Effect of abaloparatide on vertebral, nonvertebral, major osteoporotic, and clinical fractures in a subset of postmenopausal women at increased risk of fracture by FRAX probability.
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ABSTRACT:
SUBMITTER: McCloskey EV
PROVIDER: S-EPMC6373333 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
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Project description: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.IntroductionThis 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).MethodsPubMed®, 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.ResultsA 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.ConclusionsThis 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.
| S-EPMC6614166 | biostudies-literature
Project description:Although prior falls are a well-established predictor of future fracture, there is currently limited evidence regarding the specific value of falls history in fracture risk assessment relative to that of other clinical risk factors and bone mineral density (BMD) measurement. We therefore investigated, across the three Osteoporotic Fractures in Men (MrOS) Study cohorts, whether past falls predicted future fracture independently of FRAX and whether these associations varied with age and follow-up time. Elderly men were recruited from MrOS Sweden, Hong Kong, and USA. Baseline data included falls history (over the preceding 12 months), clinical risk factors, BMD at femoral neck, and calculated FRAX probabilities. An extension of Poisson regression was used to investigate the associations between falls, FRAX probability, and incident fracture, adjusting for age, time since baseline, and cohort in base models; further models were used to investigate interactions with age and follow-up time. Random-effects meta-analysis was used to synthesize the individual country associations. Information on falls and FRAX probability was available for 4365 men in USA (mean age 73.5 years; mean follow-up 10.8 years), 1823 men in Sweden (mean age 75.4 years; mean follow-up 8.7 years), and 1669 men in Hong Kong (mean age 72.4 years; mean follow-up 9.8 years). Rates of past falls were similar at 20%, 16%, and 15%, respectively. Across all cohorts, past falls predicted incident fracture at any site (hazard ratio [HR] = 1.69; 95% confidence interval [CI] 1.49, 1.90), major osteoporotic fracture (MOF) (HR = 1.56; 95% CI 1.33, 1.83), and hip fracture (HR = 1.61; 95% CI 1.27, 2.05). Relationships between past falls and incident fracture remained robust after adjustment for FRAX probability: adjusted HR (95% CI) any fracture: 1.63 (1.45, 1.83); MOF: 1.51 (1.32, 1.73); and hip: 1.54 (1.21, 1.95). In conclusion, past falls predicted incident fracture independently of FRAX probability, confirming the potential value of falls history in fracture risk assessment. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
| S-EPMC5842893 | biostudies-literature
Project description:BackgroundBecause of aging of population, osteoporotic vertebral compression fracture (OVCF) appears an increasing incidence rate. Conservative therapy (CT) and balloon kyphoplasty (BKP) have been used to treat OVCFs. However, an increase in new vertebral compression fractures at nontreated levels following BKP is of concern. It is still not clear whether new fractures were a result of BKP and the purpose of this meta-analysis was to evaluate the new fractures risk after BKP compared with CT.MethodsAn exhaustive literature search of PubMed, EMBASE, and the Cochrane Library was conducted to identify randomized controlled trials and prospective nonrandomized controlled study that compared BKP with CT for patients suffering OVCF. A random-effect model was used. Results were reported as standardized mean difference or risk ratio with 95% confidence interval.ResultsTwelve studies were included and there was no significant difference in total new fractures (P = .33) and adjacent fractures (P = .83) between 2 treatments. Subgroup analyses did not demonstrate significant differences in follow-up period, mean age, anti-osteoporosis therapy, and the proportion of women.ConclusionOur systematic review revealed that an increased risk of fracture of vertebral bodies was not associated with BKP compared with CT.
| S-EPMC6200511 | biostudies-literature
Project description:The risk of a recurrent fragility fracture is particularly high immediately following the fracture. This study provides adjustments to FRAX-based fracture probabilities accounting for the site of a recent fracture.IntroductionThe recency of prior fractures affects subsequent fracture risk. The aim of this study was to quantify the effect of a recent sentinel fracture, by site, on the 10-year probability of fracture determined with FRAX.MethodsThe study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large sample of the population of Iceland. Fracture probabilities were determined after a sentinel fracture (humeral, clinical vertebral, forearm and hip fracture) from the hazards of death and fracture. Fracture probabilities were computed on the one hand for sentinel fractures occurring within the previous 2 years and on the other hand, probabilities for a prior osteoporotic fracture irrespective of recency. The probability ratios provided adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures.ResultsProbability ratios to adjust 10-year FRAX probabilities of a major osteoporotic fracture for recent sentinel fractures were age dependent, decreasing with age in both men and women. Probability ratios varied according to the site of sentinel fracture with higher ratios for hip and vertebral fracture than for humerus or forearm fracture. Probability ratios to adjust 10-year FRAX probabilities of a hip fracture for recent sentinel fractures were also age dependent, decreasing with age in both men and women with the exception of forearm fractures.ConclusionThe probability ratios provide adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures.
