The Fracture Risk Assessment Tool Probability and Trabecular Bone Score Mediate the Relationship between Sphingosine 1-phosphate Levels and Fracture Risk.

Background: The sphingosine 1-phosphate (S1P) concentration is a potential biomarker of osteoporotic fracture and is associated with both the fracture risk assessment tool (FRAX) probability and trabecular bone score (TBS), which are well-known predictors of fracture. We sought to estimate the effect of the S1P concentration on fracture risk using the FRAX probability and TBS as mediators.

Methods: Plasma S1P concentrations, FRAX variables, and TBSs were measured in 66 postmenopausal women with fractures and 273 postmenopausal women without fractures. Associations between S1P concentration, FRAX probability, TBS, and fracture risk were analyzed using correlation, logistic regression, and mediation analyses.

Results: Subjects in the highest S1P concentration tertile had a higher fracture risk (odds ratio [OR], 5.09; 95% confidence interval [CI], 2.22-11.67) than those in the lowest S1P concentration tertile before adjustment. Subjects in the highest FRAX probability tertile had a higher fracture risk (OR, 14.59; 95% CI, 5.01-42.53) than those in the lowest FRAX probability tertile before adjustment. Subjects in the lowest TBS tertile had a higher fracture risk (OR, 4.76; 95% CI, 2.28-9.93) than those in the highest TBS tertile before adjustment. After adjustment for FRAX probability and TBS, the highest S1P concentration tertile was still associated with a higher fracture risk (OR, 3.13; 95% CI, 1.28-7.66). The FRAX probability and TBS accounted for 32.6% and 21.7%, respectively, of the relationship between the S1P concentration and fracture risk.

Conclusions: The relationship between the circulating S1P concentration and fracture risk was partly mediated by the FRAX probability, bone microarchitecture, and other factors.