Femur QCT Analysis using MIAF in Postmenopausal Women Treated with Odanacatib: Results of a 2-year Placebo-controlled Trial

Introduction:  It is known that odanacatib, which is a selective cathepsin K inhibitor, increases areal bone mineral density (BMD) in postmenopausal women at the spine and hip.  This study was done to further examine the effect of odanacatib on trabecular and cortical bone.  Femoral BMD was assessed by QCT in postmenopausal women on odanacatib.

Methods:  Two-hundred-fourteen postmenopausal women were in this international, randomized, double-blind, placebo-controlled, 2-year, phase 3 trial.  The mean age of the participants was 64 years; the mean BMD T-scores at the lumbar spine and femoral neck were 1.8.

Participants were randomized into 2 groups:  odanacatib 50 mg weekly (ODN) or placebo (PBO).  No matter which group participants were in, they also received calcium and vitamin D.

For a subset of the participants, hip QCT scans at 2 years were available (n = 158; ODN [78] and PBO [80]).  Using those images, BMD, BMC, and volume of the integral, cortical, and trabecular compartments were measured using MIAF.  The neck, trochanter, and intertrochanter were subregions.  The results are presented as the he percent change from baseline to after 2 years of treatments.

Results:  At 24 months, consistent and significant differential treatment effects were seen for integral, trabecular, and cortical BMD.

The results for BMC closely matched the BMD results for integral and trabecular compartments, but there was no significant differential treatment effect on total femur value.  Cortical volume and cortical thickness, though, showed small but mostly significant differential increases:  cortical volume was 1.0-1.3%, and cortical thickness was 1.4-1.9%.  Those increases mean that the percent cortical BMC increases were numerically larger than those increases in BMD.

The total femur BMC differential treatment effect was almost 1000 mg; therefore, the proportion of BMC attributed to cortical gain was 45% (total), 44% (neck), 52% (trochanter), and 40% (intertrochanter).

Conclusions:  Relative to placebo, odanacatib treatment for 2 years improved integral, trabecular, and cortical BMD at all regions of the femur in postmenopausal women; it also improved BMC in those regions.  In all regions but the neck, cortical volume and thickness increased significantly with odanacatib treatment.  In the neck, its effect was marginally non-significant.  This study demonstrates that odanacatib has a consistent effect on cortical bone because the increase in cortical volume and BMC paralleled cortical BMD increase.  Of the absoluter BMC gain, approximately one-half occurred in cortical bone.

Commentary by Pauline M. Camacho MD, FACE

Odanacatib is another promising agent for osteoporosis. Cathepsin K plays a vital role in the degradation of bone matrix during bone resorption. Odanacatib is a highly selective, non-lysosomotropic molecule targeted to cathepsin K.

In the phase II trial, there was a significant increase in spine BMD in the lumbar spine versus a loss with placebo. This phase III trial evaluated using quantitative CT the drug effect on several areas of the femur. There were significant increases in bone mineral density and bone mineral content in all areas of the femur.