| S-EPMC7116089 | biostudies-literature
Project description:BACKGROUND:Due to its unique mechanical characteristics, the incidence of subsequent fracture after vertebral augmentation is higher in thoracolumbar segment, but the causes have not been fully elucidated. This study aimed to comprehensively explore the potential risk factors for subsequent fracture in this region. METHODS:Patients with osteoporotic vertebral fracture in thoracolumbar segment who received vertebral augmentation from January 2019 to December 2020 were retrospectively reviewed. Patients were divided into refracture group and non-refracture group according to the occurrence of refracture. The clinical information, imaging findings (cement distribution, spine sagittal parameters, degree of paraspinal muscle degeneration) and surgery related indicators of the included patients were collected and compared. RESULTS:A total of 109 patients were included, 13 patients in refracture group and 96 patients in non-refracture group. Univariate analysis revealed a significantly higher incidence of previous fracture, intravertebral cleft (IVC) and cement leakage, greater fatty infiltration of psoas (FIPS), fatty infiltration of erector spinae plus multifidus (FIES + MF), correction of body angle (BA), BA restoration rate and vertebral height restoration rate in refracture group. Further binary logistic regression analysis demonstrated previous fracture, IVC, FIPS and BA restoration rate were independent risk factors for subsequent fracture. According to ROC curve analysis, the prediction accuracy of BA restoration rate was the highest (area under the curve was 0.794), and the threshold value was 0.350. CONCLUSIONS:Subsequent fracture might cause by the interplay of multiple risk factors. The previous fracture, IVC, FIPS and BA restoration rate were identified as independent risk factors. When the BA restoration rate exceeded 0.350, refractures were more likely to occur.
| S-EPMC8670201 | biostudies-literature
Project description:Background and purpose - Patients with osteoporosis who present with an acute onset of back pain often have multiple fractures on plain radiographs. Differentiation of an acute osteoporotic vertebral fracture (AOVF) from previous fractures is difficult. The aim of this study was to investigate the incidence of concomitant AOVFs and previous OVFs in patients with symptomatic AOVFs, and to identify risk factors for concomitant AOVFs. Patients and methods - This was a prospective epidemiological study based on the Registry of Pathological Osteoporotic Vertebral Fractures (REPAPORA) with 1,005 patients and 2,874 osteoporotic vertebral fractures, which has been running since February 1, 2006. Concomitant fractures are defined as at least 2 acute short-tau inversion recovery (STIR-) positive vertebral fractures that happen concomitantly. A previous fracture is a STIR-negative fracture at the time of initial diagnostics. Logistic regression was used to examine the influence of various variables on the incidence of concomitant fractures. Results - More than 99% of osteoporotic vertebral fractures occurred in the thoracic and lumbar spine. The incidence of concomitant fractures at the time of first patient contact was 26% and that of previous fractures was 60%. The odds ratio (OR) for concomitant fractures decreased with a higher number of previous fractures (OR =0.86; p = 0.03) and higher dual-energy X-ray absorptiometry T-score (OR =0.72; p = 0.003). Interpretation - Concomitant and previous osteoporotic vertebral fractures are common. Risk factors for concomitant fractures are a low T-score and a low number of previous vertebral fractures in cases of osteoporotic vertebral fracture. An MRI scan of the the complete thoracic and lumbar spine with STIR sequence reduces the risk of under-diagnosis and under-treatment.
