What is the recommended treatment with Evenity (romosozumab) for patients with severe osteoporosis?

Romosozumab (Evenity) Treatment Recommendations for Severe Osteoporosis

Romosozumab (Evenity) should be used for postmenopausal women with severe osteoporosis at very high risk of fracture, defined as those with a history of osteoporotic fracture or multiple risk factors for fracture, with treatment limited to 12 monthly doses followed by an antiresorptive agent. 1

Patient Selection Criteria

Appropriate candidates for romosozumab include:

• Postmenopausal women with osteoporosis at high risk for fracture 1
• Patients with:
  • History of osteoporotic fracture
  • Multiple risk factors for fracture
  • T-score ≤ -2.5 with high fracture risk
  • Failure or intolerance to other osteoporosis therapies 1, 2

Contraindications:

• Myocardial infarction or stroke within the preceding year 1
• High risk for major cardiovascular events 2
• Hypocalcemia (must be corrected before initiating treatment) 1

Dosing and Administration

• 210 mg administered subcutaneously once monthly 1
• Given as two separate 105 mg injections 1
• Limited to 12 monthly doses only (anabolic effect wanes after this period) 2, 1
• Must be followed by an antiresorptive agent (typically alendronate or denosumab) 1, 3

Monitoring and Supplementation

1. Before starting treatment:

   • Assess cardiovascular risk factors 4
   • Check calcium levels 4
   • Ensure adequate calcium and vitamin D intake 2

2. During treatment:

   • Monitor for hypocalcemia 5
   • Provide calcium supplementation (1000-1200 mg/day) 2
   • Provide vitamin D supplementation (800 IU/day) 2
   • Monitor for cardiovascular symptoms 1

3. After 12 months:

   • Transition to an antiresorptive agent (bisphosphonate or denosumab) 1, 3
   • Continue calcium and vitamin D supplementation 2

Efficacy and Mechanism of Action

Romosozumab is a sclerostin inhibitor with a dual effect:

• Increases bone formation
• Decreases bone resorption 3

This dual action results in:

• Rapid and significant increases in bone mineral density (BMD)
• Greater BMD gains than seen with bisphosphonates, denosumab, or PTH analogs 3
• Significant reduction in vertebral and clinical fracture risk 6

Treatment Sequence and Alternatives

First-line options for osteoporosis:

• Bisphosphonates (alendronate, risedronate) are strongly recommended as initial therapy for most patients with osteoporosis 2

When to use romosozumab:

• For patients at very high fracture risk 2
• For patients who have failed or are intolerant to other osteoporosis therapies 1

Alternative agents for severe osteoporosis:

• Teriparatide (another anabolic agent) 2
• Denosumab (a RANKL inhibitor) as second-line therapy 2

Important Safety Considerations

Cardiovascular risk:

• Boxed warning for potential risk of myocardial infarction, stroke, and cardiovascular death 1
• Avoid in patients with MI or stroke within the past year 1
• Consider benefits versus risks in patients with other cardiovascular risk factors 1
• Discontinue if patient experiences MI or stroke during therapy 1

Other safety considerations:

• Hypocalcemia can occur and should be corrected before initiating treatment 5
• Limited to 12 monthly doses due to waning anabolic effect 2, 1

Post-Romosozumab Treatment

• After completing 12 months of romosozumab, patients must transition to an antiresorptive agent 1
• This sequential approach maintains or further increases BMD gains and reduces fracture risk 3
• Without follow-up antiresorptive therapy, bone density gains may be lost 1, 3

Clinical Pearls

• Romosozumab produces more rapid and greater BMD increases than other osteoporosis medications 3
• The drug is particularly beneficial for patients at imminent risk of fracture due to its rapid onset of action 3
• Treatment response may be better in patients not previously treated with other anti-osteoporosis agents 7
• Patients with lower baseline BMD may show greater percentage improvements 7

By following these recommendations, clinicians can appropriately select patients for romosozumab therapy, maximize treatment benefits, and minimize potential risks.