cm. 2. vs 5.25/cm. 2. ). BP and naïve fracture bone exhibited similar trabecular microarchitecture, with significantly lower bone volume fraction and connectivity than non-fractured controls. Conclusion. BP therapy had no detectable mechanical benefit in the specimens examined. Instead, its use was associated with substantially reduced bone strength. This low strength may be due to the greater accumulation of microcracks and a lack of any discernible improvement in bone volume or microarchitecture. This preliminary study suggests that the clinical impact of BP-induced microcrack accumulation may be significant. Cite this article: A. Jin, J. Cobb, U. Hansen, R. Bhattacharya, C. Reinhard, N. Vo, R. Atwood, J. Li, A. Karunaratne, C. Wiles, R. Abel. The effect of long-term bisphosphonate therapy on trabecular bone strength and microcrack density. Bone Joint Res 2017;6:602–609. DOI: 10.1302/2046-3758.610.BJR-2016-0321.R1

Aims

Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.

Objectives. Wound complications are reported in up to 10% hip and knee arthroplasties and there is a proven association between wound complications and deep prosthetic infections. In this randomised controlled trial (RCT) we explore the potential benefits of a portable, single use, incisional negative pressure wound therapy dressing (iNPWTd) on wound exudate, length of stay (LOS), wound complications, dressing changes and cost-effectiveness following total hip and knee arthroplasties. Methods. A total of 220 patients undergoing elective primary total hip and knee arthroplasties were recruited into in a non-blinded RCT. For the final analysis there were 102 patients in the study group and 107 in the control group. Results. An improvement was seen in the study (iNPWTd) group compared to control in all areas. Peak post-surgical wound exudate was significantly reduced (p = 0.007). Overall LOS reduction (0.9 days, 95% confidence interval (CI) -0.2 to 2.5) was not significant (p = 0.07) but there was a significant reduction in patients with extreme values of LOS in the iNPWTd group (Moses test, p = 0.003). There was a significantly reduced number of dressing changes (mean difference 1.7, 95% CI 0.8 to 2.5, p = 0.002), and a trend to a significant four-fold reduction in reported post-operative surgical wound complications (8.4% control; 2.0% iNPWTd, p = 0.06). Conclusions. Based on the results of this RCT incisional negative pressure wound therapy dressings have a beneficial role in patients undergoing primary hip and knee arthroplasty to achieve predictable length of stay, especially to eliminate excessive hospital stay, and minimise wound complications. Cite this article: S. L. Karlakki, A. K. Hamad, C. Whittall, N. M. Graham, R. D. Banerjee, J. H. Kuiper. Incisional negative pressure wound therapy dressings (iNPWTd) in routine primary hip and knee arthroplasties: A randomised controlled trial. Bone Joint Res 2016;5:328–337. DOI: 10.1302/2046-3758.58.BJR-2016-0022.R1

Aims

Approximately 10% to 20% of knee arthroplasty patients are not satisfied with the result, while a clear indication for revision surgery might not be present. Therapeutic options for these patients, who often lack adequate quadriceps strength, are limited. Therefore, the primary aim of this study was to evaluate the clinical effect of a novel rehabilitation protocol that combines low-load resistance training (LL-RT) with blood flow restriction (BFR).

We carried out a prospective, randomised controlled trial on two groups of 40 patients with painful calcific tendonitis and a mean age of 48.4 years (32.5 to 67.3). All were to undergo arthroscopic removal of the calcific deposit within six months after randomisation. The 40 patients in group I received ultrasound-guided needling followed by high-energy shock-wave therapy and the 40 in group II had shock-wave therapy alone. In both groups one treatment consisting of 2500 impulses of shock waves with an energy flux density of 0.36 mJ/mm. 2. was applied. The clinical and radiological outcome was assessed using the 100-point Constant shoulder scoring system and standardised radiographs. The mean follow-up was 4.1 months and no patient was lost to follow-up. Both groups had significant improvement in their Constant shoulder score. Radiographs showed disappearance of the calcific deposit in 60.0% of the shoulders in group I and in 32.5% of group II (p < 0.05). Significantly better clinical and radiological results were obtained in group I than in group II. Arthroscopic removal of the deposit was avoided in 32 patients of group I and in 22 of group II. No severe side-effects were recorded. Ultrasound-guided needling in combination with high-energy shock-wave therapy is more effective than shock-wave therapy alone in patients with symptomatic calcific tendonitis, giving significantly higher rates of elimination of the calcium deposits, better clinical results and reduction in the need for surgery

We evaluated the safety and efficacy of total knee replacement in patients receiving continuous warfarin therapy. . We identified 24 consecutive patients receiving long-term warfarin therapy who underwent total knee replacement between 2006 and 2008 and compared them with a group of age- and gender-matched patients not on long-term anticoagulation. Primary observations were changes in haemoglobin, transfusion rates and complications. Secondary observations were fluctuations in the international normalised ratio (INR) and post-operative range of movement. . There was no significant difference between the two groups in pre- or post-operative haemoglobin, incidence of transfusion or incidence of post-operative complications. There were no surgical delays due to a high INR level. The mean change in INR during the peri-operative phase was minimal (mean 0.4; . sd. 0.7). There was no significant difference in the range of movement between the two groups after day two post-operatively. Current American College of Chest Physicians guidelines recommend bridging therapy for high-risk patients receiving oral anticoagulation and undergoing major orthopaedic procedures. We have shown that a safe alternative is to continue the steady-state warfarin peri-operatively in patients on long-term anticoagulation requiring total knee replacement

All major studies have incorporated the use of prolonged courses of parenteral or oral antibiotic therapy in the management of two-stage revision of an infected total knee arthroplasty. We present a series of 59 consecutive patients, all with microbiologically-proven deep infection of a total knee arthroplasty, in whom a prolonged course of antibiotic therapy was not routinely used. The mean follow-up was 56.4 months (24 to 114). Of the 38 patients who underwent a staged exchange, infection was successfully eradicated in 34 (89%) but recurrent or persistent infection was present in four (11%). Our rate of cure for infection is similar to that reported elsewhere. We conclude that a prolonged course of antibiotic therapy seems not to alter the incidence of recurrent or persistent infection. The costs of the administration of antibiotics are high and such a regime may be unnecessary

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

Aims. This study sought to compare the rate of deep surgical site infection (SSI), as measured by the Centers for Disease Control and Prevention (CDC) definition, after surgery for a fracture of the hip between patients treated with standard dressings and those treated with incisional negative pressure wound therapy (iNPWT). Secondary objectives included determining the rate of recruitment and willingness to participate in the trial. Methods. The study was a two-arm multicentre randomized controlled feasibility trial that was embedded in the World Hip Trauma Evaluation cohort study. Any patient aged > 65 years having surgery for hip fracture at five recruitment centres in the UK was considered to be eligible. They were randomly allocated to have either a standard dressing or iNPWT after closure of the wound. The primary outcome measure was deep SSI at 30 and 90 days, diagnosed according to the CDC criteria. Secondary outcomes were: rate of recruitment; further surgery within 120 days; health-related quality of life (HRQoL) using the EuroQol five-level five-dimension questionnaire (EQ-5D-5L); and related complications within 120 days as well as mobility and residential status at this time. Results. A total of 462 valid randomizations were carried out (232 and 230 in the standard dressing and iNPWT groups, respectively). In the standard dressing group, 14 of 218 patients (6.4%) developed deep SSI. In the iNPWT group, four of 214 patients (1.9%) developed deep SSI. This gives a total rate of SSI of 4.2% (95% confidence interval (CI) 2.7% to 6.5%). Patients and surgeons were willing to participate in the study with 462 patients being recruited from a possible 749 (62.3%). Conclusion. The rate of deep SSI 30 days after surgery for a fracture of the hip was 4%, which makes a study comparing the clinical effectiveness of standard dressings and iNPWT feasible. Cite this article: Bone Joint J 2021;103-B(4):755–761

Aims. To compare the cost-utility of standard dressing with incisional negative-pressure wound therapy (iNPWT) in adults with closed surgical wounds associated with major trauma to the lower limbs. Methods. A within-trial economic evaluation was conducted from the UK NHS and personal social services (PSS) perspective based on data collected from the Wound Healing in Surgery for Trauma (WHiST) multicentre randomized clinical trial. Health resource utilization was collected over a six-month post-randomization period using trial case report forms and participant-completed questionnaires. Cost-utility was reported in terms of incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analysis was conducted to test the robustness of cost-effectiveness estimates while uncertainty was handled using confidence ellipses and cost-effectiveness acceptability curves. Results. The incremental cost of standard dressing versus iNPWT over six months was £2,037 (95% confidence interval (CI) £349 to £3,724). There was an insignificant increment in QALYs gained in the iNPWT group (0.005, 95% CI -0.018 to 0.028). The probability of iNPWT being cost-effective at £20,000 per QALY was 1.9%. The results remained robust in the sensitivity analysis. Conclusion. The within-trial economic evaluation suggests that iNPWT is unlikely to be a cost-effective alternative to standard dressing in adults with closed surgical wounds to their lower limbs. Cite this article: Bone Joint J 2020;102-B(8):1072–1081

