Objective: The aim of this study was to report the effects of denosumab on radius cortical and trabecular bone density, mass, and strength, and wrist fracture incidence in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) study.
Methods: In the FREEDOM study, postmenopausal women with osteoporosis (N = 7,808) received placebo or 60 mg of denosumab every 6 months for 36 months. Radius bone mineral density (BMD), bone mineral content, and strength (polar moment of inertia) were evaluated in two prespecified substudies using dual-energy x-ray absorptiometry (placebo, n = 209; denosumab, n = 232) or quantitative CT (placebo, n = 48; denosumab, n = 62). Prespecified analysis assessed wrist fracture incidence in all FREEDOM participants (placebo, N = 3,906; denosumab, N = 3,902), and post hoc subgroup analyses evaluated those with higher fracture risk (baseline femoral neck T-score ≤−2.5; placebo, N = 1,406; denosumab, N = 1,384).
Results: Denosumab significantly increased areal BMD (assessed by dual-energy x-ray absorptiometry) and volumetric BMD, bone mineral content, and polar moment of inertia (assessed by quantitative CT), compared with placebo, in radius cortical and trabecular bone at all time points evaluated (all P < 0.05). Wrist fracture incidence was 2.9% for placebo and 2.5% for denosumab (relative risk reduction, 16%; P = 0.21) on month 36. Participants with a femoral neck T-score of −2.5 or lower were at increased risk for wrist fracture, and denosumab significantly reduced wrist fracture incidence compared with placebo (placebo, 4.0%; denosumab, 2.4%; relative risk reduction, 40%; absolute risk reduction, 1.6%; P = 0.03).
Conclusions: Denosumab significantly improves radius bone density, mass, and strength compared with placebo. In higher-risk women, denosumab significantly reduces wrist fracture risk.
From the 1George Washington University, Washington, DC; 2United Osteoporosis Centers, Gainesville, GA; 3OB-GYN Associates of Mid Florida, PA, Leesburg, FL; 4St Joseph’s Healthcare, McMaster University, Hamilton, ON, Canada; 5Central Clinical Hospital MSWiA, and Medical Research Center, Polish Academy of Sciences, Warsaw, Poland; 6New Mexico Clinical Research and Osteoporosis Center and University of New Mexico School of Medicine, Albuquerque, NM; 7Oregon Osteoporosis Center, Portland, OR; 8Centro de Osteopatias Medicas, Buenos Aires, Argentina; 9CEDOES Centro de Diagnostico e Pesquisa, Vitória, Brazil; 10Rural Clinical School, School of Medicine, The University of Queensland, Toowoomba, Australia; 11St Vincent Hospital, Vienna, Austria; 12University of Siena, Siena, Italy; 13Karolinska Institutet Södersjukhuset, Stockholm, Sweden; and 14Amgen Inc., Thousand Oaks, CA.
Received March 29, 2012; revised and accepted June 26, 2012.
Funding/support: This study was funded by Amgen Inc.
Financial disclosure/conflicts of interest: J.A.S. is a consultant and/or speaker for Abbott, Agile Therapeutics, Amgen Inc., Ascend Therapeutics, Azur Pharma, Bayer, BioSante, Boehringer Ingelheim, Depomed, Fabre-Kramer, Laboratoire HRA Pharma, KV, Meditrina Pharmaceuticals, Merck, Merrion Pharmaceuticals, NDA Partners, Novartis, Novo Nordisk, Novogyne, Pfizer, Shionogi, Slate Pharmaceutical, Sprout Pharmaceuticals, Teva, Warner Chilcott, Trovis Pharmaceuticals, and Watson Pharmaceuticals. He has received research grants from BioSante, Boehringer Ingelheim, Endoceutics, Novo Nordisk, Novogyne, and Teva. C.R. is a consultant for United Osteoporosis Centers. A.H.M. and C.A.M. have no conflicts of interest. J.D.A. is a consultant and/or speaker for Amgen Inc., Eli Lilly, Merck, Novartis, and Warner-Chilcott. He has received travel/accommodation/meeting expenses from Amgen Inc. and Novartis. E.F. has received research grants from Amgen Inc. and is a consultant and/or speaker for Amgen Inc., Novartis, Polpharma, Roche, Sanofi-Aventis, Servier, and Zentiva. He has received travel/accommodation/meeting expenses from Amgen Inc. and Servier. E.M.L. is a consultant and/or speaker/board member for Amgen Inc., Lilly, Merck, Novartis, and Warner Chilcott, and has received research grants from Amgen Inc. M.R.M. has received research grants from Amgen Inc. and Merck, and is a consultant and/or speaker/board member for Amgen Inc., Lilly, Merck, Novartis, and Warner-Chilcott. S.R.-E. was a consultant and/or speaker for GSK, Novartis, Eli Lilly, and Sanofi-Aventis. G.C.N. is a speaker for Servier Australia and has received travel-related expenses from Aventis. C.M. is a consultant and/or speaker for Amgen Inc., Eli Lilly, Novartis, and Servier. R.N. has been a consultant and speaker for Amgen Dompe. O.T. has been a consultant and/or speaker for Amgen Inc. and Nycomed. A.W. and C.L. are employees of and have stock ownership in Amgen Inc.
Address correspondence to: James A. Simon,MD, CCD, NCMP, FACOG, Women’s Health and Research Consultants, 1850 M Street, NW, Suite 450, Washington, DC 20036. E-mail: jsimon@JamesASimonMD.com