What is the recommended treatment for a patient with osteoporosis and high fracture risk?

Treatment for Osteoporosis with High Fracture Risk

For patients with osteoporosis and high fracture risk, oral bisphosphonates are strongly recommended as first-line therapy, with anabolic agents like teriparatide or romosozumab preferred for those at very high fracture risk. 1, 2

Risk Stratification and Treatment Selection

For Adults ≥40 Years:

• High fracture risk (defined as BMD T-score ≤-2.5 but >-3.5 OR FRAX 10-year risk of major osteoporotic fracture ≥20% but <30% or hip fracture ≥3% but <4.5%):

  • First-line: Oral bisphosphonates (alendronate, risedronate) 1
  • Alternative options: Denosumab or PTH/PTHrP agonists (conditionally recommended over bisphosphonates) 1

• Very high fracture risk (defined as prior osteoporotic fracture OR BMD T-score ≤-3.5 OR FRAX 10-year risk of major osteoporotic fracture ≥30% or hip ≥4.5%):

  • First-line: Anabolic agents (teriparatide, abaloparatide, romosozumab) followed by antiresorptive therapy 1, 2
  • Alternative: Oral bisphosphonates if anabolic agents are contraindicated 1

Specific Medication Recommendations:

Bisphosphonates:

• Alendronate: 70mg once weekly (most widely used due to efficacy, safety, and low cost) 3, 4
• Risedronate: Oral administration with rapid onset of fracture reduction (within 6 months) 5
• Zoledronic acid: IV option for those who cannot tolerate oral bisphosphonates

Anabolic Agents:

• Teriparatide: 20mcg subcutaneously once daily for up to 2 years, particularly effective for vertebral fractures 6, 7
• Romosozumab: 210mg subcutaneously monthly for 12 months only, followed by antiresorptive therapy 2

Other Options:

• Denosumab: 60mg subcutaneously every 6 months; must be followed by another antiresorptive when discontinued to prevent rebound bone loss 3

Treatment Duration and Monitoring

• Bisphosphonates: Consider drug holiday after 5 years of oral therapy to reduce risk of atypical femoral fractures 3
• Anabolic agents: Limited to 12 months (romosozumab) or 24 months (teriparatide) followed by antiresorptive therapy 2, 6
• Monitoring: BMD with vertebral fracture assessment or spinal x-ray every 1-2 years during treatment 1

Supplementation and Lifestyle Modifications

• Calcium: 1000-1200 mg daily (preferably from dietary sources) 2, 3
• Vitamin D: 800-1000 IU daily 2
• Weight-bearing exercise and resistance training 7, 8
• Smoking cessation and limiting alcohol consumption 8

Special Considerations

• Cardiovascular risk: Assess before starting romosozumab due to potential increased risk of myocardial infarction and stroke 2
• Renal impairment: Use caution with bisphosphonates; may require dose adjustment or alternative therapy
• Sequential therapy: When discontinuing denosumab or completing anabolic therapy, transition to a bisphosphonate to prevent bone loss 2, 3

Common Pitfalls to Avoid

1. Failing to recognize very high fracture risk patients who would benefit more from anabolic therapy than antiresorptives
2. Not providing adequate calcium and vitamin D supplementation, reducing treatment efficacy
3. Discontinuing denosumab without transitioning to another antiresorptive agent
4. Not limiting anabolic agents to their recommended treatment duration (12-24 months)
5. Overlooking the need for long-term treatment strategy after completing initial therapy

By following this treatment algorithm based on fracture risk assessment, you can optimize outcomes and reduce morbidity and mortality associated with osteoporotic fractures.