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Large bone defects resulting from musculoskeletal tumours, infections, or trauma are often unable to heal spontaneously. The challenge for surgeons is to avoid amputation, and provide the best functional outcomes. Allograft, vascularized fibular or iliac graft, hybrid graft, extracorporeal devitalized autograft, distraction osteogenesis, induced-membrane technique, and segmental prostheses are the most common surgical strategies to manage large bone defects. Given its optimal osteogenesis, osteoinduction, osteoconduction, and histocompatibility properties, along with the lower the risk of immunological rejection, autologous graft represents the most common used strategy for reconstruction of bone defects. However, the choice of the best surgical technique is still debated, and no consensus has been reached. The present study investigated the current reconstructive strategies for large bone defect after trauma, infections, or tumour excision, discussed advantages and disadvantages of each technique, debated available techniques and materials, and evaluated complications and new perspectives.

IntroductionRegarding the efficacy of intra-articular injections of platelet-rich plasma, hyaluronic acid and corticosteroids, current evidence is controversial. The superiority of one technique over another is questioned and debates are ongoing. The purpose of the present study was to compare and investigate the efficacy of these intra-articular infiltrations in patients with knee osteoarthritis (OA). A Bayesian network meta-analysis of randomized clinical trials (RCTs) was conducted comparing patient outcomes at 3, 6 and 12-months of follow-up.Materials and methodsThis Bayesian network meta-analysis was conducted according to the PRISMA extension statement for reporting systematic reviews incorporating network meta-analyses of health care interventions. All the RCTs comparing the outcomes of two or more intra-articular infiltrations of interest for knee OA were considered for inclusion. The outcomes of interest were the WOMAC and VAS scores. The network meta-analyses were performed using the STATA routine for Bayesian hierarchical random-effects models.ResultsData from 30 RCTs (3463 patients) were collected. At 3-months follow-up, PRP showed the best WOMAC scores, followed by the Placebo, CCS and HA. At 6-months follow-up, PRP showed the best WOMAC scores, followed by HA, CCS and Placebo. At 12-months follow-up, PRP showed the best WOMAC scores, followed by the Placebo, HA and CCS. At 3-months follow-up, the PRP showed the best VAS scores, followed by CCS, HA and Placebo. At 6-months follow-up, PRP showed the best VAS scores, followed by CCS, Placebo and HA. At 12-months follow-up, the PRP showed the best VAS scores, followed by CCS, Placebo and HA.ConclusionIntra-articular injections of PRP demonstrated the best overall outcome compared to steroids, hyaluronic acid and placebo for patients with knee osteoarthrosis at 3, 6 and 12-months follow-up. Among CCS, hyaluronic acid and placebo, no discrepancies were detected.Level of evidenceI, Bayesian network meta-analysis of RCTs.

Given the progressive ageing of Western populations, the fragility fractures market has a growing socioeconomic impact. Fragility fractures are common in the elderly, negatively impacting their quality of life, limiting autonomy, increasing disability, and decreasing life expectancy. Different causes contribute to the development of a fractures in frail individuals. Among all, targeting fragile patients before the development of a fracture may represent the greatest challenge, and current diagnostic tools suffer from limitations. This study summarizes the current evidence on the management of fragility fractures, discussing risk factors, prevention, diagnosis, and actual limitations of the clinical therapeutic options, putting forward new ideas for further scientific investigation.

