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Two‐Year Treatment With Denosumab (AMG 162) in a Randomized Phase 2 Study of Postmenopausal Women With Low BMD
Author(s) -
Lewiecki E Michael,
Miller Paul D,
McClung Michael R,
Cohen Stanley B,
Bolognese Michael A,
Liu Yu,
Wang Andrea,
Siddhanti Suresh,
Fitzpatrick Lorraine A
Publication year - 2007
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.070809
Subject(s) - denosumab , medicine , bone remodeling , urology , femoral neck , placebo , osteoporosis , bone mineral , bone resorption , pathology , alternative medicine
Denosumab is a monoclonal antibody to RANKL. In this randomized, placebo‐controlled study of 412 postmenopausal women with low BMD, subcutaneous denosumab given every 3 or 6 mo was well tolerated, increased BMD, and decreased bone resorption markers for up to 24 mo. Continued study of denosumab is warranted in the treatment of low BMD in postmenopausal women. Introduction: Denosumab is a fully human monoclonal antibody that inhibits RANKL, a key mediator of osteoclastogenesis and bone remodeling. This prespecified exploratory analysis evaluated the efficacy and safety of denosumab through 24 mo in the treatment of postmenopausal women with low BMD. Materials and Methods: Four hundred twelve postmenopausal women with lumbar spine BMD T‐scores of −1.8 to −4.0 or femoral neck/total hip T‐scores of −1.8 to −3.5 were randomly assigned to receive double‐blind, subcutaneous injections of placebo; denosumab 6, 14, or 30 mg every 3 mo; denosumab 14, 60, 100, or 210 mg every 6 mo; or open‐label oral alendronate 70 mg once weekly. Outcome measures included BMD at the lumbar spine, total hip, distal one‐third radius, and total body; bone turnover markers; and safety. Results: Denosumab increased BMD at all measured skeletal sites and decreased concentrations of bone turnover markers compared with placebo at 24 mo. At the lumbar spine, BMD increases with denosumab ranged from 4.13% to 8.89%. BMD changes with denosumab 30 mg every 3 mo and ≥60 mg every 6 mo were similar to, or in some cases greater than, with alendronate. The incidence of adverse events was similar in the placebo, denosumab, and alendronate treatment groups. Exposure‐adjusted adverse events over 2 yr of treatment were similar to those reported during the first year of treatment. Conclusions: In these postmenopausal women with low BMD, treatment with denosumab for 2 yr was associated with sustained increases in BMD and reductions in bone resorption markers compared with placebo.