Dataset Information

Comparative Efficacy of Bisphosphonates to Prevent Fracture in Men with Osteoporosis: A Systematic Review with Network Meta-Analyses.

ABSTRACT:

Introduction

Osteoporosis is an under-recognized problem threatening men. Bisphosphonates are the main treatment but their comparative efficacy is unclear for men with osteoporosis. Therefore, we performed this systematic review with network meta-analyses to summarize the evidence of comparative efficacy of bisphosphonates in men with osteoporosis.

Methods

We completed network meta-analyses with a frequentist model to compare the efficacy of different bisphosphonates. Randomized controlled trials investigating bisphosphonates used in men with osteoporosis were included. The primary outcome was the rate of patients with a new vertebral fracture. The secondary outcome was the rate of patients with a non-vertebral fracture, which was defined as any fractures reported other than vertebral fractures. Pairwise meta-analyses were performed to compare bisphosphonates with placebo. We included open-label studies in the analyses as a sensitivity analysis.

Results

Ten trials were included, using alendronate, ibandronate, risedronate, and zoledronic acid. No significant difference was found between any pairs of alendronate, ibandronate, risedronate, and zoledronic acid for both vertebral and non-vertebral fractures. Zoledronic acid ranked as the most effective in preventing vertebral fracture in primary osteoporosis. Risedronate ranked best in preventing non-vertebral fracture in both primary osteoporosis and corticosteroid-induced osteoporosis. In the sensitivity analyses with the open-label studies, the ranking order did not change.

Conclusion

The current evidence for bisphosphonates used in men with osteoporosis is inadequate. On the basis of the current evidence, zoledronic acid is most effective at preventing vertebral fractures, while risedronate has the highest possibility to rank the first in preventing non-vertebral fracture in men with primary osteoporosis and corticosteroid-induced osteoporosis. More well-designed studies are needed to test our findings and to better know the comparative efficacy of bisphosphonate to prevent vertebral fracture in men with osteoporosis.

SUBMITTER: Zhou J

PROVIDER: S-EPMC4999580 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

Comparative Efficacy of Bisphosphonates to Prevent Fracture in Men with Osteoporosis: A Systematic Review with Network Meta-Analyses.

Zhou Junwen J Wang Tiansheng T Zhao Xilan X Miller Donald R DR Zhai Suodi S

Rheumatology and therapy 20160422 1

<h4>Introduction</h4>Osteoporosis is an under-recognized problem threatening men. Bisphosphonates are the main treatment but their comparative efficacy is unclear for men with osteoporosis. Therefore, we performed this systematic review with network meta-analyses to summarize the evidence of comparative efficacy of bisphosphonates in men with osteoporosis.<h4>Methods</h4>We completed network meta-analyses with a frequentist model to compare the efficacy of different bisphosphonates. Randomized c ...[more]

PMID: 27747517

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Project description:ObjectiveTo compare the efficacy of bazedoxifene and oral bisphosphonates for the prevention of nonvertebral fractures (NVFs) in women with higher risk of postmenopausal osteoporosis (i.e., the Fracture Risk Assessment Tool [FRAX] score ≥ 20%), based on currently available evidence from randomized controlled trials.MethodsRandomized controlled trials evaluating the NVF relative risk reduction (RRR) with oral bisphosphonates or bazedoxifene were identified by a systematic literature review and combined by means of a network meta-analysis. A subgroup of patients with a FRAX score of 20% or more in the bazedoxifene phase III osteoporosis study was selected as the population of interest on the basis of the bazedoxifene label. In one analysis (analysis 1), the placebo response of the subgroup with a FRAX score of 20% or more was the benchmark to select comparable bisphosphonate trials. Additional analyses incorporated the aggregate data from the bisphosphonate trials with all the FRAX subgroups (analysis 2) or with the individual patient data from the bazedoxifene trial (analysis 3).ResultsNine identified bisphosphonate trials (alendronate, ibandronate, risedronate; N = 23,440 patients) with a similar placebo response as observed for the subgroup of high risk patients in the bazedoxifene trial were included in analysis 1. The results of the network meta-analysis of this study set suggest that bazedoxifene is expected to have an RRR of 0.43 (95% credible interval [CrI] -0.19 to 0.72) versus alendronate, 0.58 (95% CrI 0.05-0.81) versus ibandronate, and 0.39 (95% CrI -0.29 to 0.70) versus risedronate. Analyses in which treatment effects with bisphosphonates were projected to a population with a FRAX score of 20% or more with meta-regression approaches (analysis 2 and analysis 3) provide similar findings.ConclusionBased on an indirect comparison of randomized trials, bazedoxifene is expected to have at least a comparable RRR of NVF as alendronate, ibandronate, and risedronate in women with higher risk of postmenopausal osteoporosis.

