RESEARCH - Denosumab in Postmenopausal Women with Low Bone Mineral Density

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The New England Journal of Medicine

February 23, 2006

Denosumab in Postmenopausal Women with Low Bone Mineral Density

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] .)

http://content.nejm.org/cgi/content/short/354/8/821

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