Underestimation of fracture risk by conventional FRAX thresholds in axial spondyloarthritis: a proposal for disease-specific thresholds

Background: The Fracture Risk Assessment Tool (FRAX) is widely used as an intervention threshold for postmenopausal osteoporosis but has not been validated specifically for axial spondyloarthritis (axSpA). Objectives: To validate FRAX thresholds and predictive ability for fragility fractures in axSpA patients. Design: A cross-sectional study. Methods: Patients diagnosed with axSpA according to the 2009 ASAS criteria, aged 40–90 years, and treated at Phramongkutklao Hospital between December 2019 and October 2024 were consecutively included. Bone mineral density (BMD), trabecular bone score (TBS), and vertebral fracture assessment were measured using Dual-energy X-ray absorptiometry. The Thai reference database calculated FRAX probabilities for major osteoporotic fracture (MOF) and hip fracture (HF). The predictive performance of FRAX (with and without BMD) was evaluated against actual fracture occurrence, using FRAX thresholds for MOF and HF at 10% and 3%, respectively. Optimal cutoffs for FRAX against fractures were determined using receiver operating characteristic (ROC) curves and the Youden index. Results: Among 125 axSpA patients (73.6% male; mean age 50.9 ± 10.8 years; disease duration 9.7 ± 9.9 years), osteoporotic fractures were found in 24.0%, with vertebral fractures being most common. Patients with fractures had significantly higher disease activity (Bath Ankylosing Spondylitis Disease Activity Index 4.2 vs 2.2, p = 0.004; Ankylosing Spondylitis Disease Activity Score (ASDAS) 3.1 vs 1.7, p < 0.001) and higher median FRAX scores for MOF (4.9% vs 1.9% without BMD; 4.7% vs 2.4% with BMD) and HF (0.8% vs 0.2% without BMD; 0.9% vs 0.5% with BMD; all p < 0.05). Higher ASDAS scores were independently associated with increased fracture risk (odds ratio 2.35, 95% confidence interval 1.39–3.98). FRAX thresholds (MOF ⩾10%, HF ⩾3%) showed low sensitivity (MOF: 0% without BMD, 18.5% with BMD; HF: 23.3% without BMD, 22.2% with BMD) but high specificity (>84%). Optimal ROC-derived FRAX cutoffs without BMD (MOF ⩾4%, HF ⩾1.5%) improved predictive accuracy (MOF: sensitivity 40%, specificity 85.3%, area under the ROC curve (AUC) = 0.770; HF: sensitivity 46.7%, specificity 75.8%, AUC = 0.674). Conclusion: FRAX (without BMD) is a viable predictor of fractures in axSpA, yet its optimal intervention thresholds (⩾4% MOF and ⩾1.5% HF) fall substantially below standard thresholds for postmenopausal women. Adjusting clinical thresholds downward is warranted to ensure timely prevention and better reflect the specific axSpA risk profile.