Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Watts NB
PROVIDER: S-EPMC6546661 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
Publications
Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis.
Watts N B NB Hattersley G G Fitzpatrick L A LA Wang Y Y Williams G C GC Miller P D PD Cosman F F
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20190321 6
<h4>Purpose</h4>Wrist fractures are common, contribute significantly to morbidity in women with postmenopausal osteoporosis, and occur predominantly at the ultradistal radius, a site rich in trabecular bone. This exploratory analysis of the phase 3 ACTIVE study evaluated effects of abaloparatide versus placebo and teriparatide on forearm bone mineral density (BMD) and risk of wrist fracture.<h4>Methods</h4>Forearm BMD was measured by dual energy X-ray absorptiometry in a subset of 982 women from ...[more]
Similar Datasets
Project description:Abaloparatide increased ultradistal radius bone mineral density (BMD) in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. Over the subsequent 24 months in ACTIVExtend, ultradistal radius BMD gains were maintained with alendronate. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE.IntroductionAbaloparatide (ABL) increased femoral neck, total hip, and lumbar spine bone mineral density (BMD) in postmenopausal women with osteoporosis and decreased the risk of vertebral and nonvertebral fractures in ACTIVE. Effects on fracture risk and BMD were maintained subsequently with alendronate (ALN) in ACTIVExtend. In a prespecified subanalysis of ACTIVE, ABL also increased BMD at the ultradistal radius. Our objective was to determine the efficacy of ABL followed by ALN vs placebo (PBO) followed by ALN on forearm BMD and fracture risk over 43 months in ACTIVExtend.MethodsUltradistal and 1/3 radius BMD (ACTIVE baseline to month 43) were measured (ABL/ALN, n?=?213; PBO/ALN, n?=?233). Wrist fracture rates were estimated for the ACTIVExtend intent-to-treat population (ABL/ALN, n?=?558; PBO/ALN, n?=?581) by Kaplan-Meier (KM) method.ResultsAt cumulative month 25, mean increase from ACTIVE baseline in ultradistal radius BMD was 1.1% (standard error, 0.49%) with ABL/ALN vs -?0.8% (0.43%) with PBO/ALN (P?<?0.01). BMD increases with ABL were maintained with ALN through month 43 in ACTIVExtend. BMD decreases at the 1/3 radius in ACTIVE (similar with ABL and PBO) were maintained through 24 months of ALN treatment in ACTIVExtend. Wrist fractures over 43 months occurred in 15 women with ABL/ALN (KM estimate, 2.8%) and 20 with PBO/ALN (KM estimate, 3.6%) (HR?=?0.77, 95% CI 0.39, 1.50; P?=?not significant).ConclusionUltradistal radius BMD gains following treatment with ABL in ACTIVE were maintained over 24 months of ALN treatment in ACTIVExtend. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE.Trial registrationClinicalTrials.gov : NCT01657162 submitted July 31, 2012.
