WASHINGTON – Denosumab built significantly more bone at the hip and lumbar spine than did risedronate when given for 1 year to patients with glucocorticoid-induced osteoporosis in an ongoing 2-year, head-to-head, randomized trial.
Denosumab (Prolia) is currently approved for the treatment of postmenopausal osteoporosis, and it performed so well in the trial that it could be put forward for the indication of glucocorticoid-induced osteoporosis as well, Kenneth Saag, MD, said at the annual meeting of the American College of Rheumatology.
“I would say there is definitely potential for this as a new therapeutic option for these patients,” he said in a video interview about the trial’s primary outcome of denosumab’s noninferiority to risedronate in percentage change in bone mineral density (BMD) at the lumbar spine after 1 year and secondary outcomes of the superiority of denosumab over risedronate in total hip and lumbar spine BMD at 1 year.
Denosumab is a particularly intriguing treatment option for patients with glucocorticoid-induced osteoporosis. They experience a double hit on bone health: increased RANKL, a protein that stimulates osteoclast development, and decreased osteoprotegerin, a protein that inhibits osteoclasts. Denosumab is a RANKL-inhibitor and, as such, tamps down on osteoclastic bone remodeling, said Dr. Saag, vice chair of the department of medicine and director of the Center for Education and Research on Therapeutics at the University of Alabama at Birmingham.
The phase III trial comprised 795 patients who were taking corticosteroids for a variety of rheumatic diseases, including rheumatoid arthritis, polymyalgia rheumatica, and systemic lupus erythematosus, and randomized them to denosumab or risedronate, which is already FDA approved for glucocorticoid-induced bone loss. Patients were randomized to 24 months of subcutaneous denosumab 60 mg given every 6 months or oral risedronate 5-mg daily. The study is still ongoing to test secondary outcomes at 24 months.
The patients were split into those who were continuing glucocorticoid therapy (505) and those who were just initiating it (290). Patients’ mean age ranged from 61 to 67 years, with the glucocorticoid-initiating group (GC-I) being somewhat older. The mean daily prednisone-equivalent dose was 16 mg in that group and 12 mg in the glucocorticoid-continuing group (GC-C). The mean BMD T-scores in the GC-C group were –1.96 at the lumbar spine and –1.56 at the total hip. In the GC-I group, BMD T-scores were –1.06 at the lumbar spine and –0.98 at the total hip.
In the GC-C group, denosumab increased BMD significantly more than risedronate at both spine and hip. At the lumbar spine, denosumab was associated with a mean increase of 4.4% over baseline, compared with a 2.3% increase with risedronate. Total hip BMD increased 2.1% with denosumab and 0.6% with risedronate.
The results were similar in the GC-I group. Denosumab increased lumbar spine BMD by 3.8% over baseline, compared with an increase of 0.8% with risedronate. Total hip BMD increased 1.7% with denosumab and 0.2% with risedronate.
Denosumab was also associated with significantly greater increases in femoral neck BMD in both groups, Dr. Saag noted. There were no significant differences in markers of bone turnover between the treatment groups. Adverse events, including pneumonia, diverticulitis, and bronchitis, were similar.
Amgen, manufacturer of denosumab, is sponsoring the 24-month study. Dr. Saag has been a consultant for Amgen. One coauthor is an employee of Amgen, and others disclosed financial relationships with Amgen and other pharmaceutical companies.
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