1. Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized, Double-Blind, Phase 2, Parallel Group Study.
作者:McClung Michael R , Brown Jacques P , Diez-Perez Adolfo , Resch Heinrich , Caminis John , Meisner Paul , Bolognese Michael A , Goemaere Stefan , Bone Henry G , Zanchetta Jose R , Maddox Judy , Bray Sarah , Grauer Andreas
期刊:Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
作者:Lewiecki E Michael , Dinavahi Rajani V , Lazaretti-Castro Marise , Ebeling Peter R , Adachi Jonathan D , Miyauchi Akimitsu , Gielen Evelien , Milmont Cassandra E , Libanati Cesar , Grauer Andreas
期刊:Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
3. FRAME Study: The Foundation Effect of Building Bone With 1 Year of Romosozumab Leads to Continued Lower Fracture Risk After Transition to Denosumab.
作者:Cosman Felicia , Crittenden Daria B , Ferrari Serge , Khan Aliya , Lane Nancy E , Lippuner Kurt , Matsumoto Toshio , Milmont Cassandra E , Libanati Cesar , Grauer Andreas
期刊:Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
4. Increased bone mineral density for 1 year of romosozumab, vs placebo, followed by 2 years of denosumab in the Japanese subgroup of the pivotal FRAME trial and extension.
作者:Miyauchi Akimitsu , Dinavahi Rajani V , Crittenden Daria B , Yang Wenjing , Maddox Judy C , Hamaya Etsuro , Nakamura Yoichi , Libanati Cesar , Grauer Andreas , Shimauchi Junichiro
期刊:Archives of osteoporosis
日期:2019-06-05
DOI :10.1007/s11657-019-0608-z
Romosozumab, which binds sclerostin, rebuilds the skeletal foundation before transitioning to antiresorptive treatment. This subgroup analysis of an international, randomized, double-blind study in postmenopausal women with osteoporosis showed efficacy and safety outcomes for romosozumab followed by denosumab in Japanese women were generally consistent with those for the overall population. PURPOSE:In the international, randomized, double-blind, phase 3 FRActure study, in postmenopausal woMen with ostEoporosis (FRAME; NCT01575834), romosozumab followed by denosumab significantly improved bone mineral density (BMD) and reduced fracture risk. This report evaluates Japanese women in FRAME. METHODS:Postmenopausal women with osteoporosis (T-score - 3.5 to - 2.5 at total hip or femoral neck) received romosozumab 210 mg or placebo subcutaneously monthly for 12 months, then each group received denosumab 60 mg subcutaneously every 6 months for 24 months. The key endpoint for Japanese women was BMD change. Other endpoints included new vertebral, clinical, and nonvertebral fracture; the subgroup analysis did not have adequate power to demonstrate statistically significant reductions. RESULTS:Of 7180 enrolled subjects, 492 (6.9%) were Japanese (247 romosozumab, 245 placebo). BMD increases from baseline were greater (P < 0.001) for romosozumab-to-denosumab than placebo-to-denosumab at the lumbar spine (36 months, 12.7%), total hip (4.2%), and femoral neck (4.1%). Fracture risk was lower through 36 months for romosozumab-to-denosumab vs placebo-to-denosumab for new vertebral (1.7% vs 4.5%; relative risk reduction (RRR) 63%, P = 0.070), clinical (3.2% vs 7.3%; RRR 53%, P = 0.072), nonvertebral (2.8% vs 6.1%; RRR 50%, P = 0.12), and all other fracture types evaluated. Rates of adverse events and positively adjudicated serious cardiovascular events were generally balanced between groups. CONCLUSIONS:Efficacy and safety for romosozumab-to-denosumab were similar between Japanese women and the overall population. The sequence of romosozumab to rebuild the skeletal foundation before transitioning to antiresorptive treatment with denosumab is a promising regimen for Japanese postmenopausal women with osteoporosis at high risk of fracture.