T3-action is regulated by three iodothyronine deiodinases, which contain selenium in the active site. It is proposed that Se availability regulates thyroid function. OPUS is a European population-based prospective cohort study of post-menopausal women in which we showed thyroid function within the upper normal range is associated with reduced bone mineral density (BMD) and increased non-vertebral fracture risk. Using strict exclusion criteria we defined reference ranges for thyroid function and Se status (n=1565). Se (97.7±26.3 µg/L) and selenoprotein P (SePP) (3.24±0.8 µg/L) were positively correlated (Spearmans rho: 0.324, P<0.001) and higher Se and SePP were associated with lower fT4 (Se, β:−0.094, P<0.001; SePP, β:−0.129, P<0.001) and fT3 (Se, β:−0.087, P=0.001; SePP, β:−0.172, P<0.001). Following exclusion of individuals receiving drugs affecting bone, we investigated whether Se status is associated with bone formation (osteocalcin, procollagen type 1 N-terminal propeptide, P1NP), resorption (N- and C-telopeptides of type 1 collagen, NTX, CTX), BMD and fracture (n=1144). Following adjustment for age, BMI and smoking, higher Se and SePP were associated with lower osteocalcin (Se, β:−0.101, P<0.001; SePP, β:−0.076, P<0.05), P1NP (Se, β:−0.072, P<0.05; SePP, β:−0.045, P=0.132), NTX (Se, β:−0.058, P=0.05; SePP, β:−0.076, P<0.05) and CTX (Se, β:−0.097, P<0.001; SePP, β:−0.106, P<0.001). Higher Se and SePP were associated with higher hip BMD at study entry (Se, β:0.094, P=0.002; SePP, β:0.113, P<0.001), and higher SePP was associated with higher lumbar spine BMD at study entry (β:0.088, P=0.003) and higher hip BMD after 6-years follow-up (β:0.106, P=0.001). These associations persisted following further adjustment for thyroid status, but Se and SePP were not associated with fracture. In post-menopausal women, although Se and SePP were inversely related to fT4 and fT3, higher Se and SePP concentrations were independently associated with reduced bone turnover and higher BMD. Thus, the effects of variation in Se status on the skeleton are independent of thyroid function.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.