Sex Hormone-Binding Globulin Is Associated With Markers Of Vertebral Fracture And Vertebral Fracture Risk

Abstract

Background The relation between sex hormone-binding globulin (SHBG) and vertebral fracture (VFx) is unclear. We examined whether SHBG is associated with bone mineral density at lumbar spine (LS-BMD), trabecular bone score (TBS) and prevalent VFx. Methods Data of 6,224 men and women participants in the third visit of the first cohort (I-3) and the first visit of the second cohort (II-1) of the Rotterdam Study (RS), a prospective population based cohort, were available. Serum SHBG and prevalent VFx were assessed at RS I-3 and II-2, whereas LS-BMD and TBS were assessed 4 years later (RS I-4 and RS II-2). VFx were scored using the Quantitative Morphometry method (QM) and Algorithm Based Qualitative method (ABQ). Multivariate linear and logistic regression models were performed, adjusted for confounding factors such as medication use, lifestyle factors, body mass index, serum glucose, insulin, calcium and phosphate levels. Results We identified 854 prevalent VFxQM and 176 prevalent VFxABQ. After correcting for confounders, higher levels of SHBG were associated with lower LS-BMD (3rd tertile vs. 1st tertile: β: -0.04; 95%CIs= -0.06; -0.02) and higher TBS (3rd tertile vs. 1st tertile: β: 0.02; 95%CIs=0.01; 0.03). Higher levels of SHBG were positively associated with both VFxQM (3rd tertile vs. 1st tertile: OR: 1.25; 95%CIs=1.02; 1.55) and VFxABQ (3rd tertile vs. 1st tertile: OR: 2.11; 95%CIs=1.29; 3.5) independent of BMD and TBS. Adjustment for total testosterone and estradiol levels did not affect any of these associations. Also, no sex differences were observed. Conclusion This study suggests that SHBG concentration may be a sensitive and early biomarker of VFx. As measurement of serum SHBG is reliable, easy and inexpensive, its assessment may have clinical utility in identifying individuals at high risk of developing VFx later in life that could benefit from effective preventive interventions.