Prophylactic Medications for Long-Term Low-Dose Steroids

Risk Stratification and Treatment Approach

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 with uncertain benefit 1, 2
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 3
Initiate oral bisphosphonate treatment if T-score ≤-1.5 or FRAX 10-year risk ≥20% for major osteoporotic fracture 4, 5
Intravenous zoledronic acid should be used when malabsorption is present, gastrointestinal side effects from oral bisphosphonates occur, or fracture develops despite oral bisphosphonate therapy 4, 5
For bisphosphonate-intolerant patients, denosumab or teriparatide are alternative agents 4, 5
PTH/PTHrP is conditionally recommended over anti-resorptive agents for adults ≥40 years receiving high-dose glucocorticoids 1, 2
Oral bisphosphonates are strongly recommended over no treatment for adults ≥40 years receiving high-dose glucocorticoids 1, 2

Calcium 1000 mg daily and vitamin D 800 IU daily are recommended for all patients on corticosteroids 1, 4, 6
Bone mineral densitometry should be obtained as soon as possible after starting corticosteroids, as fracture risk increases within 3 months 4, 5
Repeat bone densitometry at 1 year, then every 2-3 years if stable, or annually if declining 4, 5
Pneumocystis jirovecii pneumonia prophylaxis with trimethoprim-sulfamethoxazole is recommended for patients taking ≥20 mg prednisone daily for ≥4 weeks 6, 7
Update vaccinations before starting immunosuppression, including pneumococcal, influenza, hepatitis B, and herpes zoster 6, 7
Histamine-2 receptor antagonist or proton pump inhibitor is recommended during steroid therapy to prevent peptic ulcer disease 7
Monitor blood pressure, glycemic control, and serum potassium regularly in patients on prolonged corticosteroids 4, 5
Implement tight glucose control with sliding scale insulin if steroid-induced diabetes develops 7

Osteoporosis therapy is not contraindicated but requires effective birth control if sexually active 1, 8
Risedronate and ibandronate have shorter skeletal half-lives and may be preferred among bisphosphonates 1, 8
Denosumab causes fetal harm; avoid pregnancy for 5 months after last dose 1, 8
For patients with eGFR ≥35 mL/min, conditionally recommend bisphosphonates, denosumab, PTH/PTHrP, or raloxifene based on individual factors 3
Romosozumab should be avoided due to potential cardiovascular harms in solid organ transplant recipients 3

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 2, 3
Patients on prolonged corticosteroids require tapering when discontinuing and should be warned about steroid withdrawal syndrome 4, 5