What about romosozumab (Romosozumab) for osteoporosis treatment?

Romosozumab for Osteoporosis Treatment

Romosozumab (Evenity) should be used only in postmenopausal women with primary osteoporosis who have very high risk of fracture, followed by a bisphosphonate, as it significantly reduces vertebral and clinical fracture risk compared to other treatments. 1

Mechanism of Action and Efficacy

Romosozumab is a humanized monoclonal antibody that inhibits sclerostin, a regulatory factor in bone metabolism. It has a dual mechanism of action:

• Increases bone formation on trabecular and cortical bone surfaces
• Decreases bone resorption on trabecular and endocortical surfaces 2

Clinical trials have demonstrated significant benefits:

• 73% reduction in new vertebral fractures at 12 months compared to placebo 1, 3
• Significant increases in bone mineral density (BMD) at the lumbar spine (12.7%), total hip (5.8%), and femoral neck (5.2%) 2
• When followed by antiresorptive therapy (bisphosphonates), the fracture reduction benefits persist, with 75% lower risk of vertebral fractures at 24 months 1

Indications and Patient Selection

Romosozumab is specifically indicated for:

• Postmenopausal women with primary osteoporosis who have very high fracture risk 1
• Very high risk is defined by:
  • Older age
  • Recent fracture (within past 12 months)
  • History of multiple clinical osteoporotic fractures
  • Multiple risk factors for fracture
  • Failure of other available osteoporosis therapy 1

Treatment Algorithm

1. First-line therapy: Oral bisphosphonates (e.g., alendronate) for patients with osteoporosis (T-score ≤ -2.5) or high fracture risk 4

2. Second-line therapy: Injectable antiresorptives like denosumab when oral bisphosphonates are contraindicated 4

3. Anabolic agents (including romosozumab): Reserved for very high fracture risk patients, defined as:

   • Prior fracture
   • T-score ≤ -3.5
   • FRAX ≥ 30% for major osteoporotic fracture or ≥ 4.5% for hip fracture 4

4. Sequential therapy: Romosozumab must be followed by an antiresorptive agent (typically a bisphosphonate) to prevent rapid bone loss after discontinuation 1

Administration and Duration

• Administered as a subcutaneous injection of 210 mg once monthly for 12 months 2
• Two 105 mg/1.17 mL single-use prefilled syringes are required for each dose 2
• Must be followed by antiresorptive therapy (typically bisphosphonates) to maintain benefits and prevent bone loss 1

Safety Considerations and Adverse Effects

Romosozumab has important safety considerations:

• Cardiovascular risk: Increased risk of cardiovascular events compared with alendronate (hazard ratio 1.9) 1

• Common adverse effects:

  • Arthralgia
  • Headache
  • Injection site reactions
  • Hypersensitivity reactions 2, 5

• Laboratory abnormalities: May cause hypocalcemia, particularly in patients with severe renal impairment 2

• Antibody formation: Development of anti-romosozumab antibodies can reduce serum concentrations by up to 22%, with neutralizing antibodies reducing concentrations by up to 63% 2

Special Populations

• Renal impairment: No dose adjustment required, but patients with severe renal impairment or on dialysis require close monitoring of calcium levels 2, 6

• Elderly: No overall differences in safety or efficacy observed in patients over 65 years (80% of clinical trial participants) or over 75 years (37% of participants) 2

• Not indicated for:

  • Men with osteoporosis (insufficient evidence) 1
  • Pediatric patients 2

Cost Considerations

Romosozumab is significantly more expensive than bisphosphonates:

• Average annual cost per Medicare beneficiary: $5,574 for romosozumab vs. $39-$2,700 for bisphosphonates 1
• Additional costs include clinic visits for administration and sequential therapy with bisphosphonates 1

Clinical Pearls and Pitfalls

• Critical pitfall: Failure to transition to an antiresorptive agent after romosozumab can result in rapid bone loss and increased fracture risk 1

• Monitoring: Assess bone mineral density after 2 years and monitor vitamin D levels and fracture risk 4

• Calcium/Vitamin D: Ensure adequate supplementation (calcium 1,000-1,200 mg/day and vitamin D 800-1,000 IU/day) 4

• Duration limitation: Romosozumab is only approved for a 12-month treatment course 2

• Cardiovascular screening: Consider cardiovascular risk factors before initiating therapy due to potential increased cardiovascular risk 1

In conclusion, romosozumab offers significant benefits for postmenopausal women with very high fracture risk but should be reserved for this specific population due to cost and safety considerations. The treatment must be followed by antiresorptive therapy to maintain benefits and prevent bone loss.