Effects of denosumab on bone mineral density and bone turnover in postmenopausal women.
BACKGROUND
Denosumab is an investigational fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, a mediator of osteoclastogenesis and osteoclast survival.


OBJECTIVE
This study evaluated the ability of denosumab to increase bone mineral density (BMD) and decrease bone turnover markers (BTMs) in early and later postmenopausal women with low BMD.


METHODS
This 2-yr randomized, double-blind, placebo-controlled study was conducted in North America.


METHODS
Subjects included 332 postmenopausal women with lumbar spine BMD T-scores between -1.0 and -2.5.


METHODS
SUBJECTS were randomly assigned to receive denosumab sc, 60 mg every 6 months, or placebo. Randomization was stratified by time since onset of menopause (< or =5 yr or > 5 yr).


METHODS
The primary end point was the percent change in lumbar spine BMD by dual-energy x-ray absorptiometry at 24 months. Additional end points were percent change in volumetric BMD of the distal radius by quantitative computed tomography; percent change in BMD by dual-energy x-ray absorptiometry for the total hip, one-third radius, and total body; hip structural analysis; percent change in BTMs; and safety.


RESULTS
Denosumab significantly increased lumbar spine BMD, compared with placebo at 24 months (6.5 vs. -0.6%; P<0.0001) with similar results for both strata. Denosumab also produced significant increases in BMD at the total hip, one-third radius, and total body (P < 0.0001 vs. placebo); increased distal radius volumetric BMD (P < 0.01); improved hip structural analysis parameters; and significantly suppressed serum C-telopeptide, tartrate-resistant acid phosphatase-5b, and intact N-terminal propeptide of type 1 procollagen. The overall incidence of adverse events was similar between both study groups.


CONCLUSIONS
Twice-yearly denosumab increased BMD and decreased BTMs in early and later postmenopausal women.
Bone
Henry G
HG
Michigan Bone and Mineral Clinic, 22201 Moross Road, Detroit, MI 48236, USA. hgbone.md@att.net
Bolognese
Michael A
MA
Yuen
Chui Kin
CK
Kendler
David L
DL
Wang
Huei
H
Liu
Yu
Y
San Martin
Javier
J
D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects*; D000069448:Denosumab; D004311:Double-Blind Method; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006615:Hip / Q000033:anatomy & histology; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010919:Placebos; D017698:Postmenopause / Q000187:drug effects*; D053245:RANK Ligand / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D015507:Drugs, Investigational; D010919:Placebos; D053245:RANK Ligand; D000069448:Denosumab