A new international, randomized, double-blind study indicates that denosumab is more efficacious than the bisphosphonate risedronate in boosting bone mineral density (BMD) at the lumbar spine in patients just starting or continuing steroid therapy
"Glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis and increases the risk of vertebral and nonvertebral fractures," Kenneth Saag, MD, the University of Alabama at Birmingham, and colleagues write.
"The 12-month results of this 24-month study showed that denosumab was superior to risedronate, a commonly used bisphosphonate for glucocorticoid-induced osteoporosis, in increasing bone mineral density at the lumbar spine, the two treatments groups had similar safety profiles," investigators add.
The latter has shown the potency of denosumab in increasing BMD compared with alendronate in postmenopausal osteoporosis and delaying skeletal-related events compared with zoledronic acid in patients with bone metastases in advanced cancer, they note.
They caution that BMD "is not the ideal surrogate for trials in patients with glucocorticoid-induced osteoporosis, because it underestimates fracture risk given the extraskeletal adverse effects of glucocorticoids on muscle function and falls."
Denosumab is currently indicated in the US for use in postmenopausal women with osteoporosis at high risk for fracture. It is also approved for treatment to increase bone mass in men with osteoporosis at high risk for fracture. It is indicated for the treatment of glucocorticoid-induced osteoporosis in Canada, but not in the United States.
In 795 patients, 505 of whom were glucocorticoid continuing, and 290 of whom were glucocorticoid initiating, were enrolled and randomly assigned (398 to denosumab, 397 to risedronate).
Denosumab was both non-inferior and superior to risedronate at 12 months for effect on bone mineral density at the lumbar spine in both glucocorticoid-continuing (4·4% [95% CI 3·8–5·0] vs 2·3% [1·7–2·9]; p<0·0001) and glucocorticoid-initiating (3·8% [3·1–4·5] vs 0·8% [0·2–1·5]; p<0·0001) subpopulations.
The incidence of adverse events, serious adverse events (including infections), and fractures was similar between treatment groups. The most common adverse events were back pain (17 [4%] patients in the risedronate group and 18 [5%] in the denosumab group) and arthralgia (21 [5%] patients in the risedronate group and 17 [4%] in the denosumab group). Severe infection occurred in 15 (4%) patients in the risedronate group and 17 (4%) patients in the denosumab group.
"The primary outcome was noninferiority of denosumab to risedronate regarding percentage change from baseline in lumbar spine bone mineral density at 12 months," the authors note.
The incidence of adverse events was similar in both treatment groups with no signal of an increased risk of severe infection in high-risk subgroups taking denosumab who also required concomitant biologic or immunosuppressant therapy; investigators point out.
"To our knowledge, ours is the first large, randomized controlled trial of denosumab in patients with glucocorticoid-induced osteoporosis who were either prevalent glucocorticoid users or newly initiating glucocorticoid therapy," researchers state."The study suggests that denosumab could be a useful addition to the treatment armamentarium for glucocorticoid-induced osteoporosis," they conclude.