The COVID-19 pandemic has markedly impacted on cultural, political, and economic structures all over the world. Several aspects of its pathogenesis and related clinical consequences have not yet been elucidated. Infection rates, as well morbidity and mortality differed within countries. It is intriguing for scientists to understand how patient genetics may influence the outcome of the condition, to clarify which aspects could be related the clinical variability of SARS-CoV-2 disease. We reviewed the studies exploring the role of human leukocyte antigens (HLA) genotypes on individual responses to SARS-CoV-2 infection and/or progression, discussing also the contribution of the immunological patterns MHC-related. In March 2021, the main online databases were accessed. All the articles that investigated the possible association between the HLA genotypes and related polymorphisms with susceptibility, severity and progression of COVID-19 were considered. Although both genetic and environmental factors are certainly expected to influence the susceptibility to or protection of individuals, the HLA and related polymorphisms can influence susceptibility, progression and severity of SARS-CoV-2 infection. The crucial role played by HLA molecules in the immune response, especially through pathogen-derived peptide presentation, and the huge molecular variability of HLA alleles in the human populations could be responsible for the different rates of infection and the different patients following COVID-19 infection.

Background Osteoporosis affects mostly postmenopausal women, leading to deterioration of the microarchitectural bone structure and low bone mass, with an increased fracture risk with associated disability, morbidity and mortality. This Bayesian network meta-analysis compared the effects of current anti-osteoporosis drugs on bone mineral density. Methods The present systematic review and network meta-analysis follows the PRISMA extension statement to report systematic reviews incorporating network meta-analyses of health care interventions. The literature search was performed in June 2021. All randomised clinical trials that have investigated the effects of two or more drug treatments on BMD for postmenopausal osteoporosis were accessed. The network comparisons were performed through the STATA Software/MP routine for Bayesian hierarchical random-effects model analysis. The inverse variance method with standardised mean difference (SMD) was used for analysis. Results Data from 64 RCTs involving 82,732 patients were retrieved. The mean follow-up was 29.7 ± 19.6 months. Denosumab resulted in a higher spine BMD (SMD −0.220; SE 3.379), followed by pamidronate (SMD −5.662; SE 2.635) and zoledronate (SMD −10.701; SE 2.871). Denosumab resulted in a higher hip BMD (SMD −0.256; SE 3.184), followed by alendronate (SMD −17.032; SE 3.191) and ibandronate (SMD −17.250; SE 2.264). Denosumab resulted in a higher femur BMD (SMD 0.097; SE 2.091), followed by alendronate (SMD −16.030; SE 1.702) and ibandronate (SMD −17.000; SE 1.679). Conclusion Denosumab results in higher spine BMD in selected women with postmenopausal osteoporosis. Denosumab had the highest influence on hip and femur BMD. Level of evidence Level I, Bayesian network meta-analysis of RCTs

Posterior cruciate ligament (PCL) reconstruction can be performed using single bundle (SB) and double bundle (DB) techniques. The present study investigated whether DB PCL reconstruction is superior to SB reconstruction in terms of patient reported outcome measures (PROMs) and joint stability. In December 2021 Embase, Google Scholar, Pubmed, Scopus databases were accessed. All clinical trials comparing SB versus DB reconstruction to address PCL insufficiency in skeletally mature patients were considered. Data from 483 procedures were retrieved. The mean follow-up was 31.0 (28.0 to 107.6) months, and the mean timespan between injury and surgery was 11.3 (6 to 37) months. The mean age of the patients was 29.3 ± 3.8 years. 85 of 483 patients (18%) were women. At a mean of 31.0 months post reconstruction, ROM ( P  = 0.03) was slightly greater in the SB group, while the Tegner score ( P  = 0.03) and the Telos stress ( P  = 0.04) were more favorable in the DB cohort. Similarity was found in instrumental laxity ( P  = 0.4) and Lysholm score ( P  = 0.3). The current evidence does not support the use of DB techniques for PCL reconstruction. Both methods could restore knee stability and motion with satisfactory short term patient reported outcome measures. Further high quality clinical trials are required to validate these results on a larger scale.

