Effects of odanacatib on BMD and safety in the treatment of osteoporosis in postmenopausal women previously treated with alendronate: a randomized placebo-controlled trial.

Context: Odanacatib (ODN) is a selective cathepsin K inhibitor being developed to treat osteoporosis. Objective: The effects of ODN were evaluated on bone mineral density (BMD), biochemical markers of bone turnover, and safety in patients previously treated with alendronate. Design: This was a randomized, double-blind, placebo-controlled, 24-month study. Setting: The study was conducted at private or institutional practices. Participants: Postmenopausal women (n = 243) >= 60 years of age with low BMD at the total hip, femoral neck, or trochanter (T-score <= -2.5 but >-3.5 without prior fracture or <= -1.5 but >-3.5 with prior fracture) on alendronate for >= 3 years. Intervention: The intervention included ODN 50 mg or placebo weekly. Main Outcome Measures: The primary end point was percentage change from baseline of femoral neck BMD at month 24. BMD was assessed by dual-energy x-ray absorptiometry at baseline and 6, 12, and 24 months. Biochemical markers of bone turnover (serum C-telopeptides of type 1 collagen, urinary N-telopeptides of type 1 collagen, serum bone specific alkaline phosphatase, and serum N-terminal propeptide of type 1 collagen) were measured at baseline and 3, 6, 12, 18, and 24 months. Results: In the ODN group, BMD changes from baseline at the femoral neck, trochanter, total hip, and lumbar spine at 24 months (1.7%, 1.8%, 0.8%, and 2.3%, respectively) were significantly different from the placebo group. ODN significantly decreased urinary N-telopeptides of type 1 collagen to creatinine ratio and significantly increased serum N-terminal propeptide of type 1 collagen compared with placebo. Serum C-telopeptides of type 1 collagen was unexpectedly increased with ODN treatment. The safety profile appeared similar between groups. Conclusions: ODN provided incremental BMD gains in osteoporotic women after alendronate treatment.