Patients with femoral neck fractures treated by bipolar hemiarthroplasty have superior to unipolar hip function and lower erosion rates and pain: a systematic review and meta-analysis of randomized controlled studies.

PURPOSE: We assessed acetabular erosion, hip function, quality of life (QoL), pain, deep infection, mortality, re-operation and dislocation rates in patients with displaced femoral neck fractures (dFNFs) treated with unipolar versus bipolar hemiarthroplasty at different postoperative time points. METHODS: Relevant Randomized Controlled Trials (RCTs) were identified, following comprehensive literature research in Medline, Cochrane Central and Scopus databases, from conception until August 31th, 2021 and analyzed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: Database research retrieved 120 studies; sixteen met eligibility criteria, providing 1813 (1814 hips) evaluable patients. Acetabular erosion was significantly higher for unipolar group at 6 and 12 months (p = 0.02 and p = 0.01 respectively). Patients in the bipolar group presented significantly better hip function at 12 and 24 months (p = 0.02 and p = 0.04 respectively). Postoperative pain was significantly less in the bipolar group at 12, 24 and 48 months (p = 0.01). No statistically significant differences were found regarding the postoperative rates of deep infection, mortality, re-operation and dislocation. CONCLUSION: This study showed that patients with dFNFs treated with bipolar hemiarthroplasty have lower acetabular erosion rates at 6 and 12 months postoperatively, better hip function at 12 and 24 months, better QoL and less pain, when compared with unipolar. No statistically significant difference could be established regarding deep infection, mortality, re-operation and dislocation rates.

Anterior femoral notching ≥ 3 mm is associated with increased risk for supracondylar periprosthetic femoral fracture after total knee arthroplasty: a systematic review and meta-analysis.

PURPOSE: Anterior femoral notching (AFN) may be associated with a higher risk for supracondylar periprosthetic fracture (sPPF) after total knee arthroplasty (TKA), although studies have yielded inconclusive results. We aimed to systematically investigate and meta-analyze the best available evidence regarding the association between AFN and the risk of sPPF after TKA. METHODS: A comprehensive search of PubMed, Scopus, Mendeley, Google Scholar and Cochrane databases was performed, from conception to February 29, 2020. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). I2-index was employed for heterogeneity. Newcastle-Ottawa scale was implemented for quality assessment of the included studies. RESULTS: Nine studies fulfilled the eligibility criteria, including a total of 3264 patients subjected to TKA. Among them, there were 150 patients who sustained a sPPF. Overall, patients exposed to AFN (AFN group) demonstrated an increased risk for sPPF compared to those not exposed (control group) (OR 3.91, 95% CI 1.22-12.58, p = 0.02; I2 68.52%). Subgroup analysis based on AFN depth with a cut-off value of 3 mm further clarified this association. Patients with AFN ≥ 3mm were at higher risk for sPPF compared to patients with AFN < 3 mm and control group (OR 4.85, 95% CI 2.08-11.33, p = 0.00; I2 0.0%). On the contrary, fracture risk was not significant for patients with AFN < 3 mm compared to the control group (OR 5.0, 95% CI 0.44-56.82, p = 0.19; I2 42.99%). CONCLUSION: Patients, exposed to AFN ≥ 3 mm in depth, are at higher risk for sustaining a sPPF.

Type 2 Diabetes Mellitus is Associated with Increased Risk of Sarcopenia: A Systematic Review and Meta-analysis.

