Proposed Denosumab Biosimilar SB16 vs Reference Denosumab in Postmenopausal Osteoporosis: Phase 3 Results Up to Month 12.

CONTEXT: SB16 is a proposed biosimilar to reference denosumab (DEN; brand name: Prolia). OBJECTIVE: This phase 3 randomized, double-blind, multicenter study evaluated the biosimilarity of SB16 to DEN in women with postmenopausal osteoporosis (PMO; NCT04664959). DESIGN: The study included 457 PMO patients who had a lumbar spine or total hip T-score between -2.5 and -4. Patients were randomized in a 1:1 ratio to receive either 60 mg of SB16 or DEN subcutaneously at Month 0 and Month 6. At Month 12, patients were re-randomized to continue with the assigned treatment or switch from DEN to SB16 up to Month 18. This report includes results up to Month 12. METHODS: The primary endpoint was the percent change from baseline in lumbar spine bone mineral density (BMD) at Month 12. Secondary endpoints including the percent change from baseline in BMD of the lumbar spine (except for Month 12), total hip and femoral neck; pharmacokinetic, pharmacodynamic (serum C-telopeptide of type I collagen [CTX] and procollagen type I N-terminal propeptide [P1NP]), safety, and immunogenicity profiles were measured up to Month 12. RESULTS: The least-squares mean differences in percent change from baseline in lumbar spine BMD at Month 12 were 0.33% (90% confidence interval [CI]: -0.25, 0.91) in the full analysis set and 0.39% (95% CI: -0.36, 1.13) in the per-protocol set; both within the pre-defined equivalence margin. The secondary endpoints were comparable between the two treatment groups. CONCLUSION: The reported efficacy, PK, PD, safety, and immunogenicity data support the biosimilarity of SB16 to DEN.

Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE).

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Muscle Mass Changes After Daily Consumption of Protein Mix Supplemented With Vitamin D in Adults Over 50 Years of Age: Subgroup Analysis According to the Serum 25(OH)D Levels of a Randomized Controlled Trial.

Early prevention of sarcopenia can be an important strategy for muscle maintenance, but most studies target subjects at slightly pre-sarcopenic state. Our previous paper describes the effect of protein supplements rich in leucine and vitamin D on muscle condition, and in this paper, we performed a sub-analysis to evaluate who benefitted the most in terms of improvement in muscle health. A 12-week randomized clinical trial of 120 healthy adults (aged 50 to 80) assigned to an intervention group (n = 60) or control group (n = 60) were analyzed. Subjects in the intervention group received, twice per day, a protein supplement containing (per serving) 800 IU of vitamin D, 20 g of protein (3 g of total leucine), 300 mg of calcium, 1.1 g of fat, and 2.5 g of carbohydrate. The subjects were classified into 'insufficient' and 'sufficient' groups at 25-hydroxyvitamin D (25[OH]D) value of 30 ng/mL. The skeletal muscle mass index normalized to the square of the skeletal muscle mass (SMM) height (kg/m2) increased significantly in the 'insufficient group' difference value of change between weeks 0 and 12 (Δ1.07 ± 2.20; p = 0.037). The SMM normalized by body weight (kg/kg, %) was higher, but not significantly, in the insufficient group (Δ0.38 ± 0.69; p = 0.050). For people with insufficient (serum 25[OH]D), supplemental intake of protein and vitamin D, calcium, and leucine and adequate energy intake increases muscle mass in middle-aged and older adults and would be likely to exert a beneficial effect on muscle health. Trial Registration: Clinical Research Information Service Identifier: KCT0005111.

UBAP2 plays a role in bone homeostasis through the regulation of osteoblastogenesis and osteoclastogenesis.

