Aims. Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture). Methods. PubMed, Embase, and Cochrane Library were systematically searched to retrieve relevant articles published before 15 November 2022. Studies focusing on the correlation between selenium and BMD, OP, or fracture were included. Effect sizes included regression coefficient (β), weighted mean difference (WMD), and odds ratio (OR). According to heterogeneity, the fixed-effect or random-effect model was used to assess the association between selenium and bone health. Results. From 748 non-duplicate publications, 19 studies were included. We found a significantly positive association between dietary selenium intake (β = 0.04, 95% confidence interval (CI) 0.00 to 0.07, p = 0.029) as well as serum selenium (β = 0.13, 95% CI 0.00 to 0.26, p = 0.046) and BMD. Consistently, those with higher selenium intake had a lower risk of OP (OR = 0.47, 95% CI 0.31 to 0.72, p = 0.001), and patients with OP had a significantly lower level of serum selenium than healthy controls (WMD = -2.01, 95% CI -3.91 to -0.12, p = 0.037). High dietary selenium intake was associated with a lower risk of hip fracture (OR = 0.44, 95% CI 0.37 to 0.52, p < 0.001). Conclusion. Selenium was positively associated with BMD and inversely associated with OP; dietary selenium intake was negatively associated with hip fracture. The causality and therapeutic effect of selenium on OP needs to be investigated in future studies. Cite this article: Bone Joint Res 2023;12(7):423–432

Aims. The aim of this systematic review and meta-analysis was to gather epidemiological information on selected musculoskeletal injuries and to provide pooled injury-specific incidence rates. Methods. PubMed (National Library of Medicine) and Scopus (Elsevier) databases were searched. Articles were eligible for inclusion if they reported incidence rate (or count with population at risk), contained data on adult population, and were written in English language. The number of cases and population at risk were collected, and the pooled incidence rates (per 100,000 person-years) with 95% confidence intervals (CIs) were calculated by using either a fixed or random effects model. Results. The screening of titles yielded 206 articles eligible for inclusion in the study. Of these, 173 (84%) articles provided sufficient information to be included in the pooled incidence rates. Incidences of fractures were investigated in 154 studies, and the most common fractures in the whole adult population based on the pooled incidence rates were distal radius fractures (212.0, 95% CI 178.1 to 252.4 per 100,000 person-years), finger fractures (117.1, 95% CI 105.3 to 130.2 per 100,000 person-years), and hip fractures (112.9, 95% CI 82.2 to 154.9 per 100,000 person-years). The most common sprains and dislocations were ankle sprains (429.4, 95% CI 243.0 to 759.0 per 100,000 person-years) and first-time patellar dislocations (32.8, 95% CI 21.6 to 49.7 per 100,000 person-years). The most common injuries were anterior cruciate ligament (17.5, 95% CI 6.0 to 50.2 per 100,000 person-years) and Achilles (13.7, 95% CI 9.6 to 19.5 per 100,000 person-years) ruptures. Conclusion. The presented pooled incidence estimates serve as important references in assessing the global economic and social burden of musculoskeletal injuries. Cite this article: Bone Joint Res 2022;11(11):814–825

