Differential predictive value of FRAX Hip and major osteoporotic fracture probabilities for denosumab response

The Fracture Risk Assessment Tool (FRAX) estimates 10-year probabilities of major osteoporotic fracture (MOF) and hip fracture. Whether these two components differentially predict response to denosumab remains unclear.

To determine whether baseline FRAX-MOF and FRAX-hip probabilities show opposing associations with 1-year bone mineral density (BMD) improvement after denosumab.

Patients with osteoporosis who had BMD measured at baseline and 12 months after initiating denosumab were enrolled. Clinical risk factors were obtained by structured interview, and Taiwan-specific FRAX probabilities for MOF and hip fracture were calculated. Logistic regression examined the association between each FRAX probability and BMD improvement (primary outcome).

Among 150 denosumab-treated patients, a higher FRAX-MOF probability was associated with a lower likelihood of BMD improvement (P = 0.011; OR 0.81; 95% CI 0.68-0.95), whereas a higher FRAX-hip probability was associated with a greater likelihood of improvement (P < 0.001; OR 1.74; 95% CI 1.30-2.34).

FRAX components convey differential predictive information for denosumab response: higher FRAX-hip probability predicts benefit, while higher FRAX-MOF probability predicts attenuated BMD gain. Recognizing these opposing directions may refine patient selection and expectation-setting for denosumab in osteoporosis care.

This study shows that fracture risk scores predict denosumab response differently: hip fracture risk predicts stronger bone density gains, while major osteoporotic fracture risk predicts weaker gains. Recognizing these opposing signals can improve patient selection and treatment expectations in osteoporosis management.