OP0250 Denosumab Treatment of Postmenopausal Women with Osteoporosis for 7 Years: Clinical Fracture Results from the First 4 Years of the Freedom Extension
Authors: C. Roux, K. Lippuner, H. G. Bone, C. Zapalowski, S. Minisola, E. Franek, P. Lakatos, D. Kendler, E. M. Lewiecki, C. Mautalen, S. Jensen, A. Wang, N. Daizadeh, R. B. Wagman, S. Boonen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Denosumab (DMAb) has been shown to decrease the risk for new vertebral, nonvertebral, and hip fractures in the 3-year FREEDOM trial. The FREEDOM open-label extension is evaluating the long-term effects of DMAb treatment for up to 10 years. <h3>Objectives</h3> We report the incidence of clinical fractures (nonvertebral and clinical vertebral) from the first 4 years of the extension, representing up to 7 years of DMAb exposure. <h3>Methods</h3> During the FREEDOM extension, all participants are scheduled to receive 60 mg DMAb every 6 months and calcium/vitamin D daily. For the analyses presented here, women from the FREEDOM DMAb group received 4 more years of DMAb for a total of 7 years (long-term group); women from the FREEDOM placebo group received 4 years of DMAb (cross-over group). In study year 7, nonvertebral fractures, clinical vertebral fractures, and adverse events (AEs) and serious AEs were collected. <h3>Results</h3> Of 5928 women eligible for the extension, 4550 (77%) enrolled (N=2343 long-term; N=2207 cross-over). Yearly incidence of nonvertebral fractures remained low; in the long-term group: 1.4%, 1.2%, 1.6%, and 1.5% for years 4-7 of DMAb treatment, respectively, indicating a continued effect of DMAb; in the cross-over group: 2.5%, 1.9%, 2.2%, and 1.0% for years 1-4 of DMAb treatment, respectively, consistent with the DMAb-treated group in FREEDOM. Yearly clinical vertebral fracture rates also were low (long-term: 0.1%, 0.3%, 0.5%, and 0.1%; cross-over: 0.0%, &lt;0.1%, 0.3%, and 0.2%). Exposure-adjusted AE and SAE rates were similar between the long-term and cross-over groups. Events considered consistent with ONJ were observed in 5 and 3 subjects in the long-term and cross-over groups, respectively. Two femur fracture events considered consistent with atypical femoral fracture were observed (1 long-term, 1 cross-over). <h3>Conclusions</h3> Denosumab treatment for up to 7 years continued to show a favorable benefit/risk profile and was associated with a low incidence of clinical (nonvertebral and clinical vertebral) fractures. <h3>Disclosure of Interest</h3> C. Roux Grant/research support from: Lilly, Amgen Inc., MSD, Consultant for: Amgen Inc., MSD, Novartis, UCB, Speakers bureau: Amgen Inc., MSD, Novartis, UCB, K. Lippuner Consultant for: Amgen Inc., Eli Lilly, Daiichi Sankyo, MSD, Pfizer, Speakers bureau: Amgen Inc., Eli Lilly, Daiichi Sankyo, MSD, Pfizer, H. Bone Grant/research support from: Amgen Inc., Merck, Novartis, Tarsa, Consultant for: Amgen Inc., Merck, Tarsa, Speakers bureau: Amgen Inc., Merck, Tarsa, C. Zapalowski Shareholder of: Amgen Inc., Employee of: Amgen Inc., S. Minisola Speakers bureau: Abiogen, Amgen Inc., Bruno Farmaceutici, Merck Sharp &amp; Dohme, Nycomed, Novartis, Pfizer, Sigma Tau, E. Franek Consultant for: Amgen Inc., MSD, Novartis, Sanofi-Aventis, Servier, TEVA, Speakers bureau: Amgen Inc., MSD, Novartis, Sanofi-Aventis, Servier, TEVA, P. Lakatos: None Declared, D. Kendler Grant/research support from: Merck, Amgen Inc., Eli Lilly, Novartis, J&amp;J, Roche, Pfizer, Consultant for: Merck, Amgen Inc., Eli Lilly, Novartis, Warner Chilcott, Pfizer, Speakers bureau: Merck, Amgen Inc., Eli Lilly, Novartis, Warner Chilcott, Pfizer, E. Lewiecki Grant/research support from: Amgen Inc., Merck, Eli Lilly, Novartis, Warner Chilcott, GSK, and Genentech, Consultant for: Amgen Inc., Eli Lilly, Novartis, Merck, Warner Chilcott, GSK, and Genentech, Speakers bureau: Amgen Inc., Eli Lilly, Novartis, Merck, Warner Chilcott, GSK, and Genentech, C. Mautalen Consultant for: MSD and Servier, Speakers bureau: MSD and Servier, S. Jensen: None Declared, A. Wang Shareholder of: Amgen Inc., Employee of: Amgen Inc., N. Daizadeh Shareholder of: Amgen Inc., Employee of: Amgen Inc., R. Wagman Shareholder of: Amgen Inc., Employee of: Amgen Inc., S. Boonen Grant/research support from: Amgen Inc., Novartis, Consultant for: Amgen Inc., Novartis, Speakers bureau: Amgen Inc., Novartis