Romosozumab Outperforms Denosumab and Risedronate in Glucocorticoid-Induced Osteoporosis
Overview
In patients initiating glucocorticoid therapy for rheumatic diseases, romosozumab significantly increased lumbar spine bone mineral density (BMD) over 12 months compared to denosumab and bisphosphonates. Romosozumab also demonstrated a more favorable profile in bone formation markers, suggesting its dual anabolic and antiresorptive effects in glucocorticoid-induced osteoporosis (GIOP).
Background
Glucocorticoids are commonly prescribed for rheumatic diseases but induce osteoporosis by increasing bone resorption and impairing bone formation, especially affecting trabecular bone and increasing vertebral fracture risk early after treatment initiation. The Wnt/β-catenin pathway, inhibited by sclerostin, plays a key role in bone formation and resorption balance. Romosozumab, a monoclonal antibody against sclerostin, has shown efficacy in postmenopausal osteoporosis but its role in GIOP was previously unclear. Current standard treatments include bisphosphonates and denosumab, with teriparatide used less frequently due to administration challenges.
Data Highlights
Group
Number of Patients
Median % Change in Lumbar Spine BMD at 12 Months [25th-75th Percentile]
Romosozumab (ROMO)
11
8.6% [3.1-12.4]
Denosumab (DMAb)
14
3.3% [1.5-6.2]
Bisphosphonates (BP)
14
-0.4% [-3.4-1.1]
Key Findings
Romosozumab increased lumbar spine BMD by a median of 8.6% at 12 months, significantly greater than denosumab (3.3%) and bisphosphonates (-0.4%).
Bone formation marker bone alkaline phosphatase was slightly elevated in the romosozumab group, while other formation markers decreased less than in comparator groups.
Bone resorption markers and urine bone quality markers decreased across all treatment groups.
Romosozumab’s dual action of stimulating bone formation and inhibiting resorption may underlie its superior efficacy in GIOP.
Denosumab showed moderate increases in BMD, while bisphosphonates showed minimal or negative changes in lumbar spine BMD.
Clinical Implications
Romosozumab represents a promising initial treatment option for patients starting glucocorticoid therapy who are at risk for osteoporosis, offering superior improvements in bone density compared to standard antiresorptive agents. Its dual mechanism may provide enhanced protection against early glucocorticoid-induced bone loss and fracture risk. Clinicians should consider romosozumab especially in patients with high fracture risk or inadequate response to bisphosphonates.
Conclusion
Romosozumab significantly improves lumbar spine BMD in glucocorticoid-treated patients, outperforming denosumab and bisphosphonates, and offers a novel therapeutic approach for managing glucocorticoid-induced osteoporosis.
References
UMIN000037239 -- Efficacy Assessment of Romosozumab Versus Denosumab and Risedronate in Patients Starting Glucocorticoid Treatment
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