Aims. The aim of this study was to estimate the cost-effectiveness of negative-pressure wound therapy (NPWT) in comparison with standard wound management after initial surgical wound debridement in adults with severe open fractures of the lower limb. Patients and Methods. An economic evaluation was conducted from the perspective of the United Kingdom NHS and Personal Social Services, based on evidence from the 460 participants in the Wound Management of Open Lower Limb Fractures (WOLLF) trial. Economic outcomes were collected prospectively over the 12-month follow-up period using trial case report forms and participant-completed questionnaires. Bivariate regression of costs (given in £, 2014 to 2015 prices) and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted to estimate the incremental cost per QALY gained associated with NPWT dressings. Sensitivity and subgroup analyses were undertaken to assess the impacts of uncertainty and heterogeneity, respectively, surrounding aspects of the economic evaluation. Results. The base case analysis produced an incremental cost-effectiveness ratio of £267 910 per QALY gained, reflecting higher costs on average (£678; 95% confidence interval (CI) -£1082 to £2438) and only marginally higher QALYS (0.002; 95% CI -0.054 to 0.059) in the NPWT group. The probability that NPWT is cost-effective in this patient population did not exceed 27% regardless of the value of the cost-effectiveness threshold. This result remained robust to several sensitivity and subgroup analyses. Conclusion. This trial-based economic evaluation suggests that NPWT is unlikely to be a cost-effective strategy for improving outcomes in adult patients with severe open fractures of the lower limb. Cite this article: Bone Joint J 2019;101-B:1392–1401

Limb salvage involving wide resection and reconstruction is now well established for managing musculoskeletal sarcomas. However, involvement of major nerves and vessels with a large volume of muscle and skin may result in a useless limb, contributing to depression and a low quality of life. We have been studying alternative treatments for musculoskeletal sarcoma since 1990, and have recently established a regime using photodynamic surgery with cells labelled with acridine orange, photodynamic therapy with cells treated similarly and radiodynamic treatment using the effect of X-rays on such cells. These techniques have been used after marginal or intralesional resection of tumours since 1999 and have enabled maintenance of excellent limb function in patients with sarcomas

We carried out a retrospective review over ten months of patients who had presented with a low-energy subtrochanteric fracture. We identified 13 women of whom nine were on long-term alendronate therapy and four were not. The patients treated with alendronate were younger, with a mean age of 66.9 years (55 to 82) vs 80.3 years (64 to 92) and were more socially active. The fractures sustained by the patients in the alendronate group were mainly at the femoral metaphyseal-diaphyseal junction and many had occurred after minimal trauma. Five of these patients had prodromal pain in the affected hip in the months preceding the fall, and three demonstrated a stress reaction in the cortex in the contralateral femur. Our study suggests that prolonged suppression of bone remodelling with alendronate may be associated with a new form of insufficiency fracture of the femur. We believe that this finding is important and indicates the need for caution in the long-term use of alendronate in the treatment of osteoporosis

1. A study of 2,200 patients receiving electro-convulsive therapy showed that fifty-three sustained fractures or dislocations—an incidence of 2·4 per cent. Of the fifty-three injuries, twenty-one occurred in the spine, fifteen in the neck of femur, fifteen in the upper end of humerus, one in the coracoid process; one dislocated jaw required anaesthesia for its reduction (other cases of transient dislocation of the jaw are excluded). 2. The incidence, site, and type of spinal fractures are recorded, and the relation of the fracture to the first convulsion is noted. No late changes were found in the spines of patients examined two years or more after treatment. A neutral position of the spine during the convulsion is believed to diminish the risk of fracture. 3. Fracture of the neck of the femur is a serious injury in these patients. In one case the injury was bilateral. 4. The fifteen cases of fracture-dislocation of the upper humerus are analysed. They included two cases of posterior dislocation of the humeral head; the possible mechanism of this is explained and a method of prevention suggested. 5. Fifty-three patients with chronic epilepsy with psychosis were examined. Four cases of fractured spine were discovered. The site of fracture was different from that of fractures caused by convulsive therapy and a reason for this is suggested. The type and mechanism of the fracture are similar in the two groups

We present a series of 114 patients with microbiologically-proven chronically-infected total hip replacement, treated between 1991 and 2004 by a two-stage exchange procedure with antibiotic-loaded cement, but without the use of a prolonged course of antibiotic therapy. The mean follow-up for all patients was 74 months (2 to 175) with all surviving patients having a minimum follow-up of two years. Infection was successfully eradicated in 100 patients (87.7%), a rate which is similar to that reported by others, but where prolonged adjuvant antibiotic therapy has been used. Using the technique described, a prolonged course of systemic antibiotics does not appear to be essential and the high cost of the administration of antibiotics can be avoided

Objectives. The period of post-operative treatment before surgical wounds are completely closed remains a key window, during which one can apply new technologies that can minimise complications. One such technology is the use of negative pressure wound therapy to manage and accelerate healing of the closed incisional wound (incisional NPWT). . Methods. We undertook a literature review of this emerging indication to identify evidence within orthopaedic surgery and other surgical disciplines. Literature that supports our current understanding of the mechanisms of action was also reviewed in detail. . Results. A total of 33 publications were identified, including nine clinical study reports from orthopaedic surgery; four from cardiothoracic surgery and 12 from studies in abdominal, plastic and vascular disciplines. Most papers (26 of 33) had been published within the past three years. Thus far two randomised controlled trials – one in orthopaedic and one in cardiothoracic surgery – show evidence of reduced incidence of wound healing complications after between three and five days of post-operative NPWT of two- and four-fold, respectively. Investigations show that reduction in haematoma and seroma, accelerated wound healing and increased clearance of oedema are significant mechanisms of action. . Conclusions. There is a rapidly emerging literature on the effect of NPWT on the closed incision. Initiated and confirmed first with a randomised controlled trial in orthopaedic trauma surgery, studies in abdominal, plastic and vascular surgery with high rates of complications have been reported recently. The evidence from single-use NPWT devices is accumulating. There are no large randomised studies yet in reconstructive joint replacement. Cite this article: Bone Joint Res 2013;2:276–84

Avascular necrosis of bone is a well-recognised phenomenon in patients on long-term steroid therapy, especially after renal transplantation. There are only four cases reported in the literature of multifocal avascular necrosis after short-term high-dose steroid therapy, and three additional cases are reported in this paper. All the hips have needed reconstructive surgery within two and a half years of the onset of symptoms; in one patient, however, this has been prevented by other medical problems. In two of the three patients reported in this paper the shoulders also were affected; eventually they became pain-free but movement was restricted. Short-term high-dose steroid therapy has only recently been recognised as a cause of avascular necrosis and attempts should be made to prevent the incidence increasing

This article reviews the current knowledge of the intervertebral disc (IVD) and its association with low back pain (LBP). The normal IVD is a largely avascular and aneural structure with a high water content, its nutrients mainly diffusing through the end plates. IVD degeneration occurs when its cells die or become dysfunctional, notably in an acidic environment. In the process of degeneration, the IVD becomes dehydrated and vascularised, and there is an ingrowth of nerves. Although not universally the case, the altered physiology of the IVD is believed to precede or be associated with many clinical symptoms or conditions including low back and/or lower limb pain, paraesthesia, spinal stenosis and disc herniation. New treatment options have been developed in recent years. These include biological therapies and novel surgical techniques (such as total disc replacement), although many of these are still in their experimental phase. Central to developing further methods of treatment is the need for effective ways in which to assess patients and measure their outcomes. However, significant difficulties remain and it is therefore an appropriate time to be further investigating the scientific basis of and treatment of LBP

The current standard recommendation for antibiotic therapy in the management of chronic osteomyelitis is intravenous treatment for six weeks. We have compared this regime with short-term intravenous therapy followed by oral dosage. A total of 93 patients, with chronic osteomyelitis, underwent single-stage, aggressive surgical debridement and appropriate soft-tissue coverage. Culture-specific intravenous antibiotics were given for five to seven days, followed by oral therapy for six weeks. During surgery, the scar, including the sinus track, was excised en bloc. We used a high-speed, saline-cooled burr to remove necrotic bone, and osseous laser Doppler flowmetry to ensure that the remaining bone was viable. Infected nonunions (Cierny stage-IV osteomyelitis) were stabilised by internal fixation. In 38 patients management of dead space required antibiotic-impregnated polymethylmethacrylate beads, which were exchanged for an autogenous bone graft at six weeks. Free-tissue transfer often facilitated soft-tissue coverage. These 93 patients were compared with 22 consecutive patients treated previously who had the same surgical management, but received culture-specific intravenous antibiotics for six weeks. Of the 93 patients, 80 healed without further intervention. Of the 31 Cierny-IV lesions, 27 healed without another operation, and four fractures required additional bone grafts. No more wound drainage was needed. Treatment was successful in 91% of patients, regardless of the organism involved. There was no difference in outcome in terms of these variables when the series were compared. We conclude that the long-term administration of intravenous antibiotics is not necessary to achieve a high rate of clinical resolution of wound drainage for adult patients with chronic osteomyelitis

Aims

Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing.

