Denosumab Versus Risedronate in Glucocorticoid‐Induced Osteoporosis: Final Results of a Twenty‐Four–Month Randomized, Double‐Blind, Double‐Dummy Trial

Abstract

Objective Clinical trial results have shown that, in glucocorticoid‐treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. Methods This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid‐initiating) or for ≥3 months (glucocorticoid‐continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid‐continuing patients ≥50 years old had T scores of −2.0 or less (or −1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D. Results Of 795 patients, 590 (74.2%) completed the study (in the glucocorticoid‐initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid‐continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid‐initiating patients (24‐month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24‐month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid‐continuing patients (24‐month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24‐month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups. Conclusion Denosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid‐treated patients.

Management of glucocorticoid‐induced osteoporosis: What is new?

“…These include the bisphosphonates alendronate, risedronate and zoledronic acid, teriparatide and, most recently, denosumab. 24 The evidence for efficacy of these drugs is based primarily on BMD changes and fracture prevention was not a primary outcome in any of the clinical trials. Nevertheless, some fracture data are available from secondary end-points, post hoc analyses, and observational data.…”

“…28,29 In 2 other comparator randomized controlled trials, superiority of zoledronic acid and denosumab over risedronate was demonstrated for BMD end-points, but whether this translates into greater fracture protection is unknown. 24,30 Although the number of non-vertebral and hip fractures in randomized controlled trials has been insufficient to demonstrate antifracture efficacy at these sites, observational data provide some evidence for a protective effect in bisphosphonate-treated glucocorticoid users. In women aged >65 years starting glucocorticoid therapy and treated with alendronate or risedronate, Thomas et al reported that clinical vertebral and non-vertebral fracture incidence at 1 year was significantly lower when compared to the fracture incidence during the first 3 months.…”

“…A range of pharmacological options is approved for glucocorticoid‐treated postmenopausal women and older men who are at increased risk of fracture. These include the bisphosphonates alendronate, risedronate and zoledronic acid, teriparatide and, most recently, denosumab . The evidence for efficacy of these drugs is based primarily on BMD changes and fracture prevention was not a primary outcome in any of the clinical trials.…”

“…In randomized controlled trials, a reduction in vertebral fracture was demonstrated for alendronate and risedronate; furthermore, in a comparator trial a significantly greater reduction in vertebral fracture was demonstrated for teriparatide than for alendronate, after both 24 and 36 months of treatment . In 2 other comparator randomized controlled trials, superiority of zoledronic acid and denosumab over risedronate was demonstrated for BMD end‐points, but whether this translates into greater fracture protection is unknown …”

Where Does Denosumab Stand in the Treatment of Glucocorticoid‐Induced Osteoporosis? Comment on the Article by Saag et al

“…We read with interest the article by Dr. Saag et al in which they compared the efficacy and safety of denosumab versus risedronate in glucocorticoid-induced osteoporosis (GIOP) (1). Osteoporosis in the setting of GIOP can be challenging to treat because of issues with drug adherence (due to pill burden) and the presence of multiple comorbidities.…”