Diabetes mellitus (DM) is associated with an increased risk of fractures, mainly due to impaired bone architecture and microvascular complications. Whether DM is also associated with increased risk of sarcopenia is not yet known, with studies yielding inconclusive results. The aim of this study was to systematically review and synthesize the best available evidence regarding the association between DM and sarcopenia risk. A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases. Data are expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. Only studies which had implemented at least two of the three criteria for sarcopenia diagnosis (low muscle mass, muscle strength and/or muscle performance), as defined by the international studying groups, were included. Fifteen studies fulfilled eligibility criteria, yielding a total of 1832 patients with type 2 DM (T2DM) and 1159 cases of sarcopenia. Patients with T2DM demonstrated a higher risk of sarcopenia compared with euglycemic subjects (OR 1.55, 95% CI 1.25-1.91, p < 0.001; I2 34.6%). This risk remained significant when analysis was restricted to studies matched for age and sex. Sarcopenia risk was independent of disease definition or study design. Notably, T2DM patients presented lower muscle performance and strength compared with euglycemic subjects, whereas no difference in muscle mass was observed between groups. Patients with T2DM have an increased risk of sarcopenia compared with euglycemic subjects.

Genetic Predisposition to Developmental Dysplasia of the Hip.

BACKGROUND: The etiopathogenesis of developmental dysplasia of the hip (DDH) has not been clarified. This systematic review evaluated current literature concerning all known chromosomes, loci, genes, and their polymorphisms that have been associated or not with the prevalence and severity of DDH. METHODS: Following the established methodology of Meta-analysis of Observational Studies in Epidemiology guidelines, MEDLINE, EMBASE, and Cochrane Register of Controlled Trials were systematically searched from inception to January 2019. RESULTS: Forty-five studies were finally included. The majority of genetic studies were candidate gene association studies assessing Chinese populations with moderate methodological quality. Among the most frequently studied are the first, third, 12th,17th, and 20th chromosomes. No gene was firmly associated with DDH phenotype. Studies from different populations often report conflicting results on the same single-nucleotide polymorphism (SNP). The SNP rs143384 of GDF5 gene on chromosome 20 demonstrated the most robust relationship with DDH phenotype in association studies. The highest odds of coinheritance in linkage studies have been reported for regions of chromosome 3 and 13. Five SNPs have been associated with the severity of DDH. Animal model studies validating previous human findings provided suggestive evidence of an inducing role of mutations of the GDF5, CX3CR1, and TENM3 genes in DDH etiopathogenesis. CONCLUSION: DDH is a complex disorder with environmental and genetic causes. However, no firm correlation between genotype and DDH phenotype currently exists. Systematic genome evaluation in studies with larger sample size, better methodological quality, and assessment of DDH patients is necessary to clarify the DDH heredity. The role of next-generation sequencing techniques is promising.

Early menopause and premature ovarian insufficiency may increase the risk of sarcopenia: A systematic review and meta-analysis.

PURPOSE: Menopausal transition, resulting from a decline in estrogen concentrations, may compromise musculoskeletal health. However, it is unclear if early menopause (defined as age at menopause <45 years) and premature ovarian insufficiency (defined as age at menopause <40 years) are associated with increased risk of sarcopenia. The aim of this systematic review and meta-analysis was to synthesize studies evaluating the association between age at menopause and risk of sarcopenia. METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to 31 December 2022. Data were expressed as standardized mean difference with 95 % confidence intervals. The I2 index was employed to evaluate heterogeneity. RESULTS: Six studies were included in the qualitative and quantitative analysis, with a total of 18,291 post-menopausal women. Compared with women of normal age at menopause (>45 years), women with early menopause demonstrated lower muscle mass, assessed by appendicular skeletal muscle mass/body mass index [standardized mean difference (SMD) -0.14, 95 % confidence interval (CI) -0.20 to -0.07, p < 0.001; I2 0%]. However, no differences in muscle strength, assessed by handgrip strength (SMD -0.15, 95 % CI -0.31 to 0.01, p = 0.071; I2 72%), and muscle performance, assessed by gait speed (SMD -0.11, 95 % CI -0.29 to 0.05, p = 0.18; I2 79%), were found. Women with premature ovarian insufficiency had lower handgrip strength (SMD -0.3, 95 % CI -0.58 to -0.01, p = 0.04; I2 74.6 %) and gait speed (SMD -0.13, 95 % CI -0.23 to -0.04, p = 0.004; I2 0%) compared with women of normal age at menopause. CONCLUSION: Early menopause is associated with reduced muscle mass and premature ovarian insufficiency with reduced muscle strength and performance compared with normal age at menopause.

