Dataset Information

Abaloparatide followed by alendronate in women ?80 years with osteoporosis: post hoc analysis of ACTIVExtend.

ABSTRACT: OBJECTIVE:Fracture risk increases with age, but few studies focus on persons ?80 years. In the ACTIVE trial, treatment with abaloparatide for 18 months reduced osteoporotic fracture risk and increased bone mineral density. These effects were maintained with 24 months alendronate treatment in ACTIVExtend. We postulated that similar improvements in bone mineral density and safety would be demonstrated in women ?80 years. METHODS:Post hoc analyses of bone mineral density and fracture incidence in women with osteoporosis at high risk of fracture ?80 years from ACTIVExtend. RESULTS:In total, 56 women aged ?80 years at ACTIVE baseline entered the ACTIVExtend study; 46 of these completed the study. Mean age was 83.3 years; other baseline characteristics were similar. At the end of ACTIVE, bone mineral density increased at all sites for abaloparatide versus placebo. Bone mineral density increased in parallel in both groups during alendronate therapy (19 to 43 months) in ACTIVExtend. At month 43, mean percent change in bone mineral density from baseline was 17.2% abaloparatide/alendronate versus 8.6% placebo/alendronate (P?

SUBMITTER: Greenspan SL

PROVIDER: S-EPMC7515468 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Abaloparatide followed by alendronate in women ≥80 years with osteoporosis: post hoc analysis of ACTIVExtend.

Greenspan Susan L SL Fitzpatrick Lorraine A LA Mitlak Bruce B Wang Yamei Y Harvey Nicholas C NC Deal Chad C Cosman Felicia F McClung Michael M

Menopause (New York, N.Y.) 20201001 10

<h4>Objective</h4>Fracture risk increases with age, but few studies focus on persons ≥80 years. In the ACTIVE trial, treatment with abaloparatide for 18 months reduced osteoporotic fracture risk and increased bone mineral density. These effects were maintained with 24 months alendronate treatment in ACTIVExtend. We postulated that similar improvements in bone mineral density and safety would be demonstrated in women ≥80 years.<h4>Methods</h4>Post hoc analyses of bone mineral density and fracture ...[more]

PMID: 32665529

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Project description:In the randomized, placebo-controlled, double-blind phase 3 ACTIVE study (NCT01343004), 18?months of abaloparatide 80??g daily (subcutaneous injection) in postmenopausal women at risk of osteoporotic fracture significantly reduced the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures and significantly increased bone mineral density (BMD) versus placebo regardless of baseline risk factors. Women from the abaloparatide and placebo groups who completed ACTIVE were eligible for ACTIVExtend (NCT01657162), in which all enrollees received sequential, open-label monotherapy with alendronate 70?mg once weekly for up to 24?months. This prespecified analysis evaluated whether fracture risk reductions and bone mineral density (BMD) gains associated with abaloparatide during ACTIVE persisted through the full 43-month ACTIVE-ACTIVExtend study period in nine prespecified baseline risk subgroups. Baseline risk subgroups included BMD T-score at the lumbar spine, total hip, and femoral neck (??-?2.5 versus >?-?2.5 and???-3.0 versus >?-?3.0), history of nonvertebral fracture (yes/no), prevalent vertebral fracture (yes/no), and age (<65 versus 65 to <75 versus ?75?years). Forest plots display treatment effect. Treatment-by-subgroup interactions were tested using the Breslow-Day test, Cox proportional hazards model, and ANCOVA model. After the combined ACTIVE-ACTIVExtend study period, reductions in relative risk for new vertebral, nonvertebral, clinical, and major osteoporotic fractures were greater among patients in the abaloparatide/alendronate group than among those in the placebo/alendronate group across all nine baseline risk subgroups. BMD gains at the lumbar spine, total hip, and femoral neck were greater in the abaloparatide/alendronate group versus the placebo/alendronate group. No clinically meaningful interaction between treatment assignment and any baseline risk variable was observed. The sequence of abaloparatide for 18?months followed by alendronate for up to 24?months appears to be an effective treatment option for a wide range of postmenopausal women at risk for osteoporotic fractures. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.

Project description:Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor signaling pathway that favors the stimulation of bone formation. Here, we report a prospective, exploratory analysis of bone mineral density (BMD) response rates comparing sequential abaloparatide/alendronate vs placebo/alendronate across the ACTIVE and ACTIVExtend studies. BMD was measured at the lumbar spine, total hip, and femoral neck from the beginning of ACTIVE to the end of ACTIVExtend (18 months of abaloparatide or placebo followed by about 1 month for re-consent, followed by 24 months of alendronate treatment for a total of 43 months). Responders were defined as those patients who had improvements in BMD at 3 anatomic sites-the lumbar spine, total hip, and femoral neck. Three response thresholds, >0%, >3%, and >6%, were evaluated. Five hundred fifty-eight patients in the abaloparatide/alendronate group and 581 patients in the placebo/alendronate group from ACTIVExtend were included in the analysis. At Month 43, a significantly greater proportion of those in the abaloparatide/alendronate group compared with the placebo/alendronate group responded with BMD changes from ACTIVE baseline of >0%, >3%, and >6% at all 3 anatomic sites (p < 0.001 for each comparison). At the>3% threshold, 60.7% (307/506) vs 24.0% (121/505) of patients experienced BMD increases at all 3 sites in the abaloparatide/alendronate vs placebo/alendronate groups, respectively (p < 0.001). A significantly greater proportion of the abaloparatide/alendronate group experienced BMD increases of>0%, >3%, and >6% at each individual anatomic site compared with the placebo/alendronate group at 43 months (p < 0.001). Additionally, at each visit in ACTIVExtend, there was a significantly greater proportion of patients in the abaloparatide/alendronate group above the 3% threshold at each anatomic site compared with the placebo/alendronate group. Results are consistent with the significant BMD response with abaloparatide vs placebo observed in ACTIVE and with the continued fracture risk reduction with sequential abaloparatide/alendronate compared with placebo/alendronate treatment observed in ACTIVE through ACTIVExtend.