Aims. The aims of this meta-analysis were to assess: 1) the prevalence of coronavirus disease 2019 (COVID-19) in hip fracture patients; 2) the associated mortality rate and risk associated with COVID-19; 3) the patient demographics associated with COVID-19; 4) time of diagnosis; and 5) length of follow-up after diagnosis of COVID-19. Methods. Searches of PubMed, Medline, and Google Scholar were performed in October 2020 in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Search terms included “hip”, “fracture”, and “COVID-19”. The criteria for inclusion were published clinical articles reporting the mortality rate associated with COVID-19 in hip fracture patients. In total, 53 articles were identified and following full text screening 28 articles satisfied the inclusion criteria. Results. A total of 28 studies reported the mortality of COVID-19-positive patients, of which 21 studies reported the prevalence of COVID-19-positive patients and compared the mortality rate to COVID-19-negative patients. The prevalence of COVID-19 was 13% (95% confidence interval (CI) 11% to 16%) and was associated with a crude mortality rate of 35% (95% CI 32% to 39%), which was a significantly increased risk compared to those patients without COVID-19 (odds ratio (OR) 7.11, 95% CI 5.04 to 10.04; p < 0.001). COVID-19-positive patients were more likely to be male (OR 1.51, 95% CI 1.16 to 1.96; p = 0.002). The duration of follow-up was reported in 20 (71.4%) studies. A total of 17 studies reported whether a patient presented with COVID-19 (n = 108 patients, 35.1%) or developed COVID-19 following admission (n = 200, 64.9%), of which six studies reported a mean time to diagnosis of post-admission COVID-19 at 15 days (2 to 25). Conclusion. The prevalence of COVID-19 was 13%, of which approximately one-third of patients were diagnosed on admission, and was associated with male sex. COVID-19-positive patients had a crude mortality rate of 35%, being seven times greater than those without COVID-19. Due to the heterogenicity of the reported data minimum reporting standards of outcomes associated with COVID-19 are suggested. Cite this article: Bone Joint Res 2020;9(12):873–883

Aims. There is conflicting evidence on the safety of intra-articular injections of hyaluronic acid (HA) or corticosteroids (CSs) before total knee arthroplasty (TKA). We performed a meta-analysis of the relationship between intra-articular injections and subsequent infection rates after TKA. Methods. We searched PubMed, EMBASE, and the Cochrane Library for cohort studies that assessed the effect of preoperative injection of drugs into the joint cavity on the infection rate after TKA. The outcomes analyzed included the total infection rate, as well as those for different preoperative injection time periods and different drugs. Results. Eight studies, including 73,880 in the injection group and 126,187 in the control group, met the inclusion criteria. The injection group had a significantly higher postoperative infection rate than the control group (risk ratio (RR) 1.16; 95% confidence interval (CI) 1.07 to 1.27; p < 0.001; I. 2. = 32%). For patients who received injections up to three months preoperatively, the postoperative infection risk was significantly higher than that in the control group (RR 1.26; 95% CI 1.18 to 1.35; p＜0.001; I. 2. = 0%). There was no significant difference in the infection rates between the four-to-six-month injection and control groups (RR 1.12; 95% CI 0.93 to 1.35; p = 0.240; I. 2. = 75%) or between the seven-to-12-month injection and control groups (RR 1.02; 95% CI 0.94 to 1.12; p = 0.600; I. 2. = 0%). Conclusion. Current evidence suggests that intra-articular injections of CSs or HA before TKA increase the risk of postoperative infection. Injections administered more than three months before TKA do not significantly increase the risk of infection. Cite this article: Bone Joint Res 2022;11(3):171–179

Outcomes following different types of surgical intervention for femoroacetabular impingement (FAI) are well reported individually but comparative data are deficient. The purpose of this study was to conduct a systematic review (SR) and meta-analysis to analyze the outcomes following surgical management of FAI by hip arthroscopy (HA), anterior mini open approach (AMO), and surgical hip dislocation (SHD). This SR was registered with PROSPERO. An electronic database search of PubMed, Medline, and EMBASE for English and German language articles over the last 20 years was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We specifically analyzed and compared changes in patient-reported outcome measures (PROMs), α-angle, rate of complications, rate of revision, and conversion to total hip arthroplasty (THA). A total of 48 articles were included for final analysis with a total of 4,384 hips in 4,094 patients. All subgroups showed a significant correction in mean α angle postoperatively with a mean change of 28.8° (95% confidence interval (CI) 21 to 36.5; p < 0.01) after AMO, 21.1° (95% CI 15.1 to 27; p < 0.01) after SHD, and 20.5° (95% CI 16.1 to 24.8; p < 0.01) after HA. The AMO group showed a significantly higher increase in PROMs (3.7; 95% CI 3.2 to 4.2; p < 0.01) versus arthroscopy (2.5; 95% CI 2.3 to 2.8; p < 0.01) and SHD (2.4; 95% CI 1.5 to 3.3; p < 0.01). However, the rate of complications following AMO was significantly higher than HA and SHD. All three surgical approaches offered significant improvements in PROMs and radiological correction of cam deformities. All three groups showed similar rates of revision procedures but SHD had the highest rate of conversion to a THA. Revision rates were similar for all three revision procedures