| S-EPMC7755646 | biostudies-literature
Project description:Background and objectiveAbaloparatide, an anabolic osteoporosis treatment administered by subcutaneous (SC) injection, increases bone mineral density (BMD) and reduces fracture risk in postmenopausal women with osteoporosis. The abaloparatide-solid Microstructured Transdermal System [abaloparatide-sMTS (Kindeva, St Paul, MN, USA)], which delivers abaloparatide intradermally, is in development to provide an alternative method for abaloparatide delivery. The objective of this study was to evaluate the ability of subjects to self-administer abaloparatide-sMTS, based on pharmacokinetic and pharmacodynamic markers.MethodsIn this single-arm, open-label, Phase 1b study, 22 healthy postmenopausal women aged 50-85 years with low BMD were trained to self-administer abaloparatide-sMTS 300 μg once daily to the thigh for 5 min for 29 days. The primary endpoint was systemic exposure to abaloparatide. Secondary endpoints included percent change from baseline in serum procollagen type I N-terminal propeptide (s-PINP), patient experience, and safety.ResultsAll 22 subjects completed the study. At baseline, mean age was 65.2 years, mean total hip T-score was - 1.32, and mean lumbar spine T-score was - 1.98. On Day 1, the median time to reach maximum concentration (Tmax) for abaloparatide-sMTS was 0.33 h and geometric mean (CV %) maximum concentration (Cmax) and area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-t) were 447 (38.0) pg/mL and 678 (45.3) pg·h/mL, respectively; the pharmacokinetic profile was similar on Days 15 and 29. Median percentage change in s-PINP was 45.4% and 64.4% at Days 15 and 29, respectively. The most common adverse events (AEs) were application site erythema, pain, and swelling, which were mostly of mild or moderate severity. No AEs led to study drug withdrawal and no serious AEs were reported. The success rate for self-administration at first application was 99.7%, and subject acceptability was high (~ 4.5 on a 5-point Likert Scale).ConclusionsSubjects successfully self-administered abaloparatide-sMTS, which provided a consistent pharmacokinetic profile over 29 days and produced s-PINP increases from baseline similar to that observed in the pivotal trial with abaloparatide-SC. Observed patient experience along with the clinical data support continued clinical development of abaloparatide-sMTS.Trial registration numberNCT04366726, Date of registration 04/29/2020, retrospectively registered.
| S-EPMC7946681 | biostudies-literature
Project description:ContextThe ACTIVE study demonstrated the antifracture efficacy of abaloparatide in postmenopausal women with osteoporosis. ACTIVExtend demonstrated sustained fracture risk reduction with alendronate in abaloparatide-treated participants from ACTIVE. A direct comparison of the efficacy of abaloparatide and antiresorptive therapies has not been performed.ObjectiveThe objective of this analysis is to compare the antifracture efficacy of abaloparatide in ACTIVE with that of alendronate in ACTIVExtend.DesignIn this post hoc analysis, the rate of new vertebral fractures for women in ACTIVExtend (N = 1139) was calculated based on baseline and endpoint radiographs for placebo or abaloparatide in ACTIVE and alendronate in ACTIVExtend. Vertebral fracture rates between abaloparatide and alendronate were compared in a Poisson regression model. Fracture rates for nonvertebral and clinical fractures were compared based on a Poisson model during 18 months of abaloparatide or placebo treatment in ACTIVE and 18 months of alendronate treatment in ACTIVExtend.ResultsThe vertebral fracture rate was lower during abaloparatide treatment in ACTIVE (0.47 fractures/100 patient-years) than alendronate treatment in ACTIVExtend (1.66 fractures/100 patient-years) (relative risk reduction 71%; P = .027). Although the comparisons did not meet statistical significance, after switching from placebo (ACTIVE) to alendronate (ACTIVExtend), the rate of new vertebral fractures decreased from 2.49 to 1.66 fractures per 100 patient-years, and after switching from abaloparatide to alendronate from 0.47 to 0.19 fractures per 100 patient-years. The rates of nonvertebral fractures and clinical fractures were not significantly different.ConclusionInitial treatment with abaloparatide may result in greater vertebral fracture reduction compared with alendronate in postmenopausal women with osteoporosis.
