SEATTLE — Denosumab treatment appears to increase bone mineral density at several skeletal sites and reduce bone remodeling more than zoledronic acid in postmenopausal women with osteoporosis previously treated with oral bisphosphonates, new data suggest.

In a study presented at the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting, researchers reported that patients achieved greater gains at the lumbar spine and other measured skeletal sites, as compared with intravenous (IV) zoledronic acid, in postmenopausal women with osteoporosis following previous treatment oral bisphosphonates.

Denosumab is the first approved therapy that specifically targets RANK ligand, an essential regulator of osteoclasts.

The randomized, double-blind, double-dummy, multicenter, 12-month, phase 4 study included 643 women aged 55 years or older who had postmenopausal osteoporosis (mean age, 69 years).

All the women in the study had a bone mineral density (BMD) T-score –2.5 or less at the lumbar spine, total hip, or femoral neck and had been taking oral bisphosphonate therapy for at least 2 years.

The women were randomly assigned in a 1:1 fashion to receive subcutaneous denosumab 60 mg every 6 months plus IV placebo once yearly (n=321) or IV zoledronic acid 5 mg once yearly plus subcutaneous placebo every 6 months (n= 322).

All the women also received supplemental calcium and vitamin D.

The researchers found that the change from baseline in lumbar spine BMD at 12 months — the primary end point — in the denosumab group was significantly greater than that in the zoledronic acid group (3.2% vs 1.1%; P<.0001).

The denosumab group also had significantly greater improvements than the zoledronic acid group in secondary and exploratory study end points, including BMD changes at the total hip (1.9% vs 0.6%), femoral neck (1.2% vs –0.1%), and 1/3 radius (0.6% vs 0%).

No new safety signals were identified in this study.

The two study groups had similar incidences of overall adverse events, serious adverse events, adverse events leading to discontinuation, and fatal adverse events. Three events consistent with the definition of atypical femoral fracture were observed, including 2 in the denosumab group and 1 in the zoledronic acid group.

There were no cases of osteonecrosis of the jaw, hypocalcemia, or delayed fracture healing.

Currently, oral bisphosphonates are the most commonly prescribed osteoporosis treatment. However, for several reasons, including inconvenient dosing regimens and side effects, compliance is an ongoing concern.

Once yearly zoledronic acid is part of the treatment algorithm for patients who have failed or are intolerant to oral bisphosphonates, but denosumab may be an alternative to consider, although more research is warranted.

Douglas Kiel, MD, MPH, who is president of ASBMR and a professor of medicine with Harvard Medical School in Boston, said this is an important study and may help guide clinicians. 

Nevertheless, future studies will be needed to investigate whether these improvements in bone parameters translate into lower fracture rates, he noted.

“Endocrinologists should care about this paper because there are many women treated for osteoporosis with oral bisphosphonates. These drugs are typically stopped at 3 to 5 years into treatment and risk is reassessed. If the risk for fracture is still high, most doctors will continue some sort of treatment,” Dr Kiel told Endocrinology Advisor

“If denosumab is producing greater increases in BMD than an IV bisphosphonate, a physician might be inclined to choose denosumab after a period of treatment with oral bisphosphonates. I would like to see a similar study to this one with fracture outcomes.”

Reference

  1. Miller P. Abstract SU0340: Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates: Efficacy and Safety Results From a Randomized Double-blind Study. Presented at: American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting; Oct. 9-12, 2015; Seattle.