Glucocorticoid-Induced Osteoporosis: Mechanisms, Risk Factors, and Prevention

How Steroids Cause Bone Loss

Long-term glucocorticoid therapy (prednisone ≥5 mg/day for >3 months) is the most common cause of secondary osteoporosis. Multiple mechanisms converge to reduce bone formation and increase resorption.

Key Pathophysiologic Pathways

1. ↓ Osteoblastogenesis & Osteoblast Function: Glucocorticoids inhibit Wnt/β-catenin signaling, promote osteoblast apoptosis, reduce collagen synthesis.
2. ↑ Osteoclast Survival & Activity: Increase RANKL/OPG ratio; prolong osteoclast lifespan.
3. ↓ Intestinal Calcium Absorption: Antagonize vitamin D action; reduce TRPV6 expression.
4. ↑ Renal Calcium Excretion: Reduce distal tubular reabsorption.
5. ↓ Sex Hormones: Suppress gonadal axis → hypogonadism → bone loss.
6. Muscle Weakness & Falls: Proximal myopathy → increased fracture risk independent of BMD.

Risk Stratification

• High risk: >7.5 mg/day prednisone equivalent × >3 months; postmenopausal women; men >50; prior fracture; high FRAX score.
• Dexamethasone has higher bone toxicity per mg than prednisone.

Prevention & Treatment

1. Calcium 1000–1200 mg/day + Vitamin D 800–2000 IU/day.
2. Weight-bearing & resistance exercise.
3. Oral bisphosphonate (alendronate/risedronate) first-line for high-risk patients starting steroids.
4. Denosumab or teriparatide for very high risk/intolerance.
5. Monitor BMD (DXA) at baseline and 1–2 years.