The WHO Fracture Risk Assessment Tool (FRAX; http://www.shef.ac.uk/FRAX) 
estimates the 10-year probability of major osteoporotic fracture. Clodronate and 
bazedoxifene reduced nonvertebral and clinical fracture more effectively on a 
relative scale in women with higher FRAX scores. We used data from the Fracture 
Intervention Trial (FIT) to evaluate the interaction between FRAX score and 
treatment with alendronate. We combined the Clinical Fracture (CF) arm and 
Vertebral Fracture (VF) arm of FIT. The CF and VF arm of FIT randomized 4432 and 
2027 women, respectively, to placebo or alendronate for 4 and 3 years, 
respectively. FRAX risk factors were assessed at baseline. FRAX scores were 
calculated by WHO. We used Poisson regression models to assess the interaction 
between alendronate and FRAX score on the risk of nonvertebral, clinical, major 
osteoporotic, and radiographic vertebral fractures. Overall, alendronate 
significantly reduced the risk of nonvertebral fracture (incidence rate ratio 
[IRR] 0.86; 95% confidence interval [CI], 0.75-0.99), but the effect was greater 
for femoral neck (FN) bone mineral density (BMD) T-score ≤ -2.5 (IRR 0.76; 95% 
CI, 0.62-0.93) than for FN T-score > -2.5 (IRR 0.96; 95% CI, 0.80-1.16) 
(p = 0.02, interaction between alendronate and FN BMD). However, there was no 
evidence of an interaction between alendronate and FRAX score with FN BMD for 
risk of nonvertebral fracture (interaction p = 0.61). The absolute benefit of 
alendronate was greatest among women with highest FRAX scores. Results were 
similar for clinical fractures, major osteoporotic fractures, and radiographic 
vertebral fractures and whether or not FRAX scores included FN BMD. Among this 
cohort of women with low bone mass there was no significant interaction between 
FRAX score and alendronate for nonvertebral, clinical or major osteoporotic 
fractures, or radiographic vertebral fractures. These results suggest that the 
effect of alendronate on a relative scale does not vary by FRAX score. A 
randomized controlled trial testing the effect of antifracture agents among 
women with high FRAX score but without osteoporosis is warranted.