Four-year Results of a Phase 2 Study of the Cathepsin K Inhibitor Odanacatib in Postmenopausal Women with Low Bone Mineral Density: Effects on Bone Mineral Density and Bone Turnover Markers

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Monthly oral ibandronate is indicated for the prevention and treatment of osteoporosis in postmenopausal women. The STudy Researching Osteoporosis iN Guys (STRONG) investigated the efficacy and safety of 150-mg monthly oral ibandronate in men with primary, idiopathic, or hypogonadism-related low bone density.STRONG was a 1-year, placebo-controlled, randomized (2 ibandronate: 1 placebo), double-blind study that enrolled ambulatory men aged ≥ 30 years with baseline femoral neck (FN) bone mineral density (BMD) T-scores ≤ − 2.0 and lumbar spine (LS) BMD T-scores ≤ − 1.0 or LS BMD T-scores ≤ − 2.0, FN BMD T-scores ≤ − 1.0, and BMD T-scores ≥ − 4.0 at any site assessed by dual-energy X-ray absorptiometry. The primary endpoint was mean percent change from baseline in LS BMD at 1 year (intent-to-treat [ITT] population). Secondary endpoints included mean BMD changes from baseline at the FN, total hip (TH), and trochanter (TR) and changes in bone turnover markers (BTMs), as measured by the bone resorption marker serum C-terminal telopeptide of type 1 collagen (sCTX) and the bone formation marker bone-specific alkaline phosphatase (BSAP). All men received twice daily calcium carbonate (1000 mg/day) and vitamin D (400 IU/day). Changes in BMD for treatment groups were compared using analysis of covariance with treatment, investigative site, and baseline testosterone as factors and baseline BMD as a covariate.The ITT population consisted of 132 men; 47 received placebo and 85 received monthly ibandronate. Men who received ibandronate achieved greater increases in LS BMD at 12 months than those who received placebo (3.5% vs. 0.9%, respectively; difference, 2.6; p < 0.001). The ibandronate group also achieved greater 12-month BMD increases than the placebo group, respectively, at the TH (1.8% vs. − 0.3%; difference, 2.1; p < 0.001), FN (1.2% vs. − 0.2%; difference, 1.4; p = 0.012), and TR (2.2% vs. 0.4%; difference, 1.7; p < 0.005). In men who completed the study and adhered to the protocol (per-protocol (PP) population), percent decreases in median sCTX and BSAP levels from baseline were also greater with ibandronate versus placebo (p ≤ 0.001 for both comparisons). Overall, monthly ibandronate was well tolerated.In men with low BMD, 1 year of treatment with oral once-monthly 150-mg ibandronate significantly increased BMD at the LS and hip (TH, TR, and FN), significantly reduced BTM levels in the PP population, and was generally well tolerated.