Aims. Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies. Methods. PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines. Results. A total of 517 potentially relevant articles were screened, 35 studies were included in the systematic review, and 19 studies were eligible to be included in the meta-analysis. Pooled estimates of 19 included studies (causality between 15 different risk factors and RA) revealed that obesity, smoking, coffee intake, lower education attainment, and Graves’ disease (GD) were related to the increased risk of RA. In contrast, the causality contribution from serum mineral levels (calcium, iron, copper, zinc, magnesium, selenium), alcohol intake, and chronic periodontitis to RA is not significant. Conclusion. Obesity, smoking, education attainment, and GD have real causal effects on the occurrence and development of RA. These results may provide insights into the genetic susceptibility and potential biological pathways of RA. Cite this article: Bone Joint Res 2023;12(9):601–614

Aims. Patients with metabolic syndrome (MetS) are known to be at increased risk of postoperative complications, but it is unclear whether MetS is also associated with complications after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Here, we perform a systematic review and meta-analysis linking MetS to postoperative complications in THA and TKA. Methods. The PubMed, OVID, and ScienceDirect databases were comprehensively searched and studies were selected and analyzed according to the guidelines of the Meta-analysis of Observational Studies in Epidemiology (MOOSE). We assessed the methodological quality of each study using the Newcastle-Ottawa Scale (NOS), and we evaluated the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Data were extracted and meta-analyzed or qualitatively synthesized for several outcomes. Results. Ten cohort studies involving 1,352,685 patients were included. Qualitative analysis suggested that MetS was associated with a higher incidence of cardiovascular events, and meta-analysis showed that MetS increased the risk of all-cause complications (risk ratio (RR) 1.55, 95% confidence interval (CI) 1.28 to 1.89), surgical site infection (SSI; RR 2.99, 95% CI 1.30 to 6.90), urinary tract infection (UTI; RR 2.58, 95% CI 1.03 to 6.43), and 30-day readmission (RR 1.45, 95% CI 1.33 to 1.59). There was insufficient evidence for assessing an association between MetS and venous thromboembolism events, pulmonary or gastrointestinal complications, or mortality. Conclusion. Patients with MetS undergoing THA and TKA are at increased risk of all-cause complications, cardiovascular complications, SSI, UTI, and 30-day readmission. Surgeons should be aware of the increased risk of these complications in MetS, and presurgical protocols for these complications should give special consideration to MetS patients. Cite this article:Bone Joint Res. 2020;9(3):120–129

Aims. The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential. Methods. We searched PubMed, Embase, and the Cochrane Library, with keywords including “knee osteoarthritis” and “mesenchymal stem cells”, up to June 2019. We selected randomized controlled trials (RCTs) that explored the use of MSCs to treat knee OA. The visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), adverse events, and the whole-organ MRI score (WORMS) were used as the primary evaluation tools in the studies. Our meta-analysis included a subgroup analysis of cell dose and cell source. Results. Seven trials evaluating 256 patients were included in the meta-analysis. MSC treatment significantly improved the VAS (mean difference (MD), –13.24; 95% confidence intervals (CIs) –23.28 to –3.20, p = 0.010) and WOMAC (MD, –7.22; 95% CI –12.97 to –1.47, p = 0.010). The low-dose group with less than 30 million cells showed lower p-values for both the VAS and WOMAC. Adipose and umbilical cord–derived stem cells also had lower p-values for pain scores than those derived from bone marrow. Conclusion. Overall, MSC-based cell therapy is a relatively safe treatment that holds great potential for OA, evidenced by a positive effect on pain and knee function. Using low-dose (25 million) and adipose-derived stem cells is likely to achieve better results, but further research is needed. Cite this article: Bone Joint Res 2020;9(10):719–728

