Is Evenity (romosozumab) safe to use in an older adult, possibly a postmenopausal woman, with moderate impaired renal function (GFR of 44) and a history of osteoporosis or high risk of fracture?

Evenity Use with GFR 44

Evenity (romosozumab) can be used in patients with moderate renal impairment (GFR 44 mL/min), as clinical trial data demonstrate efficacy and safety in this population, but it should only be considered if the patient meets criteria for very high fracture risk and has failed or is intolerant to bisphosphonates, with careful attention to cardiovascular risk factors and hypocalcemia monitoring. 1, 2

Renal Function Considerations

• No dose adjustment is required for moderate renal impairment (GFR 30-59 mL/min), as romosozumab clinical trials included patients with mild-to-moderate CKD and demonstrated similar efficacy and safety profiles across different kidney function levels 2

• In the FRAME and ARCH trials, 81-85% of patients had mild or moderate reduction in eGFR at baseline, with romosozumab showing consistent BMD increases and fracture risk reduction across all kidney function categories including eGFR 30-59 mL/min 2

• The incidence of adverse events and evolution of kidney function during treatment were similar across all baseline kidney function groups, including those with GFR 30-59 mL/min 2

Critical Prerequisite: Very High Risk Criteria

Romosozumab should only be used in patients meeting very high fracture risk criteria, not as first-line therapy 3, 4, 1:

• History of osteoporotic fracture 1
• Multiple risk factors for fracture 1
• Patients who have failed or are intolerant to other available osteoporosis therapy 1

Treatment Algorithm Based on Guidelines

First-Line Therapy

• Bisphosphonates remain the appropriate first-line treatment with strong evidence (high certainty) for fracture reduction 3, 4
• The American College of Physicians recommends bisphosphonates as initial pharmacologic treatment with a strong recommendation 3

Second-Line Consideration

• Denosumab is recommended as second-line therapy for patients with contraindications to bisphosphonates (conditional recommendation; moderate-certainty evidence) 3

Third-Line: Romosozumab Eligibility

• The American College of Physicians conditionally recommends romosozumab only for females with primary osteoporosis at very high risk of fracture (conditional recommendation; low-certainty evidence) 3
• The American College of Rheumatology conditionally recommends against using romosozumab due to cardiovascular risks except in patients intolerant of other agents 3

Critical Safety Warnings with GFR 44

Cardiovascular Risk (Boxed Warning)

• Romosozumab carries an FDA boxed warning for myocardial infarction, stroke, and cardiovascular death 1
• Romosozumab should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year 1
• In the ARCH trial, romosozumab showed increased cardiovascular events compared to alendronate (hazard ratio 1.9, CI 1.1-3.1) 4
• If a patient experiences MI or stroke during therapy, romosozumab must be discontinued 1

Hypocalcemia Risk (Enhanced in Renal Impairment)

• Hypocalcemia must be corrected prior to initiating romosozumab 1, 5
• Patients with reduced kidney function are at increased risk for hypocalcemia and require close monitoring of serum calcium levels 6
• All patients should receive adequate calcium (at least 500 mg) and vitamin D (600 IU) supplementation daily 1, 2
• Consider vitamin D loading dose of 50,000-60,000 IU if serum 25-hydroxyvitamin D is ≤40 ng/mL 1

Other Safety Considerations

• Increased risk of osteonecrosis of the jaw and atypical femoral fractures 3, 1
• Hypersensitivity reactions are a contraindication 1

Treatment Duration and Sequential Therapy

• Romosozumab duration is limited to 12 monthly doses (210 mg subcutaneously once monthly) 1
• The anabolic effect wanes after 12 months 1
• Sequential therapy with an anti-resorptive agent (bisphosphonate or denosumab) is required after completing romosozumab to prevent bone loss 3, 1

Recommended Clinical Approach for GFR 44

For a patient with GFR 44 mL/min, the following algorithm should guide decision-making:

1. Verify very high fracture risk status (history of osteoporotic fracture OR multiple risk factors) 1

2. Document bisphosphonate trial or contraindication - at least 1 year of oral bisphosphonate therapy should have been attempted unless contraindicated 4

3. Assess cardiovascular risk factors thoroughly:

   • No MI or stroke in preceding year (absolute contraindication) 1
   • Evaluate other cardiovascular risk factors and determine if benefits outweigh risks 1

4. Correct hypocalcemia before initiation and ensure adequate calcium/vitamin D supplementation 1, 5

5. Monitor serum calcium closely during treatment, especially given moderate renal impairment 6

6. Plan sequential anti-resorptive therapy after 12 months of romosozumab 1

Common Pitfalls to Avoid

• Do not use romosozumab as first-line therapy - bisphosphonates have stronger evidence and better safety profile 3, 4
• Do not initiate without correcting hypocalcemia - risk is enhanced with GFR 44 1, 6
• Do not use in patients with recent cardiovascular events (within 1 year) 1
• Do not continue beyond 12 months - efficacy wanes and must transition to anti-resorptive 1
• Do not discontinue without sequential therapy - bone loss will occur without anti-resorptive follow-up 3