Aims. Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes. Methods. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using the MEDLINE, Embase, PubMed, and Cochrane databases. Studies included were case series, case control series, and cohort studies looking specifically at HSF. Results. The primary analysis, which pooled the results from 17 published studies and four meeting abstracts, identified over 200 metabolites. Seven of these studies (six published studies, one meeting abstract) had asymptomatic control groups and collectively suggested 26 putative biomarkers in osteoarthritis, inflammatory arthropathies, and trauma. These can broadly be categorized into amino acids plus related metabolites, fatty acids, ketones, and sugars. Conclusion. The role of metabolic profiling in orthopaedics is fast evolving with many metabolites already identified in a variety of pathologies. However, these results need to be interpreted with caution due to the presence of multiple confounding factors in many of the studies. Future research should include largescale epidemiological metabolic profiling studies incorporating various confounding factors with appropriate statistical analysis to account for multiple testing of the data. Cite this article:Bone Joint Res. 2020;9(3):108–119

Objectives. High failure rates of metal-on-metal hip arthroplasty implants have highlighted the need for more careful introduction and monitoring of new implants and for the evaluation of the safety of medical devices. The National Joint Registry and other regulatory services are unable to detect failing implants at an early enough stage. We aimed to identify validated surrogate markers of long-term outcome in patients undergoing primary total hip arthroplasty (THA). Methods. We conducted a systematic review of studies evaluating surrogate markers for predicting long-term outcome in primary THA. Long-term outcome was defined as revision rate of an implant at ten years according to National Institute of Health and Care Excellence guidelines. We conducted a search of Medline and Embase (OVID) databases. Separate search strategies were devised for the Cochrane database and Google Scholar. Each search was performed to include articles from the date of their inception to June 8, 2015. Results. Our search strategy identified 1082 studies of which 115 studies were included for full article review. Following review, 17 articles were found that investigated surrogate markers of long-term outcome. These included one systematic review, one randomised control trial (RCT), one case control study and 13 case series. Validated surrogate markers included Radiostereometric Analysis (RSA) and Einzel-Bild-Röntgen-Analyse (EBRA), each measuring implant migration and wear. We identified five RSA studies (one systematic review and four case series) and four EBRA studies (one RCT and three case series). Patient Reported Outcome Measures (PROMs) at six months have been investigated but have not been validated against long-term outcomes. Conclusions. This systematic review identified two validated surrogate markers of long-term primary THA outcome: RSA and EBRA, each measuring implant migration and wear. We recommend the consideration of RSA in the pre-market testing of new implants. EBRA can be used to investigate acetabular wear but not femoral migration. Further studies are needed to validate the use of PROMs for post-market surveillance. Cite this article: T. T. Malak, J. A. J. Broomfield, A. J. R. Palmer, S. Hopewell, A. Carr, C. Brown, D. Prieto-Alhambra, S. Glyn-Jones. Surrogate markers of long-term outcome in primary total hip arthroplasty: A systematic review. Bone Joint Res 2016;5:206–214. DOI: 10.1302/2046-3758.56.2000568

Objectives. Microindentation has the potential to measure the stiffness of an individual patient’s bone. Bone stiffness plays a crucial role in the press-fit stability of orthopaedic implants. Arming surgeons with accurate bone stiffness information may reduce surgical complications including periprosthetic fractures. The question addressed with this systematic review is whether microindentation can accurately measure cortical bone stiffness. Methods. A systematic review of all English language articles using a keyword search was undertaken using Medline, Embase, PubMed, Scopus and Cochrane databases. Studies that only used nanoindentation, cancellous bone or animal tissue were excluded. Results. A total of 1094 abstracts were retrieved and 32 papers were included in the analysis, 20 of which used reference point indentation, and 12 of which used traditional depth-sensing indentation. There are several factors that must be considered when using microindentation, such as tip size, depth and method of analysis. Only two studies validated microindentation against traditional mechanical testing techniques. Both studies used reference point indentation (RPI), with one showing that RPI parameters correlate well with mechanical testing, but the other suggested that they do not. Conclusion. Microindentation has been used in various studies to assess bone stiffness, but only two studies with conflicting results compared microindentation with traditional mechanical testing techniques. Further research, including more studies comparing microindentation with other mechanical testing methods, is needed before microindentation can be used reliably to calculate cortical bone stiffness. Cite this article: M. Arnold, S. Zhao, S. Ma, F. Giuliani, U. Hansen, J. P. Cobb, R. L. Abel, O. Boughton. Microindentation – a tool for measuring cortical bone stiffness? A systematic review. Bone Joint Res 2017;6:542–549. DOI: 10.1302/2046-3758.69.BJR-2016-0317.R2

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

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).

Aims

The aims of this study were to identify and evaluate the current literature examining the prognostic factors which are associated with failure of total elbow arthroplasty (TEA).

Objectives. We performed a systematic review of the literature to determine the safety and efficacy of bone morphogenetic protein (BMP) compared with bone graft when used specifically for revision spinal fusion surgery secondary to pseudarthrosis. Methods. The MEDLINE, EMBASE and Cochrane Library databases were searched using defined search terms. The primary outcome measure was spinal fusion, assessed as success or failure in accordance with radiograph, MRI or CT scan review at 24-month follow-up. The secondary outcome measure was time to fusion. Results. A total of six studies (three prospective and three retrospective) reporting on the use of BMP2 met the inclusion criteria (203 patients). Of these, four provided a comparison of BMP2 and bone graft whereas the other two solely investigated the use of BMP2. The primary outcome was seen in 92.3% (108/117) of patients following surgery with BMP2. Although none of the studies showed superiority of BMP2 to bone graft for fusion, its use was associated with a statistically quicker time to achieving fusion. BMP2 did not appear to increase the risk of complication. Conclusion. The use of BMP2 is both safe and effective within the revision setting, ideally in cases where bone graft is unavailable or undesirable. Further research is required to define its optimum role. Cite this article: Mr P. Bodalia. Effectiveness and safety of recombinant human bone morphogenetic protein-2 for adults with lumbar spine pseudarthrosis following spinal fusion surgery: A systematic review. Bone Joint Res 2016;5:145–152. DOI: 10.1302/2046-3758.54.2000418

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A systematic literature review focusing on how long before surgery concurrent viral or bacterial infections (respiratory and urinary infections) should be treated in hip fracture patients, and if there is evidence for delaying this surgery.

Objectives

Degenerative disc disease (DDD) and osteoarthritis (OA) are relatively frequent causes of disability amongst the elderly; they constitute serious socioeconomic costs and significantly impair quality of life. Previous studies to date have found that aggrecan variable number of tandem repeats (VNTR) contributes both to DDD and OA. However, current data are not consistent across studies. The purpose of this study was to evaluate systematically the relationship between aggrecan VNTR, and DDD and/or OA.

Objectives

The objective of this study was to assess all evidence comparing the Thompson monoblock hemiarthroplasty with modular unipolar implants for patients requiring hemiarthroplasty of the hip with respect to mortality and complications.

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.