Objectives. As well as debridement and irrigation, soft-tissue coverage, and osseous stabilization, systemic antibiotic prophylaxis is considered the benchmark in the management of open fractures and considerably reduces the risk of subsequent fracture-related infections (FRI). The direct application of antibiotics in the surgical field (local antibiotics) has been used for decades as additional prophylaxis in open fractures, although definitive evidence confirming a beneficial effect is scarce. The purpose of the present study was to review the clinical evidence regarding the effect of prophylactic application of local antibiotics in open limb fractures. Methods. A comprehensive literature search was performed in PubMed, Web of Science, and Embase. Cohort studies investigating the effect of additional local antibiotic prophylaxis compared with systemic prophylaxis alone in the management of open fractures were included and the data were pooled in a meta-analysis. Results. In total, eight studies which included 2738 patients were eligible for quantitative synthesis. The effect of antibiotic-loaded poly(methyl methacrylate) beads was investigated by six of these studies, and two studies evaluated the effect of local antibiotics applied without a carrier. Meta-analysis showed a significantly lower infection rate when local antibiotics were applied (4.6%; 91/1986) than in the control group receiving standard systemic prophylaxis alone (16.5%; 124/752) (p < 0.001) (odds ratio 0.30; 95% confidence interval 0.22 to 0.40). Conclusion. This meta-analysis suggests a risk reduction in FRI of 11.9% if additional local antibiotics are given prophylactically for open limb fractures. However, due to limited quality, heterogeneity, and considerable risk of bias, the pooling of data from primary studies has to be interpreted with caution. Cite this article: M. Morgenstern, A. Vallejo, M. A. McNally, T. F. Moriarty, J. Y. Ferguson, S. Nijs, WJ. Metsemakers. Bone Joint Res 2018;7:447–456. The effect of local antibiotic prophylaxis when treating open limb fractures: A systematic review and meta-analysis. DOI: 10.1302/2046-3758.77.BJR-2018-0043.R1

Aims. Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations. Methods. Linkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases. Results. MDD has a significant genetic correlation with OA (r. g. = 0.29) and the two diseases share a considerable proportion of causal variants. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on OA (b. xy. = 0.24) and genetic liability to OA conferred a causal effect on MDD (b. xy. = 0.20). Cross-trait meta-analyses identified 29 shared genomic loci between MDD and OA. Together with fine-mapping of transcriptome-wide association signals, our results suggest that Estrogen Receptor 1 (ESR1), SRY-Box Transcription Factor 5 (SOX5), and Glutathione Peroxidase 1 (GPX1) may have therapeutic implications for both MDD and OA. Conclusion. The study reveals substantial shared genetic liability between MDD and OA, which may confer risk for one another. Our findings provide a novel insight into phenotypic relationships between MDD and OA. Cite this article: Bone Joint Res 2022;11(1):12–22

Aims. To map the Oxford Knee Score (OKS) and High Activity Arthroplasty Score (HAAS) items to a common scale, and to investigate the psychometric properties of this new scale for the measurement of knee health. Methods. Patient-reported outcome measure (PROM) data measuring knee health were obtained from the NHS PROMs dataset and Total or Partial Knee Arthroplasty Trial (TOPKAT). Assumptions for common scale modelling were tested. A graded response model (fitted to OKS item responses in the NHS PROMs dataset) was used as an anchor to calibrate paired HAAS items from the TOPKAT dataset. Information curves for the combined OKS-HAAS model were plotted. Bland-Altman analysis was used to compare common scale scores derived from OKS and HAAS items. A conversion table was developed to map between HAAS, OKS, and the common scale. Results. We included 3,329 response sets from 528 patients undergoing knee arthroplasty. These generally met the assumptions of unidimensionality, monotonicity, local independence, and measurement invariance. The HAAS items provided more information than OKS items at high levels of knee health. Combining both instruments resulted in higher test-level information than either instrument alone. The mean error between common scale scores derived from the OKS and HAAS was 0.29 logits. Conclusion. The common scale allowed more precise measurement of knee health than use of either the OKS or HAAS individually. These techniques for mapping PROM instruments may be useful for the standardization of outcome reporting, and pooling results across studies that use either PROM in individual-patient meta-analysis. Cite this article: Bone Joint Res 2023;12(10):624–635