Aims

Prompt and sufficient broad-spectrum empirical antibiotic treatment is key to preventing infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off (ECOFF) minimal inhibitory concentrations (T > MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC targets were applied: 1 and 4 µg/ml for vancomycin, and 0.125 and 2 µg/ml for meropenem.

In a prospective randomised trial of calcifying tendinitis of the rotator cuff, we compared the efficacy of dual treatment sessions delivering 2500 extracorporeal shock waves at either high- or low-energy, via an electromagnetic generator under fluoroscopic guidance. Patients were eligible for the study if they had more than a three-month history of calcifying tendinitis of the rotator cuff, with calcification measuring 10 mm or more in maximum dimension. The primary outcome measure was the change in the Constant and Murley Score. A total of 80 patients were enrolled (40 in each group), and were re-evaluated at a mean of 110 (41 to 255) days after treatment when the increase in Constant and Murley score was significantly greater (t-test, p = 0.026) in the high-energy treatment group than in the low-energy group. The improvement from the baseline level was significant in the high-energy group, with a mean gain of 12.5 (−20.7 to 47.5) points (p < 0.0001). The improvement was not significant in the low-energy group. Total or subtotal resorption of the calcification occurred in six patients (15%) in the high-energy group and in two patients (5%) in the low-energy group. High-energy shock-wave therapy significantly improves symptoms in refractory calcifying tendinitis of the shoulder after three months of follow-up, but the calcific deposit remains unchanged in size in the majority of patients

Although success has been achieved with implantation of bone marrow mesenchymal stem cells (bMSCs) in degenerative discs, its full potential may not be achieved if the harsh environment of the degenerative disc remains. Axial distraction has been shown to increase hydration and nutrition. Combining both therapies may have a synergistic effect in reversing degenerative disc disease. In order to evaluate the effect of bMSC implantation, axial distraction and combination therapy in stimulating regeneration and retarding degeneration in degenerative discs, we first induced disc degeneration by axial loading in a rabbit model. The rabbits in the intervention groups performed better with respect to disc height, morphological grading, histological scoring and average dead cell count. The groups with distraction performed better than those without on all criteria except the average dead cell count. Our findings suggest that bMSC implantation and distraction stimulate regenerative changes in degenerative discs in a rabbit model

In this case study, we describe the clinical presentation and treatment of 36 patients with periosteal chondrosarcoma collected over a 59-year period by the archive of the Netherlands Committee on Bone Tumours. The demographics, clinical presentation, radiological features, treatment and follow-up are presented with the size, location, the histological grading of the tumour and the survival.

We found a slight predominance of men (61%), and a predilection for the distal femur (33%) and proximal humerus (33%). The metaphysis was the most common site (47%) and the most common presentation was with pain (44%). Half the tumours were classified histologically as grade 1. Pulmonary metastases were reported in one patient after an intra-lesional resection. A second patient died from local recurrence and possible pulmonary and skin metastases after an incomplete resection.

It is clearly important to make the diagnosis appropriately because an incomplete resection may result in local recurrence and metastatic spread. Staging for metastatic disease is recommended in grade II or III lesions.

These patients should be managed with a contrast-enhanced MRI of the tumour and histological confirmation by biopsy, followed by en-bloc excision.

Cite this article: Bone Joint J 2014;96-B:823–8.

1. The dominant role of pathogenic staphylococci in surgical infections has been confirmed by positive isolations in 89·9 per cent of a wide variety of lesions in a hospital infective unit. Of 150 staphylococci isolated, 147 were sensitive to fusidic acid, two were slightly sensitive and only one was resistant. 2. Fusidic acid was administered as sodium fusidate to 100 patients with staphylococcal infections (including seventy-two with chronic post-traumatic osteomyelitis). Sterile swabs were achieved in seventy-seven of these patients and in the remaining twenty-three a change of flora was detected. 3. Bone samples were taken at operation from twenty-nine patients with chronic osteomyelitis who had been treated for at least five days with fusidic acid. Depending on dosage, the mean fusidic acid concentrations were 7·3 and 9·8 micrograms per gram. Corresponding levels in non-inflammatory bone samples from thirty-one patients were, depending on the duration of treatment, 12·3, 2l·3 and 25·4 micrograms per gram. The fusidic acid levels in cancellous bone were almost twice as high as those in compact bone. 4. The relevance of these findings to the use of fusidic acid therapy as an adjunct to surgical management of chronic osteomyelitis is discussed

In the search for a simple method of assessing the therapeutic efficacy of sodium fluoride, a prospective study of vertebral radiography during such treatment was carried out. Treatment of osteoporosis with sodium fluoride, calcium and vitamin D was found to enhance the vertical markings of the vertebral trabecular pattern in 69% of patients. This response was graded 1 (failure), 2 (good) and 3 (excellent); Grade 2 or 3 was attained after a mean treatment period of 31.7 months. Subsequent analysis of the vertebral fracture rate revealed that new vertebral fractures had occurred only in patients with Grade 1 and not in those with Grade 2 or 3. We recommend that treatment should aim at increasing the vertebral trabecular pattern to Grade 2 or 3 and that the duration of therapy should be approximately 30 months

We have performed a double-blind placebo-controlled trial of moderate doses of extracorporeal shock-wave therapy (ESWT) for non-calcific tendonitis of the rotator cuff. Adults (74) with chronic tendonitis of the rotator cuff were randomised to receive either active (1500 pulses ESWT at 0.12 mJ/mm. 2. ) or sham treatment, monthly for three months. All were assessed before each treatment, and at one and three months after the completion of treatment. The outcome was measured with regard to pain in the shoulder, including a visual analogue score for night pain, and a disability index. There were no significant differences between the two groups before treatment. The mean duration of symptoms in both groups was 23.3 months. Both showed significant and sustained improvements from two months onwards. There was no significant difference between them with respect to change in the Shoulder Pain and Disability Index (SPADI) scores or night pain over the six-month period. A mean (±. sd. ; range) change in SPADI of 16.1 ± 27.2 (0 to 82) in the treatment group and 24.3 ± 24.8 (−11 to 83) in the sham group was noted at three months. At six months the mean changes were 28.4 ± 25.9 (−24 to 69) and 30.4 ± 31.2 (−12 to 88), respectively. Similar results were noted for night pain. We conclude that there is a significant and sustained placebo effect after moderate doses of ESWT in patients with non-calcific tendonitis of the rotator cuff, but there is no evidence of added benefit when compared with sham treatment

We present a series of 48 patients with infected total knee replacements managed by the use of articulating cement spacers and short-term parenteral antibiotic therapy in the postoperative period. All patients had microbiological and/or histological confirmation of infection at the first stage of their revision. They all underwent re-implantation and had a mean follow-up of 48.5 months (26 to 85). Infection was successfully eradicated in 42 of the 48 patients (88%). Six had persistent infection which led to recurrence of symptoms and further surgery was successful in eliminating infection in four patients. These rates of success are similar to those of other comparable series. We conclude that protracted courses of intravenous antibiotic treatment may not be necessary in the management of the infected total knee replacement. In addition, we analysed the microbiological, histological and serological results obtained at the time of re-implantation of the definitive prosthesis, but could not identify a single test which alone would accurately predict a successful outcome

1. This case is presented to illustrate two etiological factors in tendon rupture occurring in one patient. 2. The rupture of the long head of the biceps brachii muscle appears to have been of acute traumatic origin. 3. Bilateral simultaneous rupture of the calcaneal tendons is rare, but it seems probable that the cortico-steroid therapy was the etiological factor in this case. 4. It has been suggested that degeneration in the tendon is caused by ischaemia, secondary to hypertrophy of the tunica media and narrowing of the medium calibre blood vessels. Betamethazone could possibly have aggravated, or may even have caused these changes, and the periarteriolar changes found in the biopsy specimen would tend to support this theory

We report a controlled, prospective study to investigate the effect of treatment by low-energy extracorporeal shock waves on pain in tennis elbow. We assigned at random 100 patients who had had symptoms for more than 12 months to two groups to receive low-energy shock-wave therapy. Group I received a total of 3000 impulses of 0.08 mJ/mm. 2. and group II, the control group, 30 impulses. The patients were reviewed after 3, 6 and 24 weeks. There was significant alleviation of pain and improvement of function after treatment in group I in which there was a good or excellent outcome in 48% and an acceptable result in 42% at the final review, compared with 6% and 24%, respectively, in group II

