BACKGROUND: Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. 
The monoclonal antibody romosozumab binds to sclerostin and increases bone 
formation.
METHODS: In a phase 2, multicenter, international, randomized, 
placebo-controlled, parallel-group, eight-group study, we evaluated the efficacy 
and safety of romosozumab over a 12-month period in 419 postmenopausal women, 55 
to 85 years of age, who had low bone mineral density (a T score of -2.0 or less 
at the lumbar spine, total hip, or femoral neck and -3.5 or more at each of the 
three sites). Participants were randomly assigned to receive subcutaneous 
romosozumab monthly (at a dose of 70 mg, 140 mg, or 210 mg) or every 3 months 
(140 mg or 210 mg), subcutaneous placebo, or an open-label active 
comparator--oral alendronate (70 mg weekly) or subcutaneous teriparatide (20 μg 
daily). The primary end point was the percentage change from baseline in bone 
mineral density at the lumbar spine at 12 months. Secondary end points included 
percentage changes in bone mineral density at other sites and in markers of bone 
turnover.
RESULTS: All dose levels of romosozumab were associated with significant 
increases in bone mineral density at the lumbar spine, including an increase of 
11.3% with the 210-mg monthly dose, as compared with a decrease of 0.1% with 
placebo and increases of 4.1% with alendronate and 7.1% with teriparatide. 
Romosozumab was also associated with large increases in bone mineral density at 
the total hip and femoral neck, as well as transitory increases in 
bone-formation markers and sustained decreases in a bone-resorption marker. 
Except for mild, generally nonrecurring injection-site reactions with 
romosozumab, adverse events were similar among groups.
CONCLUSIONS: In postmenopausal women with low bone mass, romosozumab was 
associated with increased bone mineral density and bone formation and with 
decreased bone resorption. (Funded by Amgen and UCB Pharma; ClinicalTrials.gov 
number, NCT00896532.).