Predicting Fracture Risk After Non-Recent High Risk Fracture: Improving accuracy with simple modifiers to FRAX

Area of Science:

• Osteoporosis research
• Geriatric medicine
• Epidemiology

Background:

• Prior fracture is a key predictor of future osteoporotic fractures.
• The Fracture Risk Assessment Tool (FRAX®) uses prior fracture as a dichotomous variable, potentially missing risk heterogeneity.
• The long-term impact of non-recent high-risk fractures (nrHRFs) on osteoporotic fracture risk is not fully understood.

Purpose of the Study:

• To evaluate if non-recent high-risk fractures (hip, vertebral, or multiple fractures occurring >2 years prior) confer residual risk beyond standard FRAX® inputs.
• To determine if FRAX® underestimates long-term fracture risk in individuals with specific nrHRFs.
• To develop and validate adjustment factors to improve FRAX® calibration in this population.

Main Methods:

• Population-based retrospective cohort study using linked registry and administrative health data (N=88,653 adults ≥40 years).
• Exclusion of individuals with recent fractures (<2 years pre-index).
• Calculation of 10-year major osteoporotic fracture (MOF) and hip fracture probabilities using Canadian FRAX®, followed by Cox models adjusted for baseline FRAX® probability to assess residual risk of nrHRFs. A 2:1 train-test split was used for derivation and validation of recalibration multipliers.

Main Results:

• FRAX® stratified fracture risk less effectively in individuals with prior nrHRFs compared to those without.
• Observed-to-predicted ratios indicated underestimation of MOF risk for non-recent vertebral (1.32) and multiple fractures (1.34), and hip fracture risk for non-recent multiple fractures (1.70).
• Derived multipliers (×1.3 for MOF; ×1.7 for hip fracture) demonstrated good calibration in the validation cohort, reclassifying 13.3% and 3.5% of individuals with nrHRFs into high-risk categories for MOF and hip fracture, respectively.

Conclusions:

• The Fracture Risk Assessment Tool (FRAX®) underestimates 10-year osteoporotic fracture risk in individuals with specific non-recent high-risk fractures.
• Simple adjustment factors can significantly improve FRAX® calibration and enhance the identification of patients who require fracture-preventive therapy.
• These findings support refining fracture risk assessment models to better account for the cumulative impact of prior fractures.