Aims. Open lower limb fracture is life-changing, resulting in substantial morbidity and resource demand, while inconsistent outcome-reporting hampers systematic review and meta-analysis. A core outcome set establishes consensus among key stakeholders for the recommendation of a minimum set of outcomes. This study aims to define a core outcome set for adult open lower limb fracture. Methods. Candidate outcomes were identified from a previously published systematic review and a secondary thematic analysis of 25 patient interviews exploring the lived experience of recovery from open lower limb fracture. Outcomes were categorized and sequentially refined using healthcare professional and patient structured discussion groups. Consensus methods included a multi-stakeholder two-round online Delphi survey and a consensus meeting attended by a purposive sample of stakeholders, facilitated discussion, and voting using a nominal group technique. Results. Thematic analysis and systematic review identified 121 unique outcomes, reduced to 68 outcomes following structured discussion groups. Outcomes were presented to 136 participants who completed a two-round online Delphi survey. The Delphi survey resulted in 11 outcomes identified as consensus ‘in’ only. All outcomes were discussed at a consensus meeting attended by 15 patients, 14 healthcare professionals, 11 researchers, and one patient-carer. Consensus was achieved for a four-core outcome set: ‘Walking, gait and mobility’, ‘Being able to return to life roles’, ‘Pain or discomfort’, and ‘Quality of life’. Conclusion. This study used robust consensus methods to establish a core outcome set that should be measured in all future research studies and audits of clinical practice without precluding the measurement of additional outcomes. Cite this article: Bone Joint Res 2023;12(4):294–305

Objectives. Recently, the field of tissue engineering has made numerous advances towards achieving artificial tendon substitutes with excellent mechanical and histological properties, and has had some promising experimental results. The purpose of this systematic review is to assess the efficacy of tissue engineering in the treatment of tendon injuries. Methods. We searched MEDLINE, Embase, and the Cochrane Library for the time period 1999 to 2016 for trials investigating tissue engineering used to improve tendon healing in animal models. The studies were screened for inclusion based on randomization, controls, and reported measurable outcomes. The RevMan software package was used for the meta-analysis. Results. A total of 388 references were retrieved and 35 studies were included in this systematic review. The different biomaterials developed were analyzed and we found that they improve the biomechanical and histological characteristics of the repaired tendon. At meta-analysis, despite a high heterogeneity, it revealed a statistically significant effect in favour of the maximum load, the maximum stress, and the Young’s modulus between experimental and control groups. In the forest plot, the diamond was on the right side of the vertical line and did not intersect with the line, favouring experimental groups. Conclusions. This review of the literature demonstrates the heterogeneity in the tendon tissue engineering literature. Several biomaterials have been developed and have been shown to enhance tendon healing and regeneration with improved outcomes. Cite this article: D. González-Quevedo, I. Martínez-Medina, A. Campos, F. Campos, V. Carriel. Tissue engineering strategies for the treatment of tendon injuries: a systematic review and meta-analysis of animal models. Bone Joint Res 2018;7:318–324. DOI: 10.1302/2046-3758.74.BJR-2017-0326

