Michael R McClung1, Andreas Grauer, Steven Boonen, Michael A Bolognese, Jacques P Brown, Adolfo Diez-Perez, Bente L Langdahl, Jean-Yves Reginster, Jose R Zanchetta, Scott M Wasserman, Leonid Katz, Judy Maddox, Yu-Ching Yang, Cesar Libanati, Henry G Bone. 1. From the Oregon Osteoporosis Center, Portland (M.R.M.); Amgen, Thousand Oaks, CA (A.G., S.M.W., L.K., J.M., Y.-C.Y., C.L.); Leuven University, Leuven (S.B.), and University of Liege, Liege (J.-Y.R.) - both in Belgium; Bethesda Health Research Center, Bethesda, MD (M.A.B.); Laval University and Centre Hospitalier Universitaire de Québec Research Centre, Quebec, QC, Canada (J.P.B.); Hospital del Mar, Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad, Autonomous University of Barcelona, Barcelona (A.D.-P.); Aarhus University Hospital, Aarhus, Denmark (B.L.L.); Instituto de Investigaciones Metabólicas, Buenos Aires (J.R.Z.); and Michigan Bone and Mineral Clinic, Detroit (H.G.B.).
Abstract
BACKGROUND:Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation. METHODS: In a phase 2, multicenter, international, randomized, placebo-controlled, parallel-group, eight-group study, we evaluated the efficacy and safety of romosozumab over a 12-month period in 419 postmenopausal women, 55 to 85 years of age, who had low bone mineral density (a T score of -2.0 or less at the lumbar spine, total hip, or femoral neck and -3.5 or more at each of the three sites). Participants were randomly assigned to receive subcutaneous romosozumab monthly (at a dose of 70 mg, 140 mg, or 210 mg) or every 3 months (140 mg or 210 mg), subcutaneous placebo, or an open-label active comparator--oral alendronate (70 mg weekly) or subcutaneous teriparatide (20 μg daily). The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Secondary end points included percentage changes in bone mineral density at other sites and in markers of bone turnover. RESULTS: All dose levels of romosozumab were associated with significant increases in bone mineral density at the lumbar spine, including an increase of 11.3% with the 210-mg monthly dose, as compared with a decrease of 0.1% with placebo and increases of 4.1% with alendronate and 7.1% with teriparatide. Romosozumab was also associated with large increases in bone mineral density at the total hip and femoral neck, as well as transitory increases in bone-formation markers and sustained decreases in a bone-resorption marker. Except for mild, generally nonrecurring injection-site reactions with romosozumab, adverse events were similar among groups. CONCLUSIONS: In postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption. (Funded by Amgen and UCB Pharma; ClinicalTrials.gov number, NCT00896532.).
RCT Entities:
BACKGROUND:Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation. METHODS: In a phase 2, multicenter, international, randomized, placebo-controlled, parallel-group, eight-group study, we evaluated the efficacy and safety of romosozumab over a 12-month period in 419 postmenopausal women, 55 to 85 years of age, who had low bone mineral density (a T score of -2.0 or less at the lumbar spine, total hip, or femoral neck and -3.5 or more at each of the three sites). Participants were randomly assigned to receive subcutaneous romosozumab monthly (at a dose of 70 mg, 140 mg, or 210 mg) or every 3 months (140 mg or 210 mg), subcutaneous placebo, or an open-label active comparator--oral alendronate (70 mg weekly) or subcutaneous teriparatide (20 μg daily). The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Secondary end points included percentage changes in bone mineral density at other sites and in markers of bone turnover. RESULTS: All dose levels of romosozumab were associated with significant increases in bone mineral density at the lumbar spine, including an increase of 11.3% with the 210-mg monthly dose, as compared with a decrease of 0.1% with placebo and increases of 4.1% with alendronate and 7.1% with teriparatide. Romosozumab was also associated with large increases in bone mineral density at the total hip and femoral neck, as well as transitory increases in bone-formation markers and sustained decreases in a bone-resorption marker. Except for mild, generally nonrecurring injection-site reactions with romosozumab, adverse events were similar among groups. CONCLUSIONS: In postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption. (Funded by Amgen and UCB Pharma; ClinicalTrials.gov number, NCT00896532.).
Authors: Michelle M McDonald; Michaela R Reagan; Scott E Youlten; Sindhu T Mohanty; Anja Seckinger; Rachael L Terry; Jessica A Pettitt; Marija K Simic; Tegan L Cheng; Alyson Morse; Lawrence M T Le; David Abi-Hanna; Ina Kramer; Carolyne Falank; Heather Fairfield; Irene M Ghobrial; Paul A Baldock; David G Little; Michaela Kneissel; Karin Vanderkerken; J H Duncan Bassett; Graham R Williams; Babatunde O Oyajobi; Dirk Hose; Tri G Phan; Peter I Croucher Journal: Blood Date: 2017-05-17 Impact factor: 22.113
Authors: Kristine M Erlandson; MaryAnn O'Riordan; Corrilynn O Hileman; Eric Rapaport; Danielle Labbato; Thomas B Campbell; Grace A McComsey Journal: AIDS Res Hum Retroviruses Date: 2015-05-27 Impact factor: 2.205