“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,” Dr. Saag and colleagues write. The findings suggest that denosumab “could be a useful addition to the treatment armamentarium for glucocorticoid-induced osteoporosis,” they conclude.
Drs. Tsourdi and Hofbauer note that the trial was not powered to detect differences in fracture rates between the denosumab and risedronate group, and BMD is “not the ideal surrogate for trials in patients with glucocorticoid-induced osteoporosis, because it underestimates fracture risk in view of the extraskeletal adverse effects of glucocorticoids on muscle function and falls.”
Also, the data are for only the first 12 months of denosumab treatment. The question of how long denosumab should be used for remains unanswered, they say.
“Many patients require long-term, if not life-long glucocorticoid therapy (eg, those with some autoimmune diseases or who have undergone allogeneic transplantation), and thus need concomitant long-term bone-protective therapy,” they point out.
They also caution that in postmenopausal osteoporosis, discontinuing denosumab leads to a rapid decrease in BMD. “This rebound effect after denosumab discontinuation, which is accompanied by upregulation of bone turnover markers, should guide clinical judgement against stopping denosumab in patients continuing glucocorticoid treatment,” write Dr. Tsourdi and Dr. Hofbauer.
“In patients discontinuing glucocorticoids, assessment of fracture risk should be done. Overall, Saag and colleagues’ study is an important step towards improved treatment options for glucocorticoid-induced osteoporosis,” they conclude.
The study was funded by Amgen, which markets denosumab as Prolia. Dr. Saag and Drs. Tsourdi and Hofbauer have disclosed financial relationships with the company.
- Saag KG, Wagman RB, Geusens P, et al. Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study. Lancet Diabetes Endocrinol. 2018 Apr 6. pii: S2213-8587(18)30075-5. [Epub ahead of print]