When should Evenity (romosozumab) be prescribed to postmenopausal women with osteoporosis?

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When to Prescribe Evenity (Romosozumab)

Evenity should be prescribed to postmenopausal women with osteoporosis who are at very high risk for fracture, specifically those with a history of osteoporotic fracture, multiple risk factors for fracture, or who have failed or are intolerant to bisphosphonate therapy. 1, 2

Patient Selection Criteria

Very High-Risk Patients Who Qualify for Evenity:

  • History of osteoporotic fracture (vertebral or hip fracture) 2
  • Multiple risk factors for fracture in the setting of documented osteoporosis (T-score ≤ -2.5) 2
  • Failed bisphosphonate therapy (continued fractures or inadequate BMD response after appropriate duration) 2
  • Intolerant to bisphosphonates (unable to tolerate oral or IV formulations due to adverse effects) 2

Absolute Contraindications - Do NOT Prescribe:

  • Myocardial infarction or stroke within the preceding year 2
  • Active myocardial infarction or stroke during therapy (must discontinue immediately) 2

Relative Contraindications - Exercise Extreme Caution:

  • Other significant cardiovascular risk factors (coronary artery disease, peripheral vascular disease, cerebrovascular disease, multiple cardiac risk factors) - the FDA black box warning emphasizes that benefits must clearly outweigh cardiovascular risks 2

Treatment Algorithm

Step 1: Confirm Osteoporosis Diagnosis

  • T-score ≤ -2.5 on DEXA scan at spine, hip, or femoral neck 3

Step 2: Assess Fracture Risk Level

  • Very high risk = history of osteoporotic fracture OR multiple risk factors (age >75, very low BMD, prior falls, glucocorticoid use, parental hip fracture) 1, 2

Step 3: Determine Treatment Line

  • First-line therapy: Bisphosphonates (alendronate, risedronate, zoledronic acid) are strongly recommended as initial treatment 1, 3
  • Second-line therapy: Denosumab for bisphosphonate contraindications 1
  • Third-line therapy (very high risk only): Evenity or teriparatide for patients at very high fracture risk who have failed or cannot tolerate bisphosphonates 1

Step 4: Screen for Cardiovascular Contraindications

  • Review cardiovascular history for MI/stroke in past 12 months 2
  • Assess current cardiovascular risk factors and document risk-benefit discussion 2

Step 5: Prescribe and Monitor

  • Dose: 210 mg subcutaneously (two 105 mg injections) once monthly for exactly 12 months 2
  • Duration limit: The anabolic effect wanes after 12 doses; do not extend beyond 12 months 2
  • Mandatory transition: After completing 12 months of Evenity, transition to an anti-resorptive agent (bisphosphonate or denosumab) to maintain bone gains 1, 2
  • Supplementation: Ensure adequate calcium (1,200 mg daily) and vitamin D (600-800 IU daily) throughout treatment 3, 2

Key Clinical Considerations

Why Evenity is NOT First-Line:

The American College of Physicians provides conditional (not strong) recommendation for romosozumab, with only low-certainty evidence, specifically reserving it for very high-risk patients 1. Bisphosphonates have high-certainty evidence, better safety profiles, and significantly lower cost 1.

Cardiovascular Safety Concerns:

The FDA black box warning stems from increased cardiovascular events observed in the ARCH trial 2. Analysis of FDA adverse event reporting suggested higher risk for major adverse cardiovascular events 1. This makes cardiovascular screening mandatory before prescribing 2.

Common Pitfalls to Avoid:

  • Do not use as first-line therapy - this violates guideline recommendations and exposes patients to unnecessary cardiovascular risk and cost 1
  • Do not extend beyond 12 months - the anabolic effect disappears after 12 doses 2
  • Do not stop without transition therapy - patients must transition to bisphosphonate or denosumab to prevent bone loss 1, 2
  • Do not prescribe without cardiovascular screening - failure to assess MI/stroke history violates FDA black box warning 2

Expected Adverse Effects:

  • Arthralgia and injection site reactions are common 4, 5
  • Hypersensitivity reactions occur more frequently than with comparators 6
  • Serious cardiovascular events (MI, stroke, cardiovascular death) are the primary safety concern 2, 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Osteoporosis Treatment in Postmenopausal Women

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Romosozumab: A Novel Agent in the Treatment for Postmenopausal Osteoporosis.

The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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