| S-EPMC5385115 | biostudies-literature
Project description:Vertebral fractures account for ~27% of all osteoporotic fractures in both men and women. The economic burden is substantial and growing: osteoporosis is expected to affect 14 million people by the year 2020. There is substantial morbidity associated with osteoporotic vertebral compression fractures (VCFs) including decreased quality of life, reduced pulmonary function, and increased mortality. Relatively recent additions to the treatment armamentarium include vertebral augmentation using vertebroplasty and kyphoplasty. Numerous retrospective and case studies demonstrate short-term efficacy and low complication rates of vertebroplasty and kyphoplasty in the treatment of osteoporotic VCFs, but controlled trials are needed for validation. The pathophysiology, risk factors, consequences, characteristics, and imaging of osteoporotic VCFs are presented in detail along with a discussion of treatment options and patient selection. Vertebral augmentation is comprehensively reviewed, including the technical aspects of the procedures, contraindications, complications, and clinical outcomes.
| S-EPMC3036532 | biostudies-other
Project description:UNLABELLED:Daily teriparatide injections have been shown to reduce vertebral and non-vertebral fractures. Here, we demonstrate that the magnitude of fracture risk reduction is independent of baseline fracture probability assessed by FRAX. INTRODUCTION:Daily administration of 20 or 40 ?g teriparatide has been shown to significantly decrease the risk of vertebral and non-vertebral fracture compared with placebo. The aim of the present study was to evaluate fracture risk assessed at baseline using the FRAX® tool and to determine the efficacy of teriparatide as a function of baseline fracture risk. METHODS:One thousand six hundred thirty-seven postmenopausal women in the pivotal phase three trial, randomly assigned to receive placebo (n?=?544), teriparatide 20 ?g per day (n?=?541) or teriparatide 40 ?g per day (n?=?552), were studied. Baseline clinical risk factors were entered into country-specific FRAX models to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. Because there was no difference in effect of 20 and 40 ?g teriparatide daily on fracture occurrence, the two active groups were merged. The interaction between probability of a major fracture and treatment efficacy was examined by Poisson regression. RESULTS:The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.2-67.2 %. Treatment with teriparatide was associated with a 37 % decrease in all non-vertebral fractures (95 % CI 10-56 %) and a 56 % decrease in low-energy non-vertebral fractures (95 % CI 24-75 %) compared with placebo. The risk of morphometric vertebral fractures decreased significantly by 66 % (95 % CI 50-77 %). Hazard ratios for the effect of teriparatide on the fracture outcome did not change significantly with increasing fracture probability (p?>?0.30). Similar findings were noted for the interaction when BMD was excluded from the FRAX model, or when probability of hip fracture was used as the marker of baseline risk. CONCLUSION:We conclude that teriparatide significantly decreases the risk of non-vertebral and morphometric vertebral fractures in women by a similar extent, irrespective of baseline fracture probability.
| S-EPMC4913866 | biostudies-literature
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:ObjectiveTo evaluate the association between Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD) and risk for major osteoporotic fractures (MOF) in type 1 diabetes.MethodsSubjects with type 1 diabetes and without diabetes from the 'Coronary Artery Calcification in Type 1 Diabetes' study were included. Risk for MOF was calculated using FRAX-based clinical risk factors and without BMD at visit 3 (2006-2008). Incident fractures were defined as fractures that occurred between visit 3 and visit 4 (2013-2017). Survival models were used to study the predictability of new MOF by diabetes status.Results346 type 1 diabetes (mean age 43.3 ± 9, BMI 26.4 ± 5, diabetes duration 29.4 ± 8.6 years, A1c 7.8 ± 1.1) and 411 controls (mean age 46.9 ± 9 years, BMI 26.3 ± 5 kg/m2, A1c 5.5 ± 0.4) were analyzed in this study. In unadjusted survival analysis, the FRAX score without BMD was significantly associated with MOF (HR 1.08, 95% CI: 1.04-1.13, p < 0.0001), and remained significantly associated after adjustment for age and sex (HR 1.09, 95% CI: 1.04-1.15, p = 0.0007) and type 1 diabetes (HR 1.08, 95% CI: 1.04-1.12, p = 0.0002). In the fully adjusted model (adjusted for age, sex and type 1 diabetes), the FRAX score without BMD was the only variable significantly associated with risk of MOF (HR 1.08, 95% CI: 1.02-1.14, p = 0.006).ConclusionClinical use of FRAX without BMD is useful tool in identifying adults with type 1 diabetes at higher risk for MOF risk and may help clinicians to guide therapeutic decision-making in this high fracture risk population.
| S-EPMC7770010 | biostudies-literature