| S-EPMC7112966 | biostudies-literature
Project description:Denosumab, a human monoclonal antibody, acts against the receptor activator of nuclear factor-κB ligand and is a promising antiresorptive agent in patients with osteoporosis. This study aimed to update the efficacy and safety of denosumab vs. placebo in osteoporosis or low bone mineral density (BMD) postmenopausal women. PubMed, Embase, Cochrane library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) reporting the efficacy and safety data of denosumab vs. placebo in osteoporosis or low BMD postmenopausal women. A random-effects model was used to calculate pooled weight mean differences (WMDs) or relative risks (RRs) with corresponding 95% confidence intervals (CIs) for treatment effectiveness of denosumab vs. placebo. Eleven RCTs including 12,013 postmenopausal women with osteoporosis or low BMD were preferred for the final meta-analysis. The summary results indicated that the percentage change of BMD in the denosumab group was greater than that of BMD in placebo at 1/3 radius (WMD: 3.43; 95%CI: 3.24-3.62; p < 0.001), femoral neck (WMD: 3.05; 95%CI: 1.78-4.33; p < 0.001), lumbar spine (WMD: 6.25; 95%CI: 4.59-7.92; p < 0.001), total hip (WMD: 4.36; 95%CI: 4.07-4.66; p < 0.001), trochanter (WMD: 6.00; 95%CI: 5.95-6.05; p < 0.001), and total body (WMD: 3.20; 95%CI: 2.03-4.38; p < 0.001). Moreover, denosumab therapy significantly reduced the risk of clinical fractures (RR: 0.57; 95%CI: 0.51-0.63; p < 0.001), nonvertebral fracture (RR: 0.83; 95%CI: 0.70-0.97; p = 0.018), vertebral fracture (RR: 0.32; 95%CI: 0.25-0.40; p < 0.001), and hip fracture (RR: 0.61; 95%CI: 0.37-0.98; p = 0.042). Finally, denosumab did not cause excess risks of adverse events. These findings suggested that postmenopausal women receiving denosumab had increased BMDs and reduced fractures at various sites without inducing any adverse events.
| S-EPMC8080120 | biostudies-literature
Project description:Osteoporosis is a multifactorial disease in which genetic determinants are modulated by hormonal, environmental and nutritional factors. An important clinical risk factor in the pathogenesis of osteoporosis is the presence of genetics polymorphism in/around susceptibility genes/regions. This study explored whether the region of 4q22.1, which confers risk of developing osteoporosis in some populations, associated with bone mineral density and osteoporosis susceptibility in postmenopausal women of Han Chinese. We investigated 32 SNPs with minor allele frequencies ?0.05 between 20 kb upstream and 20 kb downstream (40 kb window) of rs6532023, mapping in the 4q22.1 region, which was reported to be significantly associated with osteoporosis in previous studies. We found that rs6532023 was significantly associated with bone mineral density and osteoporosis (corrected p?=?0.015) in our sample, including 440 cases and 640 controls, and allele G was supposed as a risk factor while T worked as a protective factor. Further genotype association analyses suggested a similar pattern (corrected p?=?0.040). Additionally, analyses by haplotypes indicated that a haplotype block rs7683315-rs6532023-rs1471400-rs1471403 in the region associated with bone mineral density and osteoporosis (global p?=?0.032), and risk haplotype A-G-G-C had almost 1.5-fold increased in the cases. To our knowledge, this is the first report to examine 4q22.1 region polymorphisms and osteoporosis in Han Chinese. Our results provide further evidence for an effect of the region of 4q22.1 on the etiology of osteoporosis and suggest that 4q22.1 may be a genetic risk factor for bone mineral density and osteoporosis.
| S-EPMC3836996 | biostudies-literature
Project description:BACKGROUND:The study investigated the associations of rs9340799:A?>?G (XbaI) and rs2234693:T?>?C (PvuII) polymorphisms in the estrogen receptor 1 gene (ESR1) with femoral neck (BMD-FN) and lumbar spine bone mineral density (BMD-LS), biochemical markers of bone turnover, calcium and phosphate levels, fracture prevalence, and a response to two types of anti-osteoporotic therapy in postmenopausal women from southern Slovakia. METHODS:We analysed 343 postmenopausal Slovak women (62.40?±?0.46 years). The influence of rs9340799 (AA vs. AG?+?GG) and rs2234693 (TT vs. TC?+?CC) genotypes on BMD and biochemical markers was evaluated by covariance analysis adjusted for age and BMI. Binary logistic regression was used to evaluate the genotype effect on fracture prevalence. Pharmacogenetic part of the study included women who received a regular therapy of HT (17ß estradiol with progesterone; 1 mg/day for both; N?