Kenneth G. Saag
Adults with a history of glucocorticoid-induced osteoporosis assigned to therapy with the monoclonal antibody denosumab experienced a greater increase in bone mineral density at the lumber spine and total hip at 12 months vs. similar patients assigned the bisphosphonate risedronate, according to findings from a global, randomized, active-controlled trial.
“Glucocorticoid-induced osteoporosis is a very common cause of metabolic bone disease, perhaps the second most common cause for osteoporosis beyond menopause and aging,” Kenneth G. Saag, MD, professor in the division of clinical immunology and rheumatology at the University of Alabama, told Endocrine Today. “We need more ways to manage it. There are a great number of patients that aren’t getting tested or treated for osteoporosis, and now there is promising evidence from a study comparing denosumab with risedronate that it is efficacious, and, in fact, it looks to be more efficacious than risedronate in terms of increasing BMD at the typical sites that we assess.”
Saag and colleagues analyzed data from 795 adults prescribed glucocorticoid therapy ( 7.5 mg prednisone daily or equivalent) for at least 3 months (glucocorticoid continuing; n = 505) or less than 3 months (glucocorticoid initiating; n = 290) before screening from 79 primary care and specialist centers in Asia, Europe, Latin America and North America. Participants younger than 50 years had a history of osteoporosis-related fracture, whereas those aged at least 50 years had a lumbar spine, total hip or femoral neck T score of –2 or less or a T score of –1 or less with a history of osteoporosis-related fracture. Researchers randomly assigned participants to 60 mg subcutaneous denosumab (Prolia, Amgen) every 6 months and an oral placebo daily for 24 months (n = 398) or 5 mg oral risedronate daily and subcutaneous placebo every 6 months for 24 months (n = 397). Primary outcome was noninferiority of denosumab to risedronate in percentage change from baseline in lumbar spine BMD at 12 months, based on noninferiority margins. Superiority was assessed as a secondary outcome.
Researchers found that denosumab was noninferior to risedronate for the primary outcome in glucocorticoid-continuing participants (4.4% vs. 2.3%) and in glucocorticoid-initiating participants (3.8% vs. 0.8%). Denosumab was superior to risedronate for both secondary and exploratory BMD endpoints at 12 months, according to the researchers. The difference in mean percentage change from baseline in BMD at 12 months between denosumab and risedronate was 2.2% (95% CI, 1.4-3) for lumbar spine, 1.5% (95% CI, 1-2.1) for total hip and 1% (95% CI, 0.3-1.7) for the femoral neck in the glucocorticoid-continuing participants. For those in the glucocorticoid-initiating group, the difference in mean percentage change from baseline in BMD at 12 months between denosumab and risedronate was 2.9% (95% CI, 2-3.9) for lumbar spine, 1.5% (95% CI, 0.8-2.1) for total hip and 1.1% (95% CI, 0.2-2.1) for the femoral neck.
There were no serious adverse events reported in more than 2% of patients in either group. There were no positively adjudicated cases of osteonecrosis of the jaw in either study arm, according to the researchers. The most commonly reported serious adverse event in the risedronate and denosumab groups was pneumonia (2% vs. 1%, respectively).
Osteoporosis-related fractures were similar in the risedronate and denosumab groups (6% for both), as were new and worsening vertebral fractures (4% vs. 3%, respectively) and low-trauma, nonvertebral fractures (3% vs. 4%, respectively).
“The increases in bone mineral density at the lumbar spine with denosumab in our study were similar to, or better than, those with alendronate and zoledronic acid seen in previous non-head-to-head studies in glucocorticoid-induced osteoporosis, and those with denosumab in a study in patients with rheumatoid arthritis not on glucocorticoids,” the researchers wrote.
The researchers noted that therapies that need to be taken frequently might result in low adherence, adding that denosumab does not embed into the bone matrix, making its effect reversible after discontinuation.
“Denosumab is very targeted in its mechanism, targeting the cross-talk between bone cells, the osetoclasts and the osteocytes, and blocks bone resorption through that mechanism,” Saag said. “It doesn’t accumulate in bone like bisphosphonates and may be safer to use in younger individuals and in people with some degree of kidney dysfunction.” – by Regina Schaffer
For more information:
Kenneth G. Saag, MD, can be reached at the University of Alabama, 820 Faculty Office Tower, 510 20th Street South, Birmingham, AL 35294; email: firstname.lastname@example.org.
Disclosures: Amgen funded this study. Saag reports he has received grants and consultant fees from Amgen, Lilly, Merck and Radius. Please see the study for all other authors’ relevant financial disclosures.