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

Arthritis Rheumatol. 2019 Jul;71(7):1174-1184. doi: 10.1002/art.40874. Epub 2019 May 25.

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.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Aged
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Density*
  • Bone Remodeling
  • Collagen Type I / metabolism
  • Denosumab / therapeutic use*
  • Double-Blind Method
  • Female
  • Femur Neck / diagnostic imaging
  • Glucocorticoids / adverse effects*
  • Hip / diagnostic imaging
  • Humans
  • Lumbar Vertebrae / diagnostic imaging
  • Male
  • Middle Aged
  • Osteoporosis / chemically induced
  • Osteoporosis / drug therapy*
  • Osteoporosis / metabolism
  • Osteoporotic Fractures / prevention & control*
  • Peptide Fragments / metabolism
  • Peptides / metabolism
  • Procollagen / metabolism
  • Risedronic Acid / therapeutic use*
  • Treatment Outcome

Substances

  • Bone Density Conservation Agents
  • Collagen Type I
  • Glucocorticoids
  • Peptide Fragments
  • Peptides
  • Procollagen
  • collagen type I trimeric cross-linked peptide
  • procollagen Type I N-terminal peptide
  • Denosumab
  • Risedronic Acid

Associated data

  • ClinicalTrials.gov/NCT01575873