Recker R, Dempster D, Langdahl B, et al. - In the randomized, double-blind, placebo-controlled, event-driven, Phase 3, Long-term Odanacatib Fracture Trial (LOFT) and planned double-blind extension, the impacts of odanacatib (ODN), a selective oral inhibitor of cathepsin K, on bone remodeling/modeling and structure were investigated in postmenopausal women with osteoporosis. In total, 386 transilial bone biopsies, obtained from consenting patients at baseline (ODN n = 17, placebo n = 23), Month 24 (ODN n = 112, placebo n = 104), −36 (ODN n = 42, placebo n = 41), and − 60 (ODN n = 27, placebo n = 20), were evaluated by dynamic and static bone histomorphometry. The 5-year ODN therapy did not reduce bone remodeling and increased the periosteal bone formation proportion of patients. Such outcomes are consistent with the mechanism of action of ODN, and are linked to continued BMD increases and lessened risk of fractures vs placebo in the LOFT Phase 3 fracture trial.