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N Engl J Med. 2016 Oct 20;375(16):1532-1543. Epub 2016 Sep 18.

Romosozumab Treatment in Postmenopausal Women with Osteoporosis.

Author information

1
From Helen Hayes Hospital, West Haverstraw, and Columbia University, New York (F.C.) - both in New York; Amgen, Thousand Oaks, CA (D.B.C., C.E.M., L.C., J.M., A.G.); McMaster University, Hamilton, ON, Canada (J.D.A.); University of Wisconsin-Madison Osteoporosis Clinical Center and Research Program, Madison (N.B.); Krakow Medical Center, Krakow, Poland (E.C.); Geneva University Hospital, Geneva (S.F.); the Division of Endocrinology, Diabetes, and Bone Diseases, Center for Healthy Aging, Technische Universität Dresden Medical Center, Dresden, Germany (L.C.H.); the Center for Clinical and Basic Research, Hong Kong (E.L.); New Mexico Clinical Research and Osteoporosis Center, Albuquerque (E.M.L.); Miyauchi Medical Center, Osaka, Japan (A.M.); Centro Paulista de Investigação Clinica, São Paulo (C.A.F.Z.); and UCB Pharma, Brussels (P.D.M., C.L.).

Abstract

BACKGROUND:

Romosozumab, a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption.

METHODS:

We enrolled 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck. Patients were randomly assigned to receive subcutaneous injections of romosozumab (at a dose of 210 mg) or placebo monthly for 12 months; thereafter, patients in each group received denosumab for 12 months, at a dose of 60 mg, administered subcutaneously every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 months and 24 months. Secondary end points included clinical (a composite of nonvertebral and symptomatic vertebral) and nonvertebral fractures.

RESULTS:

At 12 months, new vertebral fractures had occurred in 16 of 3321 patients (0.5%) in the romosozumab group, as compared with 59 of 3322 (1.8%) in the placebo group (representing a 73% lower risk with romosozumab; P<0.001). Clinical fractures had occurred in 58 of 3589 patients (1.6%) in the romosozumab group, as compared with 90 of 3591 (2.5%) in the placebo group (a 36% lower risk with romosozumab; P=0.008). Nonvertebral fractures had occurred in 56 of 3589 patients (1.6%) in the romosozumab group and in 75 of 3591 (2.1%) in the placebo group (P=0.10). At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab (0.6% [21 of 3325 patients] in the romosozumab group vs. 2.5% [84 of 3327] in the placebo group, a 75% lower risk with romosozumab; P<0.001). Adverse events, including instances of hyperostosis, cardiovascular events, osteoarthritis, and cancer, appeared to be balanced between the groups. One atypical femoral fracture and two cases of osteonecrosis of the jaw were observed in the romosozumab group.

CONCLUSIONS:

In postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year. (Funded by Amgen and UCB Pharma; FRAME ClinicalTrials.gov number, NCT01575834 .).

PMID:
27641143
DOI:
10.1056/NEJMoa1607948
[Indexed for MEDLINE]
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