What are the considerations and alternative treatments for patients receiving Evenity (romosozumab) injections for osteoporosis?

Evenity (Romosozumab) Injections for Osteoporosis: Considerations and Alternatives

Romosozumab (Evenity) should be reserved for postmenopausal women with severe osteoporosis at very high fracture risk, used for only 12 monthly doses, and should not be initiated in patients with a history of myocardial infarction or stroke within the preceding year. 1

Mechanism and Administration

• Romosozumab is a sclerostin inhibitor with a dual mechanism:
  • Increases bone formation
  • Decreases bone resorption 2, 3
• Administered as two 105 mg subcutaneous injections (total 210 mg) once monthly 1
• Limited to 12 monthly doses due to waning anabolic effect after this period 1

Indications

• FDA approved for postmenopausal women with osteoporosis at high risk for fracture, defined as:
  • History of osteoporotic fracture
  • Multiple risk factors for fracture
  • Failure or intolerance to other osteoporosis therapies 1
• Ideal use is as first-line treatment in postmenopausal women with a recent major fracture 4

Key Considerations and Limitations

Cardiovascular Risk

• WARNING: May increase risk of myocardial infarction, stroke, and cardiovascular death 1
• Absolute contraindications:
  • Myocardial infarction or stroke within the preceding year
  • Hypocalcemia 1, 4
• Consider whether benefits outweigh risks in patients with other cardiovascular risk factors 1
• Discontinue if patient experiences myocardial infarction or stroke during therapy 1

Treatment Duration and Sequencing

• Limited to 12 monthly doses only 1
• Must transition to an anti-resorptive agent after completing romosozumab to maintain bone mineral density gains 1, 5
• Sequential therapy with romosozumab followed by alendronate has shown greater fracture reduction compared to alendronate alone 6
• Less effective in patients previously treated with denosumab 7

Alternative Treatments Based on Fracture Risk

First-Line Options for High Fracture Risk

• Oral bisphosphonates (alendronate, risedronate):
  • Strong recommendation for patients with osteoporosis 5
  • Reduce hip fracture risk by 36% 5
  • Cost-effective with generic formulations available 5

Alternatives for Those Unable to Take Oral Bisphosphonates

• IV bisphosphonates (zoledronic acid)
• Denosumab 5

For Very High Fracture Risk

• Anabolic agents:
  • Teriparatide
  • Abaloparatide
  • Romosozumab 5
  • Consider for patients with T-score ≤-3.5, recent fractures, or FRAX ≥30% for major osteoporotic fracture 5

Non-Pharmacologic Interventions

• Calcium and vitamin D supplementation:
  • 1,000-1,200 mg calcium daily (diet plus supplements)
  • 800-1,000 IU vitamin D daily 5
• Exercise:
  • Weight-bearing or resistance training
  • Balance training and flexibility exercises
  • At least 30 minutes, 3 days per week 6, 5
• Lifestyle modifications:
  • Smoking cessation
  • Limiting alcohol consumption 6

Monitoring

• BMD testing every 1-2 years for patients on anabolic therapy 5
• After completing romosozumab, transition to an anti-resorptive agent and continue monitoring 1

Cost Considerations

• Romosozumab is more expensive than bisphosphonates (annual cost approximately £5,574 vs. £39-2,700) 6, 8
• Consider cost-effectiveness when selecting treatment options, especially for patients with financial constraints

Treatment Algorithm

1. Assess fracture risk using FRAX score and BMD measurements
2. For high-risk patients (T-score ≤-2.5 or FRAX ≥20% for major osteoporotic fracture):
   • Start with oral bisphosphonates if no contraindications
3. For very high-risk patients (recent fracture, T-score ≤-3.5, or FRAX ≥30%):
   • Consider romosozumab if no cardiovascular contraindications
   • Alternative anabolic agents (teriparatide, abaloparatide) if cardiovascular risk
4. After 12 months of romosozumab, transition to an anti-resorptive agent
5. For patients with contraindications to bisphosphonates, consider denosumab

Remember that romosozumab should be avoided in patients with solid organ transplants due to risk of myocardial infarction, stroke, or death 6.