We report a prospective study of the effects of extracorporeal shock-wave therapy in 195 patients with chronic calcifying tendinitis. In part A 80 patients with chronic symptoms were randomly assigned to a control and three subgroups which had different treatment by low-energy and high-energy shock waves. In part B 115 patients had either one or two high-energy sessions. We recorded subjective, functional and radiological findings at six months after treatment. The results showed energy-dependent success, with relief of pain ranging from 5% in our control group up to 58% after two high-energy sessions. The Constant scores and the radiological disintegration of calcification were also dose-dependent. Shockwave therapy should be considered for chronic pain due to calcific tendinitis which is resistant to conservative treatment

We have examined whether primary human muscle-derived cells can be used in ex vivo gene therapy to deliver BMP-2 and to produce bone in vivo. Two in vitro experiments and one in vivo experiment were used to determine the osteocompetence and BMP-2 secretion capacity of cells isolated from human skeletal muscle. We isolated five different populations of primary muscle cells from human skeletal muscle in three patients. In the first in vitro experiment, production of alkaline phosphatase by the cells in response to stimulation by rhBMP-2 was measured and used as an indicator of cellular osteocompetence. In the second, secretion of BMP-2 was measured after the cell populations had been transduced by an adenovirus encoding for BMP-2. In the in vivo experiment, the cells were cotransduced with a retrovirus encoding for a nuclear localised β-galactosidase gene and an adenovirus encoding for BMP-2. The cotransduced cells were then injected into the hind limbs of severe combined immune-deficient (SCID) mice and analysed radiographically and histologically. The nuclear localised β-galactosidase gene allowed identification of the injected cells in histological specimens. In the first in vitro experiment, the five different cell populations all responded to in vitro stimulation of rhBMP-2 by producing higher levels of alkaline phosphatase when compared with non-stimulated cells. In the second, the five different cell populations were all successfully transduced by an adenovirus to express and secrete BMP-2. The cells secreted between 444 and 2551 ng of BMP-2 over three days. In the in vivo experiment, injection of the transduced cells into the hind-limb musculature of SCID mice resulted in the formation of ectopic bone at 1, 2, 3 and 4 weeks after injection. Retroviral labelling of the cell nuclei showed labelled human muscle-derived cells occupying locations of osteoblasts in the ectopic bone, further supporting their osteocompetence. Cells from human skeletal muscle, because of their availability to orthopaedic surgeons, their osteocompetence, and their ability to express BMP-2 after genetic engineering, are an attractive cell population for use in BMP-2 gene therapy approaches

1. A case is reported of a girl aged fifteen with growth hormone deficiency who developed a slip of the left femoral capital epiphysis at the age of seventeen during human growth hormone therapy. 2. The epiphysiolysis is regarded as iatrogenic

We undertook a prospective, randomised study to compare the analgesic effect of injection of steroid and of extracorporeal shock-wave therapy (ESWT) for the treatment of tennis elbow. Group 1 received a single injection of 20 mg of triamcinolone with lignocaine while group 2 received 2000 shock waves in three sessions at weekly intervals. After six weeks there was a significant difference between the groups with the mean pain score for the injection group falling from 66 to 21 compared with a decrease from 61 to 35 in the shock-wave group (p = 0.05). After three months, 84% of patients in group 1 were considered to have had successful treatment compared with 60% in group 2. In the medium term local injection of steroid is more successful and 100 times less expensive than ESWT in the treatment of tennis elbow

Management of bisphosphonate-associated subtrochanteric fractures remains opinion- or consensus-based. There are limited data regarding the outcomes of this fracture.

We retrospectively reviewed 33 consecutive female patients with a mean age of 67.5 years (47 to 91) who were treated surgically between May 2004 and October 2009. The mean follow-up was 21.7 months (0 to 53). Medical records and radiographs were reviewed to determine the post-operative ambulatory status, time to clinical and radiological union and post-fixation complications such as implant failure and need for second surgery.

The predominant fixation method was with an extramedullary device in 23 patients. 25 (75%) patients were placed on wheelchair mobilisation or no weight-bearing initially. The mean time to full weight-bearing was 7.1 months (2.2 to 29.7). The mean time for fracture site pain to cease was 6.2 months (1.2 to 17.1). The mean time to radiological union was 10.0 months (2.2 to 27.5). Implant failure was seen in seven patients (23%, 95 confidence interval (CI) 11.8 to 40.9). Revision surgery was required in ten patients (33%, 95 CI 19.2 to 51.2).

A large proportion of the patients required revision surgery and suffered implant failure. This fracture is associated with slow healing and prolonged post-operative immobility.

Cite this article: Bone Joint J 2014;96-B:658–64.

Bisphosphonates reduce peri-prosthetic bone loss in the short term after total hip replacement but the mid- and longer term effects are not known. The aims of this randomised trial were to examine the effect of a single dose of 90 mg of pamidronate on the clinical and radiological outcome and peri-prosthetic bone mineral density in 50 patients (56 hips) over a five-year period, following total hip replacement.

At five years, 37 patients (42 hips) returned for assessment. The Harris hip scores were similar in the pamidronate and placebo groups throughout the study. Also at five years, four patients, two from each group had osteolytic lesions on plain radiography. These were located around the acetabular component in three patients and in the femoral calcar in one. The femoral and acetabular peri-prosthetic bone mineral density in the pamidronate group and the control group was similar at five years.

Pamidronate given as a single post-operative dose does not appear to influence the clinical outcome or prevent the development of osteolytic lesions at five years after total hip replacement.

We reviewed 1085 consecutive compound limb fractures treated in 914 patients at the University of Louisville over a nine-year period. Of these fractures, 240 (group 1) received only systemic antibiotic prophylaxis and 845 (group 2) were managed by the supplementary local use of aminoglycoside-polymethylmethacrylate (PMMA) beads. There were no significant differences in age, gender, fracture type, fracture location or follow-up between the two groups. All had copious wound irrigation, meticulous debridement and skeletal stabilisation, but wound management and the use of local antibiotic depended on the surgeon's individual preference and there was no randomisation. In group 1 there was an overall infection rate of 12% as against 3.7% in group 2 (p < 0.001). Both acute infection and local osteomyelitis showed a decreased incidence in group 2, but this was statistically significant only in Gustilo type-IIIB and type-IIIC fractures for acute infection, and only in type-II and type-IIIB fractures for chronic osteomyelitis. Our review suggests that the adjuvant use of local antibiotic-laden PMMA beads may reduce the incidence of infection in severe compound fractures.

The February 2024 Wrist & Hand Roundup. 360. looks at: Occupational therapy for thumb carpometacarpal osteoarthritis?; Age and patient-reported benefits from operative management of intra-articular distal radius fractures: a meta-regression analysis; Long-term outcomes of nonsurgical treatment of thumb carpometacarpal osteoarthritis: a cohort study; Semi-occlusive dressing versus surgery in fingertip injuries: a randomized controlled trial; Re-fracture in partial union of the scaphoid waist?; The WALANT distal radius fracture: a systematic review; Endoscopic carpal tunnel release with or without hand therapy?; Ten-year trends in the level of evidence in hand surgery

The February 2024 Foot & Ankle Roundup. 360. looks at: Survival of revision ankle arthroplasty; Tibiotalocalcaneal nail for the management of open ankle fractures in the elderly patient; Accuracy of a patient-specific total ankle arthroplasty instrumentation; Fusion after failed primary ankle arthroplasty: can it work?; Treatment options for osteochondral lesions of the talus; Managing hair tourniquet syndrome of toe: a rare emergency; Ultrasound-guided collagenase therapy for recurrent plantar fibromatosis: a promising line of therapy?

