Effects of Odanacatib on Bone Structure and Quality in Postmenopausal Women With Osteoporosis: 5‐Year Data From the Phase 3 Long‐Term Odanacatib Fracture Trial (LOFT) and its Extension

Autor: Robert R. Recker, Le T. Duong, Tobias J. de Villiers, Arthur C. Santora, Seth Clark, David W. Dempster, Hilde Giezek, Bente L. Langdahl, Ivo Valter, Cristiano A. F. Zerbini, D Cohn, Graham Ellis
Rok vydání: 2020
Předmět:
0301 basic medicine
medicine.medical_specialty
Endocrinology
Diabetes and Metabolism
Osteoporosis
Population
Urology
030209 endocrinology & metabolism
MASS
OSTEOPOROSIS
Placebo
Bone remodeling
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Double-Blind Method
Bone Density
Osteoclast
STRENGTH
medicine
Cathepsin K
Humans
Orthopedics and Sports Medicine
BONE HISTOMORPHOMETRY
education
Osteoporosis
Postmenopausal
DENOSUMAB
education.field_of_study
Bone Density Conservation Agents
business.industry
Biphenyl Compounds
BONE MODELING AND REMODELING
HISTOMORPHOMETRY
hemic and immune systems
respiratory system
medicine.disease
FREEDOM
Postmenopause
Clinical trial
030104 developmental biology
medicine.anatomical_structure
chemistry
THERAPEUTICS
TURNOVER
Female
CATHEPSIN-K INHIBITOR
business
CLINICAL TRIALS
Odanacatib
Zdroj: Recker, R, Dempster, D, Langdahl, B, Giezek, H, Clark, S, Ellis, G, de Villiers, T, Valter, I, Zerbini, C A F, Cohn, D, Santora, A & Duong, L T 2020, ' Effects of Odanacatib on Bone Structure and Quality in Postmenopausal Women with Osteoporosis : 5-year Data from the Phase 3 Long-Term Odanacatib Fracture Trial (LOFT) and its Extension ', Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, vol. 35, no. 7, pp. 1289-1299 . https://doi.org/10.1002/jbmr.3994
ISSN: 1523-4681
0884-0431
DOI: 10.1002/jbmr.3994
Popis: Odanacatib (ODN), a selective oral inhibitor of cathepsin K, was an investigational agent previously in development for the treatment of osteoporosis. In this analysis, the effects of ODN on bone remodeling/modeling and structure were examined in the randomized, double-blind, placebo-controlled, event-driven, Phase 3, Long-term Odanacatib Fracture Trial (LOFT; NCT00529373) and planned double-blind extension in postmenopausal women with osteoporosis. A total of 386 transilial bone biopsies, obtained from consenting patients at baseline (ODN n = 17, placebo n = 23), month 24 (ODN n = 112, placebo n = 104), month 36 (ODN n = 42, placebo n = 41), and month 60 (ODN n = 27, placebo n = 20) were assessed by dynamic and static bone histomorphometry. Patient characteristics at baseline and BMD changes over 5 years for this subset were comparable to the overall LOFT population. Qualitative assessment of biopsies revealed no abnormalities. Consistent with the mechanism of ODN, osteoclast number was higher with ODN versus placebo over time. Regarding bone remodeling, dynamic bone formation indices in trabecular, intracortical, and endocortical surfaces were generally similar in ODN-treated versus placebo-treated patients after 2 years of treatment. Regarding periosteal modeling, the proportion of patients with periosteal double labels and the bone formation indices increased over time in the ODN-treated patients compared with placebo. This finding supported the observed numerical increase in cortical thickness at month 60 versus placebo. In conclusion, ODN treatment for 5 years did not reduce bone remodeling and increased the proportion of patients with periosteal bone formation. These results are consistent with the mechanism of action of ODN, and are associated with continued BMD increases and reduced risk of fractures compared with placebo in the LOFT Phase 3 fracture trial. © 2020 American Society for Bone and Mineral Research.
Databáze: OpenAIRE
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