BOSTON — The investigational antiresorptive denosumab is at least as effective as alendronate for increasing bone mineral density in postmenopausal women, Dr. Nelson Watts said at the annual meeting of the Endocrine Society.
The drug inhibits RANKL (receptor activator of nuclear factor kappa B ligand), which is a mediator of the resorptive phase of bone remodeling. Interfering with the binding of RANK to its ligand inhibits the differentiation and proliferation of osteoclasts, thus reducing bone turnover, said Dr. Watts, director of the bone health and osteoporosis center at the University of Cincinnati. He presented the 24-month bone mineral density (BMD) results of a phase II safety and efficacy trial of denosumab. The trial compared denosumab with open-label alendronate, 70 mg weekly, and placebo in 412 postmenopausal women with low bone mass. Three doses of denosumab were tested; Dr. Watts discussed the results for 60-mg doses given subcutaneously every 6 months. This dosage was selected for evaluation in phase III clinical testing.
At 24 months, denosumab was associated with a significantly higher mean increase in BMD than was alendronate at all skeletal sites measured, including lumbar spine (7% vs. 6%), total hip (5% vs. 3.5%), and distal radius (1.75% vs. 0.5%).
Adverse events occurred in about 93% of patients in both groups, and the types of events were not significantly different, with the exception of more dyspepsia among those taking alendronate, Dr. Watts said. There were no signs of increased immune problems, infections, or neoplasms in either group.
In a post hoc analysis, significantly more women in the denosumab group experienced a gain of more than 3% in BMD at each site measured, including lumbar spine (93% vs. 87%), total hip (80% vs. 56%), femoral neck (60% vs. 41%), and distal radius (25% vs. 11%).
The trial was sponsored by Amgen Inc., which manufactures denosumab.