Osteoporosis is a condition characterized by decreased bone mineral density (BMD) and reduced bone strength, leading to an increased risk of fractures. Here, to identify novel risk variants for susceptibility to osteoporosis-related traits, an exome-wide association study is performed with 6,485 exonic single nucleotide polymorphisms (SNPs) in 2,666 women of two Korean study cohorts. The rs2781 SNP in UBAP2 gene is suggestively associated with osteoporosis and BMD with p-values of 6.1 × 10-7 (odds ratio = 1.72) and 1.1 × 10-7 in the case-control and quantitative analyzes, respectively. Knockdown of Ubap2 in mouse cells decreases osteoblastogenesis and increases osteoclastogenesis, and knockdown of ubap2 in zebrafish reveals abnormal bone formation. Ubap2 expression is associated with E-cadherin (Cdh1) and Fra1 (Fosl1) expression in the osteclastogenesis-induced monocytes. UBAP2 mRNA levels are significantly reduced in bone marrow, but increased in peripheral blood, from women with osteoporosis compared to controls. UBAP2 protein level is correlated with the blood plasma level of the representative osteoporosis biomarker osteocalcin. These results suggest that UBAP2 has a critical role in bone homeostasis through the regulation of bone remodeling.

Asia-pacific consensus on osteoporotic fracture prevention in postmenopausal women with low bone mass or osteoporosis but no fragility fractures.

Postmenopausal women are at significant risk for osteoporotic fractures due to their rapid bone loss. Half of all postmenopausal women will get an osteoporosis-related fracture over their lifetime, with 25% developing a spine deformity and 15% developing a hip fracture. By 2050, more than half of all osteoporotic fractures will occur in Asia, with postmenopausal women being the most susceptible. Early management can halt or even reverse the progression of osteoporosis. Consequently, on October 31, 2020, the Taiwanese Osteoporosis Association hosted the Asia-Pacific (AP) Postmenopausal Osteoporotic Fracture Prevention (POFP) consensus meeting, which was supported by the Asian Federation of Osteoporosis Societies (AFOS) and the Asia Pacific Osteoporosis Foundation (APOF). International and domestic experts developed ten applicable statements for the prevention of osteoporotic fractures in postmenopausal women with low bone mass or osteoporosis but no fragility fractures in the AP region. The experts advocated, for example, that postmenopausal women with a high fracture risk be reimbursed for pharmaceutical therapy to prevent osteoporotic fractures. More clinical experience and data are required to modify intervention tactics.

Updates on Paget's Disease of Bone.

Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries, including China, Japan, and Korea. The exact cause still remains unknown. In genetically susceptible individuals, environmental triggers such as paramyxoviral infections are likely to cause the disease. Increased osteoclast activity results in increased bone resorption, which attracts osteoblasts and generates new bone matrix. Fast bone resorption and formation lead to the development of disorganized bone tissue. Increasing serum alkaline phosphatase or unique radiographic lesions may serve as the diagnostic indicators. Common symptoms include bone pain, bowing of the long bones, an enlarged skull, and hearing loss. The diagnosis is frequently confirmed by radiographic and nuclear scintigraphy of the bone. Further, bisphosphonates such as zoledronic acid and pamidronate are effective for its treatment. Moreover, biochemical monitoring is superior to the symptoms as a recurrence indicator. This article discusses the updates of Paget's disease of bone with a clinical case.

Adherence of bisphosphonate and decreased risk of clinical vertebral fracture in osteoporotic patients: A propensity score matching analysis.

Objectives: Bisphosphonate is associated with a decreased risk of vertebral fractures due to osteoporosis. However, there are limited studies on how poor compliance with bisphosphonate affects the risk of vertebral fractures in a nationwide cohort. We aim to evaluate whether adherence to bisphosphonate affects the risk of fracture in osteoporosis patients. Methods: We used the data of the Korean National Health Insurance Service Senior Cohort. A total of 33,315 (medication possession ratio [MPR]: 50) osteoporosis patients were matched using the propensity score matching method: those who received low-dose bisphosphonate and those who received high-dose bisphosphonate. Twenty-two confounding variables, including age, socioeconomic status, medications prescribed, and underlying diseases that may affect the risk of fracture were adjusted for propensity score matching. The risk of vertebral fracture was assessed by Cox proportional hazards regression. Results: Patients with a higher MPR showed a decreased vertebral fracture risk than those with a lower MPR (MPR 50 = hazard ratio [HR] 0.909; 95% confidence interval [CI] 0.877-0.942 P < 0.001; MPR 70 = HR: 0.874, 95% CI: 0.838-0.913, P < 0.001; MPR 90 = HR: 0.822, 95% CI: 0.780-0.866, P < 0.001). MPR was associated with a decreased vertebral fracture risk in both groups with or without history of fracture. In the subgroup analysis, MPR was associated with a decreased vertebral fracture risk in women, in all ages, with or without T2DM, and with or without hypertension. Conclusions: Higher MPR is associated with a lower vertebral fracture risk.

The Positive Association between Muscle Mass and Bone Status Is Conserved in Men with Diabetes: A Retrospective Cross-Sectional and Longitudinal Study.

Bone and muscle are known to be correlated and interact chemically each other. Diabetes affects the health status of these two types of organ. There has been lack of studies of men on this topic. This study aims to investigate the relationship between bone and muscle status in men with and without diabetes. This study enrolled 318 and 88 men with and without diabetes, respectively, between April 2007 and December 2017. The appendicular skeletal muscle index (ASMI) was correlated with femoral neck bone mineral density (BMD), total hip BMD, and the trabecular bone score (TBS) in both groups (p < 0.001−0.008). In analysis of the changes in muscle mass and bone-related parameters over the 3 years, the ASMI was correlated with total hip BMD only in diabetes group (p = 0.016) and the TBS in both groups (p < 0.001−0.046). This study showed that the positive correlation between muscle mass and bone status was largely conserved in diabetic group in men. Moreover, in a long-term perspective, muscle mass might be more correlated with the bone microarchitecture or bone quality than bone density, and the association between muscle mass and total hip BMD could be stronger in the diabetic group.

Quality of life and patient satisfaction with raloxifene/cholecalciferol combination therapy in postmenopausal women.

This study was performed to evaluate quality of life (QOL) and patient satisfaction with raloxifene/cholecalciferol combination therapy in postmenopausal women with low bone mass. This multicenter, prospective, noninterventional observational study included 3907 postmenopausal women who received a combination of raloxifene 60 mg and cholecalciferol 800 IU daily to treat or prevent osteoporosis. Changes in QOL and patient satisfaction were evaluated after 3 and 6 months of treatment. In addition, the safety profile was assessed. Mean age was 67.7 ± 9.3 years old. QOL, assessed by European Quality of life instrument 5 Dimensions (EQ-5D) index, improved significantly after 3 months (0.81 ± 0.11, P < 0.001) and 6 months (0.82 ± 0.11, P < 0.001) of treatment compared to the baseline (0.78 ± 0.14). Improvement in QOL was also significant regardless of previous regimens both in women who were switched from other drugs (bisphosphonates or selective estrogen receptor modulators) and in women who received the study drug for the first time (P < 0.001 for all comparisons). Percentage of women satisfied with the effects (from 37.3 to 67.7%, P < 0.001) and convenience (from 42.8 to 74.1%, P < 0.001) of treatment compared to previous medication significantly increased after 6 months of treatment. In addition, serious adverse drug reactions did not occur, and hot flushes were observed only in 12 women (0.3%). Combination therapy with raloxifene and cholecalciferol significantly improves quality of life with no serious adverse events and high patient satisfaction at 6 months. Our real-world data suggest that this regimen is a promising option for postmenopausal women with low bone mass.

Musculoskeletal Health of the Adults Over 50 Years of Age in Relation to Antioxidant Vitamin Intakes.

As the proportion of the elderly population increases rapidly, interest in musculoskeletal health is also emerging. Here, we investigated how antioxidant vitamin intake and musculoskeletal health are related. Adults aged 50 to 80 years with a body mass index (BMI) of 18.5 to 27.0 kg/m2 were included. Bone mineral density (BMD), lean mass (LM), appendicular skeletal muscle mass index (ASMI) were measured using dual-energy X-ray absorptiometry (DXA), and the grip strength and knee extension using hand dynamometer. Nutrient intakes were measured using a 24-hour recall questionnaire. A total of 153 adults (44 men and 109 women) participated in this study. A partial correlation analysis showed a significant positive relationship between vitamin E and BMD and between vitamin C and LM/Height. Participants were classified into three groups according to whether their vitamin E and C intake met the recommended intake for Dietary Reference Intakes for Koreans (KDRIs). The prevalence of having low T-score (< -1.0) and low ASMI (< 7.0 for men and < 5.4 for women) was 51.3% and 15.4% in the group with vitamins C and E intakes below KDRIs. After adjusting for sex, smoking status and energy, protein, vitamin D, and calcium intake, the group with vitamins C and E both below the KDRIs displayed a significantly lower BMD at all test sites and LM/Height compared with vitamin C and/or E intake above the KDRIs groups. We conclude that sufficient intake of vitamin E and C is important for maintaining BMD and lean mass in Korean adults over 50 years of age.