Aims. Patients with differentiated thyroid carcinomas (DTCs) have a favourable long-term survival. Spinal metastases (SMs) cause a decline in performance status (PS), directly affecting mortality and indirectly preventing the use of systemic therapies. Metastasectomy is indicated, if feasible, as it yields the best local tumour control. Our study aimed to examine the long-term clinical outcomes of metastasectomy for SMs of thyroid carcinomas. Methods. We collected data on 22 patients with DTC (16 follicular and six papillary carcinomas) and one patient with medullary carcinoma who underwent complete surgical resection of SMs at our institution between July 1992 and July 2017, with a minimum postoperative follow-up of five years. The cancer-specific survival (CSS) from the first spinal metastasectomy to death or the last follow-up was determined using Kaplan-Meier analysis. Potential factors associated with survival were evaluated using the log-rank test. We analyzed the clinical parameters and outcome data, including pre- and postoperative disability (Eastern Cooperative Oncology Group PS 3), lung and non-spinal bone metastases, and history of radioiodine and kinase inhibitor therapies. Results. Lung and other bone metastases at the time of surgery were observed in ten and eight patients, respectively. Three patients experienced local tumour recurrences at the operated site. The five- and ten-year CSS rates in the 22 patients with DTC were 77% and 52%, respectively. Pre- and postoperative disability and operative site tumour recurrence were identified as risk factors for short postoperative survival. Conclusion. Metastasectomy for resectable SM from DTC yielded favourable results and has the potential to improve survival. Cite this article: Bone Joint J 2023;105-B(5):575–582

Aims. This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification. Methods. We conducted a retrospective analysis of 162 knees (162 patients) that received treatment for PJI post-TKA with combined IV and topical antibiotic infusions at a single academic hospital from 1 January 2010 to 31 December 2022. The incidence of AKI was evaluated using the KDIGO criteria, focussing on the identification of significant predictors and the temporal pattern of AKI development. Results. AKI was identified in 9.26% (15/162) of the cohort, predominantly presenting as stage 1 AKI, which was transient in nature and resolved prior to discharge. The analysis highlighted moderate anaemia and lower baseline serum creatinine levels as significant predictors for the development of AKI. Notably, the study found no instances of severe complications such as wound dehiscence, skin erosion, or the need for haemodialysis following treatment. Conclusion. The findings suggest that the combined use of IV and topical antibiotic therapy in the management of PJIs post-TKA is associated with a low incidence of primarily transient stage 1 AKI. This indicates a potentially favourable renal safety profile, advocating for further research to confirm these outcomes and potentially influence treatment protocols in PJI management. Cite this article: Bone Joint Res 2024;13(10):525–534

Aims. To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment. Methods. We included 72 AS patients with detailed medical records, disease activity score (Bath Ankylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL)-2, IL-4, IL-10, TNF-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, ESR, and CRP). Their peripheral blood mononuclear cells (PBMCs) were marked with anti-CD4, anti-CD25, and anti-FoxP3 antibodies, and triple positive T cells were gated by flow cytometry as T-regs. Their correlations were calculated and the changes after anti-TNF-α therapy were compared. Results. The frequency of T-regs in PBMCs was positively correlated to ESR and CRP in AS (r = 0.35 and 0.43; p = 0.032 and 0.027, respectively), and there was also a significant correlation between serum level of TNF-α and CRP (p = 0.041). The frequency of T-regs in PBMCs positively correlated to serum levels of TNF-α, IL-10, and TGF-β, while IL-2, IL-4, and IFN-γ showed opposite results. After anti-TNF-α treatment, there were significantly lower serum levels of TNF-α, IL-10, TGF-β, and frequency of T-regs in PBMCs among these AS patients (p = 0.026, 0.032, 0.029, and 0.037, respectively). Conclusion. In AS patients, proinflammatory cytokine may give positive feedback to induce more T-reg production and anti-inflammatory cytokine secretion to suppress this inflammatory status, and they can be reversed by anti-TNF-α therapy. However, the detailed interactions among T-regs and complex cytokine networks in autoinflammatory diseases still need more studies and further functional assay. Cite this article: Bone Joint Res 2023;12(2):133–137

Aims. Following cast removal for nonoperatively treated distal radius fractures, rehabilitation facilitated by advice leaflet and advice video were compared to a course of face-to-face therapy. Methods. Adults with an isolated, nonoperatively treated distal radius fracture were included at six weeks post-cast removal. Participants were randomized to delivery of rehabilitation interventions in one of three ways: an advice leaflet; an advice video; or face-to-face therapy session(s). The primary outcome measure was the Disabilities of the Arm, Shoulder and Hand (DASH) score at six weeks post intervention and secondary outcome measures included DASH at one year, DASH work subscale, grip strength, and range of motion at six weeks and one year. Results. A total of 116 (97%) of 120 enrolled participants commenced treatment. Of those, 21 were lost to follow-up, resulting in 30 participants in the advice leaflet, 32 in the advice video, and 33 face-to-face therapy arms, respectively at six weeks of follow-up. There was no significant difference between the treatment groups in the DASH at six weeks (advice leaflet vs face-to-face therapy, p = 0.69; advice video vs face-to-face therapy, p = 0.56; advice leaflet vs advice video, p = 0.37; advice leaflet vs advice video vs face-to-face therapy, p = 0.63). At six weeks, there were no differences in any secondary outcome measures except for the DASH work subscale, where face-to-face therapy conferred benefit over advice leaflet (p = 0.01). Conclusion. Following cast removal for nonoperatively treated distal radius fractures, offering an advice leaflet or advice video for rehabilitation gives equivalent patient-reported outcomes to a course of face-to-face therapy. Cite this article: Bone Joint J 2021;103-B(6):1033–1039

Aims. Successful cell therapy in hip osteonecrosis (ON) may help to avoid ON progression or total hip arthroplasty (THA), but the achieved bone regeneration is unclear. The aim of this study was to evaluate amount and location of bone regeneration obtained after surgical injection of expanded autologous mesenchymal stromal cells from the bone marrow (BM-hMSCs). Methods. A total of 20 patients with small and medium-size symptomatic stage II femoral head ON treated with 140 million BM-hMSCs through percutaneous forage in the EudraCT 2012-002010-39 clinical trial were retrospectively evaluated through preoperative and postoperative (three and 12 months) MRI. Then, 3D reconstruction of the original lesion and the observed postoperative residual damage after bone regeneration were analyzed and compared per group based on treatment efficacy. Results. The mean preoperative lesion volume was 18.7% (SD 10.2%) of the femoral head. This reduced to 11.6% (SD 7.5%) after three months (p = 0.015) and 3.7% (SD 3%) after one year (p < 0.001). Bone regeneration in healed cases represented a mean 81.2% (SD 13.8%) of the initial lesion volume at one year. Non-healed cases (n = 1 stage progression; n = 3 THAs) still showed bone regeneration but this did not effectively decrease the ON volume. A lesion size under mean 10% (SD 6%) of the femoral head at three months predicted no ON stage progression at one year. Regeneration in the lateral femoral head (C2 under Japanese Investigation Committee (JCI) classification) and in the central and posterior regions of the head was predominant in cases without ON progression. Conclusion. Bone regeneration was observed in osteonecrotic femoral heads three months after expanded autologous BM-hMSC injection, and the volume and location of regeneration indicated the success of the therapy. Cite this article: Bone Joint Res 2022;11(12):881–889

Aims. The aim of this study was to prepare a scoping review to investigate the use of biologic therapies in the treatment of musculoskeletal injuries in professional and Olympic athletes. Methods. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews and Arksey and O’Malley frameworks were followed. A three-step search strategy identified relevant published primary and secondary studies, as well as grey literature. The identified studies were screened with criteria for inclusion comprising clinical studies evaluating the use of biologic therapies in professional and Olympic athletes, systematic reviews, consensus statements, and conference proceedings. Data were extracted using a standardized tool to form a descriptive analysis and a thematic summary. Results. A total of 202 studies were initially identified, and 35 met criteria for the scoping review; 33 (94.3%) were published within the last eight years, and 18 (51.4%) originated from the USA. Platelet rich plasma was the most studied biologic therapy, being evaluated in 33 (94.3%) studies. Ulnar collateral ligament and hamstring injuries were the conditions most studied (nine (25.7%) studies and seven (20.0%) studies, respectively). Athletes most frequently participated in baseball, soccer, and American football. Only two (5.7%) studies were level 1 evidence, with interpretation and comparison between studies limited by the variations in the injury profile, biologic preparations, and rehabilitation protocols. Conclusion. There is diverse use of biologic therapies in the management of musculoskeletal injuries in professional and Olympic athletes. There is currently insufficient high-level evidence to support the widespread use of biologic therapies in athletes. Further research priorities include the development of condition/pathology-specific preparations of biologic therapies, and of outcome measures and imaging modalities sufficiently sensitive to detect differences in outcomes, should they exist. Cite this article: Bone Joint J 2021;103-B(7):1189–1196

Aims. Fungal periprosthetic joint infections (fPJIs) are rare complications, constituting only 1% of all PJIs. Neither a uniform definition for fPJI has been established, nor a standardized treatment regimen. Compared to bacterial PJI, there is little evidence for fPJI in the literature with divergent results. Hence, we implemented a novel treatment algorithm based on three-stage revision arthroplasty, with local and systemic antifungal therapy to optimize treatment for fPJI. Methods. From 2015 to 2018, a total of 18 patients with fPJI were included in a prospective, single-centre study (DKRS-ID 00020409). The diagnosis of PJI is based on the European Bone and Joint Infection Society definition of periprosthetic joint infections. The baseline parameters (age, sex, and BMI) and additional data (previous surgeries, pathogen spectrum, and Charlson Comorbidity Index) were recorded. A therapy protocol with three-stage revision, including a scheduled spacer exchange, was implemented. Systemic antifungal medication was administered throughout the entire treatment period and continued for six months after reimplantation. A minimum follow-up of 24 months was defined. Results. Eradication of infection was achieved in 16 out of 18 patients (88.8%), with a mean follow-up of 35 months (25 to 54). Mixed bacterial and fungal infections were present in seven cases (39%). The interval period, defined as the period of time from explantation to reimplantation, was 119 days (55 to 202). In five patients, a salvage procedure was performed (three cementless modular knee arthrodesis, and two Girdlestone procedures). Conclusion. Therapy for fPJI is complex, with low cure rates according to the literature. No uniform treatment recommendations presently exist for fPJI. Three-stage revision arthroplasty with prolonged systemic antifungal therapy showed promising results. Cite this article: Bone Jt Open 2021;2(8):671–678

