FP10-3 Comparative Treatment Outcomes In Patients With Prior Fracture Previously Treated With A Bisphosphonate: Results From The Denosumab/Ibandronate and Denosumab/Risedronate Trials

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP10-Osteoporosis & Other Metabolic Bone Diseases
Bench to Bedside
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:10 AM
Room 121 (Moscone Center)

Poster Board SAT-227
Christopher Recknor*1, Christian Roux2, Pei-Ran Ho3, Jesse Hall3, Henry G Bone III4, Sydney Bonnick5, Joop van den Bergh6, Irene Ferreira7, Rachel B Wagman8 and Jacques P Brown9
1United Osteoporosis Centers, Gainesville, GA, 2Paris Descartes University, Paris, France, 3Amgen Inc., Thousand Oaks, CA, 4Michigan Bone & Mineral Clinic, Detroit, MI, 5Clinical Research Center of North Texas, Denton, TX, 6VieCuri Medical Centre and Maastricht University, Netherlands, 7Amgen Ltd, Cambridge, United Kingdom, 8Amgen, Thousand Oaks, CA, 9CHU de Québec Research Centre, Laval University, Québec City, QC, Canada
Poor adherence to bisphosphonate (BP) therapy in osteoporosis is both common and associated with poor outcomes and increased treatment costs (1,2). Although improved compliance has been shown with monthly vs weekly dosing regimens (3), there is no evidence to suggest that cycling through BP agents offers therapeutic benefit, as assessed by BMD. In two randomized, open-label studies (TTI and TTR), postmenopausal women aged ≥55 yrs previously treated with, but suboptimally adherent to, BP therapy received denosumab (DMAb) 60mg SC Q6M, ibandronate (IBN) 150mg PO QM or risedronate (RIS) 150mg PO QM for 12 months; DMAb treatment was associated with greater increases in bone mineral density (BMD) than either IBN or RIS (4,5). We evaluated whether these comparative differences were similarly observed in a subset of subjects who had BMD data recorded at baseline and month 12, stratified by high risk for fracture, defined by previous fragility fracture. In TTI, 399 subjects received DMAb and 368 received IBN, and in TTR, 405 subjects received DMAb and 404 received RIS. In TTI, 31% (237/767) and in TTR, 35% (280/809) of subjects had a prior fracture. There were no significant differences in BMD at baseline between treatment groups or prior fracture subgroups. In TTI, BMD increases were greater with DMAb than IBN at the total hip (TH), femoral neck (FN) and lumbar spine (LS) in subjects with prior fracture (2.4% vs 0.6%, 2.2% vs 0.1% and 4.2% vs 1.6%, respectively; p<0.0001 for all) and without prior fracture (2.2% vs 1.3%, 1.5% vs 1.0% and 4.1% vs 2.2%; p<0.05 for all). There was no significant difference in treatment effect between subjects with or without fracture at the TH or LS (pinteraction>0.1) while at the FN, DMAb seemed to have a greater treatment effect in those with a prior fracture (pinteraction=0.002 ). In TTR, BMD increases were greater with DMAb than RIS at the TH, FN and LS in subjects with prior fracture (2.2% vs 0.5%, 1.4% vs 0.3% and 3.4% vs 1.4%; p<0.0001 for all) and without fracture (1.9% vs 0.3%, 1.5% vs -0.3% and 3.4% vs 1.4%; p<0.01 for all). There was no significant difference in treatment effect between subjects with or without fracture at any measured site (pinteraction>0.1 for all). In subjects who were suboptimally adherent with an oral BP, transitioning to DMAb provided greater gains in BMD at all key skeletal sites measured compared with transitioning to either IBN or RIS. Our findings suggest that the magnitude of treatment effect is not significantly influenced by classification of high risk, as deofined by prior fragility fracture.

(1) Siris et al, 2006. (2) Recker et al, 2005. (3) Reginster et al, 2008. (4) Recknor et al., 2012. (5) Roux et al., 2012

Disclosure: CR: Speaker, Novartis Pharmaceuticals, , Ion Med Systems. CR: Investigator, Eli Lilly & Company, Advisory Group Member, Novartis Pharmaceuticals, Board Member, Novartis Pharmaceuticals, Board Member, Merck & Co., Speaker, Merck & Co., Investigator, Merck & Co., Board Member, Amgen, Speaker, Amgen, Advisory Group Member, Amgen, Investigator, Amgen, Advisory Group Member, UCB. PRH: Employee, Amgen, Employee, Amgen. JH: Employee, Amgen, Employee, Amgen. HGB III: Advisory Group Member, Merck & Co., Advisory Group Member, Amgen, Investigator, Tarsa, Investigator, Novartis Pharmaceuticals, Investigator, Merck & Co., Investigator, Amgen, Advisory Group Member, Tarsa. SB: Speaker Bureau Member, Amgen, Investigator, Wyeth, Investigator, Takeda, Investigator, Merck & Co., Investigator, Amgen, Speaker Bureau Member, Novartis Pharmaceuticals. JV: Investigator, Nycomed, Investigator, Eli Lilly & Company, Investigator, Amgen. IF: Employee, Amgen, Employee, Amgen. RBW: Employee, Amgen, Employee, Amgen. JPB: Advisory Group Member, Amgen, Investigator, Warner Chilcott, Investigator, Takeda, Investigator, Roche Pharmaceuticals, Investigator, Servier, Investigator, Pfizer Global R&D, Investigator, Novartis Pharmaceuticals, Investigator, Merck & Co., Investigator, Eli Lilly & Company, Investigator, Amgen, Advisory Group Member, Eli Lilly & Company, Advisory Group Member, Merck & Co., Speaker Bureau Member, Amgen, Speaker Bureau Member, Eli Lilly & Company, Speaker Bureau Member, Merck & Co., Speaker Bureau Member, Novartis Pharmaceuticals.

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm