What is the recommended treatment regimen for osteoporosis using Romisozumab (romosozumab)?

Romosozumab Treatment Regimen for Osteoporosis

Romosozumab should be administered as a 210 mg subcutaneous injection once monthly for 12 months only, followed by transition to an antiresorptive agent (preferably a bisphosphonate) to maintain bone density gains and fracture risk reduction. 1

Indication and Patient Selection

• Romosozumab is indicated for postmenopausal women with primary osteoporosis who are at very high risk of fracture 1
• Very high fracture risk is defined by:
  • Older age (typically >74 years) 1
  • Recent fracture (within past 12 months) 1
  • History of multiple clinical osteoporotic fractures 1
  • Multiple risk factors for fracture 1
  • Failure of other available osteoporosis therapy 1
• Romosozumab should NOT be used in patients with:
  • History of myocardial infarction or stroke within the preceding year 1, 2
  • High risk for major cardiovascular events 1

Administration Protocol

• Dosage: 210 mg administered subcutaneously once monthly 3, 4
• Duration: Limited to 12 months only, as the anabolic effect wanes after this period 1
• Administration method: Subcutaneous injection, often administered by clinicians rather than self-administered 1
• Supplementation: Patients should receive concurrent calcium and vitamin D supplementation 1

Sequential Therapy

• After completing 12 months of romosozumab, patients MUST transition to an antiresorptive agent 1
• Preferred sequential therapy: Bisphosphonate (particularly alendronate) 1, 4
• Rationale for sequential therapy:
  • Discontinuation of romosozumab without follow-up therapy results in rapid bone loss and increased fracture risk 1, 5
  • Sequential therapy with alendronate maintains and enhances fracture reduction benefits 4

Efficacy

• Romosozumab followed by alendronate provides superior fracture reduction compared to alendronate alone:
  • 48% lower risk of new vertebral fractures 4
  • 27% lower risk of clinical fractures 4
  • 38% lower risk of hip fractures 4
  • 19% lower risk of nonvertebral fractures 4
• Bone mineral density (BMD) increases:
  • Spine: approximately +7.7% after 12 months 3
  • Total hip: approximately +1.8% after 12 months 3

Safety Considerations

• Cardiovascular risk:
  • Higher risk of cardiovascular events compared to alendronate (2.5% vs 1.9%) 1, 2
  • FDA black box warning against use in patients with myocardial infarction or stroke in the preceding year 2
  • Real-world data shows cardiovascular events in approximately 2.0% of patients, with 0.65% being fatal 3
• Other adverse effects:
  • Injection site reactions (4-5% of patients) 2
  • New fracture incidence during treatment: approximately 3.0% 3

Special Considerations

• Predictors of better response to romosozumab:
  • Good renal function 3
  • Low baseline spine BMD 3
  • High baseline TRACP-5b levels 3
  • Low TRACP-5b or high P1NP after 1 month of treatment 3
• Prior treatment effects:
  • Patients transitioning from denosumab show lower BMD increases compared to treatment-naïve patients 3
  • Romosozumab is more effective when used before antiresorptive medications rather than after 2

Re-administration Considerations

• For patients who remain at high fracture risk despite sequential therapy, re-administration of romosozumab may be considered 6
• Re-administration efficacy varies based on the sequential therapy used:
  • Most effective after teriparatide 6
  • Moderately effective after bisphosphonates 6
  • Least effective after denosumab 6