What are the best strategies for bone protection in patients taking high-dose corticosteroids?

Bone Protection with High-Dose Corticosteroids

Universal Baseline Protection

All patients starting corticosteroids must receive calcium 800-1000 mg/day (or 1000-1200 mg/day) and vitamin D 800 IU/day immediately upon initiation of therapy. 1 This is a strong recommendation based on evidence that corticosteroids reduce calcium absorption from the gut and increase urinary calcium losses, leading to secondary hyperparathyroidism and bone resorption. 1

• If vitamin D deficiency is documented, treat with 50,000 IU weekly for 6 weeks initially, then maintain with 800 IU daily. 1
• Calcium can be achieved through dietary intake or supplements; if dietary calcium is adequate (≥800 mg/day), vitamin D alone may suffice. 1
• Calcium citrate is preferred over calcium carbonate for patients on proton pump inhibitors or with reduced gastric acid. 2

Risk Stratification and Bisphosphonate Therapy

High-Risk Patients (Require Immediate Bisphosphonate Therapy)

Start oral bisphosphonate therapy immediately in addition to calcium/vitamin D for patients with: 1

• Previous fragility fracture 1
• Age ≥40 years with:
  • T-score ≤ -2.5 at hip or spine 1
  • FRAX-adjusted 10-year risk ≥20% for major osteoporotic fracture 1
  • FRAX-adjusted 10-year risk >1% for hip fracture 1
• Age <40 years with:
  • Z-score < -3 at hip or spine AND prednisone ≥7.5 mg/day 1
  • ≥10%/year bone loss at hip or spine AND prednisone >7.5 mg/day 1
• Prolonged corticosteroid use (>3 months) or repeated courses 1
• Very high-dose glucocorticoids (≥30 mg/day prednisone with cumulative dose >5 gm in past year) 1

FRAX Score Adjustment for High-Dose Steroids

Critical caveat: FRAX assumes average prednisolone dose of 2.5-7.5 mg/day, thus underestimates fracture risk in high-dose users. 1 For doses >7.5 mg/day:

• Multiply hip fracture risk by 1.2 1
• Multiply major osteoporotic fracture risk by 1.15 1

Moderate-Risk Patients

Consider bisphosphonate therapy for patients age ≥40 years with FRAX-adjusted risk below high-risk thresholds but with additional risk factors: 1

• Uncontrolled inflammation 1
• Weight loss and malabsorption 1
• Lack of weight-bearing physical activity 1
• Smoking 1
• Alcohol excess 1

Low-Risk Patients

For patients <40 years at low risk, optimize calcium and vitamin D intake with lifestyle modifications only—do not add bisphosphonates. 1

Bisphosphonate Selection and Alternatives

First-Line: Oral Bisphosphonates

Oral bisphosphonates (alendronate, risedronate) are first-line pharmacologic therapy due to proven efficacy, safety profile, and cost. 1

• Alendronate demonstrated +5.9% lumbar BMD increase over 2 years versus -0.5% with vitamin D/calcium alone in glucocorticoid users. 3
• Zero vertebral fractures occurred in alendronate group versus 6 in calcitriol group over 2 years. 3

Second-Line Options (in order of preference when oral bisphosphonates inappropriate):

1. Intravenous zoledronic acid (annually): 1

   • Use first-line if evidence of malabsorption or increased GI side effect risk 1
   • Consider if fracture develops despite oral bisphosphonate 1

2. Teriparatide: 1

   • Preferred for women of childbearing potential not planning pregnancy (after oral bisphosphonates) 1
   • Higher cost and daily injection burden 1

3. Denosumab: 1, 4

   • Lack of safety data in immunosuppressed patients is a concern 1
   • Critical warning: Risk of multiple vertebral fractures if stopped, skipped, or delayed—requires transition to bisphosphonate if discontinued 4

4. Raloxifene (postmenopausal women only, last resort): 1

   • Use only when no other therapy appropriate 1
   • Lacks adequate fracture data in glucocorticoid users 1

Bone Density Monitoring

Arrange bone mineral densitometry as soon as possible, ideally within 1 month of starting corticosteroids. 1

• If testing cannot occur within 1 month, start bisphosphonate therapy in high-risk patients immediately without waiting for DXA results, as fracture risk increases within 3 months of starting corticosteroids. 1
• Repeat DXA at 1 year, then every 2-3 years if stable, or annually if declining. 1
• High-risk threshold for intervention is T-score -1.5 (not the usual -2.5). 1

Essential Lifestyle Modifications

All patients must receive counseling on: 1

• Smoking cessation 1
• Limit alcohol to ≤1-2 drinks/day 1
• Regular weight-bearing and resistance training exercise 1
• Maintain healthy weight 1
• Balanced diet 1

Dental Precautions

Before starting bisphosphonates or denosumab, examine mouth and address dental disease. 1, 5

• Consider dental evaluation before initiating therapy 1, 5
• Maintain good oral hygiene throughout treatment 1, 5
• Report new oral symptoms (dental mobility, pain) immediately 1, 5
• Risk of osteonecrosis of the jaw, particularly with IV bisphosphonates and denosumab 4, 5

Critical Safety Monitoring

Monitor throughout corticosteroid therapy: 1

• Blood pressure 1
• Glycemic control 1
• Serum potassium 1
• Hypercalciuria (especially with calcium/vitamin D therapy) 6, 7

Special Populations

Women of Childbearing Potential

For moderate-to-high risk patients not planning pregnancy and using effective contraception: 1

• First-line: Oral bisphosphonate 1
• Second-line: Teriparatide (safer in pregnancy than IV bisphosphonates or denosumab) 1
• Avoid IV bisphosphonates and denosumab if possible due to potential fetal risks 1

Duration of Therapy

Continue bisphosphonate therapy for minimum 5 years with periodic BMD evaluations, or throughout corticosteroid exposure if prolonged. 6 Reassess fracture risk at 3-5 year intervals based on individual risk factors. 1