Prolia reverses cortical bone density loss in women with postmenopausal osteoporosis

SAN DIEGO — Treatment with Prolia helped stop and reverse cortical bone density loss at the wrist among women with postmenopausal osteoporosis, according to study findings presented here.

“The skeleton is 80% cortical bone and cortical bone loss contributes importantly to increased fracture risk,” the researchers wrote. “Denosumab has been shown to increase [bone mineral density] at sites of cortical bone, including the 1/3 radius, a skeletal site not responsive to most osteoporosis treatments.”

John P. Bilezikian, MD, of Columbia University, and colleagues evaluated data from 2,207 women from the FREEDOM Trial for 1/3 radius BMD changes and wrist fracture rates during 3 years of treatment with placebo who were then treated with 60 mg Prolia (denosumab, Amgen) for 6 years in the FREEDOM Extension Trial. All participants received daily calcium and vitamin D supplementation.

“The important point to make is that this study tracked the first 3 years of the placebo arm and the subsequent years when the placebo-treated subjects were treated with denosumab,” Bilezikian told Endocrine Today.

A substudy of 115 participants also received DXA measurements at baseline, FREEDOM (1-3 years) and FREEDOM Extension (years 1-3 and 5).

Compared with FREEDOM baseline, a progressive and significant loss of BMD at the 1/3 radius was found during the 3 years of the FREEDOM trial (–1.2%; P < .05). However, during FREEDOM Extension, denosumab resulted in a reversal and 1.5% BMD gain at the 1/3 radius by year 5 (P < .05).

Wrist fracture rate was 1.02 per 100 person-years during the FREEDOM trial; wrist fracture rate remained comparable during the first 3 years of the Extension Trial, whereas BMD was recovered with denosumab and returned to original baseline levels.

BMD increased over baseline during years 4 and 5 of the Extension Trial, and the rate of wrist fractures reduced significantly compared with FREEDOM (RR = 0.57; 95% CI, 0.34-0.95).

Similarly, through the end of the Extension Trial, the rate of wrist fractures remained lower than that during the FREEDOM Trial (RR = 0.61; 95% CI, 0.39-0.94).

“During the first 3 years of FREEDOM, the placebo arm lost distal radius density, but during the period when the placebo arm was treated with denosumab, bone density was reversed and was associated with a reduction in wrist fractures,” Bilezikian said. “The study is important because it associates an effect of denosumab to improve cortical bone density with a clinically significant endpoint, namely wrist fractures.” ­– by Amber Cox


Bilezikian JP, et al. OR22-1. Presented at: The Endocrine Society Annual Meeting; March 5-8, 2015; San Diego.

Disclosure: Bilezikian reports various financial ties with Amgen, Asahi, Johnson and Johnson, Merck and NPS Pharma. The study was funded in part by Amgen. Please see the full study for a list of all other authors’ financial disclosures.