What are the potential side effects of EVENITY (romosozumab) in postmenopausal women with osteoporosis?

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EVENITY Side Effects

EVENITY (romosozumab) carries a significant risk of major adverse cardiovascular events including heart attack, stroke, and cardiovascular death, along with other serious side effects including hypersensitivity reactions, hypocalcemia, osteonecrosis of the jaw, and atypical femoral fractures. 1

Cardiovascular Events (Black Box Warning)

The FDA has issued a black box warning for increased risk of cardiovascular events with EVENITY. 1

  • Major adverse cardiac events (MACE) occur at higher rates compared to alendronate (2.5% vs 1.9%) 2
  • Contraindicated in patients with myocardial infarction or stroke within the preceding year 2, 1
  • Symptoms requiring immediate medical attention include: 1
    • Chest pain or pressure
    • Shortness of breath
    • Feeling light-headed or dizzy
    • Headache, numbness or weakness in face/arm/legs
    • Difficulty talking or changes in vision

Clinical Pitfall: The cardiovascular risk was identified in the ARCH trial comparing romosozumab to alendronate, making this a critical consideration when selecting patients for therapy. 3, 4

Serious Allergic Reactions

  • Hypersensitivity reactions including angioedema, erythema multiforme, dermatitis, rash, and urticaria can occur 1
  • Patients should seek immediate medical attention for: 1
    • Rash or hives
    • Swelling of face, lips, mouth, tongue, or throat
    • Difficulty swallowing or breathing

Hypocalcemia (Low Blood Calcium)

Pre-existing hypocalcemia must be corrected before initiating EVENITY. 1, 5

  • Mandatory supplementation: Patients must take daily calcium and vitamin D throughout treatment 1
  • Symptoms requiring immediate attention include: 1
    • Muscle spasms, twitches, or cramps
    • Numbness or tingling in fingers, toes, or around mouth

Osteonecrosis of the Jaw (ONJ)

  • Dental examination recommended before starting EVENITY 1
  • Patients should maintain good oral hygiene and inform dentists of EVENITY use before dental procedures 1
  • Risk increases with invasive dental procedures 1

Atypical Femoral Fractures

  • Unusual thigh bone fractures can occur with romosozumab 1
  • Patients should report new or unusual pain in: 1
    • Thigh
    • Hip
    • Groin

Common Side Effects

The most frequently reported adverse effects include: 1

  • Joint pain (arthralgia) 1, 3
  • Headache 1, 3
  • Injection site reactions 3

Safety Profile from Clinical Trials

Romosozumab followed by alendronate probably did not increase risk for serious harms or withdrawal due to adverse effects compared with bisphosphonate alone at 12-36 month assessment (moderate to low certainty evidence). 6

Critical Treatment Limitations

  • Treatment duration strictly limited to 12 monthly doses as the anabolic effect wanes after this period 6, 7
  • Sequential therapy required: Patients must transition to an antiresorptive agent (preferably alendronate) after completing romosozumab to maintain bone density gains 2, 7
  • Failure to transition results in loss of bone density benefits 7

Patient Selection Considerations

EVENITY should be reserved for postmenopausal women at very high risk of fracture who cannot use or have failed other osteoporosis therapies. 6

Avoid in patients with: 2, 1, 3

  • History of myocardial infarction or stroke (especially within past year)
  • High cardiovascular risk
  • Documented coronary heart disease
  • Uncorrected hypocalcemia

References

Guideline

Romosozumab Treatment Regimen for Osteoporosis

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

Research

Romosozumab (sclerostin monoclonal antibody) for the treatment of osteoporosis in postmenopausal women: A review.

Journal of population therapeutics and clinical pharmacology = Journal de la therapeutique des populations et de la pharmacologie clinique, 2020

Research

Romosozumab: A first-in-class sclerostin inhibitor for osteoporosis.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2020

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Romosozumab Treatment Guidelines for Osteoporosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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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