Denosumab Treatment Is Associated With Progressive Improvements in Cortical Mass and Thickness Throughout the Hip
Category: Osteoporosis - Treatment (Clinical)
Oral Presentations, Presentation Number: 1133
Session: Concurrent Oral Session 23: Osteoporosis - Treatment (Clinical)
Sunday, October 14, 2012 2:45 PM - 3:00 PM, Minneapolis Convention Center, Auditorium-Main
Ken Poole, University of Cambridge , * Graham M. Treece, University of Cambridge, Andrew Gee, University of Cambridge, , CANADA, Michael R. McClung, Oregon Osteoporosis Center , Andrea Wang, Amgen Inc., Cesar Libanati, Amgen Inc.
Purpose:Denosumab (a RANK ligand antibody) reduces remodeling, increases bone mineral density, and reduces cortical porosity in postmenopausal women with osteoporosis. In FREEDOM, denosumab treatment reduced the relative risk of hip fracture by 62% in those ≥ 75 years (Boonen JCEM 2011). Bone strength at the hip, estimated by FEA from QCT scans, was significantly improved from baseline and compared with placebo (Keaveny ASBMR 2010). To better characterize the changes, we used a novel cortical bone mapping technique on those same serial QCT scans, to determine the extent and distribution of mass and thickness changes at the proximal femur, a key skeletal site for fracture risk.
Methods: Eighty women age 74±5 years who participated in a FREEDOM substudy underwent hip QCT scanning at baseline, and months 12, 24, and 36 during denosumab (60 mg SC Q6M) or placebo treatment; all subjects received calcium and vitamin D supplementation. For each femur, in addition to overall cortical density, the distributions of cortical mass (in mg per unit cm2 of periosteal surface) and thickness were measured in a blinded-to-treatment manner. Distributed measures were transferred to an average femur by first registering each individual femur to this surface. Statistical parametric mapping was used to calculate significance of denosumab or placebo effects at each time point in relation to baseline, and between treatments. Distributed results were visualised as a color map over the average femur.
Results:In denosumab-treated women, there was a progressive increase in cortical mass over time, reaching a difference vs placebo of ~6% at 3 years (p<0.0001) (Fig. 1). Approximately one-third of this increase was attributed to an increase in cortical density of 7.6±1.8 mg/cm3/year (p<0.0001), which in turn remained unchanged in placebo-treated subjects (p=0.62). With denosumab, cortical thickness was also significantly increased, which may represent in-filling of the cortical compartment. In contrast, average cortical mass and thickness decreased in subjects who received calcium and vitamin D alone. Mass color maps (Fig. 2) reveal the distribution of increases in cortical mass with denosumab, which were significant over an increasingly large area of the proximal femur.
Conclusion: In postmenopausal women with osteoporosis, administration of denosumab significantly and progressively increased cortical mass and thickness in regions of the proximal femur associated with hip fracture.
M. McClung, Amgen Inc., Lilly, Novartis, Warner Chilcott: Speaker's Bureau. J. Brown, Amgen Inc., Eli Lilly, Merck, Novartis, sanofi-aventis, Warner Chilcott: Consulting fees or other remuneration (payment). A. Gee, Amgen Inc.: Research Grants. J. Brown, Amgen Inc., Abbott, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, sanofi-aventis, Servier, Warner Chilcott: Research Grants. J. Brown, Amgen Inc., Eli Lilly, Novartis: Speaker's Bureau. M. McClung, Amgen Inc., Merck: Research Grants. K. Poole, Amgen Inc.: Research Grants. C. Libanati, Amgen Inc.: Employment (full or part-time). A. Wang, Amgen Inc.: Employment (full or part-time). C. Libanati, Amgen Inc.: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. K. Poole, Amgen Inc., Servier: Consulting fees or other remuneration (payment). A. Wang, Amgen Inc.: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. G. Treece, Amgen Inc.: Research Grants. K. Poole, Amgen Inc., Lilly: Speaker's Bureau. M. McClung, Amgen Inc., Lilly, Merck, Novartis: Consulting fees or other remuneration (payment).
* Presenting Authors(s):
Graham M. Treece, University of Cambridge