Gene Network Analysis for Osteoporosis, Sarcopenia, Diabetes, and Obesity in Human Mesenchymal Stromal Cells.

The systemic gene interactions that occur during osteoporosis and their underlying mechanisms remain to be determined. To this end, mesenchymal stromal cells (MSCs) were analyzed from bone marrow samples collected from healthy individuals (n = 5) and patients with osteoporosis (n = 5). A total of 120 osteoporosis-related genes were identified using RNA-sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) software. In order to analyze these genes, we constructed a heatmap of one-way hierarchical clustering and grouped the gene expression patterns of the samples. The MSCs from one control participant showed a similar expression pattern to that observed in the MSCs of three patients with osteoporosis, suggesting that the differentiating genes might be important genetic determinants of osteoporosis. Then, we selected the top 38 genes based on fold change and expression, excluding osteoporosis-related genes from the control participant. We identified a network among the top 38 genes related to osteoblast and osteoclast differentiation, bone remodeling, osteoporosis, and sarcopenia using the Molecule Activity Predictor program. Among them, 25 genes were essential systemic genes involved in osteoporosis. Furthermore, we identified 24 genes also associated with diabetes and obesity, among which 10 genes were involved in a network related to bone and energy metabolism. The study findings may have implications for the treatment and prevention of osteoporosis.

Bone mineral density, cervical spine degeneration, head and neck posture, and neck pain in the post-menopausal females: A pilot study.

The purpose of the present study was to reveal the relationship between degenerative changes in the cervical spine, head and neck postures, neck pain, and bone mineral density (BMD) of the total hip, femoral neck, and lumbar spine in post-menopausal females. In total, 116 females (mean age 60.4 ± 7.1 years; age range 50-80 years) were included. Participants were classified into three groups based on the T-score criteria of the total hip, femoral neck, and lumbar spine set by World Health Organization, respectively. The degree of neck pain was assessed using self-administered questionnaire, the Neck Disability Index. Cervical spine degeneration and head and neck postures were identified using the lateral cephalograms. Grading system for cervical degeneration included three categories of the radiographic alterations including disc height loss, osteophyte formation, and diffuse sclerosis. The areal BMD of the total hip, femoral neck, and lumbar spine were determined using dual-energy x-ray absorptiometry. Females with lower BMD exhibited lesser degree of neck pain and forward head posture (FHP) compared to those with normal BMD. Higher BMD seemed to be associated with more notable loss of the disc height at the level of C4-5. More prominent degenerative changes in the cervical spine were associated with higher areal BMD of the hip, femoral neck, and lumbar spine, altered head posture, and development of neck pain.

Romosozumab in Postmenopausal Korean Women with Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study.

BACKGROUND: This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmenopausal women with osteoporosis. METHODS: Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤-2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months. RESULTS: At month 6, the difference in the least square (LS) mean percent change from baseline in lumbar spine BMD (primary efficacy endpoint) between the romosozumab (9.5%) and placebo (-0.1%) groups was significant (9.6%; 95% confidence interval, 7.6 to 11.5; P<0.001). The difference in the LS mean percent change from baseline was also significant for total hip and femoral neck BMD (secondary efficacy endpoints). After treatment with romosozumab, the percent change from baseline in procollagen type 1 N-terminal propeptide transiently increased at months 1 and 3, while that in C-terminal telopeptide of type 1 collagen showed a sustained decrease. No events of cancer, hypocalcemia, injection site reaction, positively adjudicated atypical femoral fracture or osteonecrosis of the jaw, or positively adjudicated serious cardiovascular adverse events were observed. At month 9, 17.6% and 2.9% of patients in the romosozumab group developed binding and neutralizing antibodies, respectively. CONCLUSION: Treatment with romosozumab for 6 months was well tolerated and significantly increased lumbar spine, total hip, and femoral neck BMD compared with placebo in Korean postmenopausal women with osteoporosis (ClinicalTrials.gov identifier NCT02791516).