The effect of vitamin D plus protein supplementation on sarcopenia: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The exact effect of vitamin D supplementation, either as monotherapy or in combination with protein, on musculoskeletal health in patients with sarcopenia is currently unknown. This study aimed to determine the effect of vitamin D alone or with protein supplementation on muscle strength, mass, and performance in this population. METHODS: A comprehensive search was conducted in Medline, Cochrane Central and Scopus databases, up to March 31st, 2020. Data were expressed as standardized mean difference (SMD) with 95 % confidence intervals (CI). I2 index was employed for heterogeneity. RESULTS: The initial search identified 1164 studies, eight of which met the eligibility criteria for qualitative and quantitative analysis, yielding a total of 776 patients. Vitamin D (100-1600 IU/day) plus protein (10-44 g/day) supplementation exhibited a beneficial effect on muscle strength, as demonstrated by an improvement in handgrip strength (SMD 0.38 ± 0.07, 95 % CI 0.18-0.47, p = 0.04; I2 76.2 %) and a decrease in the sit-to-stand time (SMD 0.25 ± 0.09, 95 % CI 0.06-0.43, p = 0.007; I2 0%) compared with placebo. However, the effect on muscle mass, assessed by skeletal muscle index, was marginally non-significant (SMD 0.25 ± 0.13, 95 % CI -0.006-0.51, p = 0.05; I2 0%). No effect on appendicular skeletal muscle mass or muscle performance (assessed by walking speed) was observed with vitamin D plus protein. CONCLUSIONS: Vitamin D supplementation, combined with protein, improves muscle strength in patients with sarcopenia, but has no effect on muscle mass or performance.

New therapeutic targets for osteoporosis.

New anti-osteoporotic agents have been developed, potentially enriching the therapeutic armamentarium. Currently available osteoanabolic therapies are the parathyroid hormone (PTH) and PTH-related peptide (PTHrP) synthetic analogues, teriparatide and abaloparatide. Daily administration at doses of 20 and 80 µg, respectively, in contrast to continuous PTH secretion, leads to increased bone formation and reduces vertebral and non-vertebral fracture risk. Teriparatide is more effective than bisphosphonates (alendronate, risedronate) in increasing bone mineral density (BMD), improving bone architecture and reducing fracture risk. Abaloparatide leads to greater BMD gain, has greater anti-fracture efficacy regarding major osteoporotic fractures (upper arm, wrist, hip or clinical spine) compared with teriparatide (without a difference in morphometric vertebral and non-vertebral fractures), and has a lower risk of hypercalcaemia. Romosozumab, a sclerostin inhibitor, both induces bone formation and suppresses bone resorption. Administered at monthly subcutaneous doses of 210 mg, it reduces vertebral, non-vertebral and hip fracture risk compared with either placebo or alendronate. However, concerns have arisen about increased cardiovascular risk, which has suspended its approval by the FDA. Anabolic therapy should always be followed by administration of an anti-resorptive agent, such as bisphosphonates or denosumab, which preserves and may further increase BMD gain. Denosumab provides the greatest benefit for BMD when administered sequentially after its combination with teriparatide for 24 months and constitutes a reasonable option for patients at high risk of fracture. However, longitudinal data are needed to confirm the efficacy and safety of these therapeutic interventions.

Association between age at menopause and fracture risk: a systematic review and meta-analysis.

