Femur QCT Analysis using MIAF in Postmenopausal Women Treated with Odanacatib - Results of a 2-year Placebo-controlled Trial
Osteoporosis - Treatment (Clinical)
Osteoporosis - Assessment
Oral Presentations, Presentation Number: 1173
Session: Concurrent Oral Session 29: Osteoporosis - Treatment (Clinical)
Monday, October 15, 2012 11:00 AM - 11:15 AM, Minneapolis Convention Center, Auditorium-Main
* Klaus Engelke, University of Erlangen, DEU, Thomas Fuerst, Synarc Inc, USA, Bernard Dardzinski, Merck Sharp & Dohme Corp.,, USA, John Kornak, UCSF, Dep. of Epidemiology and Biostatistics, USA, Shabana Ather, Merck and Co, Inc., USA, Harry Genant, UCSF/Synarc, USA, Anne De Papp, Merck & Co., Inc., USA
Background: Odanacatib, a selective cathepsin K inhibitor, increases areal BMD at the spine and hip of postmenopausal women. To gain additional insight into the clinical effects in trabecular and cortical bone of odanacatib, we assessed femoral BMD by QCT in postmenopausal women treated with odanacatib.
Methods: This international, randomized, double-blind, placebo-controlled, 2-year, phase 3 trial enrolled 214 postmenopausal women with a mean age of 64 years and mean BMD T-scores of -1.8 at the lumbar spine and femoral neck. Subjects were randomized to odanacatib 50 mg weekly (ODN) or placebo (PBO); all participants received calcium and vitamin D. Hip QCT scans at 2 years were available for a subset of these women (n=158, ODN (78), PBO (80)). BMD, BMC and volume of the integral, cortical and trabecular compartments were measured in the QCT images using MIAF (Erlangen, Germany). Subregions included the neck, trochanter and intertrochanter . Results are presented as percent change from baseline after 2 years of treatment.
Results: There were consistent and significant differential treatment effects (ODN-PBO) for integral, trabecular and cortical BMD at 24 months (see table). With no significant differential treatment effect on total femur volume, the results for BMC closely matched those of BMD for integral and trabecular compartments, respectively. However, with small but mostly significant differential increases in cortical volume (1.0-1.3%) and thickness (1.4-1.9%), the percent cortical BMC increases were numerically larger than those of BMD.
With a total femur BMC differential treatment effect (ODN-PBO) of nearly 1000mg, the proportion of BMC attributed to cortical gain was 45%, 44% 52%, 40% for the total, neck, trochanter and intertrochanter subregions, respectively.
Conclusions: In postmenopausal women treated for 2 years, odanacatib improved integral, trabecular and cortical BMD as well as BMC at all regions of the femur relative to placebo. Cortical volume and thickness significantly increased in all regions except the neck, where it was marginally non-significant. The increase in cortical volume and BMC paralleled the increase in cortical BMD, demonstrating a consistent effect of ODN on cortical bone. Approximately one-half of the absolute BMC gain occurred in cortical bone.
Disclosures: T. Fuerst, Synarc: Employment (full or part-time). A. De Papp, Merck: Employment (full or part-time). S. Ather, Merck: Employment (full or part-time). K. Engelke, Synarc: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. A. De Papp, Merck: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. K. Engelke, Synarc: Employment (full or part-time). H. Genant, Merck: Consulting fees or other remuneration (payment). B. Dardzinski, Merck: Employment (full or part-time). H. Genant, Synarc: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. B. Dardzinski, Merck: Stock options or bond holdings in a for-profit corporation or self-directed pension plan. T. Fuerst, Synarc: Stock options or bond holdings in a for-profit corporation or self-directed pension plan.
* Presenting Authors(s): Klaus Engelke, University of Erlangen, DEU