Project description:We aimed to evaluate the comparative efficacy and safety of drugs respectively for primary prevention and secondary prevention of osteoporotic fractures in postmenopausal women (PMW), and to further identify the optimal intervention(s) respectively for the two groups when efficacy and safety both considered. We searched three databases. Bayesian network meta-analyses were conducted for two efficacy outcomes (vertebral fractures and nonvertebral fractures) and two safety outcomes (tolerability and acceptability) respectively in primary prevention group and secondary prevention group. We synthesized hazard ratios (HRs) and 95% confidence intervals (CIs) for nonvertebral fractures, and risk ratios (RRs) for three others. Factor and cluster analyses on surface under the cumulative ranking curve (SUCRA) values were conducted to identify the best intervention(s) with efficacy and safety both considered. The study protocol has been registered in PROSPERO. We included 57 randomized trials involving fifteen anti-osteoporotic interventions and 106320 PMW. For primary prevention, only zoledronate (once per 18 months) reduced both vertebral (RR 0.46, 95% CI 0.28-0.74) and nonvertebral (HR 0.66, 95% CI 0.51-0.85) fractures. For secondary prevention, abaloparatide, alendronate, denosumab, lasofoxifene, risedronate, romosozumab, teriparatide, and zoledronate (once per 12 months) reduced both vertebral (RRs: from 0.17 to 0.62) and nonvertebral (HRs: from 0.54 to 0.81) fractures. PTH (1-84) and abaloparatide increased withdrawal risk. Romosozumab, teriparatide, denosumab and risedronate, with the greatest composite scores, constituted the optimal cluster having both superior efficacy and superior safety. Zoledronate used at 5 mg per 18 months, with the similar safety as placebo, is the only drug intervention which has been shown to significantly reduce both vertebral and nonvertebral fractures for primary prevention of osteoporotic fractures in PMW; while romosozumab, teriparatide, denosumab, and risedronate are the optimal treatments for secondary prevention when efficacy and safety both considered. A limitation is that safety outcomes failed to consider the severity of adverse effects.

Project description:Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level are known to take part in the control of bone formation and bone resorption. Recently, targeted secretion of miRNAs from cells originating from various tissues has been described, which allows for their minimal-invasive detection in serum/plasma and use as biomarkers for presence and progression of pathological conditions. One pilot study has reported circulating miRNAs in serum and tissue of fracture patients. However, further studies are required to explore whether a dysbalance in bone homeostasis of fracture patients can reliably be reflected by specific circulating miRNAs, and whether these miRNAs might serve as drugable targets. Here, we report results from a comprehensive multiplex study of 175 miRNAs in serum samples obtained from 7 patients with osteoporotic fractures at the femoral neck, and 7 age-matched controls. Following elaborate quality control statistical analysis of this exploratory dataset identified 9 microRNAs with altered serum levels in response to fracture (adjusted p-value < 0.1). Of these, hsa-miR-10a/b gave excellent discrimination of both groups (AUC = 1.0), and clustering of samples based on the top10 miRNAs confirmed the high discriminatory power of circulating microRNAs for osteoporotic fractures. In the next step 3 miRNAs with unknown roles in osteogenic differentiation and 4 miRNA from a previous study were tested for their effects on osteogenic differentiation. Of these, 3 miRNAs showed robust effects on osteogenic differentiation. Overall, these data provide important insights into changes in serum miRNA in post-traumatic patients. Future studies will show, whether this knowledge can be used to improve current diagnostic methodologies to predict fracture risk and design novel treatment strategies for osteoporosis patients. Two groups with n=7 per group; one groups represents cases with osteoporotic fractures, the control group is age-matched without fractures

Project description:Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level are known to take part in the control of bone formation and bone resorption. Recently, targeted secretion of miRNAs from cells originating from various tissues has been described, which allows for their minimal-invasive detection in serum/plasma and use as biomarkers for presence and progression of pathological conditions. One pilot study has reported circulating miRNAs in serum and tissue of fracture patients. However, further studies are required to explore whether a dysbalance in bone homeostasis of fracture patients can reliably be reflected by specific circulating miRNAs, and whether these miRNAs might serve as drugable targets. Here, we report results from a comprehensive multiplex study of 175 miRNAs in serum samples obtained from 7 patients with osteoporotic fractures at the femoral neck, and 7 age-matched controls. Following elaborate quality control statistical analysis of this exploratory dataset identified 9 microRNAs with altered serum levels in response to fracture (adjusted p-value < 0.1). Of these, hsa-miR-10a/b gave excellent discrimination of both groups (AUC = 1.0), and clustering of samples based on the top10 miRNAs confirmed the high discriminatory power of circulating microRNAs for osteoporotic fractures. In the next step 3 miRNAs with unknown roles in osteogenic differentiation and 4 miRNA from a previous study were tested for their effects on osteogenic differentiation. Of these, 3 miRNAs showed robust effects on osteogenic differentiation. Overall, these data provide important insights into changes in serum miRNA in post-traumatic patients. Future studies will show, whether this knowledge can be used to improve current diagnostic methodologies to predict fracture risk and design novel treatment strategies for osteoporosis patients.

Project description:As life expectancy increases, the prevalence of osteoporosis is increasing. In addition to vitamin D which is well established to have an association with osteoporosis, B vitamins, such as thiamine, folate (vitamin B9), and cobalamin (vitamin B12), could affect bone metabolism, bone quality, and fracture risk in humans by influencing homocysteine/folate metabolism. Despite the crucial role of B vitamins in bone metabolism, there are few studies regarding associations between B vitamin-related genes and osteoporosis. In this study, we investigated the genetic association of four single nucleotide polymorphisms (SNPs) within the 3'-untranslated regions of vitamin B-related genes, including TCN2 (encodes transcobalamin II), CD320 (encodes transcobalamin II receptor), SLC19A1 (encodes reduced folate carrier protein 1), and SLC19A2 (encodes thiamine carrier 1), with osteoporosis and osteoporotic vertebral compression fracture (OVCF). We recruited 301 postmenopausal women and performed genotyping of CD320 rs9426 C>T, TCN2 rs10418 C>T, SLC19A1 rs1051296 G>T, and SLC19A2 rs16862199 C>T using a polymerization chain reaction-restriction fragment length polymorphism assay. There was a significantly higher incidence of both osteoporosis (AOR 5.019; 95% CI, 1.533-16.430, p < 0.05) and OVCF (AOR, 5.760; 95% CI, 1.480-22.417, p < 0.05) in individuals with genotype CD320 CT+TT and high homocysteine concentrations. Allele combination analysis revealed that two combinations, namely CD320 C-TCN2 T-SLC19A1 T-SLC19A2 C (OR, 3.244; 95% CI, 1.478-7.120, p < 0.05) and CD320 T-TCN2 C-SLC19A1 G-SLC19A2 C (OR, 2.287; 95% CI, 1.094-4.782, p < 0.05), were significantly more frequent among the osteoporosis group. Our findings suggest that SNPs within the CD320 gene in 3´-UTR may contribute to osteoporosis and OVCF occurrences in some individuals. Furthermore, specific allele combinations of CD320, TCN2, SLC19A1, and SLC19A2 may contribute to increased susceptibility to osteoporosis and OVCF.

Dataset Information

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

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