A study comparing denosumab (Prolia) with risedronate (Actone) found that denosumab could be a useful treatment option for patients newly initiating or continuing glucocorticoids who are at risk of fractures. It is the first study to show that denosumab can increase bone mineral density at both the spine and the hip in patients with glucocorticoid-induced osteoporosis.
A study comparing denosumab (Prolia) with risedronate (Actonel) found that denosumab could be a useful treatment option for patients newly initiating or continuing glucocorticoids who are at risk of fractures.
It is the first study to show that denosumab can increase bone mineral density at both the spine and the hip in patients with glucocorticoid-induced osteoporosis.
Glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis and is associated with an estimated annual fracture rate of 5%, according to a recent study in The Lancet Diabetes and Endocrinology. Glucocorticoids are used in autoimmune conditions, rheumatological diseases like rheumatoid arthritis, and respiratory diseases like asthma and gastrointestinal disorders.
Denosumab is given by injection every 6 months and is approved for postmenopausal women who are at high risk for fracture or who cannot use another osteoporosis medicine or do not tolerate other osteoporosis medicines well. Risedronate comes in a tablet form. Both drugs belong to a class of agents called bisphosphonates.
Amgen received FDA approval in May for an expanded indication for glucocorticoid-induced osteoporosis for denosumab.
The study, conducted over 24 months in 79 locations worldwide, sought to assess the efficacy and safety of denosumab compared with risedronate in glucocorticoid-induced osteoporosis.
The primary outcome was noninferiority of denosumab to risedronate in terms of percentage change from baseline in lumbar spine bone mineral density at 12 months based on noninferiority margins (—0.7 and –1.1 percentage points for the glucocorticoid-continuing and glucocorticoid-initiating subpopulations, respectively).
Superiority was assessed as a secondary outcome.
Eligible patients were aged 18 years or older and were receiving glucocorticoids (≥7.5 mg prednisone daily, or equivalent) for at least 3 months (glucocorticoid-continuing group) or less than 3 months (glucocorticoid-initiating group).
Patients younger than 50 years needed to have a history of osteoporosis-related fracture.
Glucocorticoid-continuing patients 50 years or older needed a lumbar spine, total hip, or femoral neck bone mineral density T score of —2.0 or less, or –1.0 or less if they had a history of osteoporosis-related fracture.
Participants were randomly assigned (1:1) to either 60 mg subcutaneous denosumab every 6 months and oral placebo daily for 24 months, or 5 mg oral risedronate daily and subcutaneous placebo every 6 months for 24 months.
The study included 795 patients, 505 of whom were glucocorticoid-continuing and 290 of whom were glucocorticoid-initiating. They were then randomly assigned, with 398 to denosumab and 397 to risedronate.
Denosumab was both noninferior and superior to risedronate at 12 months in terms of lumbar spine bone mineral density in both glucocorticoid-continuing (4.4% [95% CI, 3.8%-5.0%] vs 2.3% [95% CI, 1.7%-2.9%]; P <.0001) and glucocorticoid-initiating (3.8% [95% CI, 3.1%-4.5%] vs 0.8% [95% CI, 0.2%-0.5%]; P <.0001) subpopulations, and superior to risedronate in terms of total hip bone mineral density in both glucocorticoid-continuing (2.1% vs 0.6%; P <.0001) and glucocorticoid-initiating (1.7% vs 0.2%; P <.0001) subpopulations.
Saag KG, Wagman RB, Geusens P. Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study [published online April 6, 2018]. Lancet Diabetes Endocrinol. doi: 10.1016/ S2213-8587(18)30075-5.