Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.
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SUBMITTER: Wells GA
PROVIDER: S-EPMC9062986 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
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Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.
Wells George A GA Hsieh Shu-Ching SC Zheng Carine C Peterson Joan J Tugwell Peter P Liu Wenfei W
The Cochrane database of systematic reviews 20220503
<h4>Background</h4>Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Risedronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts. This is an update of a Cochrane Review that was originally published in 2003.<h4>Objectives</h4>We assessed the benefits and harms of risedronate in the primary and secondary prevention of osteoporotic fractures for postmenopaus ...[more]
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Project description:BackgroundThere are many pharmaceutical interventions available to prevent osteoporotic vertebral fractures in postmenopausal women, but the efficacy and safety of these drugs are unknown. This study aimed to investigate the efficacy and safety of drugs in the prevention of osteoporotic vertebral fractures.MethodsPubMed, Embase, and the Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) published up to February 15, 2020, including postmenopausal women with osteoporosis. Network meta-analysis was conducted based on the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The relative risk (RR) and 95% confidence interval (CI) were used to report the results. This study was registered with PROSPERO, number CRD42020201167. Main Outcomes were incidences of new vertebral fracture and serious adverse events.ResultsFifty-five RCTs (n = 104 580) evaluating vertebral fractures of sixteen kinds of pharmacologic therapies were included in the network meta-analysis. Abaloparatide (RR, 0.21; [95% CI, 0.09 to 0.51]), alendronate (RR, 0.55; [95% CI, 0.38 to 0.81]), calcitonin (RR, 0.44; [95% CI, 0.25 to 0.78]), denosumab (RR, 0.33; [95% CI, 0.14 to 0.61]), parathyroid hormone (PTH) (RR, 0.32; [95% CI, 0.10 to 0.97]), risedronate (RR, 0.65; [95% CI, 0.42 to 1.00]), romosozumab (RR, 0.31; [95% CI, 0.16 to 0.61]), strontium ranelate (RR, 0.62; [95% CI, 0.42 to 0.93]), teriparatide (RR, 0.27; [95% CI, 0.17 to 0.43]), and zoledronate (RR, 0.41; [95% CI, 0.93]) were associated with lower vertebral fracture risk compared to placebo. PTH was associated with more adverse event rates. For any two drug treatments, the RR of serious adverse events was not statistically significant. Hormone replacement therapy (HRT) and calcitonin may be slower to work because they have only been shown to reduce the risk of vertebral fractures in long-term (>18 months) follow-up.ConclusionsA variety of drugs are safe and effective in preventing osteoporotic vertebral fractures. HRT and calcitonin only reduced the risk of vertebral fractures during a follow-up of 21-72 months.
| S-EPMC9958453 | biostudies-literature
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.
| S-EPMC7269244 | biostudies-literature
Project description:ObjectivesEmerging 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.MethodThe 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.ResultsFull-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.ConclusionThe 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.
| S-EPMC7645632 | biostudies-literature
Project description: Not available
| S-EPMC558688 | biostudies-literature
Project description:ObjectiveTo compare incidence of first osteoporotic fracture in two cohorts of postmenopausal women, one treated with bisphosphonates and the other only with calcium and vitamin D.DesignRetrospective population cohort study with paired matching based on data from electronic health records.SettingWomen aged 60 years and older in 2005, from 21 primary care centers in a healthcare region of Spain.ParticipantsTwo groups of women aged 60 years and older (n = 1208), prescribed either calcium and vitamin D (CalVitD) or bisphosphonates (BIPHOS) with or without calcium and vitamin D, were compared for the end point of first recorded osteoporotic-related fracture, with 5-years follow-up.Main outcome measureIncidence of first fracture: Vertebral fracture, osteoporosis with pathological fracture, fracture of the upper humeral epiphysis, fracture of the lower radial epiphysis, or femur fracture.ResultsEstimated 10-year risk of fracture was 11.4% (95% confidence interval: 9.6 to 13.2), 11.8% (9.2 to 14.3) in the BIPHOS group and 11.1% (8.6 to 13.6) in the CalVitD group. No significant differences were found between groups in total fractures (Hazard ratio = 0.934 (0.67 to 1.31)) or location (vertebral, femoral, radial or humeral).ConclusionsIn postmenopausal women, bisphosphonates have not been shown to better decrease risk of first fracture compared with calcium and vitamin D therapy alone.