Aims. A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. Methods. A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 10. 6. cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis. Results. Combination therapy treatment led to increased callus formation compared to controls. In the high-dose combination group there was significantly greater mineralized tissue volume and trabecular parameters compared to controls (p = 0.039). This translated to significantly improved stiffness (and ultimate load to failure (p = 0.049). The high-dose combination therapy group had the most significant improvement in mean modified Radiographic Union Score for Tibia fractures (RUST) compared to controls (13.8 (SD 1.3) vs 5.8 (SD 0.5)). All groups demonstrated significant increases in the radiological scores – RUST and Allen score – histologically compared to controls. Conclusion. We demonstrate the beneficial effect of localized MSC injections on fracture healing combined with low- or high-dose teriparatide, with efficacy dependent on PTH dose. Cite this article: Bone Joint Res 2021;10(10):659–667

The June 2024 Wrist & Hand Roundup. 360. looks at: One-year outcomes of the anatomical front and back reconstruction for scapholunate dissociation; Limited intercarpal fusion versus proximal row carpectomy in the treatment of SLAC or SNAC wrist: results after 3.5 years; Prognostic factors for clinical outcomes after arthroscopic treatment of traumatic central tears of the triangular fibrocartilage complex; The rate of nonunion in the MRI-detected occult scaphoid fracture: a multicentre cohort study; Does correction of carpal malalignment influence the union rate of scaphoid nonunion surgery?; Provision of a home-based video-assisted therapy programme in thumb carpometacarpal arthroplasty; Is replantation associated with better hand function after traumatic hand amputation than after revision amputation?; Diagnostic performance of artificial intelligence for detection of scaphoid and distal radius fractures: a systematic review

The April 2024 Research Roundup. 360. looks at: Prevalence and characteristics of benign cartilaginous tumours of the shoulder joint; Is total-body MRI useful as a screening tool to rule out malignant progression in patients with multiple osteochondromas?; Effects of vancomycin and tobramycin on compressive and tensile strengths of antibiotic bone cement: a biomechanical study; Biomarkers for early detection of Charcot arthropathy; Strong association between growth hormone therapy and proximal tibial physeal avulsion fractures in children and adolescents; UK pregnancy in orthopaedics (UK-POP): a cross-sectional study of UK female trauma and orthopaedic surgeons and their experiences of pregnancy; Does preoperative weight loss change the risk of adverse outcomes in total knee arthroplasty by initial BMI classification?

The December 2022 Wrist & Hand Roundup. 360. looks at: Anti-tumour necrosis factor therapy for early-stage Dupuytren’s disease; Patient experiences of scaphoid waist fractures and their treatment; Postoperative complications following open a1 pulley release for a trigger finger or thumb; How certain are findings in distal radius fractures: a systematic review of randomized controlled trials; Partial wrist denervation in wrist osteoarthritis: patient-reported outcomes and objective function; Dorsal bridge plating versus bridging external fixation for management of complex distal radius fractures; How is reduction lost in distal radius fractures in females aged 50 years and older; The HAND-Q: psychometrics of a new patient-reported outcome measure for clinical and research applications

The June 2024 Children’s orthopaedics Roundup. 360. looks at: Proximal femoral unicameral bone cysts: is ESIN the answer?; Hybrid-mesh casts in the conservative management of paediatric supracondylar humeral fractures: a randomized controlled trial; Rate and risk factors for contralateral slippage in adolescents treated for slipped capital femoral epiphysis; CRP predicts the need to escalate care after initial debridement for musculoskeletal infection; Genu valgum in paediatric patients presenting with patellofemoral instability; Nusinersen therapy changed the natural course of spinal muscular atrophy type 1: what about spine and hip?; The necessity of ulnar nerve exploration and translocation in open reduction of medial humeral epicondyle fractures in children

The June 2023 Wrist & Hand Roundup. 360. looks at: Residual flexion deformity after scaphoid nonunion surgery: a seven-year follow-up study; The effectiveness of cognitive behavioural therapy for patients with concurrent hand and psychological disorders; Bite injuries to the hand and forearm: analysis of hospital stay, treatment, and costs; Outcomes of acute perilunate injuries - a systematic review; Abnormal MRI signal intensity of the triangular fibrocartilage complex in asymptomatic wrists; Patient comprehension of operative instructions with a paper handout versus a video: a prospective, randomized controlled trial; Can common hand surgeries be undertaken in the office setting?; The effect of corticosteroid injections on postoperative infections in trigger finger release

The April 2024 Knee Roundup. 360. looks at: Challenging the status quo: re-evaluating the impact of obesity on unicompartmental knee arthroplasty outcomes; Timing matters: the link between ACL reconstruction delays and cartilage damage; Custom fit or off the shelf: evaluating patient outcomes in tailored versus standard knee replacements; Revolutionizing knee replacement: a comparative study on robotic-assisted and computer-navigated techniques; Pre-existing knee osteoarthritis and severe joint depression are associated with the need for total knee arthroplasty after tibial plateau fracture in patients aged over 60 years; Modern digital therapies?; A matched study on fracture rates following knee replacement surgeries;

Aims. The aims of this study were to describe the epidemiology of metacarpal shaft fractures (MSFs), assess variation in treatment and complications following standard care, document hospital resource use, and explore factors associated with treatment modality. Methods. A multicentre, cross-sectional retrospective study of MSFs at six centres in the UK. We collected and analyzed healthcare records, operative notes, and radiographs of adults presenting within ten days of a MSF affecting the second to fifth metacarpal between 1 August 2016 and 31 July 2017. Total emergency department (ED) attendances were used to estimate prevalence. Results. A total of 793 patients (75% male, 25% female) with 897 MSFs were included, comprising 0.1% of 837,212 ED attendances. The annual incidence of MSF was 40 per 100,000. The median age was 27 years (IQR 21 to 41); the highest incidence was in men aged 16 to 24 years. Transverse fractures were the most common. Over 80% of all fractures were treated non-surgically, with variation across centres. Overall, 12 types of non-surgical and six types of surgical treatment were used. Fracture pattern, complexity, displacement, and age determined choice of treatment. Patients who were treated surgically required more radiographs and longer radiological and outpatient follow-up, and were more likely to be referred for therapy. Complications occurred in 5% of patients (39/793). Most patients attended planned follow-up, with 20% (160/783) failing to attend at least one or more clinic appointments. Conclusion. MSFs are common hand injuries among young, working (economically active) men, but there is considerable heterogeneity in treatment, rehabilitation, and resource use. They are a burden on healthcare resources and society, thus further research is needed to optimize treatment. Cite this article: Bone Jt Open 2024;5(8):652–661

Aims. People with severe, persistent low back pain (LBP) may be offered lumbar spine fusion surgery if they have had insufficient benefit from recommended non-surgical treatments. However, National Institute for Health and Care Excellence (NICE) 2016 guidelines recommended not offering spinal fusion surgery for adults with LBP, except as part of a randomized clinical trial. This survey aims to describe UK clinicians’ views about the suitability of patients for such a future trial, along with their views regarding equipoise for randomizing patients in a future clinical trial comparing lumbar spine fusion surgery to best conservative care (BCC; the FORENSIC-UK trial). Methods. An online cross-sectional survey was piloted by the multidisciplinary research team, then shared with clinical professional groups in the UK who are involved in the management of adults with severe, persistent LBP. The survey had seven sections that covered the demographic details of the clinician, five hypothetical case vignettes of patients with varying presentations, a series of questions regarding the preferred management, and whether or not each clinician would be willing to recruit the example patients into future clinical trials. Results. There were 72 respondents, with a response rate of 9.0%. They comprised 39 orthopaedic spine surgeons, 17 neurosurgeons, one pain specialist, and 15 allied health professionals. Most respondents (n = 61,84.7%) chose conservative care as their first-choice management option for all five case vignettes. Over 50% of respondents reported willingness to randomize three of the five cases to either surgery or BCC, indicating a willingness to participate in the future randomized trial. From the respondents, transforaminal interbody fusion was the preferred approach for spinal fusion (n = 19, 36.4%), and the preferred method of BCC was a combined programme of physical and psychological therapy (n = 35, 48.5%). Conclusion. This survey demonstrates that there is uncertainty about the role of lumbar spine fusion surgery and BCC for a range of example patients with severe, persistent LBP in the UK. Cite this article: Bone Jt Open 2024;5(7):612–620

