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.

Trial registration: ClinicalTrials.gov NCT01575873.

Figure 1

Disposition of the patients enrolled in the study.

Figure 2

Percentage change from baseline in bone mineral density (BMD) at the lumbar spine (A), total hip (B), femoral neck (C), and 1/3 radius (D) for each subpopulation. Between‐group comparisons are based on analysis of covariance models with adjustment for treatment, baseline BMD, sex, machine type, and baseline BMD × machine type interaction. For the glucocorticoid‐continuing subpopulation, duration of prior glucocorticoid use (<12 months versus ≥12 months) was included as an additional covariate. Values are the least squares means and 95% confidence intervals. Q6M = once every 6 months; QD = once daily.

Figure 3

Percentage change from baseline (BL) in serum concentrations of C‐telopeptide of type I collagen (CTX) (A), a marker of bone resorption, and of N‐propeptide of type I collagen (PINP) (B), a marker of bone formation, in the combined subpopulations of the bone turnover marker substudy. Values are the median and interquartile range.* = P ≤ 0.05; ** = P ≤ 0.025; *** = P ≤ 0.001, by Wilcoxon's rank sum test. D10 = day 10; Q6M = once every 6 months; QD = once daily.