Dataset Information

Abaloparatide for risk reduction of nonvertebral and vertebral fractures in postmenopausal women with osteoporosis: a network meta-analysis.

ABSTRACT: This network meta-analysis assessed the efficacy of abaloparatide versus other treatment options to reduce the risk of fractures in women with postmenopausal osteoporosis. The analysis indicates that abaloparatide reduces the risk of fractures in women with postmenopausal osteoporosis versus placebo and compared with other treatment options.

Introduction

This network meta-analysis (NMA) assessed the relative efficacy of abaloparatide versus other treatments to reduce the risk of fractures in women with postmenopausal osteoporosis (PMO).

Methods

PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials published before December 20, 2017, that included women with PMO who were eligible to receive interventions for primary or secondary fracture prevention. The NMA was conducted by fracture site (vertebral [VF], nonvertebral [NVF], and wrist), with the relative risk (RR) of fracture versus placebo the main clinical endpoint. The NMA used fixed-effects and random-effects approaches.

Results

A total of 4978 articles were screened, of which 22 were included in the analysis. Compared with other treatments, abaloparatide demonstrated the greatest treatment effect relative to placebo in the VF network (RR?=?0.13; 95% credible interval [CrI] 0.04-0.34), the NVF network (RR?=?0.50; 95% CrI 0.28-0.85), and the wrist fracture network (RR?=?0.39; CrI 0.15-0.90). Treatment ranking showed that abaloparatide had the highest estimated probability of preventing fractures in each of the networks (79% for VF, 70% for NVF, and 53% for wrist fracture) compared with other treatments. Individual networks demonstrated a good level of agreement with direct trial evidence and direct pair-wise comparisons.

Conclusions

This NMA indicates that abaloparatide reduces the RR of VF, NVF, and wrist fracture in women with PMO with or without prior fracture versus placebo, compared with other treatment options. Limitations include that adverse events and drug costs were not considered, and that generalizability is limited to the trial populations and endpoints included in the NMA.

SUBMITTER: Reginster J-

PROVIDER: S-EPMC6614166 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Abaloparatide for risk reduction of nonvertebral and vertebral fractures in postmenopausal women with osteoporosis: a network meta-analysis.

Reginster J -Y J- Bianic F F Campbell R R Martin M M Williams S A SA Fitzpatrick L A LA

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20190406 7

This network meta-analysis assessed the efficacy of abaloparatide versus other treatment options to reduce the risk of fractures in women with postmenopausal osteoporosis. The analysis indicates that abaloparatide reduces the risk of fractures in women with postmenopausal osteoporosis versus placebo and compared with other treatment options.<h4>Introduction</h4>This network meta-analysis (NMA) assessed the relative efficacy of abaloparatide versus other treatments to reduce the risk of fractures ...[more]

PMID: 30953114

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Project description:We evaluated the efficacy of abaloparatide in women who were at increased risk for fracture, based on CHMP recommended risk thresholds, at the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) study baseline. Among patients at high risk based on FRAX probabilities, 18 months of abaloparatide significantly decreased risk for all fracture endpoints compared with placebo.PurposeAbaloparatide, a novel anabolic agent for the treatment of postmenopausal osteoporosis, significantly reduced the risk of vertebral and nonvertebral fractures in the ACTIVE study compared with placebo. In this post hoc analysis, we evaluated abaloparatide's efficacy in a subset of women in the study at an increased risk of fracture at baseline, based on the Committee for Medicinal Products for Human Use (CHMP) recommended risk thresholds for inclusion in clinical trials.MethodsWomen with a baseline 10-year risk of major osteoporotic fracture ≥ 10% or hip fracture ≥ 5%, assessed using the FRAX® tool (including femoral neck bone mineral density), were included in the analysis. The proportion with one or more events of new morphometric vertebral fractures was calculated. Event rates for nonvertebral, major osteoporotic, and all clinical fractures were estimated using Kaplan-Meier analysis.ResultsFollowing 18 months of treatment, abaloparatide significantly reduced incident vertebral fractures compared with placebo (relative risk reduction = 91%; 0.5% versus 5.6%; p < 0.001). Abaloparatide treatment was also associated with significantly fewer nonvertebral, major osteoporotic, and clinical fractures compared with placebo: 2.7% versus 5.8%, p = 0.036; 1.3% versus 6.0%, p < 0.001; and 3.5% versus 8.2%, p = 0.006, respectively. The effect of abaloparatide on major osteoporotic fractures (78% reduction) was significantly greater than that seen with teriparatide (23% reduction, p = 0.007).ConclusionIn a subset of postmenopausal women at increased risk of fracture as judged by CHMP guidance, abaloparatide significantly decreased the risk of all fracture endpoints compared with placebo.

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:BackgroundTo investigate whether thoracolumbar kyphosis (TLK) of the spine is related to the reduction of bone mineral density (BMD) in postmenopausal osteoporosis women, and whether BMD of postmenopausal osteoporosis women can predict the occurrence of TLK.MethodsThis retrospective cohort study included 224 postmenopausal female patients hospitalized for osteoporosis from December 2017 to December 2020, and the control group included 270 postmenopausal female patients hospitalized for thoracolumbar degenerative diseases. The age, body mass index (BMI), visual analogue scale (VAS), and BMD of the lumbar spine [BMD(L)] and femoral neck [BMD(F)] of all patients during admission were recorded. We measured and recorded the Cobb angle of thoracolumbar and the height of the thoracolumbar intervertebral space in the spinal X-ray lateral radiograph. The Pearson and Spearman correlation coefficients were used to calculate the correlation between each parameter in the group. The Chi-square test was used for categorical variables, the independent-sample t-test was used for normally distributed continuous variables, and two-sample non-parametric tests were used for non-normally distributed variables. Binary logistic regression analysis and receiver operating characteristic (ROC) curves were applied to determine independent risk factors and cut-off values, respectively.ResultsThere were significant differences in the BMD(L), BMD(F), thoracolumbar junction Cobb angle, lumbar spine Cobb angle, T11/12-L1/2 height difference of the posterior and anterior edge of intervertebral space (HDPAIS), single vertebra Cobb angle (SVC), procollagen type 1 N-terminal propeptide (PINP) and 25-hydroxyvitamin D [25-(OH)D] between the study and control groups. Through binary logistic regression analysis, we found that BMD(L), PINP, bone alkaline phosphatase, and 25-(OH)D were independent risk factors for future TLK in postmenopausal women. According to the ROC curve, the prediction accuracy of BMD(L) was the highest. By calculating the critical value, we found that when the BMD(L) T-score <-1.65, postmenopausal women were more likely to develop TLK.ConclusionsIn postmenopausal osteoporosis patients, TLK will occur even if there is no compression fracture, and when the BMD(L) T-score <-1.65, postmenopausal women are more likely to develop TLK in the future.

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 rs9426C>T,TCN2 rs10418C>T, SLC19A1 rs1051296G>T, and SLC19A2 rs16862199C>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

Abaloparatide for risk reduction of nonvertebral and vertebral fractures in postmenopausal women with osteoporosis: a network meta-analysis.

Introduction

Methods

Results

Conclusions

Publications

Abaloparatide for risk reduction of nonvertebral and vertebral fractures in postmenopausal women with osteoporosis: a network meta-analysis.

Similar Datasets

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