Aims. Periprosthetic joint infection (PJI) demonstrates the most feared complication after total joint replacement (TJR). The current work analyzes the demographic, comorbidity, and complication profiles of all patients who had in-hospital treatment due to PJI. Furthermore, it aims to evaluate the in-hospital mortality of patients with PJI and analyze possible risk factors in terms of secondary diagnosis, diagnostic procedures, and complications. Methods. In a retrospective, cross-sectional study design, we gathered all patients with PJI (International Classification of Diseases (ICD)-10 code: T84.5) and resulting in-hospital treatment in Germany between 1 January 2019 and 31 December 2022. Data were provided by the Institute for the Hospital Remuneration System in Germany. Demographic data, in-hospital deaths, need for intensive care therapy, secondary diagnosis, complications, and use of diagnostic instruments were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated. Results. A total of 52,286 patients were included, of whom 1,804 (3.5%) died. Hypertension, diabetes mellitus, and obesity, the most frequent comorbidities, were not associated with higher in-hospital mortality. Cardiac diseases as atrial fibrillation, cardiac pacemaker, or three-vessel coronary heart disease showed the highest risk for in-hospital mortality. Postoperative anaemia occurred in two-thirds of patients and showed an increased in-hospital mortality (OR 1.72; p < 0.001). Severe complications, such as organ failure, systemic inflammatory response syndrome (SIRS), or septic shock syndrome showed by far the highest association with in-hospital mortality (OR 39.20; 95% CI 33.07 to 46.46; p < 0.001). Conclusion. These findings highlight the menace coming from PJI. It can culminate in multi-organ failure, SIRS, or septic shock syndrome, along with very high rates of in-hospital mortality, thereby highlighting the vulnerability of these patients. Particular attention should be paid to patients with cardiac comorbidities such as atrial fibrillation or three-vessel coronary heart disease. Risk factors should be optimized preoperatively, anticoagulant therapy stopped and restarted on time, and sufficient patient blood management should be emphasized. Cite this article: Bone Jt Open 2024;5(4):367–373

Aims. The aims of this study were to report the outcomes of patients with a complex fracture of the lower limb in the five years after they took part in the Wound Healing in Surgery for Trauma (WHIST) trial. Methods. The WHIST trial compared negative pressure wound therapy (NPWT) dressings with standard dressings applied at the end of the first operation for patients undergoing internal fixation of a complex fracture of the lower limb. Complex fractures included periarticular fractures and open fractures when the wound could be closed primarily at the end of the first debridement. A total of 1,548 patients aged ≥ 16 years completed the initial follow-up, six months after injury. In this study we report the pre-planned analysis of outcome data up to five years. Patients reported their Disability Rating Index (DRI) (0 to 100, in which 100 = total disability), and health-related quality of life, chronic pain scores and neuropathic pain scores annually, using a self-reported questionnaire. Complications, including further surgery related to the fracture, were also recorded. Results. A total of 1,015 of the original patients (66%) provided at least one set of outcome data during the five years of follow-up. There was no evidence of a difference in patient-reported disability between the two groups at five years (NPWT group mean DRI 30.0 (SD 26.5), standard dressing group mean DRI 31.5 (SD 28.8), adjusted difference -0.86 (95% CI -4.14 to 2.40; p = 0.609). There was also no evidence of a difference in the complication rates at this time. Conclusion. We found no evidence of a difference in disability ratings between NPWT compared with standard wound dressings in the five years following the surgical treatment of a complex fracture of the lower limb. Patients in both groups reported high levels of persistent disability and reduced quality of life, with little evidence of improvement during this time. Cite this article: Bone Joint J 2024;106-B(8):858–864

Aims. Implant-related postoperative spondylodiscitis (IPOS) is a severe complication in spine surgery and is associated with high morbidity and mortality. With growing knowledge in the field of periprosthetic joint infection (PJI), equivalent investigations towards the management of implant-related infections of the spine are indispensable. To our knowledge, this study provides the largest description of cases of IPOS to date. Methods. Patients treated for IPOS from January 2006 to December 2020 were included. Patient demographics, parameters upon admission and discharge, radiological imaging, and microbiological results were retrieved from medical records. CT and MRI were analyzed for epidural, paravertebral, and intervertebral abscess formation, vertebral destruction, and endplate involvement. Pathogens were identified by CT-guided or intraoperative biopsy, intraoperative tissue sampling, or implant sonication. Results. A total of 32 cases of IPOS with a mean patient age of 68.7 years (37.6 to 84.1) were included. Diabetes, age > 60 years, and history of infection were identified as risk factors. Patient presentation upon admission included a mean body temperature of 36.7°C (36.1 to 38.0), back pain at rest (mean visual analogue scale (VAS) mean 5/10) and when mobile (mean VAS 6/10), as well as elevated levels of CRP (mean 76.8 mg/l (0.4 to 202.9)) and white blood cell count (mean 9.2 units/nl (2.6 to 32.8)). Pathogens were identified by CT-guided or conventional biopsy, intraoperative tissue sampling, or sonication, and Gram-positive cocci presented as the most common among them. Antibiotic therapy was established in all cases with pathogen-specific treatment in 23 (71.9%) subjects. Overall 27 (84.4%) patients received treatment by debridement, decompression, and fusion of the affected segment. Conclusion. Cases of IPOS are rare and share similarities with spontaneous spondylodiscitis. While procedures such as CT-guided biopsy and sonication are valuable tools in the diagnosis of IPOS, MRI and intraoperative tissue sampling remain the gold standard. Research on known principles of PJI such as implant retention versus implant exchange need to be expanded to the field of spine surgery. Cite this article: Bone Jt Open 2023;4(11):832–838

Aims. Our aim was to estimate the total costs of all hospitalizations for treating periprosthetic joint infection (PJI) by main management strategy within 24 months post-diagnosis using activity-based costing. Additionally, we investigated the influence of individual PJI treatment pathways on hospital costs within the first 24 months. Methods. Using admission and procedure data from a prospective observational cohort in Australia and New Zealand, Australian Refined Diagnosis Related Groups were assigned to each admitted patient episode of care for activity-based costing estimates of 273 hip PJI patients and 377 knee PJI patients. Costs were aggregated at 24 months post-diagnosis, and are presented in Australian dollars. Results. The mean cost per hip and knee PJI patient was $64,585 (SD $53,550). Single-stage revision mean costs were $67,029 (SD $47,116) and $80,063 (SD $42,438) for hip and knee, respectively. Two-stage revision costs were $113,226 (SD $66,724) and $122,425 (SD $60,874) for hip and knee, respectively. Debridement, antibiotics, and implant retention in hips and knees mean costs were $53,537 (SD$ 39,342) and $48,463 (SD $33,179), respectively. Suppressive antibiotic therapy without surgical management mean costs were $20,296 (SD $8,875) for hip patients and $16,481 (SD $6,712) for knee patients. Hip patients had 16 different treatment pathways and knee patients had 18 treatment pathways. Additional treatment, episodes of care, and length of stay contributed to substantially increased costs up to a maximum of $369,948. Conclusion. Treating PJI incurs a substantial cost burden, which is substantially influenced by management strategy. With an annual PJI incidence of 3,900, the cost burden would be in excess of $250 million to the Australian healthcare system. Treatment pathways with additional surgery, more episodes of care, and a longer length of stay substantially increase the associated hospital costs. Prospectively monitoring individual patient treatment pathways beyond initial management is important when quantifying PJI treatment cost. Our study highlights the importance of optimizing initial surgical treatment, and informs treating hospitals of the resources required to provide care for PJI patients. Cite this article: Bone Joint J 2024;106-B(10):1084–1092

Aims. Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants. Methods. pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 10. 9. particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs. Results. Significantly higher content of DNA and collagen was observed for the pEV-treated group compared to control and cEV groups. No differences were found in GAG quantification nor in EVs uptake within any treated group. Conclusion. In conclusion, pEVs showed better performance than cEVs in our in vitro OA model. Although further studies are needed, pEVs are shown as a potential alternative to cEVs for cell-free regenerative medicine. Cite this article: Bone Joint Res 2023;12(10):667–676