Project description:ObjectivesTo evaluate the efficacy of treatment options to reduce osteoporotic fracture risk in men.DesignSystematic review and meta-analysis.SettingRandomized clinical trials that evaluated the efficacy of a treatment for osteoporosis or low bone mineral density for adult men and reported fracture outcomes.ParticipantsMen.MeasurementsPubMed, Embase, and the Cochrane Library databases were searched for relevant studies. Information was extracted from included studies on participant sociodemographic characteristics, number of male participants, treatment evaluated, comparator for evaluated treatment, study duration, and fracture outcomes. Risk of bias of individual studies was assessed using measures recommended by the Cochrane Collaboration.ResultsTwenty-four articles reporting results for 22 studies (including 4,868 male participants) met strict inclusion criteria. Fixed-effects meta-analyses using the Mantel-Haenszel method demonstrated significantly lower risk of vertebral fractures with alendronate (relative risk (RR) = 0.328, 95% confidence interval (CI) = 0.155-0.692) and risedronate (RR = 0.428, 95% CI = 0.245-0.746) but not with calcitonin (RR = 0.272, 95% CI = 0.046-1.608) or denosumab (RR = 0.256, 95% CI = 0.029-2.238) than in controls. For bisphosphonates as a treatment category, meta-analyses demonstrated significantly lower risk of vertebral fractures (RR = 0.368, 95% CI = 0.252-0.537) and nonvertebral fractures (RR = 0.604, 95% CI = 0.404-0.904) than in controls. The meta-analysis finding that bisphosphonates significantly reduce nonvertebral fracture risk was not robust to sensitivity analysis.ConclusionBisphosphonates reduce the risk of vertebral and possibly nonvertebral fractures for men with osteoporosis. Further studies are needed to evaluate the efficacy of bisphosphonates for reducing nonvertebral fracture risk and the efficacy of nonbisphosphonates for reducing vertebral and nonvertebral fracture risk in men with osteoporosis.

Project description:Frailty is common in older adults with fractures. Osteoporosis medications reduce subsequent fracture, but limited data exist on medication efficacy in frail individuals. Our objective was to determine whether medications reduce the risk of subsequent fracture in frail, older adults. A retrospective cohort of Medicare fee-for-service beneficiaries was conducted (2014-2016). We included adults aged ≥65 years who were hospitalized with fractures without osteoporosis treatment. Pre-fracture frailty was defined using claims-based frailty index (≥0.2 = frail). Exposure to any osteoporosis treatment (oral or intravenous bisphosphonates, denosumab, and teriparatide) was ascertained using Part B and D claims and categorized according to the cumulative duration of exposure: none, 1-90 days, and >90 days. Subsequent fractures were ascertained from Part A or B claims. Cause-specific hazard models with time-varying exposure were fit to examine the association between treatment and fracture outcomes, controlling for relevant covariates. Among 29,904 patients hospitalized with fractures, 15,345 (51.3%) were frail, and 2148 (7.2%) received osteoporosis treatment (median treatment duration 183.0 days). Patients who received treatment were younger (80.2 versus 82.2 years), female (86.5% versus 73.0%), and less frail (0.20 versus 0.22) than patients without treatment. During follow-up, 5079 (17.0%) patients experienced a subsequent fracture. Treatment with osteoporosis medications for >90 days compared with no treatment reduced the risk of fracture (hazard ratio [HR] = 0.82; 95% confidence interval [CI] 0.68-1.00) overall. Results were similar in frail (HR = 0.85; 95% CI 0.65-1.12) and non-frail (HR = 0.80; 95% CI 0.61-1.04) patients but not significant. In conclusion, osteoporosis treatment >90 days was associated with similar trends in reduced risk of subsequent fracture in frail and non-frail persons. Treatment rates were very low, particularly among the frail. When weighing treatment options in frail older adults with hospitalized fractures, clinicians should be aware that drug therapy does not appear to lose its efficacy. © 2022 American Society for Bone and Mineral Research (ASBMR).