=?76) or SERMs/raloxifene (60 mg/day; N?=?64) during 48 months. The genotype-based BMD change was assessed by variance analysis for repeated measurements. RESULTS:Women with AA genotype of rs9340799 had higher BMD-FN (+?0.12?±?0.57 of T-score) and BMD-LS (+?0.17?±?0.08 of T-score) in comparison with AG?+?GG. The rs2234693 polymorphism did not affect any of the monitored parameters. No effect of any ESR1 polymorphisms was found on fracture prevalence. Both types of anti-osteoporotic therapy had a positive effect on BMD improvement in FN and LS sites. Considering the effect of the ESR1 gene within the HT, the subjects with rs9340799/AA genotype showed worse response than those with GG genotype (-?0.26?±?0.10 of BMD-FN T-score; -?0.35?±?0.10 of BMD-LS T-score) and also with AG genotype (-?0.22?±?0.08 of BMD-LS T-score). The rs2234693/TT genotype responded poorer in BMD-LS in comparison with TC (-?0.22?±?0.08 of T-score) and CC (-?0.35?±?0.09 of T-score). The effect of the ESR1 gene on raloxifene therapy was reported only in BMD-LS. Subjects with rs9340799/AA genotype had a?-?0.30?±?0.11 of T-score worse response compared to AG genotype. The rs2234693/TT genotype showed -?0.39?±?0.11 and?-?0.46?±?0.15 lower T-scores in comparison with TC and CC genotypes, respectively. CONCLUSIONS:The rs9340799 polymorphism may contribute to decreased BMD in postmenopausal women from southern Slovakia; however, this is not related to higher fracture prevalence. Concurrently, both polymorphisms affected a response to analysed anti-osteoporotic therapies.
| S-EPMC6150952 | biostudies-literature
Project description:Growing evidence indicates that the vitamin D receptor (VDR) gene is an important candidate gene for influencing the development of osteoporosis. The aim of the study was to evaluate the potential association between genetic variants of VDR gene and bone mineral density (BMD) and osteoporosis in Chinese postmenopausal women. The study included 970 Chinese postmenopausal women at the postmenopausal osteoporosis (482) and healthy controls (488). The BMD of lumbar spine (L(2-4) anterior-posterior view), femoral neck hip, and total hip was evaluated using the Norland XR-46 dual energy X-ray absorptiometry (DEXA). The genotypes of VDR genetic variants were determined by the created restriction site-PCR (CRS-PCR) and confirmed by DNA sequencing methods. Our data indicated that the VDR p.Glicine (Gly)14 alanine (Ala) and p.histidine (His) 305 glutanine (Gln) genetic variants were statistically associated with adjusted femoral neck hip BMD, adjusted lumbar spine BMD, and adjusted total hip BMD (P values < 0.05). Results from this study suggest that the VDR p.Gly14Ala and p.His305Gln genetic variants are significantly associated with BMD decrease in Chinese postmenopausal women and might be used as molecular markers for assessing the risk of BMD and osteoporosis.
| S-EPMC4346683 | biostudies-literature
Project description:INTRODUCTION:Polymorphism in the promoter region of collagen type 1? (COL1A1) +1245G/T (Sp1, rs1800012) was in some studies shown to be relevant for bone mineral density (BMD) and low-energy fracture prediction. The aim of the study was to confirm this finding in a group of postmenopausal women diagnosed with osteoporosis. MATERIAL AND METHODS:We investigated 311 Caucasian women (mean age: 65.2 ±9.39 years) either after low-energy fractures (regardless of the location) or meeting World Health Organization (WHO) criteria for osteoporosis. All patients underwent clinical examination in order to exclude secondary osteoporosis; hip and lumbar spine DEXA was performed (Lunar). The three genotypes of Sp1 polymorphism were determined by RFLP (restriction fragment length polymorphism). RESULTS:Distribution of COL1A1 genotypes (SS/Ss/ss) agreed with Hardy-Weinberg equilibrium. No relation between COL1A1 genotypes and hip/L1-L4 BMD was found. Fractures were reported in 26.3% of women. Prevalence of low-energy fractures, regardless of the type, was 50.0% in ss genotype carriers, 26.4% in SS homozygotes and 23.7% in Ss heterozygotes. There was no statistically significant recessive or dominant effect of any Sp1 genotype on fracture prevalence (p = 0.613). CONCLUSIONS:We failed to observe that COL1A1 Sp 1 genotypes contribute to BMD determination or are associated with prevalent low-energy fractures in a Polish cohort of postmenopausal osteoporotic women.