Aims. Proximal femur fractures treatment can involve anterograde nailing with a single or double cephalic screw. An undesirable failure for this fixation is screw cut-out. In a single-screw nail, a tip-apex distance (TAD) greater than 25 mm has been associated with an increased risk of cut-out. The aim of the study was to examine the role of TAD as a risk factor in a cephalic double-screw nail. Methods. A retrospective study was conducted on 112 patients treated for intertrochanteric femur fracture with a double proximal screw nail (Endovis BA2; EBA2) from January to September 2021. The analyzed variables were age, sex, BMI, comorbidities, fracture type, side, time of surgery, quality of reduction, pre-existing therapy with bisphosphonate for osteoporosis, screw placement in two different views, and TAD. The last follow-up was at 12 months. Logistic regression was used to study the potential factors of screw cut-out, and receiver operating characteristic curve to identify the threshold value. Results. A total of 98 of the 112 patients met the inclusion criteria. Overall, 65 patients were female (66.3%), the mean age was 83.23 years (SD 7.07), and the mean follow-up was 378 days (SD 36). Cut-out was observed in five patients (5.10%). The variables identified by univariate analysis with p < 0.05 were included in the multivariate logistic regression model were screw placement and TAD. The TAD was significant with an odds ratio (OR) 5.03 (p = 0.012) as the screw placement with an OR 4.35 (p = 0.043) in the anteroposterior view, and OR 10.61 (p = 0.037) in the lateral view. The TAD threshold value identified was 29.50 mm. Conclusion. Our study confirmed the risk factors for cut-out in the double-screw nail are comparable to those in the single screw. We found a TAD value of 29.50 mm to be associated with a risk of cut-out in double-screw nails, when good fracture reduction is granted. This value is higher than the one reported with single-screw nails. Therefore, we suggest the role of TAD should be reconsidered in well-reduced fractures treated with double-screw intramedullary nail. Cite this article: Bone Jt Open 2024;5(6):457–463

Aims. Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models. Methods. Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted. Results. A total of 43 studies were included. Animal models used included fracture-related infections (ten studies), periprosthetic joint infections (five studies), spinal infections (three studies), other implant-associated infections, and osteomyelitis. The most common bacteria were Staphylococcus species. Biofilm was most often observed with scanning electron microscopy. The natural history of biofilm revealed that the process of bacteria attachment, proliferation, maturation, and dispersal would take 14 days. For systemic mono-antibiotic therapy, only two of six studies using vancomycin reported significant biofilm reduction, and none reported eradication. Ten studies showed that combined systemic and topical antibiotics are needed to achieve higher biofilm reduction or eradication, and the effect is decreased with delayed treatment. Overall, 13 studies showed promising therapeutic potential with surface coating and antibiotic loading techniques. Conclusion. Combined topical and systemic application of antimicrobial agents effectively reduces biofilm at early stages. Future studies with sustained release of antimicrobial and biofilm-dispersing agents tailored to specific pathogens are warranted to achieve biofilm eradication. Cite this article: Bone Joint Res 2022;11(10):700–714

Aims. Machine learning (ML), a branch of artificial intelligence that uses algorithms to learn from data and make predictions, offers a pathway towards more personalized and tailored surgical treatments. This approach is particularly relevant to prevalent joint diseases such as osteoarthritis (OA). In contrast to end-stage disease, where joint arthroplasty provides excellent results, early stages of OA currently lack effective therapies to halt or reverse progression. Accurate prediction of OA progression is crucial if timely interventions are to be developed, to enhance patient care and optimize the design of clinical trials. Methods. A systematic review was conducted in accordance with PRISMA guidelines. We searched MEDLINE and Embase on 5 May 2024 for studies utilizing ML to predict OA progression. Titles and abstracts were independently screened, followed by full-text reviews for studies that met the eligibility criteria. Key information was extracted and synthesized for analysis, including types of data (such as clinical, radiological, or biochemical), definitions of OA progression, ML algorithms, validation methods, and outcome measures. Results. Out of 1,160 studies initially identified, 39 were included. Most studies (85%) were published between 2020 and 2024, with 82% using publicly available datasets, primarily the Osteoarthritis Initiative. ML methods were predominantly supervised, with significant variability in the definitions of OA progression: most studies focused on structural changes (59%), while fewer addressed pain progression or both. Deep learning was used in 44% of studies, while automated ML was used in 5%. There was a lack of standardization in evaluation metrics and limited external validation. Interpretability was explored in 54% of studies, primarily using SHapley Additive exPlanations. Conclusion. Our systematic review demonstrates the feasibility of ML models in predicting OA progression, but also uncovers critical limitations that currently restrict their clinical applicability. Future priorities should include diversifying data sources, standardizing outcome measures, enforcing rigorous validation, and integrating more sophisticated algorithms. This paradigm shift from predictive modelling to actionable clinical tools has the potential to transform patient care and disease management in orthopaedic practice. Cite this article: Bone Joint J 2024;106-B(11):1216–1222

Aims. Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury. Methods. A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm. 2. ) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations. Results. No obvious adverse events related to UPAL gel implantation were observed. Self-assessed clinical scores, including pain, symptoms, activities of daily living, sports activity, and quality of life, were improved significantly at three years after surgery. Defect filling was confirmed using second-look arthroscopy at 72 weeks. Significantly improved MRI scores were observed from 12 to 144 weeks postoperatively. Histological examination of biopsy specimens obtained at 72 weeks after implantation revealed an extracellular matrix rich in glycosaminoglycan and type II collagen in the reparative tissue. Histological assessment yielded a mean overall International Cartilage Regeneration & Joint Preservation Society II score of 69.1 points (SD 10.4; 50 to 80). Conclusion. This study provides evidence supporting the safety of acellular UPAL gel implantation in facilitating cartilage repair. Despite being a single-arm study, it demonstrated the efficacy of UPAL gel implantation, suggesting it is an easy-to-use, one-step method of cartilage tissue repair circumventing the need to harvest donor cells. Cite this article: Bone Joint J 2023;105-B(8):880–887

Aims. Aneurysmal bone cysts (ABCs) are locally aggressive lesions typically found in the long bones of children and adolescents. A variety of management strategies have been reported to be effective in the treatment of these lesions. The purpose of this review was to assess the effectiveness of current strategies for the management of primary ABCs of the long bones. Methods. A systematic review of the published literature was performed to identify all articles relating to the management of primary ABCs. Studies required a minimum 12-month follow-up and case series reporting on under ten participants were not included. Results. A total of 28 articles meeting the eligibility criteria were included in this review, and all but one were retrospective in design. Due to heterogeneity in study design, treatment, and outcome reporting, data synthesis and group comparison was not possible. The most common treatment option reported on was surgical curettage with or without a form of adjuvant therapy, followed by injection-based therapies. Of the 594 patients treated with curettage across 17 studies, 86 (14.4%) failed to heal or experienced a recurrence. Similar outcomes were reported for 57 (14.70%) of the 387 patients treated with injection therapy across 12 studies. Only one study directly compared curettage with injection therapy (polidocanol), randomizing 94 patients into both treatment groups. This study was at risk of bias and provided low-quality evidence of a lack of difference between the two interventions, reporting success rates of 93.3% and 84.8% for injection and surgical treatment groups, respectively. Conclusion. While both surgery and sclerotherapy are widely implemented for treatment of ABCs, there is currently no good quality evidence to support the use of one option over the other. There is a need for prospective multicentre randomized controlled trials (RCTs) on interventions for the treatment of ABCs. Cite this article: Bone Jt Open 2021;2(2):125–133

Aims. Fungal periprosthetic joint infections (PJIs) are rare, but their diagnosis and treatment are highly challenging. The purpose of this study was to investigate the clinical outcomes of patients with fungal PJIs treated with two-stage exchange knee arthroplasty combined with prolonged antifungal therapy. Methods. We reviewed our institutional joint arthroplasty database and identified 41 patients diagnosed with fungal PJIs and treated with two-stage exchange arthroplasty after primary total knee arthroplasty (TKA) between January 2001 and December 2020, and compared them with those who had non-fungal PJIs during the same period. After propensity score matching based on age, sex, BMI, American Society of Anesthesiologists grade, and Charlson Comorbidity Index, 40 patients in each group were successfully matched. The surgical and antimicrobial treatment, patient demographic and clinical characteristics, recurrent infections, survival rates, and relevant risk factors that affected joint survivorship were analyzed. We defined treatment success as a well-functioning arthroplasty without any signs of a PJI, and without antimicrobial suppression, at a minimum follow-up of two years from the time of reimplantation. Results. The fungal PJI group demonstrated a significantly worse treatment success rate at the final follow-up than the non-fungal PJI group (65.0% (26/40) vs 85.0% (34/40); p < 0.001). The mean prosthesis-free interval was longer in the fungal PJI group than in the non-fungal PJI group (6.7 weeks (SD 5.8) vs 4.1 weeks (SD 2.5); p = 0.020). The rate of survivorship free from reinfection was worse in the fungal PJI group (83.4% (95% confidence interval (CI) 64.1 to 92.9) at one year and 76.4% (95% CI 52.4 to 89.4) at two years) than in the non-fungal PJI group (97.4% (95% CI 82.7 to 99.6) at one year and 90.3% (95% CI 72.2 to 96.9) at two years), but the differences were not significant (p = 0.270). Cox proportional hazard regression analysis identified the duration of the prosthesis-free interval as a potential risk factor for failure (hazard ratio 1.128 (95% CI 1.003 to 1.268); p = 0.043). Conclusion. Fungal PJIs had a lower treatment success rate than non-fungal PJIs despite two-stage revision arthroplasty and appropriate antifungal treatment. Our findings highlight the need for further developments in treating fungal PJIs. Cite this article: Bone Joint J 2023;105-B(12):1286–1293