PURPOSE: Early menopause (EM, age at menopause < 45 years) and premature ovarian insufficiency (POI, age at menopause < 40 years) are associated with an increased risk of osteoporosis. However, their association with increased fracture risk has not been established, with studies yielding conflicting results. The primary aim of this systematic review and meta-analysis was to synthesize studies evaluating the association between age at menopause and fracture risk. The secondary aim was to evaluate this effect concerning the site of fractures. METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to 31 January 2018. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for quantifying heterogeneity. RESULTS: Eighteen studies were included in the qualitative and quantitative analysis (462,393 postmenopausal women, 12,130 fractures). Compared with women with age at menopause > 45 years, women with EM demonstrated higher fracture risk (OR 1.36, 95% CI 1.11-1.66, p < 0.002, I² 81.5%). Women with POI did not display any difference in fracture risk compared either with women with age at menopause > 40 (OR 1.23, 95% CI 0.72-2.09, p = 0.436, I² 62.5%) or >45 years (OR 0.54, 95% CI 0.22-1.29, p = 0.17, I2 0%). No difference was evident when a separate analysis was performed for vertebral, non-vertebral and hip fractures. CONCLUSIONS: This is the first meta-analysis showing that EM is associated with increased fracture risk compared with normal age at menopause, without any distinct effect on the site of the fracture.

Early menopause and premature ovarian insufficiency are associated with increased risk of type 2 diabetes: a systematic review and meta-analysis.

Objective/Design Menopausal transition has been associated with a derangement of glucose metabolism. However, it is not known if early menopause (EM, defined as age at menopause <45 years) or premature ovarian insufficiency (POI, defined as age at menopause <40 years) are associated with increased risk of type 2 diabetes mellitus (T2DM). To systematically investigate and meta-analyze the best evidence regarding the association of age at menopause with the risk of T2DM. Methods A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to January 31, 2018. Data are expressed as odds ratio (OR) with 95% confidence intervals (CI). The I 2 index was employed for heterogeneity. Results Thirteen studies were included in the qualitative and quantitative analysis (191 762 postmenopausal women, 21 664 cases with T2DM). Both women with EM and POI were at higher risk of T2DM compared with those of age at menopause of 45-55 years (OR: 1.15, 95% CI: 1.04-1.26, P = 0.003; I 2: 61%, P < 0.002 and OR: 1.50, 95% CI: 1.03-2.19, P = 0.033; I 2: 75.2%, P < 0.003), respectively). Similar associations emerged when women with EM and POI were compared with those of age at menopause >45 years (OR: 1.12, 95% CI: 1.01-1.20, P < 0.02; I 2: 78%, P < 0.001 and OR: 1.53, 95% CI: 1.03-2.27, P = 0.035; I 2: 78%, P < 0.001), respectively). Conclusions Both EM and POI are associated with increased risk of T2DM.

The effect of antidiabetic medications on the cardiovascular system: a critical appraisal of current data.

Both type 1 and type 2 diabetes are associated with increased risk for cardiovascular disease (CVD) events. This risk seems to be reduced by achievement of euglycemia. However, after the withdrawal of rosiglitazone from the market, the question arose as to whether this risk concerns simply a matter of euglycemia or the distinct role played by each antidiabetic drug with respect to its effect on CVD risk. To address this issue, many studies have been published during the last decade involving old and new antidiabetic agents, which however yielded contradictory results. Briefly, metformin is still considered safe and confers a beneficial effect on CVD risk. Conflicting data exist as concerns sulfonylureas, although the second and third generation representatives are regarded as relatively safe. Pioglitazone use seems to be associated with a reduction in CVD risk, whereas the dipeptidyl-dipeptidase-4 inhibitors (DPP-4i), lixisenatide and exenatide-LAR [from the category of glucagon-like-peptide-1 receptor (GLP-1R) agonists], confer a neutral effect. Two other GLP-1R agonists, liraglutide and semaglutide, as well as the sodium-glucose transporter-2 (SGLT2)-inhibitors, empagliflozin and cangliflozin, have shown an additional effect on CVD risk reduction, although their safety is in doubt. Insulin analogues and newer long-acting compounds are also safe for the cadiovascular system. The aim of this narrative review is to present and critically analyse the current data for each antidiabetic drug category with regard to their effect on CVD risk.