| S-EPMC4848358 | biostudies-literature
Project description:BackgroundHigher protein diets are promoted for effective weight loss. Striated tissues in omnivorous diets contain high-quality protein, but limited data exist regarding their effects on bone.MethodsTo examine the effects of energy restriction-induced weight loss with higher protein omnivorous diets versus lower protein vegetarian diets on bone mineral density in overweight postmenopausal women, two randomized controlled feeding studies were conducted. In Study 1, 28 women consumed 750 kcal/day energy deficit diets with 18% energy from protein via lacto-ovo vegetarian sources (normal protein, n = 15) or 30% energy from protein with 40% of protein from lean pork (higher protein, n = 13, omnivorous) for 12 weeks. In Study 2, 54 women consumed their habitual diet (control, n = 11) or 1,250 kcal/day diets with 16% energy from nonmeat protein sources (n = 14) or 26% energy from protein, including chicken (n = 15) or beef (n = 14) for 9 weeks.ResultsStudy 1: With weight loss (normal protein -11.2%, higher protein -10.1%), bone mineral density was not significantly changed in normal protein (-0.003 ± 0.003 g/cm(2), -0.3%) but decreased in higher protein (-0.0167 ± 0.004 g/cm(2), -1. 4%, group-by-time p < .05). Study 2: The control, nonmeat, chicken, and beef groups lost 1.5%, 7.7%, 10.4%, and 8.1% weight and 0.0%, 0.4%, 1.1%, and 1.4% bone mineral density, respectively. The change of bone mineral density was significant for chicken and beef compared with the control (group-by-time, p < .05). Markers of calcium metabolism and bone homeostasis in blood and urine were not changed over time or differentially affected by diet.ConclusionConsumption of higher protein omnivorous diets promoted decreased bone mineral density after weight loss in overweight postmenopausal women.
| S-EPMC3031450 | biostudies-literature
Project description:Previous studies suggest that bone loss and fracture risk are associated with higher inflammatory milieu, potentially modifiable by diet. The primary objective of this analysis was to evaluate the association of the dietary inflammatory index (DII), a measure of the inflammatory potential of diet, with risk of hip, lower-arm, and total fracture using longitudinal data from the Women's Health Initiative Observational Study and Clinical Trials. Secondarily, we evaluated changes in bone mineral density (BMD) and DII scores. DII scores were calculated from baseline food frequency questionnaires (FFQs) completed by 160,191 participants (mean age 63 years) without history of hip fracture at enrollment. Year 3 FFQs were used to calculate a DII change score. Fractures were reported at least annually; hip fractures were confirmed by medical records. Hazard ratios for fractures were computed using multivariable-adjusted Cox proportional hazard models, further stratified by age and race/ethnicity. Pairwise comparisons of changes in hip BMD, measured by dual-energy X-ray absorptiometry from baseline, year 3, and year 6 were analyzed by quartile (Q1?=?least inflammatory diet) of baseline DII scores in a subgroup of women (n?=?10,290). Mean DII score improved significantly over 3 years (p < 0.01), but change was not associated with fracture risk. Baseline DII score was only associated with hip fracture risk in younger white women (HR Q4,1.48; 95% CI, 1.09 to 2.01; p?=?0.01). There were no significant associations among white women older than 63 years or other races/ethnicities. Women with the least inflammatory DII scores had less loss of hip BMD (p?=?0.01) by year 6, despite lower baseline hip BMD, versus women with the most inflammatory DII scores. In conclusion, a less inflammatory dietary pattern was associated with less BMD loss in postmenopausal women. A more inflammatory diet was associated with increased hip fracture risk only in white women younger than 63 years. © 2016 American Society for Bone and Mineral Research.
| S-EPMC5413384 | biostudies-literature