Background/Purpose: Treatment with romosozumab (Romo) has been shown to rapidly increase BMD in postmenopausal women with low BMD through a dual effect on bone, increasing bone formation and decreasing bone resorption (McClung NEJM 2014), and is being investigated for anti-fracture efficacy in postmenopausal women with osteoporosis. Here we report the results of the primary analysis of a phase 3 placeBo-contRolled study evaluatIng the efficacy anD safety of Romo in treatinG mEn with osteoporosis (BRIDGE; NCT02186171).  

Methods: This randomized, double-blind, multicenter study enrolled ambulatory men age 55–90 with a lumbar spine (LS), total hip (TH), or femoral neck (FN) T‑score ≤ –1.5 and a history of fracture after age 45, or a T‑score ≤ –2.5. Men were randomized 2:1 to receive Romo 210 mg or placebo (Pbo) SC once monthly for 12 months. All subjects received daily calcium and vitamin D. The primary endpoint was the percentage change from baseline in LS BMD by dual x-ray absorptiometry (DXA) at month 12. Secondary and exploratory endpoints included the percentage change from baseline in BMD by DXA at months 6 (LS, TH, and FN) and 12 (TH and FN), and the percentage change from baseline in the serum bone turnover markers P1NP and CTX, respectively. Safety endpoints included incidence of adverse events (AEs).  

Results: A total of 245 men were enrolled (163 Romo, 82 Pbo). Subjects had a baseline mean (SD) age of 72 (7.3) years, baseline mean LS, TH, and FN T-scores of –2.3, –1.9, and –2.3, respectively, and 54% had a historical fracture. In the Romo group, statistically significant gains in BMD from baseline were observed at all sites evaluated at months 6 and 12 (month 12: LS [12.1%] [Figure], TH [2.5%], and FN [2.2%]) (all P < 0.05 vs Pbo). Romo treatment also resulted in a rapid and transient increase in the bone formation marker P1NP that peaked at month 1 (median increase from baseline 86%) and gradually returned toward baseline. The bone resorption marker CTX decreased after the first dose of Romo, with the greatest decrease observed at month 1 (median decrease from baseline 31%), and remained below baseline through month 12. The overall subject incidence rates of AEs and serious AEs were balanced between treatment groups. Injection site reactions were reported in 5.5% and 3.7% of subjects in the Romo and Pbo groups, respectively; most reactions were reported as mild in severity. The subject incidence of positively adjudicated cardiovascular serious AEs was 4.9% (8/163) in the Romo group and 2.5% (2/81) in the Pbo group. The subject incidence of positively adjudicated cardiovascular death was 0.6% (1/163) in the Romo group and 1.2% (1/81) in the Pbo group.  

Conclusion: In men with osteoporosis, treatment with Romo for 12 months demonstrated a dual effect by increasing bone formation and decreasing bone resorption resulting in significant gains in BMD at the spine and the hip compared with Pbo, and was generally well tolerated.