Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD.
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.


BACKGROUND
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.


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 > or =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.
Lewiecki
E Michael
EM
New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM 87106, USA. lewiecki@aol.com
Miller
Paul D
PD
McClung
Michael R
MR
Cohen
Stanley B
SB
Bolognese
Michael A
MA
Liu
Yu
Y
Wang
Andrea
A
Siddhanti
Suresh
S
Fitzpatrick
Lorraine A
LA
D000368:Aged; D019386:Alendronate / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects* / Q000276:immunology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D001862:Bone Resorption / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D000069448:Denosumab; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D017698:Postmenopause; D053245:RANK Ligand / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D000069448:Denosumab; D019386:Alendronate