Bente L Langdahl1, Christence Stubbe Teglbjærg, Pei-Ran Ho, Roland Chapurlat, Edward Czerwinski, David L Kendler, Jean-Yves Reginster, Alan Kivitz, E Michael Lewiecki, Paul D Miller, Michael A Bolognese, Michael R McClung, Henry G Bone, Östen Ljunggren, Bo Abrahamsen, Ugis Gruntmanis, Yu-Ching Yang, Rachel B Wagman, Faisal Mirza, Suresh Siddhanti, Eric Orwoll. 1. Aarhus University Hospital (B.L.L.), DK-8000 Aarhus, Denmark; Center for Clinical and Basic Research (C.S.T.), 2750 Ballerup, Denmark; Amgen Inc. (P.-R.H., Y.-C.Y., R.B.W., F. M., S.S.), Thousand Oaks, California 91320; INSERM UMR 1033 (R.C.), Université de Lyon, Hôpital Edouard Herriot, F-69437, Lyon, France; Krakow Medical Center (E.C.), Krakow, 31-501 Poland; University of British Columbia (D.L.K.), Vancouver, British Columbia V6T 1Z4, Canada; University of Liège (J.-Y.R.), 4000 Liège, Belgium; Altoona Center for Clinical Research (A.K.), Duncansville, Pennsylvania 16635; New Mexico Clinical Research and Osteoporosis Center (E.M.L.), Albuquerque, New Mexico 87106; Colorado Center for Bone Research (P.D.M.), Lakewood, Colorado 80227; Bethesda Health Research Center (M.A.B.), Bethesda, Maryland 20817; Oregon Osteoporosis Center (M.R.M.), Portland, Oregon 97213; Michigan Bone and Mineral Clinic (H.G.B.), Detroit, Michigan 48236; Uppsala University (Ö.L.), 751 05 Uppsala, Sweden; University of Southern Denmark and Glostrup Hospital (B.A.), DK-5000 Odense and Copenhagen, Denmark; Dallas Veterans Affairs Medical Center and University of Texas Southwestern (U.G.), Dallas, Texas 75390; and Oregon Health and Science University (E.O.), Portland, Oregon 97239.
Abstract
CONTEXT: One in 4 men in the United States aged >50 years will have an osteoporosis-related fracture. Fewer data are available on osteoporosis treatment in men than in women. OBJECTIVE: The purpose of this study was to evaluate denosumab therapy in men with low bone mineral density (BMD). DESIGN: This was a phase 3 study with 2 treatment periods: a previously reported 12-month double-blind, placebo-controlled phase and a 12-month open-label phase. SETTING: This was a multicenter study conducted in North America and Europe. PARTICIPANTS: A total of 228 men entered the open-label phase and 219 completed the study. INTERVENTION: Men from the original denosumab (long-term) and placebo (crossover) groups received 60 mg of denosumab sc every 6 months. MAIN OUTCOME MEASURES: BMD, serum collagen type I C-telopeptide, and safety were measured. RESULTS: During the open-label phase, continued BMD increases occurred with long-term denosumab treatment (2.2% lumbar spine, 0.9% total hip, 1.3% femoral neck, 1.3% trochanter, and 0.2% 1/3 radius), resulting in cumulative 24-month gains from baseline of 8.0%, 3.4%, 3.4%, 4.6%, and 0.7%, respectively (all P < .01). The crossover group showed BMD gains after 12 months of denosumab treatment similar to those of the long-term denosumab group during the first treatment year. Significant reductions in serum collagen type I C-teleopeptide were observed after denosumab administration. Adverse event rates were similar between groups, and no new safety signals were identified. CONCLUSIONS: In men with low BMD, denosumab treatment for a second year continued to increase BMD, maintained reductions in bone resorption, and was well tolerated. BMD increased in men initiating denosumab during the second year. These effects were similar to those previously seen in postmenopausal women with osteoporosis and in men with prostate cancer receiving androgen deprivation therapy.
RCT Entities:
CONTEXT: One in 4 men in the United States aged >50 years will have an osteoporosis-related fracture. Fewer data are available on osteoporosis treatment in men than in women. OBJECTIVE: The purpose of this study was to evaluate denosumab therapy in men with low bone mineral density (BMD). DESIGN: This was a phase 3 study with 2 treatment periods: a previously reported 12-month double-blind, placebo-controlled phase and a 12-month open-label phase. SETTING: This was a multicenter study conducted in North America and Europe. PARTICIPANTS: A total of 228 men entered the open-label phase and 219 completed the study. INTERVENTION: Men from the original denosumab (long-term) and placebo (crossover) groups received 60 mg of denosumab sc every 6 months. MAIN OUTCOME MEASURES: BMD, serum collagen type I C-telopeptide, and safety were measured. RESULTS: During the open-label phase, continued BMD increases occurred with long-term denosumab treatment (2.2% lumbar spine, 0.9% total hip, 1.3% femoral neck, 1.3% trochanter, and 0.2% 1/3 radius), resulting in cumulative 24-month gains from baseline of 8.0%, 3.4%, 3.4%, 4.6%, and 0.7%, respectively (all P < .01). The crossover group showed BMD gains after 12 months of denosumab treatment similar to those of the long-term denosumab group during the first treatment year. Significant reductions in serum collagen type I C-teleopeptide were observed after denosumab administration. Adverse event rates were similar between groups, and no new safety signals were identified. CONCLUSIONS: In men with low BMD, denosumab treatment for a second year continued to increase BMD, maintained reductions in bone resorption, and was well tolerated. BMD increased in men initiating denosumab during the second year. These effects were similar to those previously seen in postmenopausal women with osteoporosis and in men with prostate cancer receiving androgen deprivation therapy.
Authors: Sofia Bougioukli; Ashish Jain; Osamu Sugiyama; Brian A Tinsley; Amy H Tang; Matthew H Tan; Douglas J Adams; Paul J Kostenuik; Jay R Lieberman Journal: Bone Date: 2015-12-23 Impact factor: 4.398
Authors: Sarah Davis; Emma Simpson; Jean Hamilton; Marrissa Martyn-St James; Andrew Rawdin; Ruth Wong; Edward Goka; Neil Gittoes; Peter Selby Journal: Health Technol Assess Date: 2020-06 Impact factor: 4.014
Authors: Thomas R Coughlin; Ricardo Romero-Moreno; Devon E Mason; Lukas Nystrom; Joel D Boerckel; Glen Niebur; Laurie E Littlepage Journal: Curr Drug Targets Date: 2017 Impact factor: 3.465