Forearm bone mineral density and fracture incidence in postmenopausal women with osteoporosis: results from the ACTIVExtend phase 3 trial

Abstract

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.

Introduction: Abaloparatide (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.

Methods: Ultradistal 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.

Results: At 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).

Conclusion: Ultradistal 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 registration: ClinicalTrials.gov : NCT01657162 submitted July 31, 2012.

Keywords: Abaloparatide; Alendronate; Bone mineral density; Osteoporosis; Wrist fracture.

Conflict of interest statement

NB Watts is a speaker for Amgen and Radius Health, Inc., and a consultant for AbbVie, Amgen, and Sanofi. RK Dore is a speaker for Radius Health, Inc., and is a speaker, consultant, and has been involved in clinical trials for Amgen and Eli Lilly and Company. MS LeBoff receives grant/research support from the National Institute of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases and owns a company stock in Amgen. B Mitlak and Y Wang are employees of and own company stock in Radius Health, Inc. G Hattersley is a former employee of and consultant to Radius Health, Inc. S Baim declares that he has no conflicts of interest to disclose and TD Rozental is the Editor in Chief of the Journal of Hand Surgery Global Online.

Figures

Fig. 1

Mean (± SE) percent change in UD radius BMD from baseline through month 43 *P < 0.001 vs PBO; †P < 0.01 vs PBO/ALN. ABL, abaloparatide; ALN, alendronate; BMD, bone mineral density; PBO, placebo; SE, standard error. P value was based on the analysis of covariance model. Missing BMD data imputed using the method of last observation carried forward

Fig. 2

Mean (± SE) percent change in 1/3 radius BMD from baseline through month 43 §P < 0.05 vs PBO. ABL, abaloparatide; ALN, alendronate; BMD, bone mineral density; PBO, placebo; SE, standard error. P value was based on the analysis of covariance model. Missing BMD data imputed using the method of last observation carried forward

Fig. 3

Kaplan-Meier curve of time to first incident clinical wrist fracture from ACTIVE baseline through month 43. ABL, abaloparatide; ALN, alendronate; HR, hazard ratio; NS, not significant; PBO, placebo