Is evenity (romosozumab) safe to use in a postmenopausal woman with polycythemia and a history of osteoporosis?

Evenity (Romosozumab) and Polycythemia

Polycythemia is not a contraindication to romosozumab (Evenity), but the cardiovascular risk associated with polycythemia combined with romosozumab's black box warning for cardiovascular events makes this combination extremely high-risk and generally inadvisable unless the patient has no history of cardiovascular disease and very high fracture risk. 1

Critical Cardiovascular Contraindications

The FDA black box warning explicitly states that romosozumab should not be initiated in patients who have had: 1

• Myocardial infarction within the preceding year
• Stroke within the preceding year

Romosozumab may increase the risk of myocardial infarction, stroke, and cardiovascular death. 1 If a patient experiences MI or stroke during therapy, romosozumab must be discontinued immediately. 1

Polycythemia as a Cardiovascular Risk Factor

Polycythemia significantly increases cardiovascular risk through:

• Increased blood viscosity leading to thrombotic events
• Higher risk of stroke and myocardial infarction
• Elevated risk of venous and arterial thromboembolism

This creates a compounding risk when combined with romosozumab's cardiovascular safety profile. The FDA labeling requires clinicians to "consider whether the benefits outweigh the risks in patients with other cardiovascular risk factors." 1

Alternative Treatment Algorithm

First-line recommendation: Use bisphosphonates instead. 2 The American College of Physicians strongly recommends bisphosphonates as initial pharmacologic treatment for postmenopausal women with primary osteoporosis, with high-certainty evidence showing fracture risk reduction without increased cardiovascular risk. 2

Second-line option: Consider denosumab. 2 The ACP suggests denosumab as second-line treatment for patients with contraindications to bisphosphonates, with moderate-certainty evidence and no increased cardiovascular risk. 2

Reserve romosozumab only if: 2, 3, 4

• Patient is at very high fracture risk (age >74 years, multiple documented fragility fractures, recent major fracture within 2 years)
• Patient has failed or is intolerant to bisphosphonates AND denosumab
• No cardiovascular disease history (no prior MI, stroke, coronary disease)
• Polycythemia is well-controlled with normal hematocrit
• Benefits clearly outweigh the compounded cardiovascular risks

If Romosozumab Is Used Despite Risks

Treatment protocol: 3, 4, 1

• Limit to exactly 12 monthly doses of 210 mg subcutaneous injections 1
• Mandatory transition to antiresorptive therapy (preferably alendronate) after completion 3, 4
• Supplement with calcium and vitamin D throughout treatment 1
• Monitor cardiovascular status closely throughout the 12-month course

Common pitfall: The anabolic effect wanes after 12 doses, and failure to transition to antiresorptive therapy results in rapid bone loss and rebound fracture risk. 3, 1

Clinical Decision Framework

In a postmenopausal woman with polycythemia and osteoporosis, the safest approach is bisphosphonate therapy (alendronate, risedronate, or zoledronate) as first-line treatment. 2 This provides excellent fracture risk reduction with high-certainty evidence and avoids the cardiovascular risks inherent to romosozumab. 2