Project description:Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis.We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value.With respect to preventing new vertebral fractures (NVF), all ten drugs outperformed placebo, and etidronate proved to be the most effective treatment (OR 0.24, 95% CI 0.14 to 0.39). In addition, zoledronic acid and parathyroid hormone ranked higher compared with the other drugs. With respect to preventing clinical vertebral fractures (CVF), zoledronic acid proved to be the most effective drug (OR = 0.25, 95% CI 0.08 to 0.92), with denosumab as a desirable second option (OR = 0.48, 95% CI 0.22 to 0.96), when both were compared with placebo. As for adverse events (AE) and severe adverse events (SAE), no significant difference was observed. According to SUCRA, etidronate ranked first in preventing CVF; parathyroid hormone and zoledronic acid ranked highly in preventing NVF and CVF. Raloxifene was safe with a high rank in preventing AEs and SAEs though performed unsatisfactorily in efficacy.This study suggests that, taking efficacy and safety into account, parathyroid hormone and zoledronic acid had the highest probability of satisfactory performance in preventing osteoporotic fractures.Cite this article: G. Wang, L. Sui, P. Gai, G. Li, X. Qi, X. Jiang. The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment: Which therapies work best? a network meta-analysis. Bone Joint Res 2017;6:452-463. DOI: 10.1302/2046-3758.67.BJR-2016-0292.R1.

Project description:IntroductionOsteoporosis (OP) is a prevalent skeletal disease with high mortality and morbidity, followed by acute and chronic back pain, severe spinal deformity and dysfunction. First-line drugs for OP work through antiresorptive or anabolic mechanisms. Although with good efficacy, these drugs still have certain limitations in clinical application due to delivery routes, medication cycles and cost issues. Nowadays, statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) appear to be potentially promising drugs for OP. Despite the controversy, previous studies have shown the efficacy of statins in treating OP. Other studies have further indicated that the therapeutic effect of OP in statin-treated patients is dose dependent. However, scientists have not yet reached a consensus on the use of statins for the treatment or which statin to choose first. This study aims to review the literature, ascertaining the relative efficacy and safety of statins for patients with OP using a Bayesian network meta-analysis.Methods and analysisWe will systematically search the following databases: MEDLINE, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, Chinese BioMedical Literature Database and preprint servers to include randomised controlled trials that compare different statins for treating OP. Primary outcomes are the incidence of overall fractures and bone mineral density changes. Secondary outcomes contain adverse effects and bone turnover markers. All items of this review will comply with the Cochrane Handbook, and the quality of evidence will be evaluated by Grading of Recommendations Assessment, Development and Evaluation. A traditional pairwise meta-analysis and the Bayesian network meta-analysis will be performed to compare the efficacy of different statins.Ethics and disseminationEthical approval is not required since this is a protocol study for meta-analyses. Results will be submitted to a peer-reviewed journal.Prospero registration numberCRD42021242619.Search datesFrom database inception to February 2022.

Dataset Information

Comparative Efficacy of Bisphosphonates to Prevent Fracture in Men with Osteoporosis: A Systematic Review with Network Meta-Analyses.

Introduction

Methods

Results

Conclusion

Publications

Comparative Efficacy of Bisphosphonates to Prevent Fracture in Men with Osteoporosis: A Systematic Review with Network Meta-Analyses.

Similar Datasets

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