Safety and effectiveness of linagliptin in Korean patients with type 2 diabetes: A postmarketing surveillance study.

We designed a postmarketing surveillance study of linagliptin for patients with type 2 diabetes (T2D) in Korea. This prospective, observational, multicentre study investigated the safety and glycaemic effectiveness of linagliptin as monotherapy or combination therapy with other antidiabetic drugs in routine clinical practice. Endpoints were the incidence of adverse drug reactions (ADRs) and the change in HbA1c. Overall, 3119 and 2171 patients were included in the safety and effectiveness analysis sets, respectively. A total of 56 patients (1.8%) experienced ADRs. The most common ADR was gastrointestinal disorders (0.7%), followed by metabolism and nutrition disorders (0.5%). ADRs of special interest, including pancreatic diseases, cardiac diseases and hypoglycaemia, occurred in 12 patients, 11 of whom had hypoglycaemia, while one had a skin lesion. Mean HbA1c change during the study period was -0.8%. Lower body mass index, shorter diabetes duration and higher baseline HbA1c were independently associated with a better effectiveness, while the presence of diabetic complications, dyslipidaemia and the use of sulphonylureas were associated with a poor response. In conclusion, linagliptin showed an excellent safety profile and glycaemic effectiveness in Korean patients with T2D.

Consensus Statement on the Use of Bone Turnover Markers for Short-Term Monitoring of Osteoporosis Treatment in the Asia-Pacific Region.

Osteoporosis is a major health issue. By 2050, a greater than 2-fold increase in patients number with hip fractures will occur in Asia representing 50% of all hip fractures worldwide. For the Asia-Pacific (AP) region, more efforts on controlling osteoporosis and the subsequent fractures are crucial. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is commonly used to diagnose osteoporosis and monitor osteoporosis treatment. However, the inconvenience, cost, limited availability of DXA and the delay in detection of BMD changes after treatment initiation support an important role for bone turnover markers (BTMs), as short-term tools to monitor therapy. With regards to low adherence rates of medical treatment of osteoporosis, the experts reached consensus on the use of BTMs for both raising awareness and short-term monitoring of osteoporosis treatment in the AP region. The experts endorse the use of BTMs, especially serum C-terminal telopeptide of type 1 collagen (CTX) and serum procollagen type 1 N propeptide (P1NP), as short-term monitoring tools to help clinicians assess the responses to osteoporosis therapies and appropriately adjust treatment regimens earlier than BMD. Either the absolute values or the degree of change from baseline in BTMs can be used to monitor the potential efficacy of osteoporosis therapies. The use of BTMs can be incorporated in osteoporosis care programs, such as fracture liaison service (FLS), to improve patient adherence and treatment outcomes. Encouraging sufficient reimbursement from health care systems may facilitate widespread use of BTMs in clinical practice in the AP region.

Reference Ranges of Serum Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3: Results from a Multicenter Study in Healthy Korean Adults.

Insulin-like growth factor-I (IGF-I) plays a pivotal role in the diagnosis and treatment of growth hormone (GH) excess or deficiency. The GH study group of the Korean Endocrine Society aims to establish the Korean reference ranges of serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) and assess the relationship between IGF-I and IGFBP-3 and clinical parameters. Fasting serum was collected from healthy Korean adults at health promotion centers of five hospitals nationwide. Serum IGF-I and IGFBP-3 were measured via an immunoradiometric assay using a DSL kit (Diagnostic Systems Laboratories). Serum samples from 354 subjects (180 male, 174 female) were analyzed based on sex at 10-year intervals from 21 to 70 years. IGF-I levels were inversely correlated with age. After adjustment of age, the IGF-I/IGFBP-3 ratio was significantly negatively associated with blood pressure and free thyroxine and positively associated with weight, hemoglobin, creatinine, alanine transferase, fasting glucose, and thyroid stimulating hormone. Therefore, age- and sex-specific reference ranges of serum IGF-I and IGFBP-3 can be efficient in evaluating GH excess or deficiency in Korean population.

Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis.

