What prophylactic medications are recommended for patients on long-term low-dose steroids (corticosteroids)?

Prophylactic Medications for Long-Term Low-Dose Steroids

For patients on long-term low-dose corticosteroids, calcium and vitamin D supplementation are universally recommended, while bisphosphonate therapy should be initiated based on fracture risk stratification by age and bone mineral density.

Risk Stratification and Treatment Approach

Low Fracture Risk Patients

• Adults <40 years old should NOT receive osteoporosis pharmacotherapy regardless of steroid dose, as they have significant capacity to rebuild bone mineral density losses and face clear potential harms from treatment (osteonecrosis of jaw, atypical femur fractures, thromboembolism) with uncertain benefit 1.
• Adults ≥40 years on low-dose steroids meeting low-risk criteria have uncertain benefit from osteoporosis therapy and should generally avoid bisphosphonates, denosumab, raloxifene, or romosozumab 1.

Moderate to High Fracture Risk Patients (≥40 years)

Oral bisphosphonates (alendronate or risedronate) are first-line therapy for fracture prevention in patients on long-term corticosteroids 2, 3.

• Initiate treatment if T-score ≤-1.5 or FRAX 10-year risk ≥20% for major osteoporotic fracture 1.
• Intravenous zoledronic acid (annually) should be used when malabsorption is present, gastrointestinal side effects from oral bisphosphonates occur, or fracture develops despite oral bisphosphonate therapy 1.
• For bisphosphonate-intolerant patients, denosumab or teriparatide are alternative agents 1.

Very High Fracture Risk Patients

For adults ≥40 years receiving high-dose glucocorticoids (≥30 mg/day prednisone equivalent for ≥30 days or cumulative dose ≥5 g over 1 year):

• PTH/PTHrP (teriparatide) is conditionally recommended over anti-resorptive agents regardless of FRAX score or BMD 1.
• Oral bisphosphonates are strongly recommended over no treatment 1.

Universal Prophylactic Measures

Bone Health

• Calcium 1000 mg daily and vitamin D 800 IU daily for all patients on corticosteroids 1, 2.
• Bone mineral densitometry should be obtained as soon as possible after starting corticosteroids, as fracture risk increases within 3 months 1.
• Repeat bone densitometry at 1 year, then every 2-3 years if stable, or annually if declining 1.

Infection Prophylaxis

• Pneumocystis jirovecii pneumonia (PCP) prophylaxis with trimethoprim-sulfamethoxazole is recommended for patients taking ≥20 mg prednisone daily for ≥4 weeks 1.
• Standard dosing: trimethoprim-sulfamethoxazole 960 mg three times weekly or 480 mg daily 1.
• Update vaccinations before starting immunosuppression, including pneumococcal, influenza (intramuscular), hepatitis B, and herpes zoster (if not already on immunosuppressants) 1.

Gastrointestinal Protection

• Histamine-2 receptor antagonist or proton pump inhibitor during steroid therapy to prevent peptic ulcer disease 1.

Metabolic Monitoring

• Monitor blood pressure, glycemic control, and serum potassium regularly in patients on prolonged corticosteroids 1.
• Implement tight glucose control with sliding scale insulin if steroid-induced diabetes develops 1.

Special Populations

Patients Who Can Become Pregnant

• Osteoporosis therapy is not contraindicated but requires effective birth control if sexually active 1.
• Risedronate and ibandronate have shorter skeletal half-lives and may be preferred among bisphosphonates 1.
• Denosumab causes fetal harm; avoid pregnancy for 5 months after last dose 1.

Solid Organ Transplant Recipients

• For patients with eGFR ≥35 mL/min, conditionally recommend bisphosphonates, denosumab, PTH/PTHrP, or raloxifene based on individual factors 1.
• Romosozumab should be avoided due to potential cardiovascular harms in this population 1.

Critical Caveats

Bisphosphonate Considerations

• The fracture risk in corticosteroid-induced osteoporosis is higher than postmenopausal osteoporosis for the same bone density, justifying earlier intervention 4.
• Bone loss occurs most rapidly in the first 12-24 months after starting high-dose corticosteroids, making early prophylaxis critical 5, 4.

Medications to Avoid in Moderate Risk Patients

• Raloxifene and romosozumab should be conditionally avoided except in patients intolerant of other osteoporosis medications, due to risks of thromboembolism, fatal stroke, myocardial infarction, and death 1.

Adrenal Suppression

• Patients on prolonged corticosteroids require tapering when discontinuing and should be warned about steroid withdrawal syndrome (weakness, nausea, arthralgia) 1.