Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy.
Patients treated with bisphosphonates for osteoporosis may discontinue or require a switch to other therapies. Denosumab binds to RANKL and is a potent inhibitor of bone resorption that has been shown to increase bone mineral density (BMD) and decrease fracture risk in postmenopausal women with osteoporosis. This was a multicenter, international, randomized, double-blind, double-dummy study in 504 postmenopausal women > or = 55 years of age with a BMD T-score of -2.0 or less and -4.0 or more who had been receiving alendronate therapy for at least 6 months. Subjects received open-label branded alendronate 70 mg once weekly for 1 month and then were randomly assigned to either continued weekly alendronate therapy or subcutaneous denosumab 60 mg every 6 months and were followed for 12 months. Changes in BMD and biochemical markers of bone turnover were evaluated. In subjects transitioning to denosumab, total hip BMD increased by 1.90% at month 12 compared with a 1.05% increase in subjects continuing on alendronate (p < .0001). Significantly greater BMD gains with denosumab compared with alendronate also were achieved at 12 months at the lumbar spine, femoral neck, and 1/3 radius (all p < .0125). Median serum CTX levels remained near baseline in the alendronate group and were significantly decreased versus alendronate (p < .0001) at all time points with denosumab. Adverse events and serious adverse events were balanced between groups. No clinical hypocalcemic adverse events were reported. Transition to denosumab produced greater increases in BMD at all measured skeletal sites and a greater reduction in bone turnover than did continued alendronate with a similar safety profile in both groups.
Kendler
David L
DL
Clinical Research Centre, Vancouver, British Columbia, Canada. kendler@ca.inter.net
Roux
Christian
C
Benhamou
Claude Laurent
CL
Brown
Jacques P
JP
Lillestol
Michael
M
Siddhanti
Suresh
S
Man
Hoi-Shen
HS
San Martin
Javier
J
Bone
Henry G
HG
D000368:Aged; D019386:Alendronate / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects*; D024042:Collagen Type I / Q000097:blood; D003710:Demography; D000069448:Denosumab; D005260:Female; D005272:Femur Neck / Q000187:drug effects; D006615:Hip; D006801:Humans; D008159:Lumbar Vertebrae / Q000187:drug effects; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D017698:Postmenopause / Q000097:blood / Q000187:drug effects*; D011347:Procollagen / Q000097:blood; D053245:RANK Ligand / Q000009:adverse effects / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D053245:RANK Ligand; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D000069448:Denosumab; D019386:Alendronate