Background Denosumab (DMAb) reduces the risk of new vertebral, nonvertebral and hip fractures (Cummings NEJM 2009). It is associated with greater gains in bone mineral density (BMD) and decreases in bone turnover markers than alendronate, in both treatment-naïve subjects and those previously treated with alendronate (Brown JBMR 2009; Kendler JBMR 2010).
Objectives To compare the efficacy and safety of DMAb and risedronate (RIS) over 12 months in postmenopausal women considered suboptimally adherent to prior daily or weekly alendronate therapy.
Methods This study randomised postmenopausal women aged ≥55 years to open-label DMAb 60 mg SC Q6M or open-label RIS 150 mg PO QM for 12 months. Primary endpoint: % change from baseline in total hip (TH) BMD at month 12. Other endpoints: % change from baseline in femoral neck (FN) and lumbar spine (LS) BMD at month 12; % change from baseline in serum CTX at months 1 and 6; and safety.
Results In 870 subjects (435 DMAb, 435 RIS), mean (SD) age was 68 (7) years, mean (SD) BMD T-scores at TH, FN and LS were –1.6 (0.9), –1.9 (0.7) and –2.2 (1.2), respectively, and median CTX was 0.3 ng/mL. DMAb significantly increased mean (95% confidence interval) BMD from baseline to month 12 compared with RIS at TH [2.0% (1.8%, 2.3%) vs 0.5% (0.2%, 0.7%), respectively], FN [1.4% (1.0%, 1.7%) vs 0% (-0.4%, 0.3%)] and LS [3.4% (3.1%, 3.8%) vs 1.1% (0.7%, 1.5%); all p<0.0001]. DMAb significantly decreased CTX compared with RIS at month 1 (median change from baseline: –78% vs –17%) and month 6 (–61% vs –23%; both p<0.0001). Overall adverse events (AEs) and serious AEs were similar between groups.
Conclusions In postmenopausal women suboptimally adherent to alendronate treatment, switching to DMAb was more effective than to RIS, based on significantly greater increases in BMD at all measured sites and greater reductions in CTX with DMAb.
Acknowledgements This study and abstract were sponsored by Amgen and GSK.
Disclosure of Interest C. Roux Grant/research support from: Amgen, Bongrain, MSD, Consultant for: Amgen, Lilly, MSD, Novartis, Roche, A. Fahrleitner-Pammer: None Declared, P. Ho Shareholder of: Amgen, Employee of: Amgen, F. Hawkins: None Declared, L. Hofbauer: None Declared, M. Micaelo: None Declared, S. Minisola Consultant for: Amgen, Bruno Farmaceutici, Eli Lilly, Merck Sharp & Dohme, Pfizer, Sigma Tau, Stroder, Speakers bureau: Abiogen, Amgen., Bruno Farmaceutici, Merck Sharp & Dohme, Nycomed, Novartis, Pfizer, Sigma Tau, N. Papaioannou Grant/research support from: Eli Lilly, Amgen, Consultant for: Amgen, Speakers bureau: Eli Lilly, Amgen, Servier, M. Stone: None Declared, J. Wark: None Declared, M. Zillikens: None Declared, I. Ferreira Shareholder of: Bristol Myers-Squibb, Novartis and Amgen, Employee of: Amgen, S. Siddhanti: None Declared, R. Wagman Shareholder of: Amgen, Employee of: Amgen, J. Brown Grant/research support from: Amgen, Eli Lilly, Merck, Novartis, Pfizer, Servier, Roche, Takeda, Warner Chilcott, Consultant for: Amgen, Eli Lilly, Merck, Speakers bureau: Amgen, Eli Lilly, Merck