Abaloparatide increases forearm BMD and lowers wrist fracture risk
Abaloparatide increases bone mineral density (BMD) at the ultradistal radius along with lower risk of wrist fracture compared with placebo and teriparatide in postmenopausal women with osteoporosis, according to a study presented at The Endocrine Society Annual Meeting (ENDO 2017) in Orlando, Florida, US.
The analysis was on a subset of 982 postmenopausal women from a total cohort of 2,463 women enrolled in the global, double-blind, phase III ACTIVE* trial who were randomized to subcutaneous abaloparatide 80 µg (n=321), open-label teriparatide 20 µg daily (n=327), or placebo (n=334) for 18 months. [ENDO 2017, abstract LB SUN 46]
At the ultradistal radius, an anatomical site considered relevant to wrist fractures, BMD significantly increased from baseline with abaloparatide (mean percent change, +1.0 percent) compared with a decrease with placebo (-1.2 percent; p<0.0001) and with teriparatide (-0.5 percent; p<0.001) after 18 months.
Measurements at the 1/3 radius, which is constituted of a substantial proportion of cortical bone, showed an overall BMD decrease from baseline in all three arms (-1.0 percent, -2.3 percent, and -0.6 percent, respectively for abaloparatide, teriparatide, and placebo). Although the difference between the abaloparatide and the placebo arms was not significant (p=0.19), the decrease was significantly greater in the teriparatide arm when compared with abaloparatide (p<0.001) and with placebo (p<0.0001).
Compared with the abaloparatide arm (seven women [1.0 percent by Kaplan-Meier estimate]), there were more women who reported wrist fractures in both the teriparatide (17 [2.3 percent]) and the placebo arms (15 [2.2 percent]). This translates to a lower wrist fracture risk in the abaloparatide group compared with the teriparatide group (hazard ratio, 0.43; p=0.052), although the reduction was not statistically significant.
“These data are also consistent with the reduction in nonvertebral fractures, sites rich in cortical bone, with [subcutaneous abaloparatide] compared with placebo treatment observed during ACTIVE,” said lead author Dr Nelson Watts from Mercy Health Osteoporosis and Bone Health Services in Cincinnati, Ohio, US.
Abaloparatide is an osteoanabolic agent currently under development for treating postmenopausal osteoporosis by selectively binding to and activating the parathyroid 1 receptor. The ACTIVE trial has previously shown significantly decreased risk of vertebral (VF) and nonvertebral fractures (NVF) compared with placebo, and lower risk of major osteoporotic fractures (MOF) compared with teriparatide. [JAMA 2016;316:722-733]
Also presented was a separate subanalysis of the ACTIVE cohort, which suggests that the beneficial effects of abaloparatide on reducing the risks of VF, NVF, and MOF were consistent across different geographic subgroups (including Europe, North America, South America, and Asia) compared with placebo. [ENDO 2017, abstract OR08-7]
According to Dr Michael McClung of Oregon Osteoporosis Center in Portland, Oregon, US, who presented the subanalysis, the protective effects of abaloparatide are likely to be clinically meaningful for patients who are at a very high risk for NVF, but probably less so for lower-risk patients, for whom anabolic drug are also less likely to be considered.