Does chronic systemic hydrocortisone (≥5 mg prednisone‑equivalent daily for >3 months) increase osteoporosis risk and how should bone health be monitored and managed?

Chronic Hydrocortisone and Osteoporosis Risk

Yes, chronic systemic hydrocortisone at doses ≥5 mg prednisone-equivalent daily for >3 months significantly increases osteoporosis risk, with fracture risk rising rapidly within 3-6 months of treatment initiation. 1, 2

Magnitude of Risk

• Any dose ≥2.5 mg/day prednisone-equivalent increases fracture risk, with no safe lower threshold identified 1, 3
• Doses ≥5 mg/day cause measurable bone loss and suppress multiple bone formation markers 4, 2
• Doses >7.5 mg/day confer high fracture risk requiring aggressive bone protection 1
• Very high doses (≥30 mg/day with cumulative dose >5 gm) dramatically increase vertebral and hip fracture risk 1
• Fracture risk increases within 3-6 months of starting glucocorticoids, making early intervention critical 1, 2
• More than 10% of long-term glucocorticoid users develop clinical fractures, and 30-40% show radiographic vertebral fractures 1

Initial Risk Assessment

For adults ≥40 years, calculate fracture risk using FRAX with bone mineral density (BMD) testing 1:

• If prednisone dose >7.5 mg/day, multiply the 10-year major osteoporotic fracture risk by 1.15 and hip fracture risk by 1.2 1
• Obtain detailed glucocorticoid history including dose, duration, and pattern of use 1
• Assess for prior fragility fractures, falls, low body weight, family history of hip fracture, smoking, and alcohol use ≥3 units/day 1
• Measure height and weight, check for spinal tenderness or deformity 1

For adults <40 years, consider moderate-to-high fracture risk if 1:

• History of previous fragility fracture
• Significant decrease in BMD or low BMD Z-score
• Continued prednisone ≥7.5 mg/day for ≥6 months
• Very high-dose treatment (initial prednisone ≥30 mg/day with cumulative dose >5 gm) 1

Immediate Universal Interventions

All patients on prednisone ≥2.5 mg/day for ≥3 months must receive 1:

• Calcium 1,000-1,200 mg daily (dietary plus supplementation as needed) 1
• Vitamin D 800-1,000 IU daily (target serum level ≥20 ng/mL) 1
• Lifestyle modifications: balanced diet, weight-bearing exercise, smoking cessation, limit alcohol to 1-2 drinks/day 1

These interventions should begin immediately at glucocorticoid initiation, not after risk stratification 1

Pharmacologic Treatment Indications

For adults ≥40 years at moderate-to-high fracture risk (based on FRAX calculation), strongly recommend oral bisphosphonates (alendronate or risedronate) as first-line therapy in addition to calcium and vitamin D 1:

• Start bisphosphonates promptly; do not delay for BMD testing if testing cannot be completed within 1 month 1
• Risedronate is equally effective as alendronate 1

For adults <40 years, recommend oral bisphosphonates if 1:

• History of fragility fracture
• Significant BMD decline or low Z-score with continued prednisone ≥7.5 mg/day for ≥6 months
• Very high-dose glucocorticoid exposure (≥30 mg/day prednisone with cumulative dose >5 gm) 1

Alternative agents 1:

• Intravenous zoledronic acid annually for malabsorption, GI intolerance to oral bisphosphonates, or fracture despite oral bisphosphonate 1
• Denosumab or teriparatide if bisphosphonates contraindicated or not tolerated 1
• For very high-risk patients, anabolic agents (PTH/PTHrP) are conditionally recommended over antiresorptive agents as initial therapy 1

Monitoring Strategy

During active treatment with osteoporosis medication 1:

• Repeat BMD every 2-3 years in high-risk patients 1
• More frequent monitoring (annually) if very high-dose glucocorticoids, history of fracture after ≥18 months of treatment, poor medication adherence, or malabsorption 1

For patients not on osteoporosis medication 1:

• Reassess FRAX with BMD every 1-3 years 1
• Earlier reassessment for higher glucocorticoid doses or history of fracture 1

Clinical fracture risk reassessment every 12 months should include 1:

• Updated glucocorticoid dose and duration
• New fractures or falls
• Height measurement (loss suggests vertebral fracture)
• Weight changes
• New osteoporosis risk factors 1

Critical Pitfalls to Avoid

• Do not wait for BMD results to start calcium and vitamin D—begin immediately at glucocorticoid initiation 1
• Do not underestimate fracture risk in patients on very high doses (≥30 mg/day)—FRAX may significantly underestimate their risk 1
• Do not assume doses <5 mg/day are safe—even 2.5 mg/day increases fracture risk 1, 3
• Do not delay bisphosphonate initiation in high-risk patients if BMD testing unavailable within 1 month 1
• Never discontinue denosumab without transitioning to bisphosphonate 6-9 months after last dose to prevent rebound bone loss 5