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Previous Volume 354:821-831 February 23, 2006 Number 8 Next

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ABSTRACT

Background Receptor activator of nuclear factor-B ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162) binds RANKL with high affinity and specificity and inhibits RANKL action.

Methods The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of –1.8 to –4.0 at the lumbar spine or –1.8 to –3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open-label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase.

Results Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent.

Conclusions In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment 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.

Full Text of this Article

Related Letters:

Denosumab in Postmenopausal Women with Low Bone Mineral Density
Schwartzman J., Yazici Y., Rifkin W. D., McClung M. R.
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N Engl J Med 2006; 354:2390-2391, Jun 1, 2006. Correspondence

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