Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis

Purpose 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. Methods Forearm BMD was measured by dual energy X-ray absorptiometry in a subset of 982 women from ACTIVE, evenly distributed across the three treatment groups. Wrist fractures were ascertained in the total cohort (N = 2463). Results After 18 months, ultradistal radius BMD changes from baseline were 2.25 percentage points greater for abaloparatide compared with placebo (95% confidence interval (CI) 1.38, 3.12, p < 0.001) and 1.54 percentage points greater for abaloparatide compared with teriparatide (95% CI 0.64, 2.45, p < 0.001). At 18 months, 1/3 radius BMD losses (versus baseline) were similar for abaloparatide compared with placebo (-0.42; 95% CI -1.03, 0.20; p = 0.19) but losses with teriparatide exceeded those of placebo (-1.66%; 95% CI -2.27, -1.06; p < 0.001). The decline with abaloparatide was less than that seen with teriparatide (group difference 1.22%; 95% CI 0.57, 1.87; p < 0.001). The radius BMD findings, at both ultradistal and 1/3 sites, are consistent with the numerically lower incidence of wrist fractures observed in women treated with abaloparatide compared with teriparatide (HR = 0.43; 95% CI 0.18, 1.03; p = 0.052) and placebo (HR = 0.49, 95% CI 0.20, 1.19, p = 0.11). Conclusions Compared with teriparatide, abaloparatide increased BMD at the ultradistal radius (primarily trabecular bone) and decreased BMD to a lesser extent at the 1/3 radius (primarily cortical bone), likely contributing to the numerically lower wrist fracture incidence observed with abaloparatide.