What is the clinical significance of the Frax (Fracture Risk Assessment) score in guiding osteoporosis treatment?

FRAX Score: Clinical Significance and Application

FRAX is the primary tool for calculating 10-year absolute fracture probability and should guide treatment decisions in patients with osteopenia or clinical risk factors, as it addresses the critical limitation that most fractures occur in patients with BMD T-scores above -2.5. 1

Core Clinical Purpose

FRAX calculates two specific probabilities: 10-year risk of major osteoporotic fracture (hip, clinical spine, humerus, or wrist) and 10-year risk of hip fracture specifically. 1 The algorithm integrates clinical risk factors that are at least partly independent of BMD—including prior fragility fracture, parental hip fracture history, current smoking, long-term glucocorticoid use, rheumatoid arthritis, secondary osteoporosis causes, and excessive alcohol consumption—along with age and BMI. 1

The fundamental value of FRAX is that BMD alone is specific but not sensitive for fracture prediction—individuals with low BMD are at high individual risk, but the majority of fractures occur in the larger population with BMD above the osteoporosis threshold of T-score -2.5. 1 FRAX captures risk from non-BMD factors that BMD testing misses entirely. 1

Treatment Thresholds

Initiate pharmacologic treatment when FRAX demonstrates ≥3% 10-year hip fracture risk OR ≥20% 10-year major osteoporotic fracture risk. 2, 3 These thresholds represent the standard recommendation from the National Osteoporosis Foundation and are widely applied in clinical practice. 3

For postmenopausal women aged 50-64 years undergoing screening, use a threshold equivalent to a 65-year-old white woman's baseline risk (9.3% 10-year major fracture probability). 2

Risk Stratification for Treatment Selection

Beyond simply deciding whether to treat, FRAX enables stratification into "high risk" versus "very high risk" categories to guide which medication class to initiate. 1, 2

Define "very high risk" as fracture probability above 1.2 times the intervention threshold, which translates to ≥30% 10-year major osteoporotic fracture risk or ≥4.5% hip fracture risk. 1, 2 Patients in this category should receive anabolic therapy (teriparatide or romosozumab) first due to greater and more rapid therapeutic effects, while those at "high risk" (meeting treatment thresholds but not very high risk criteria) can be directed to antiresorptive agents like bisphosphonates or denosumab. 1

Key contributors to very high risk status include: 1

• Recent fracture (within past 24 months)—31-45% of recurrent fractures occur within 1 year of the sentinel fracture
• High-dose glucocorticoid use
• Multiple risk factor combinations, particularly older age with recent fracture and glucocorticoid use

Glucocorticoid-Specific Adjustments

For patients receiving prednisone >7.5 mg/day (or equivalent), multiply the standard FRAX major osteoporotic fracture risk by 1.15 and hip fracture risk by 1.2. 1, 2, 3 The base FRAX algorithm assumes glucocorticoid doses of 2.5-7.5 mg/day, so this adjustment accounts for dose-dependent effects not captured in the standard calculation. 1

The American College of Rheumatology provides specific risk categories for glucocorticoid-treated patients aged ≥40 years: 1

• High fracture risk: Prior osteoporotic fracture, hip/spine T-score ≤-2.5, FRAX (GC-adjusted) ≥20% major osteoporotic fracture OR ≥3% hip fracture
• Moderate fracture risk: FRAX (GC-adjusted) 10-19% major osteoporotic fracture OR >1% and <3% hip fracture
• Low fracture risk: FRAX (GC-adjusted) <10% major osteoporotic fracture AND ≤1% hip fracture

Reassessment Intervals

For patients on continued glucocorticoids at low or moderate fracture risk who are not receiving osteoporosis therapy, reassess FRAX every 1-2 years. 2, 3 For those already on osteoporosis treatment, reassess every 1-2 years to determine if BMD is stable, improving, or declining. 2

Earlier reassessment is warranted for patients on very high-dose glucocorticoids or those with history of osteoporotic fracture. 3

Critical Limitations and Appropriate Use

FRAX is validated only for untreated patients aged 40-90 years and should NOT be used in adults <40 years, children, or those already on osteoporosis therapy. 2, 3 For younger adults on glucocorticoids, use clinical risk assessment with BMD Z-scores instead. 2, 3

The tool does not account for dose-dependent effects of risk factors beyond the glucocorticoid adjustment mentioned above, and it has limitations regarding race-specific calculations. 3 However, research demonstrates that FRAX maintains good calibration and risk stratification even in treated patients, though it should not be used to assess reduction in fracture risk from treatment itself. 4

Including femoral neck BMD in the FRAX calculation significantly improves predictive accuracy and should be done whenever possible. 3, 5 Calculating FRAX without BMD can lead to treatment recommendations for patients with normal bone density (particularly older patients) or miss treatment needs in younger patients with high BMI and low T-scores. 5 Agreement between FRAX with and without BMD is only 89.4%, with clinically meaningful disagreement in 10.6% of cases. 5

Application in Special Populations

In rheumatoid arthritis patients, FRAX remains well-calibrated for most risk levels but may slightly overestimate risk in those already at high predicted risk (>20%). 6 The tool continues to appropriately stratify fracture risk in contemporary RA patients despite predating current RA treatment approaches. 6

For celiac disease patients, FRAX has high negative predictive value (94%) and can effectively identify patients who do not require DXA scanning, though its positive predictive value is limited. 7