What is the clinical significance and management of a high Frax (Fracture Risk Assessment) score in postmenopausal women and older adults with increased risk of fracture?

FRAX Score: Clinical Significance and Management

What is FRAX and When to Use It

FRAX is a validated fracture risk assessment tool that calculates 10-year probability of hip fracture and major osteoporotic fracture (MOF) in postmenopausal women and men aged 50 years and older, using clinical risk factors with or without bone mineral density (BMD). 1, 2

The tool incorporates 11 clinical risk factors: age, sex, weight, height, prior fragility fracture, parental hip fracture, current smoking, glucocorticoid use, rheumatoid arthritis, secondary osteoporosis, and alcohol consumption (3+ units daily), with optional femoral neck BMD input. 1, 2, 3

Treatment Thresholds: When High FRAX Scores Mandate Action

Pharmacologic treatment is recommended when FRAX scores indicate ≥3% 10-year hip fracture risk OR ≥20% 10-year major osteoporotic fracture risk. 1, 2

These thresholds are based on cost-effectiveness analyses and represent the fracture probability equivalent to a postmenopausal woman with a prior osteoporotic fracture. 4

Risk Stratification for Treatment Selection

• Very high risk (MOF >30% or hip fracture >4.5%): Consider anabolic therapy first (e.g., teriparatide, romosozumab) 2
• High risk (MOF ≥20% or hip fracture ≥3%): Consider antiresorptive therapy (bisphosphonates, denosumab) 2, 5, 6
• Moderate risk (MOF 10-19% or hip fracture 1-3%): Individualize based on additional factors 1, 2

Critical Adjustments for Glucocorticoid Users

For patients taking prednisone >7.5 mg/day, manually adjust FRAX scores by multiplying MOF risk by 1.15 and hip fracture risk by 1.2. 1, 2

This adjustment is essential because FRAX uses only binary (yes/no) glucocorticoid exposure and underestimates risk at higher doses. 1

Glucocorticoid-Induced Osteoporosis Risk Categories

For adults ≥40 years on glucocorticoids, high fracture risk is defined as: 1

• Prior osteoporotic fracture(s)
• Hip or spine BMD T-score ≤-2.5 (in men ≥50 and postmenopausal women)
• FRAX-adjusted 10-year MOF risk ≥20%
• FRAX-adjusted 10-year hip fracture risk ≥3%

Predictive Accuracy: Understanding FRAX Performance

FRAX demonstrates moderate-to-good predictive accuracy with area under the curve (AUC) values of 0.74-0.79 for hip fracture prediction and 0.67-0.71 for MOF prediction when BMD is included. 1

Including BMD in FRAX calculations improves predictive accuracy compared to clinical risk factors alone, with hip fracture prediction consistently more accurate than MOF prediction. 1

In women younger than 65 years, FRAX performance is reduced (AUC 0.56-0.68), indicating lower discriminatory ability in this population. 1

Evidence for Screening and Treatment Benefits

Screening with FRAX followed by DXA for high-risk individuals reduces hip fractures by 17% (RR 0.83,95% CI 0.73-0.93) and major osteoporotic fractures by 6% (RR 0.94,95% CI 0.88-0.99) over 3.7-5 years. 1

This translates to 5 fewer hip fractures and 6 fewer MOFs per 1000 women screened over approximately 5 years. 1

Treatment with bisphosphonates in high-risk patients reduces vertebral fractures by 49% (RR 0.51,95% CI 0.39-0.66) and hip fractures by 33% (RR 0.67,95% CI 0.45-1.00). 1

Screening Recommendations by Age and Risk

Postmenopausal Women ≥65 Years

• Screen all women regardless of risk factors using DXA with or without FRAX 1

Postmenopausal Women 50-64 Years

• Screen if FRAX score (without BMD) approaches or exceeds the baseline risk of a 65-year-old white woman (approximately 9.3% 10-year MOF risk, 1.3% hip fracture risk) 1
• Alternative tools for identifying who needs DXA: OST (Osteoporosis Self-Assessment Tool) or ORAI (Osteoporosis Risk Assessment Instrument) 1

Men ≥50 Years

• Apply same FRAX thresholds as postmenopausal women 2, 3

Reassessment Intervals

Repeat FRAX assessment every 1-3 years for patients on glucocorticoids not receiving osteoporosis treatment, with earlier reassessment for very high-dose users. 2

For patients with osteopenia and low initial FRAX scores, repeat in 2 years, or in 1 year if new risk factors develop. 2

BMD testing intervals of 4-8 years are generally sufficient for monitoring, as more frequent testing does not improve fracture prediction. 1

Important Limitations and Clinical Pitfalls

Race and Ethnicity Considerations

FRAX uses race-specific calculators that systematically predict lower fracture risk for Asian, Black, and Hispanic individuals compared to White individuals with identical clinical profiles, potentially leading to treatment disparities. 1

Factors NOT Captured by FRAX

FRAX does not account for: 1, 2

• Dose-dependent effects of glucocorticoids (only yes/no)
• Fall history or frailty status
• Lumbar spine BMD or trabecular bone score
• Diabetes mellitus
• Number of prior fractures (only yes/no)
• Recency of fractures

Patients with frequent falls, multiple prior fractures, or very recent fractures warrant treatment consideration even if FRAX scores fall below standard thresholds. 2, 3

Validation Constraints

FRAX is validated only for untreated patients aged 40-90 years and should not be used to assess fracture risk in patients already receiving osteoporosis therapy. 2, 3

Practical Implementation Algorithm

1. Calculate FRAX score using online WHO calculator with all available clinical risk factors 2
2. Include femoral neck BMD when available (improves accuracy) 1
3. Adjust for high-dose glucocorticoids if prednisone >7.5 mg/day 1, 2
4. Apply treatment thresholds: Treat if hip fracture risk ≥3% OR MOF risk ≥20% 1, 2
5. Consider clinical judgment for patients with falls, frailty, or factors not captured by FRAX 2, 3
6. Select appropriate therapy based on risk stratification (anabolic vs. antiresorptive) 2