Project description:Previous subgroup analyses from the ACTIVE trial in women with postmenopausal osteoporosis (NCT01343004) using three-dimensional (3D)-processing of dual X-ray absorptiometry (DXA) scans indicated greater increases in total hip cortical volumetric bone mineral density (Ct.vBMD) and estimated indices of hip strength following 18 months of abaloparatide (ABL) versus placebo or teriparatide. The current post hoc analyses describe hip 3D-DXA data for ACTIVExtend (NCT01657162), in which 18 months of ABL followed by 24 months of alendronate (ABL/ALN) increased hip and spine areal BMD (aBMD) and reduced fracture risk versus placebo (PBO) followed by ALN (PBO/ALN). In an ACTIVExtend subgroup (ABL/ALN, n = 204; PBO/ALN, n = 202), hip DXA scans retrospectively underwent 3D modeling via 3D-Shaper software. Changes from baseline in cortical and trabecular compartments were calculated for total hip and hip subregions (femoral neck, trochanter, and shaft). Estimated strength indices comprising cross-sectional moment of inertia, section modulus, and buckling ratio were calculated for each hip subregion. Correlations between bone turnover marker levels at the time of alendronate initiation and subsequent BMD gains with alendronate were also investigated within each group. Total hip trabecular and cortical 3D-DXA parameters increased from baseline in both groups (all p < 0.001), with greater average increases for ABL/ALN versus PBO/ALN (trabecular vBMD: 10.87% versus 4.3%; cortical thickness: 2.32% versus 1.14%; Ct.vBMD: 3.41% versus 1.86%; cortical surface BMD: 5.82% versus 3.0%; all p < 0.001). Strength indices in the ABL/ALN group improved in all subregions versus baseline (all p < 0.0001) and versus PBO/ALN (all p < 0.02). In the ABL/ALN group, collagen type I N-terminal propeptide (P1NP) levels at the time of alendronate initiation correlated with subsequent percent changes in all 3D-DXA parameters with 24 months of alendronate therapy. In conclusion, sequential ABL/ALN or PBO/ALN treatment improves trabecular and cortical 3D-DXA parameters at the hip, as well as strength indices of hip subregions, with greater increases with ABL/ALN versus PBO/ALN. © 2022 Radius Health, Inc. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Project description:We performed a cost-effectiveness analysis comparing 5 versus 10 years of alendronate treatment prior to 5-year drug holiday for US postmenopausal women with hip BMD T-scores between - 2.5 and - 3.5. We found that for most postmenopausal women 5 years of treatment prior to drug holiday is the more effective and cost-effective option.IntroductionWe performed a cost-effectiveness analysis to compare 5 versus 10 years of alendronate treatment prior to 5-year drug holiday for postmenopausal osteoporotic women.MethodsWe created an individual-level state-transition microsimulation model to compare 3 treatment strategies for US postmenopausal women with osteoporosis and femoral neck BMD T-scores between - 2.5 and - 3.5 at baseline: recurrent periods of 5 years of alendronate followed by 5 years of drug holiday (alendronate 5/5), recurrent periods of 10 years of alendronate followed by 5 years of drug holiday (alendronate 10/5), and no alendronate treatment.ResultsBase-case analysis revealed for women initiating treatment at ages 50, 60, and 70, the alendronate 5/5 strategy dominated (was more effective and less costly than) the alendronate 10/5 strategy and no treatment. For women age 80, the alendronate 10/5 strategy dominated. When assuming a lower relative risk of nonvertebral fracture during years 6-10 of alendronate treatment than the base-case assumption, the alendronate 10/5 strategy became the most cost-effective strategy even at younger treatment initiation ages. Probabilistic sensitivity analysis results supported the base-case findings; for treatment initiation ages of 50, 60, and 70, the alendronate 5/5 strategy was favored, whereas for treatment initiation age of 80, the alendronate 10/5 strategy was favored; however, there was uncertainty in these findings.ConclusionsAfter 5 years of alendronate treatment, younger postmenopausal women (ages 50-70) with osteoporosis would likely benefit from a drug holiday, whereas older women (age 80) are likely to benefit from treatment for 10 years before a drug holiday.

Dataset Information

Abaloparatide followed by alendronate in women ?80 years with osteoporosis: post hoc analysis of ACTIVExtend.

Publications

Abaloparatide followed by alendronate in women ≥80 years with osteoporosis: post hoc analysis of ACTIVExtend.

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