Objectives. The objective of this study was to perform a meta-analysis of all randomised controlled trials (RCTs) comparing surgical and non-surgical management of fractures of the proximal humerus, and to determine whether further analyses based on complexity of fracture, or the type of surgical intervention, produced disparate findings on patient outcomes. Methods. A systematic review of the literature was performed identifying all RCTs that compared surgical and non-surgical management of fractures of the proximal humerus. Meta-analysis of clinical outcomes was performed where possible. Subgroup analysis based on the type of fracture, and a sensitivity analysis based on the type of surgical intervention, were also performed. Results. Seven studies including 528 patients were included. The overall meta-analysis found that there was no difference in clinical outcomes. However, subgroup and sensitivity analyses found improved patient outcomes for more complex fractures managed surgically. Four-part fractures that underwent surgery had improved long-term health utility scores (mean difference, MD 95% CI 0.04 to 0.28; p = 0.007). They were also less likely to result in osteoarthritis, osteonecrosis and non/malunion (OR 7.38, 95% CI 1.97 to 27.60; p = 0.003). Another significant subgroup finding was that secondary surgery was more common for patients that underwent internal fixation compared with conservative management within the studies with predominantly three-part fractures (OR 0.15, 95% CI 0.04 to 0.63; p = 0.009). Conclusion. This meta-analysis has demonstrated that differences in the type of fracture and surgical treatment result in outcomes that are distinct from those generated from analysis of all types of fracture and surgical treatments grouped together. This has important implications for clinical decision making and should highlight the need for future trials to adopt more specific inclusion criteria. Cite this article: S. Sabharwal, N. K. Patel, D. Griffiths, T. Athanasiou, C. M. Gupte, P. Reilly. Trials based on specific fracture configuration and surgical procedures likely to be more relevant for decision making in the management of fractures of the proximal humerus: Findings of a meta-analysisBone Joint Res 2016;5:470–480. DOI: 10.1302/2046-3758.510.2000638

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. The aim of this study was to systematically compare the safety and accuracy of robot-assisted (RA) technique with conventional freehand with/without fluoroscopy-assisted (CT) pedicle screw insertion for spine disease. Methods. A systematic search was performed on PubMed, EMBASE, the Cochrane Library, MEDLINE, China National Knowledge Infrastructure (CNKI), and WANFANG for randomized controlled trials (RCTs) that investigated the safety and accuracy of RA compared with conventional freehand with/without fluoroscopy-assisted pedicle screw insertion for spine disease from 2012 to 2019. This meta-analysis used Mantel-Haenszel or inverse variance method with mixed-effects model for heterogeneity, calculating the odds ratio (OR), mean difference (MD), standardized mean difference (SMD), and 95% confidence intervals (CIs). The results of heterogeneity, subgroup analysis, and risk of bias were analyzed. Results. Ten RCTs with 713 patients and 3,331 pedicle screws were included. Compared with CT, the accuracy rate of RA was superior in Grade A with statistical significance and Grade A + B without statistical significance. Compared with CT, the operating time of RA was longer. The difference between RA and CT was statistically significant in radiation dose. Proximal facet joint violation occurred less in RA than in CT. The postoperative Oswestry Disability Index (ODI) of RA was smaller than that of CT, and there were some interesting outcomes in our subgroup analysis. Conclusion. RA technique could be viewed as an accurate and safe pedicle screw implantation method compared to CT. A robotic system equipped with optical intraoperative navigation is superior to CT in accuracy. RA pedicle screw insertion can improve accuracy and maintain stability for some challenging areas. Cite this article: Bone Joint Res 2020;9(10):653–666

Aims. This study explores the reported rate of surgical site infection (SSI) after hip fracture surgery in published studies concerning patients treated in the UK. Methods. Studies were included if they reported on SSI after any type of surgical treatment for hip fracture. Each study required a minimum of 30 days follow-up and 100 patients. Meta-analysis was undertaken using a random effects model. Heterogeneity was expressed using the I. 2. statistic. Risk of bias was assessed using a modified Newcastle-Ottawa Scale (NOS) system. Results. There were 20 studies reporting data from 88,615 patients. Most were retrospective cohort studies from single centres. The pooled incidence was 2.1% (95% confidence interval (CI) 1.54% to 2.62%) across ‘all types’ of hip fracture surgery. When analyzed by operation type, the SSI incidences were: hemiarthroplasty 2.87% (95% CI 1.99% to 3.75%) and sliding hip screw 1.35% (95% CI 0.78% to 1.93%). There was considerable variation in definition of infection used, as well as considerable risk of bias, particularly as few studies actively screened participants for SSI. Conclusion. Synthesis of published estimates of infection yield a rate higher than that seen in national surveillance procedures. Biases noted in all studies would trend towards an underestimate, largely due to inadequate follow-up

