By Frances Morin  

BOSTON  April 4, 2016

We found that in postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab treatment was associated with greater transient increases in serum iPTH versus zoledronic acid and greater gains in bone mineral density at all measured skeletal sites,” said Paul D. Miller, MD, Colorado Center for Bone Research, Lakewood, Colorado.

The transient increases in serum iPTH that are associated with the drug may further increase bone modelling when osteoclastic bone resorption is fully inhibited, he explained.

The greater increase in serum iPTH has been observed with denosumab compared to oral alendronate; however, the comparison with an intravenous (IV) bisphosphonate has not been previously demonstrated.

For the current study, the researchers analysed data from a randomised, double-blind, double-dummy study of 643 postmenopausal women who had been treated with oral bisphosphonates for 2 or more years and had bone mineral density (BMD) scores of -2.5 or less at the lumbar spine, total hip or femoral neck.

The women were randomised 1:1 to denosumab 60 mg subcutaneously every 6 months plus placebo (IV once) or zoledronic acid 5 mg (IV once) plus placebo for 12 months. All patients received daily calcium and vitamin D.

In a subset of 117 subjects, including 61 in the denosumab group and 56 in the zoledronic acid group that were evaluated for serum iPTH levels, those in the denosumab group showed significant median increases in serum iPTH compared with baseline at month 1 (33.9%), month 3 (19.7%), and month 9 (10.3%), while those in the zoledronic acid group only showed iPTH increases at month 1 (15.1%; P < .05 for all).

Compared with the median percentage changes from baseline in serum iPTH at months 3 and 9 with denosumab (19.7% and 10.3%, respectively), the zoledronic acid group showed reductions (-5.6% and -8.9%, respectively; P < .05).

Neither group showed significant percentage changes from baseline in serum albumin-adjusted calcium, with the exception of the zoledronic acid group at month 12 (+1.0%; P < .01).

“These data help support the hypothesis that the unique mechanism of action of denosumab is due to its direct effect to fully and rapidly inhibit osteoclastic activity at cortical and trabecular bone and its indirect effect to increase serum iPTH,” said Dr. Miller.