OBJECTIVES: Emerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the efficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture. METHOD: The Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. Only randomized placebo-controlled trials evaluating postmenopausal women with -1.0 > bone mineral density (BMD) T-score > -2.5 (low bone mass) and those with BMD T-score ≤ -2.5 (osteoporosis) but without baseline fractures, who were receiving anti-osteoporotic agents, providing quantitative outcomes data and evaluating risk of vertebral and/or non-vertebral fragility fracture at follow-up. The PRISMA guidelines were followed, applying a random-effects model. The primary endpoint was the effect of anti-osteoporotic regimens in reducing the incidence of vertebral fractures. Secondary endpoints were percentage changes in baseline BMD at the lumbar spine and total hip at 1 and 2 years follow up. RESULTS: Full-text review of 144 articles yielded, 20 for meta-analysis. Bisphosphonates reduced the risk of vertebral fracture (pooled OR = 0.50, 95%CIs = 0.36-0.71) and significantly increased lumbar spine BMD after 1 year, by 4.42% vs placebo (95%CIs = 3.70%-5.14%). At the hip, this value was 2.94% (95%CIs = 2.13%-3.75%). Overall results of limited studies for non-bisphosphonate drugs showed increased BMD and raloxifene significantly decreases the risk of subsequent clinical vertebral fractures. CONCLUSION: The bisphosphonates are efficacious and most evident for the primary prevention of osteoporotic vertebral fractures, reducing their incidence and improving BMD in postmenopausal women with osteopenia or osteoporosis.

Bimagrumab vs Optimized Standard of Care for Treatment of Sarcopenia in Community-Dwelling Older Adults: A Randomized Clinical Trial.

Importance: The potential benefit of novel skeletal muscle anabolic agents to improve physical function in people with sarcopenia and other muscle wasting diseases is unknown. Objective: To confirm the safety and efficacy of bimagrumab plus the new standard of care on skeletal muscle mass, strength, and physical function compared with standard of care alone in community-dwelling older adults with sarcopenia. Design, Setting, and Participants: This double-blind, placebo-controlled, randomized clinical trial was conducted at 38 sites in 13 countries among community-dwelling men and women aged 70 years and older meeting gait speed and skeletal muscle criteria for sarcopenia. The study was conducted from December 2014 to June 2018, and analyses were conducted from August to November 2018. Interventions: Bimagrumab 700 mg or placebo monthly for 6 months with adequate diet and home-based exercise. Main Outcomes and Measures: The primary outcome was the change in Short Physical Performance Battery (SPPB) score after 24 weeks of treatment. Secondary outcomes included 6-minute walk distance, usual gait speed, handgrip strength, lean body mass, fat body mass, and standard safety parameters. Results: A total of 180 participants were recruited, with 113 randomized to bimagrumab and 67 randomized to placebo. Among these, 159 participants (88.3%; mean [SD] age, 79.1 [5.3] years; 109 [60.6%] women) completed the study. The mean SPPB score increased by a mean of 1.34 (95% CI, 0.90 to 1.77) with bimagrumab vs 1.03 (95% CI, 0.53 to 1.52) with placebo (P = .13); 6-minute walk distance increased by a mean of 24.60 (95% CI, 7.65 to 41.56) m with bimagrumab vs 14.30 (95% CI, -4.64 to 33.23) m with placebo (P = .16); and gait speed increased by a mean of 0.14 (95% CI, 0.09 to 0.18) m/s with bimagrumab vs 0.11 (95% CI, 0.05 to 0.16) m/s with placebo (P = .16). Bimagrumab was safe and well-tolerated and increased lean body mass by 7% (95% CI, 6% to 8%) vs 1% (95% CI, 0% to 2%) with placebo, resulting in difference of 6% (95% CI, 4% to 7%) (P < .001). Conclusions and Relevance: This randomized clinical trial found no significant difference between participants treated with bimagrumab vs placebo among older adults with sarcopenia who had 6 months of adequate nutrition and light exercise, with physical function improving in both groups. Bimagrumab treatment was safe, well-tolerated, increased lean body mass, and decreased fat body mass. The effects of sarcopenia, an increasing cause of disability in older adults, can be reduced with proper diet and exercise. Trial Registration: ClinicalTrials.gov Identifier: NCT02333331; EudraCT number: 2014-003482-25.