| S-EPMC4393307 | biostudies-literature
Project description:Plastin 3 (PLS3) has been identified as a candidate gene for bone fragility in the Rotterdam study (RS) population. So far, however, whether PLS3 polymorphisms are genetic risk factors for osteoporosis in Asian population remains unclear. In order to investigate the association between genetic variants in PLS3 and the risk of fragility fracture and/or bone mineral density (BMD) in postmenopausal Chinese women, we conducted a case-control association study. A total of 1083 postmenopausal patients with osteoporotic fractures and 2578 unrelated non-fracture controls in Shanghai were enrolled. Seven SNPs, including six tagSNPs in PLS3 and one identified genetic risk factor (rs140121121) for osteoporosis in the RS population, were genotyped in all the participants. BMD at lumbar spine and hip sites were measured in 2578 controls. Association between SNPs and the risk of osteoporotic fractures and/or BMD were analyzed. The GC genotype of rs757124 and AC genotype of rs10521693 were associated with lumbar vertebral fracture (P = 0.020 and 0.046, respectively). The association between tagSNPs and BMD were analyzed only in 2546 controls to avoid biased conclusion. rs757124 was significantly associated with BMD at lumbar spine and hip sites. GG genotype had the highest BMD at lumbar spine (L1-4), while CC genotype had the highest BMD at hip sites. Our results suggest that polymorphisms in PLS3 are genetic loci for osteoporosis in postmenopausal Chinese women.
| S-EPMC6786434 | biostudies-literature
Project description: Not available
| S-EPMC2780487 | biostudies-literature
Project description:BackgroundOsteoporosis is highly polygenic and heritable, with heritability ranging from 50 to 80%; most inherited susceptibility is associated with the cumulative effect of many common genetic variants. However, existing genetic risk scores (GRS) only provide a few percent predictive power for osteoporotic fracture.MethodsWe derived and validated a novel genome-wide polygenic score (GPS) comprised of 103,155 common genetic variants to quantify this susceptibility and tested this GPS prediction ability in an independent dataset (n = 15,776).ResultsAmong postmenopausal women, we found a fivefold gradient in the risk of major osteoporotic fracture (MOF) (p < 0.001) and a 15.25-fold increased risk of severe osteoporosis (p < 0.001) across the GPS deciles. Compared with the remainder of the GPS distribution, the top GPS decile was associated with a 3.59-, 2.48-, 1.92-, and 1.58-fold increased risk of any fracture, MOF, hip fracture, and spine fracture, respectively. The top GPS decile also identified nearly twofold more high-risk osteoporotic patients than the top decile of conventional GRS based on 1103 conditionally independent genome-wide significant SNPs. Although the relative risk of severe osteoporosis for postmenopausal women at around 50 is relatively similar, the cumulative incident at 20-year follow-up is significantly different between the top GPS decile (13.7%) and the bottom decile (< 1%). In the subgroup analysis, the GPS transferability in non-Hispanic White is better than in other racial/ethnic groups.ConclusionsThis new method to quantify inherited susceptibility to osteoporosis and osteoporotic fracture affords new opportunities for clinical prevention and risk assessment.
| S-EPMC9933300 | biostudies-literature
Project description:AimA previous study shows that bone morphogenetic protein 7 (BMP7) gene polymorphisms are associated with bone mineral density (BMD) in 920 European Americans. To determine the association of BMP7 polymorphisms and BMD and osteoporotic fracture susceptibility, we performed a case-control association study in postmenopausal Chinese women with or without osteoporotic fracture.MethodsA total of 3815 unrelated postmenopausal Chinese women (1238 with osteoporotic fracture and 2577 healthy controls) were recruited. BMDs of the lumbar spine 1-4 (L1-4) and proximal femur (including total hip and femoral neck) were measured using dual-energy X-ray absorptiometry. Eight tagging single nucleotide polymorphisms (SNPs) in BMP7 gene, including rs11086598, rs4811822, rs12481628, rs6025447, rs230205, rs17404303, rs162316 and rs6127980, were genotyped.ResultsAmong the 8 SNPs, rs6025447 and rs230205 were associated with total hip BMD (P=0.013 and 0.045, respectively). However, the associations became statistically insignificant after adjusting for age, height and weight. The TGTG haplotype of BMP7 gene was associated with total hip BMD (P=0.032), even after adjusting for age, height and weight (P=0.048); but the association was insignificant after performing the Bonferroni multiple-significance-test correction. Moreover, the 8 SNPs and 9 haplotypes of BMP7 gene were not associated with L1-4 or femoral neck BMD or osteoporotic fracture.ConclusionThis large-sample case-control association study suggests that the common genetic polymorphisms of BMP7 gene are not major contributors to variations in BMD or osteoporotic fracture in postmenopausal Chinese women.
| S-EPMC4973379 | biostudies-literature
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
2015-06-26 | E-GEOD-60230 | biostudies-arrayexpress