Background Biochemical markers of bone turnover (BTMs), such as the bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type I collagen (bCTx), and urinary cross-linked N-telopeptides of type I collagen (NTx), are used to manage therapy monitoring in osteoporotic patients. This systematic review analyzed the potential of these BMTs in predicting the clinical outcomes in terms of BMD, t-score, rate of fractures, and adverse events during the therapy setting in postmenopausal osteoporosis. Methods All randomized clinical trials (RCTs) reporting data on biomarkers for postmenopausal osteoporosis were accessed. Only articles reporting quantitative data on the level of biomarkers at baseline and on the outcomes of interest at the last follow-up were eligible. Results A total of 36,706 patients were retrieved. Greater values of bALP were associated with a greater rate of vertebral (P = 0.001) and non-vertebral fractures (P = 0.0001). Greater values of NTx at baseline were associated with a greater rate of adverse events at the last follow-up (P = 0.02). Greater values of CTx at baseline were associated with a greater rate of adverse events leading to discontinuation (P = 0.04), gastrointestinal adverse events (P = 0.0001), musculoskeletal adverse events (P = 0.04), and mortality (P = 0.04). Greater values of PINP at baseline were associated with greater rates of gastrointestinal adverse events (P = 0.02) at the last follow-up. Conclusion The present analysis supports the adoption of BMTs during pharmacological therapy setting of patients suffering from osteoporosis. Level of evidence I, systematic review of RCTs

The pharmacological management of nonspecific chronic low back pain (NCLBP) aims to restore daily activities and improve the quality of life. No magic bullet exists for NCLBP; interventions to reduce pain and disability are available, but long-term results are unpredictable. Education in this regard needs to improve. This is often hard to accept for clinicians and patients, and provides a fertile soil to quacks, faith healers, and gurus to promote miraculous non-evidence-based solutions. The management of NCLBP is not well codified and extremely heterogeneous, and residual symptoms are common. Depending on the individual severity of NCLPB, pharmacological management may range from nonopioid to opioid analgesics. It is important to identify patients with generalized sensory hypersensitivity, who may benefit from a dedicated therapy. In this editorial, we provide an evidenced-based overview of the principles of pharmacological management of NCLPB.

Articular cartilage (AC) sheathes joint surfaces and minimizes friction in diarthrosis. The resident cell population, chondrocytes, are surrounded by an extracellular matrix and a multitude of proteins, which bestow their unique characteristics. AC is characterized by a zonal composition (superficial (tangential) zone, middle (transitional) zone, deep zone, calcified zone) with different mechanical properties. An overview is given about different testing (load tests) methods as well as different modeling approaches. The widely accepted biomechanical test methods, e.g., the indentation analysis, are summarized and discussed. A description of the biphasic theory is also shown. This is required to understand how interstitial water contributes toward the viscoelastic behavior of AC. Furthermore, a short introduction to a more complex model is given.

Background Biochemical markers of bone turnover (BTMs), such as bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type I collagen (bCTx), and urinary cross-linked N-telopeptides of type I collagen (NTx), are commonly used for therapy monitoring purposes for osteoporotic patients. The present study evaluated the potential role of BTMs as therapy monitoring. Methods All randomized clinical trials (RCTs) comparing two or more pharmacological treatments for postmenopausal osteoporosis were accessed. Only studies that reported the value of bALP, PINP, bCTx, and NTx at last follow-up were included. A multivariate analysis was performed to assess associations between these biomarkers and clinical outcomes and rate of adverse events in patients with postmenopausal osteoporosis. A multiple linear model regression analysis through the Pearson product-moment correlation coefficient was used. Results A total of 16 RCTs (14,446 patients) were included. The median age was 67 years, and the median BMI 25.4 kg/m 2 . The median vertebral BMD was 0.82, hip BMD 0.79, and femur BMD 0.64 g/cm 2 . The ANOVA test found optimal within-group variance concerning mean age, body mass index, and BMD. Greater bALP was associated with lower femoral BMD ( P = 0.01). Greater NTx was associated with a greater number of non-vertebral fractures ( P = 0.02). Greater NTx was associated with greater rate of therapy discontinuation ( P = 0.04). No other statistically significant associations were detected. Conclusion Our analysis supports the adoption of BTMs in therapy monitoring of osteoporotic patients. Level of evidence Level I, systematic review of RCTs.