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

Objectives. Tranexamic acid (TXA) is an antifibrinolytic agent used as a blood-sparing technique in total knee arthroplasty (TKA), and is routinely administered by intravenous (IV) or intra-articular (IA) injection. Recently, a novel method of TXA administration, the combined IV and IA application of TXA, has been applied in TKA. However, the scientific evidence of combined administration of TXA in TKA is still meagre. This meta-analysis aimed to investigate the efficacy and safety of combined IV and IA TXA in patients undergoing TKA. Materials and Methods. A systematic search was carried out in PubMed, the Cochrane Clinical Trial Register (Issue12 2015), Embase, Web of Science and the Chinese Biomedical Database. Only randomised controlled trials (RCT) evaluating the efficacy and safety of combined use TXA in TKA were identified. Two authors independently identified the eligible studies, extracted data and assessed the methodological quality of included studies. Meta-analysis was conducted using Review Manager 5.3 software. Results. A total of ten RCTs (1143 patients) were included in this study. All the included studies were randomised and the quality of included studies still needed improvement. The results indicated that, compared with either placebo or the single-dose TXA (IV or IA) group, the combination of IV and IA TXA group had significantly less total blood loss, hidden blood loss, total drain output, a lower transfusion rate and a lower drop in haemoglobin level. There were no statistically significant differences in complications such as wound infection and deep vein thrombosis between the combination group and the placebo or single-dose TXA group. Conclusions. Compared with placebo or the single-dose TXA, the combined use of IV and IA TXA provided significantly better results with respect to all outcomes related to post-operative blood loss without increasing the risk of thromboembolic complications in TKA. Cite this article: Z. F. Yuan, H. Yin, W. P. Ma, D. L. Xing. The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: combined tranexamic acid for TKA. Bone Joint Res 2016;5:353–361. DOI: 10.1302/2046-3758.58.BJR-2016-0001.R2

Objectives. Alarm over the reported high failure rates for metal-on-metal (MoM) hip implants as well as their potential for locally aggressive Adverse Reactions to Metal Debris (ARMDs) has prompted government agencies, internationally, to recommend the monitoring of patients with MoM hip implants. Some have advised that a blood ion level >7 µg/L indicates potential for ARMDs. We report a systematic review and meta-analysis of the performance of metal ion testing for ARMDs. Methods. We searched MEDLINE and EMBASE to identify articles from which it was possible to reconstruct a 2 × 2 table. Two readers independently reviewed all articles and extracted data using explicit criteria. We computed a summary receiver operating curve using a Bayesian random-effects hierarchical model. Results. Our literature search returned 575 unique articles; only six met inclusion criteria defined a priori. The discriminative capacity of ion tests was homogeneous across studies but that there was substantial cut-point heterogeneity. Our best estimate of the “true” area under curve (AUC) for metal ion testing is 0.615, with a 95% credible interval of 0.480 to 0.735, thus we can state that the probability that metal ion testing is actually clinically useful with an AUC ≥ 0.75 is 1.7%. Conclusion. Metal ion levels are not useful as a screening test for identifying high risk patients because ion testing will either lead to a large burden of false positive patients, or otherwise marginally modify the pre-test probability. With the availability of more accurate non-invasive tests, we did not find any evidence for using blood ion levels to diagnose symptomatic patients. Cite this article: M. Pahuta, J. M. Smolders, J. L. van Susante, J. Peck, P. R. Kim, P. E. Beaule. Blood metal ion levels are not a useful test for adverse reactions to metal debris: a systematic review and meta-analysis. Bone Joint Res 2016;5:379–386. DOI: 10.1302/2046-3758.59.BJR-2016-0027.R1