What treatment options are available for patients with a high Frax (Fracture Risk Assessment) score?

Treatment Options for High FRAX Score

For patients with a high FRAX score (≥20% 10-year risk of major osteoporotic fracture or ≥3% hip fracture risk), initiate pharmacologic treatment with oral bisphosphonates as first-line therapy, reserving anabolic agents like teriparatide or romosozumab for those at very high risk (≥30% major fracture or ≥4.5% hip fracture). 1

Risk Stratification Based on FRAX

The FRAX score determines treatment intensity through clear thresholds 1:

• High Risk: 10-year major osteoporotic fracture risk 20-30% OR hip fracture risk 3-4.5% 1
• Very High Risk: Major fracture risk ≥30% OR hip fracture risk ≥4.5% OR prior osteoporotic fracture OR T-score ≤-3.5 1

Critical caveat: For patients ≥65 years with a prior fragility fracture, 98% exceed treatment thresholds regardless of BMD or other factors, making FRAX calculation often unnecessary in this population 2. Similarly, for women ≥70 years with parental hip fracture history, 99% exceed treatment thresholds 2.

First-Line Treatment: Oral Bisphosphonates

For high-risk patients, strongly recommend oral bisphosphonates (alendronate or risedronate) as initial therapy 1:

• Proven fracture reduction in patients with FRAX scores meeting treatment thresholds 3
• Cost-effective across all ages when 10-year major fracture probability exceeds 7% 4
• Treatment duration: 5 years, then reassess 5

Essential co-interventions 1, 5:

• Optimize calcium and vitamin D supplementation (age-appropriate RDA levels) - bisphosphonate efficacy is reduced without adequate supplementation 5
• Implement fall prevention strategies 5
• Prescribe weight-bearing exercise programs 5

Escalation to Anabolic Therapy

For very high-risk patients (FRAX ≥1.2 times intervention threshold), conditionally recommend anabolic agents (teriparatide, abaloparatide, or romosozumab) over bisphosphonates 1:

• Anabolic agents demonstrate greater and more rapid fracture reduction than oral antiresorptives 1
• Particularly indicated for recent fracture (within 24 months), as fracture risk is acutely elevated and wanes over 2 years 1
• Teriparatide: 20 mcg subcutaneously daily; lifetime use should not exceed 2 years unless patient remains at very high risk 6

Alternative Antiresorptive Options

For patients intolerant of oral bisphosphonates 1:

• Intravenous bisphosphonates (zoledronic acid, ibandronate): Conditionally recommended for high and very high risk 1
• Denosumab (60 mg subcutaneously every 6 months): Conditionally recommended, but requires careful monitoring in chronic kidney disease (eGFR <30 mL/min) due to severe hypocalcemia risk 1, 7

Agents to avoid or use with extreme caution 1:

• Raloxifene: Conditionally recommend against due to increased VTE and fatal stroke risk 1
• Romosozumab: Conditionally recommend against except in very high-risk patients intolerant of other agents, due to increased cardiovascular events 1

Special Populations

Glucocorticoid-induced osteoporosis 1:

• Adjust FRAX scores: multiply major fracture risk by 1.15 and hip fracture risk by 1.2 if glucocorticoid dose >7.5 mg/day 1
• Very high risk defined as glucocorticoid ≥30 mg/day for >30 days or cumulative ≥5 g/year 1

Chronic kidney disease (eGFR <30 mL/min) 7:

• Evaluate for CKD-MBD with iPTH, serum calcium, vitamin D levels before initiating denosumab 7
• Supervision by specialist with CKD-MBD expertise required 7

Monitoring Strategy

During treatment 1, 5:

• BMD with vertebral fracture assessment every 1-2 years 1
• After discontinuation: BMD every 1-2 years 1
• Reinitiate therapy if T-score declines to ≤-2.5 or new fragility fracture occurs 5

Key Clinical Pitfalls

• Do not rely on FRAX without BMD in younger osteoporotic patients with high BMI: FRAX without T-score may underestimate risk and miss treatment indication 8
• Do not use FRAX in patients already on treatment: FRAX is validated only for untreated patients 9
• Hip fracture risk drives 98% of treatment decisions: Major osteoporotic fracture risk adds minimal value to treatment determination 2
• Age and T-score are the dominant FRAX contributors: Clinical risk factors have additive but smaller effects, with parental fracture history and glucocorticoid use being most impactful 2