What measures preserve bone density in adults starting glucocorticoid therapy (≥5 mg/day prednisone equivalent for ≥3 months)?

Bone Density Preservation on Glucocorticoids

All adults starting glucocorticoid therapy ≥2.5 mg/day prednisone equivalent for ≥3 months should receive calcium (1,000-1,200 mg/day) and vitamin D (600-800 IU/day) supplementation, combined with weight-bearing exercise, smoking cessation, and alcohol avoidance—and those at high or very high fracture risk require pharmacologic osteoporosis therapy, with oral bisphosphonates as first-line treatment. 1

Universal Preventive Measures (All Patients)

Calcium and Vitamin D supplementation is conditionally recommended for all patients on glucocorticoids ≥2.5 mg/day for ≥3 months, regardless of fracture risk level. 1 The specific dosing is:

• Calcium: 1,000-1,200 mg/day (age-appropriate) 1, 2
• Vitamin D: 600-800 IU/day 1, 2

Lifestyle modifications are strongly encouraged for all glucocorticoid users: 1

• Weight-bearing exercise 1
• Smoking cessation 1
• Avoidance of excessive alcohol intake 1

These measures are considered good clinical practice despite low certainty evidence, as they are benign, low cost, and without harms. 1

Risk Stratification (Critical First Step)

Fracture risk assessment must be performed as soon as possible (within 6 months) after initiating glucocorticoids ≥2.5 mg/day for >3 months. 1

For adults ≥40 years: 1

• Use FRAX calculator with glucocorticoid dose adjustment 1
• Perform BMD testing with DXA including vertebral fracture assessment (VFA) or spinal x-rays 1
• If prednisone dose >7.5 mg/day, multiply FRAX major osteoporotic fracture risk by 1.15 and hip fracture risk by 1.2 1

For adults <40 years: 1

• FRAX is not validated in this population 1
• Perform BMD with VFA or spinal x-rays 1
• Use z-scores ≤-2.0 to indicate low bone mass for age 1

Pharmacologic Treatment Algorithm

High or Very High Fracture Risk (Adults ≥40 years)

Oral bisphosphonates are strongly recommended over no treatment as first-line therapy. 1 This is the only strong recommendation for pharmacologic treatment, based on fracture reduction data at 24 months showing decreased total and vertebral fractures plus increased hip and lumbar spine BMD. 1

For very high fracture risk patients, anabolic agents (teriparatide or abaloparatide) are conditionally recommended over antiresorptive agents (bisphosphonates or denosumab). 1 The rationale is that anabolism is blunted in patients previously treated with bisphosphonates, making upfront anabolic therapy more effective in this highest-risk group. 1

For high fracture risk patients, teriparatide/abaloparatide or denosumab are conditionally recommended over bisphosphonates. 1 Teriparatide showed superior BMD increases at 24 and 36 months and prevented vertebral fractures at 36 months compared to oral bisphosphonates. 1

Moderate Fracture Risk (Adults ≥40 years)

Oral or IV bisphosphonates, denosumab, and teriparatide/abaloparatide are all conditionally recommended. 1 The choice depends on individual patient factors, tolerability, and contraindications. 1

Romosozumab should be avoided in moderate-risk patients except when intolerant of other agents, due to cardiovascular risks (myocardial infarction, stroke, death). 1

Low Fracture Risk (Adults ≥40 years)

Osteoporosis medications are strongly recommended against due to known harms and no evidence of benefit. 1 Continue calcium, vitamin D, and lifestyle modifications only. 1

Very High-Dose Glucocorticoids (≥30 mg/day for >30 days or cumulative >5g/year)

These patients warrant more aggressive treatment: 1, 2

• Teriparatide/abaloparatide conditionally recommended over antiresorptives 1
• Oral bisphosphonates strongly recommended over no treatment 1
• IV bisphosphonates and denosumab conditionally recommended 1

Adults <40 Years with Moderate Fracture Risk

Oral or IV bisphosphonates, denosumab, or teriparatide/abaloparatide are conditionally recommended. 1 However, bisphosphonates and denosumab should only be used in patients not planning pregnancy or using effective contraception. 1

Critical Sequential Treatment Considerations

Sequential osteoporosis treatment is essential to prevent rebound bone loss and vertebral fractures after discontinuation of denosumab, romosozumab, or teriparatide/abaloparatide. 1 This is a critical pitfall—stopping these agents without transition therapy can result in rapid bone loss and increased fracture risk. 1

Monitoring Strategy

Annual clinical fracture risk reassessment is required for all patients continuing glucocorticoids. 1

For adults ≥40 years not on osteoporosis medication: 1

• Repeat FRAX with BMD every 1-3 years 1
• Earlier reassessment (within 1 year) for very high-dose glucocorticoid users or those with prior osteoporotic fractures 1

BMD provides the baseline for reassessment because FRAX is not validated for fracture risk reassessment during osteoporosis therapy. 1

Common Pitfalls to Avoid

Poor adherence to preventive therapies is extremely common—only 5-62% of glucocorticoid users receive appropriate preventive measures. 3 Proactive counseling and systematic protocols are essential. 3

Failing to adjust FRAX for glucocorticoid dose leads to underestimation of fracture risk. 1 Always apply the 1.15 and 1.2 multipliers for doses >7.5 mg/day prednisone. 1

Starting bisphosphonates without excluding vitamin D deficiency or other secondary causes of bone loss can lead to treatment failure. 3 Screen for and correct vitamin D deficiency, hypogonadism, excessive alcohol use, and other reversible contributors before initiating therapy. 3

Trabecular bone loss occurs rapidly with glucocorticoids—the rate is highest in the first 6-12 months of therapy. 4 This exponential pattern of early rapid loss emphasizes the importance of early intervention. 4