What is the recommended dose of Evenity (romosozumab) for postmenopausal women with osteoporosis?

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Evenity Dosing for Postmenopausal Osteoporosis

The recommended dose of Evenity (romosozumab) is 210 mg administered as two separate subcutaneous injections of 105 mg each, given once monthly for exactly 12 months, followed by transition to an antiresorptive agent such as a bisphosphonate. 1

Administration Details

  • Two injections are required at each monthly visit to deliver the complete 210 mg dose—one 105 mg injection immediately followed by a second 105 mg injection 1
  • Must be administered by a healthcare provider (not self-administered) 1
  • Injection sites: abdomen, thigh, or upper arm 1
  • Duration is strictly limited to 12 monthly doses because the anabolic effect diminishes after this period 2, 1

Essential Pre-Treatment Requirements

  • Correct hypocalcemia before initiating therapy—this is an absolute contraindication 1
  • Ensure adequate calcium and vitamin D supplementation throughout the 12-month treatment course 1
  • Screen for cardiovascular risk: Do not initiate in patients with myocardial infarction or stroke within the preceding year 1

Sequential Therapy Protocol

After completing the 12-month romosozumab course, patients must transition to an antiresorptive agent (typically alendronate or another bisphosphonate) to maintain fracture risk reduction 1, 3. The evidence strongly supports this sequential approach:

  • Romosozumab followed by alendronate reduces vertebral fractures by 48%, clinical fractures by 27%, and hip fractures by 38% compared to alendronate alone 3
  • Moderate-certainty evidence demonstrates that this sequential strategy (romosozumab → bisphosphonate) significantly outperforms bisphosphonate monotherapy without increasing serious adverse events 2

Patient Selection Criteria

Evenity is indicated specifically for postmenopausal women at high risk for fracture, defined as: 1

  • History of osteoporotic fracture, OR
  • Multiple risk factors for fracture, OR
  • Patients who have failed or are intolerant to other osteoporosis therapies

The American College of Physicians recommends romosozumab for postmenopausal women with very high fracture risk (mean age >74 years in trials), representing approximately 10% of women over 50 in the general population 2

Critical Safety Warnings

Cardiovascular Risk (Black Box Warning)

  • Romosozumab may increase risk of myocardial infarction, stroke, and cardiovascular death 1
  • During the first year of treatment, serious cardiovascular events occurred in 2.5% of romosozumab patients versus 1.9% with alendronate 3
  • Discontinue immediately if MI or stroke occurs during therapy 1
  • Carefully weigh benefits versus risks in patients with cardiovascular risk factors 1

Other Important Adverse Effects

  • Hypocalcemia: Monitor calcium levels, especially in patients with severe renal impairment or on dialysis 1
  • Osteonecrosis of the jaw: Rare but reported; monitor for jaw symptoms 2
  • Atypical femoral fractures: 2 cases reported in clinical trials 3, 4
  • Most common adverse reactions (≥5%): arthralgia and headache 1

Cost Considerations

  • Romosozumab costs approximately $5,574 per year per Medicare beneficiary 2
  • This is substantially more expensive than bisphosphonates ($39-$2,700/year) but potentially less than denosumab ($1,913-$12,241/year) 2
  • The requirement for healthcare provider administration adds additional cost compared to self-injectable alternatives 2
  • Total treatment cost will be higher when accounting for the mandatory sequential bisphosphonate therapy after the 12-month romosozumab course 2

Clinical Efficacy Data

The pivotal ARCH trial demonstrated that compared to alendronate alone, romosozumab followed by alendronate resulted in: 3

  • 73% reduction in new vertebral fractures at 12 months 4
  • 75% reduction in vertebral fractures at 24 months (after transition to denosumab) 4
  • 36% reduction in clinical fractures 4
  • 19% reduction in nonvertebral fractures 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Romosozumab Treatment in Postmenopausal Women with Osteoporosis.

The New England journal of medicine, 2016

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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