Evenity and Polycythemia: Critical Cardiovascular Contraindication
Evenity (romosozumab) should NOT be used in patients with polycythemia due to the significantly elevated cardiovascular risk inherent to polycythemia combined with romosozumab's FDA black box warning for increased myocardial infarction, stroke, and cardiovascular death. 1
FDA Black Box Warning: Cardiovascular Risk
The FDA prescribing information carries a black box warning stating that romosozumab may increase the risk of myocardial infarction, stroke, and cardiovascular death 1. This represents the highest level of safety concern and must guide clinical decision-making.
Absolute Contraindications
Romosozumab must not be initiated in patients who have had:
If a patient experiences MI or stroke during therapy, romosozumab must be discontinued immediately 1
Polycythemia as a Cardiovascular Risk Factor
Polycythemia substantially increases cardiovascular risk through:
- Increased blood viscosity leading to thrombotic events
- Elevated risk of myocardial infarction
- Elevated risk of stroke
- Increased risk of venous thromboembolism
The FDA label explicitly states: "Consider whether the benefits outweigh the risks in patients with other cardiovascular risk factors" 1. Polycythemia represents a major cardiovascular risk factor that would tip this risk-benefit analysis against romosozumab use.
Guideline-Based Recommendations Against Romosozumab in High CV Risk
The 2023 American College of Rheumatology guideline conditionally recommends against romosozumab in moderate fracture risk patients due to possible life-threatening harms, including thrombosis, major cardiovascular events, and death 2. The guideline emphasizes that romosozumab should be reserved for those unable to tolerate other agents 2.
The ACR guideline explicitly states that romosozumab should not be started in patients with myocardial infarction or stroke within 12 months, and that shared decision-making is needed for patients with other cardiovascular risk factors including untreated hyperlipidemia, hypertension, and smoking 2. Polycythemia represents an even more severe cardiovascular risk than these listed factors.
Appropriate Alternative Treatments for Osteoporosis
First-Line Therapy: Oral Bisphosphonates
For postmenopausal women with osteoporosis and polycythemia, oral bisphosphonates are the mandatory first-line therapy 3, 4:
- Alendronate 70 mg once weekly 3
- Risedronate 35 mg once weekly 3
- High-certainty evidence shows 50% reduction in hip fractures and 47-56% reduction in vertebral fractures 3
- Most favorable balance of efficacy, safety, and cost 3
Essential Supplementation
All patients must receive:
Second-Line Options if Bisphosphonates Not Tolerated
If oral bisphosphonates cannot be tolerated:
Treatment Duration
- Initial bisphosphonate treatment duration is 5 years 3
- Do not monitor bone density during the initial 5-year treatment period 3
- After 5 years, reassess fracture risk to determine if continued therapy is warranted 3
Critical Pitfall to Avoid
The most dangerous pitfall would be prescribing romosozumab to a patient with polycythemia based solely on high fracture risk without adequately weighing the cardiovascular contraindication. While romosozumab demonstrates superior fracture reduction efficacy 4, 5, the cardiovascular safety concerns in the FDA black box warning 1 and ACR guideline recommendations 2 make it inappropriate for patients with underlying thrombotic/cardiovascular risk factors like polycythemia.
When Romosozumab Might Be Considered (Not in This Case)
Romosozumab is reserved for postmenopausal women with very high fracture risk who have:
- No history of MI or stroke in the past year 1
- No significant cardiovascular risk factors 2, 1
- Failed or are intolerant to bisphosphonates and other alternatives 1
This clinical scenario does not apply to patients with polycythemia due to the inherent cardiovascular risk.