Denosumab in Postmenopausal Women with Low Bone Mineral Density
Michael R. McClung, M.D., E. Michael Lewiecki, M.D., Stanley B. Cohen, M.D., Michael A. Bolognese, M.D., Grattan C. Woodson, M.D., Alfred H. Moffett, M.D., Munro Peacock, M.D., Paul D. Miller, M.D., Samuel N. Lederman, M.D., Charles H. Chesnut, M.D., Douglas Lain, M.D., Alan J. Kivitz, M.D., Donna L. Holloway, Ph.D., Charlie Zhang, Ph.D., Mark C. Peterson, Ph.D., Pirow J. Bekker, M.D., Ph.D., for the AMG 162 Bone Loss Study Group
Background Receptor activator of nuclear factor-B ligand (RANKL)is essential for osteoclast differentiation, activation, andsurvival. The fully human monoclonal antibody denosumab (formerlyknown as AMG 162) binds RANKL with high affinity and specificityand inhibits RANKL action.
Methods The efficacy and safety of subcutaneously administereddenosumab were evaluated over a period of 12 months in 412 postmenopausalwomen with low bone mineral density (T score of 1.8 to4.0 at the lumbar spine or 1.8 to 3.5 atthe proximal femur). Subjects were randomly assigned to receivedenosumab either every three months (at a dose of 6, 14, or30 mg) or every six months (at a dose of 14, 60, 100, or 210mg), open-label oral alendronate once weekly (at a dose of 70mg), or placebo. The primary end point was the percentage changefrom baseline in bone mineral density at the lumbar spine at12 months. Changes in bone turnover were assessed by measurementof serum and urine telopeptides and bone-specific alkaline phosphatase.
Results Denosumab treatment for 12 months resulted in an increasein bone mineral density at the lumbar spine of 3.0 to 6.7 percent(as compared with an increase of 4.6 percent with alendronateand a loss of 0.8 percent with placebo), at the total hip of1.9 to 3.6 percent (as compared with an increase of 2.1 percentwith alendronate and a loss of 0.6 percent with placebo), andat the distal third of the radius of 0.4 to 1.3 percent (ascompared with decreases of 0.5 percent with alendronate and2.0 percent with placebo). Near-maximal reductions in mean levelsof serum C-telopeptide from baseline were evident three daysafter the administration of denosumab. The duration of the suppressionof bone turnover appeared to be dose-dependent.
Conclusions In postmenopausal women with low bone mass, denosumabincreased bone mineral density and decreased bone resorption.These preliminary data suggest that denosumab might be an effectivetreatment for osteoporosis. (ClinicalTrials.gov number, NCT00043186
[ClinicalTrials.gov]
.)
Source Information
From Providence Portland Medical Center, Portland, Oreg. (M.R.M.); New Mexico Clinical Research and Osteoporosis Center, Albuquerque (E.M.L.); Radiant Research, Dallas (S.B.C.); Bethesda Health Research Center, Bethesda, Md. (M.A.B.); Atlanta Research Center, Decatur, Ga. (G.C.W.); OB-GYN Associates of Mid Florida, Leesburg, Fla. (A.H.M.); Indiana University School of Medicine, Indianapolis (M.P.); Colorado Center for Bone Research, Lakewood (P.D.M.); Radiant Research, Lake Worth, Fla. (S.N.L.); University of Washington Medical Center, Seattle(C.H.C.); Arthritis Associates and Osteoporosis Center of Colorado Springs, Colorado Springs, Colo. (D.L.); Altoona Center for Clinical Research, Duncansville, Pa. (A.J.K.); and Amgen, Thousand Oaks, Calif. (D.L.H., C.Z., M.C.P., P.J.B.).
Address reprint requests to Dr. McClung at the Oregon Osteoporosis Center, 5050 NE Hoyt St., Suite 651, Portland, OR 97213, or at mmcclung{at}orost.com.
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