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Odanacatib increased BMD, bone strength in postmenopausal women
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Results from a phase 3 trial of an investigational cathepsin inhibitor suggest improved overall proximal femoral strength due to increasing trabecular bone mineral density and endosteal bone apposition at the femoral neck in postmenopausal women.
Researcher Kim Brixen, MD, PhD, professor and head of the Institute of Clinical Research at the University of Southern Denmark, and colleagues conducted the randomized, double blind, international, 2-year phase 3 trial to compare once-weekly odanacatib (Merck) 50 mg with placebo in postmenopausal women (n=214; average age, 64 years) treated with calcium and vitamin D. According to data, patients’ baseline T-score was –1.8 at the lumbar spine, –1.8 at the femoral neck and –1.3 at the total hip.
“The percent change from baseline in areal BMD (aBMD) at the lumbar spine at 1 year, the primary endpoint of the trial, was significantly (P<.001) higher in women receiving odanacatib compared with placebo (treatment differences: 3.5%),” the researchers wrote. “The treatment difference increased in the second year to 5.4%.”
Other data indicate significantly greater mean percent changes at 2 years in aBMD at the femoral neck (3.8%), total hip (3.3%) and trochanter (5.5%; P<.001) in women who received odanacatib.
Furthermore, bone resorption marker C-telopeptide of type 1 collagen was significantly lower in patients assigned odanacatib vs. placebo at 6 months and 2 years (P<.001). By 6 months, the researchers discovered that women treated with odanacatib displayed greater increases in trabecular volumetric BMD and estimated compressive strength at the spine and integral and trabecular volumetric BMD, and estimated strength at the hip (P<.001). At 24 months, the cortical envelope of the femoral neck, bone mineral content, thickness, volume and cross-sectional area also increased from baseline with patients assigned odanacatib vs. placebo (P<.001), they wrote.
“It is likely that this osteoclast-rich environment provides the stimulus for osteoblastic bone formation. This is distinctly different from what is seen historically with the use of bisphosphonates and denosumab [Prolia, Xgeva; Amgen], which reduce both bone formation and bone resorption.”
Overall, odanacatib was well tolerated with no skin, respiratory, dental, delayed fracture union or other adverse events suggestive of a scleroderma-like skin thickening, as seen in balicatib in phase 2 clinical trials, the researchers concluded.
These findings suggest that odanacatib improved overall proximal femoral strength.
Disclosure: Several researchers report relevant financial ties with Amgen, Lilly, Merck, Novartis and Synarc.
Perspective
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Clifford J. Rosen, MD
I believe the data from Brixen and colleagues further lend support to the tenet that odanacatib can improve bone mass in postmenopausal women. The effects are most likely due to decreased bone resorption, although unlike the bisphosphonates, this agent does not suppress bone formation. Its effects on bone strength are likely to be positive but have to be demonstrated with several surrogates beyond what has been shown in this study. And of course fracture risk reduction will be the ultimate determinant of how effective this drug is.
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