Is it safe to give EVENITY (romosozumab) to a patient with osteoporosis who is status post kidney transplant and on immunosuppressive agents?

Safety of EVENITY (Romosozumab) in Kidney Transplant Recipients on Immunosuppression

The American College of Rheumatology conditionally recommends against romosozumab in solid organ transplant recipients due to cardiovascular risks (myocardial infarction, stroke, or death), making EVENITY generally not advisable for post-kidney transplant patients on immunosuppressive therapy. 1

Guideline-Based Contraindication

The most recent and authoritative guidance explicitly addresses this clinical scenario:

• Romosozumab carries a conditional recommendation against use in solid organ transplants specifically due to elevated risk of myocardial infarction, stroke, or death 1
• This recommendation applies directly to kidney transplant recipients regardless of immunosuppression status 1
• The cardiovascular black box warning states romosozumab should not be initiated in patients with myocardial infarction or stroke in the preceding year 2

Emerging Real-World Evidence Creates Clinical Tension

Despite guideline recommendations against use, a 2025 retrospective case series challenges this position:

• 12 kidney transplant recipients treated with romosozumab for 12 months showed favorable safety and efficacy, with no severe hypocalcemia, no marked kidney function deterioration, and significant BMD increases (spine +15.18%, total hip +8.83%) 3
• No serious adverse events were reported in this transplant cohort during the treatment period 3
• Metabolic bone markers responded similarly to the general osteoporosis population 3

However, this single small retrospective series (n=12) cannot override the guideline recommendation, which is based on broader cardiovascular safety concerns across transplant populations 1

Alternative Management Strategies for Post-Transplant Osteoporosis

The established approach for kidney transplant recipients with osteoporosis includes:

First-Line Interventions

• Bisphosphonates (particularly parenteral aminobisphosphonates like pamidronate) are recommended for transplant recipients with BMD t-score ≤-2.0 4
• Alendronate has demonstrated progressive BMD increases at spine, hip, and total body with 48% reduction in vertebral fractures in osteoporosis 4
• DEXA scanning should be performed at transplant, 1 year, and 2 years post-transplant to monitor BMD 4

Immunosuppression Optimization

• Minimize glucocorticoid exposure to the lowest effective dose to reduce bone mass loss and osteonecrosis risk 4
• High-dose glucocorticoids increase avascular necrosis risk 1.5-fold compared to low-dose regimens 4

Monitoring Requirements

• Measure serum calcium, phosphorus, total CO2, and intact PTH at intervals based on time post-transplant and CKD stage 4
• Daily phosphorus monitoring in the first week post-transplant, with supplementation if persistently <2.5 mg/dL 4
• In CKD stages 3-5T (common in transplant recipients), calcium and phosphorus should be monitored every 1-6 months depending on stage 4

Critical Clinical Caveats

Cardiovascular Risk Assessment is Paramount

• The ARCH trial demonstrated higher cardiovascular event rates with romosozumab versus alendronate 2
• Transplant recipients often have pre-existing cardiovascular disease, compounding this risk 1
• Any consideration of romosozumab requires thorough cardiovascular risk stratification 2

Renal Function Considerations

• Use of romosozumab in males with CKD G4-G5D is considered off-label 1
• Many transplant recipients have reduced kidney function, adding another layer of complexity 4

Sequential Therapy Planning

• If romosozumab were used, sequential anti-resorptive therapy (denosumab or bisphosphonate) is mandatory to maintain BMD gains 1, 5
• Prior bisphosphonate use reduces romosozumab efficacy (lower spine BMD increases in bisphosphonate-pretreated patients) 6, 7

Practical Algorithm

For kidney transplant recipients with severe osteoporosis on immunosuppression:

1. Optimize immunosuppression: Reduce glucocorticoids to minimum effective dose 4
2. Correct metabolic abnormalities: Ensure adequate calcium (1,000 mg/day) and vitamin D (600 IU/day) supplementation 8
3. First-line pharmacotherapy: Initiate bisphosphonates (parenteral aminobisphosphonates preferred) if BMD t-score ≤-2.0 4
4. Reserve romosozumab consideration only for: Patients with very high fracture risk who have failed or are intolerant to bisphosphonates AND have low cardiovascular risk 1, 2
5. If romosozumab is considered despite guidelines: Obtain cardiology clearance, ensure no MI/stroke in past year, and plan sequential anti-resorptive therapy 1, 2

The weight of current guideline evidence favors avoiding romosozumab in this population, with bisphosphonates remaining the evidence-based standard of care 4, 1