Variation in free T3 (fT3) within the reference range is associated with bone development in children, and mediated via alteration in body mass indices
Peter Taylor1, Adrian Sayers2, Ahmed Iqbal1, Andrew Taylor3, Colin Dayan2 & Jonathan Tobias1
Objective: The hypothalamuspituitarythyroid axis profoundly influences skeletal development. Whilst the adverse effects of thyroid dysfunction on bone are well established; the effects of variation within the normal range is less clear.
Design: In a subset of the Avon Longitudinal Study of Parents and Children we performed full thyroid function tests from stored samples taken at age 7. 668 children had thyroid hormone parameters within the reference range. They underwent a total body DXA scan aged 9 to analyse body mass indices, bone mineral density (BMD), bone area (BA), bone mineral content (BMC) and BMC adjusted for area-(aBMC). At age 15, 460 children underwent repeat total body DXA. We adjusted analyses for age, fat mass, lean mass and height.
FT3 and body mass indices (age 9).
|T3||Fat mass||0.16||(0.09, 0.22)||<0.0001|
|Lean mass||0.131||(0.062, 0.199)||0.043|
FT3 and bone outcomes (age 9).
Results: FT3 was associated with fat mass at age 15 (P≤0.0001). No associations were seen with TSH and fT4 levels on body mass indices or bone outcomes.
Conclusion: Variation within the reference range in fT3, but not fT4 or TSH was strongly associated with body mass indices, and BMC. The BMC association was via BA, not BMD as no association was observed with aBMC. The associations between fT3 and bone were lost when adjusted for body mass indices highlighting that this association is mediated through them. Surprisingly there was a positive association between fT3 and fat mass consistent at ages 9 and 15; likely due to an unexplained mechanism between fT3 and childhood adiposity rather than a direct effect between fT3 and fat mass.