Thyroid hormone status within the physiological range affects bone mass and density in healthy men at the age of peak bone mass Running Title: Thyroid parameters and bone status

Context: The hormonal factors involved in the regulation of peak bone mass in men have not been fully investigated. Aside from gonadal steroids and somatotropic hormones, thyroid hormones are known to affect bone maturation and homeostasis, and are additional candidate determinants of adult bone mass. Objective: We aimed to investigate between-subject physiological variation in free and total thyroid hormone concentrations, TSH and thyroid binding globulin (TBG) in relation to parameters of bone mass, geometry and mineral density in healthy men at age of peak bone mass. Design and setting: 677 healthy male siblings aged 25-45 yrs were recruited in a cross-sectional, population-based study. Areal and volumetric bone parameters were determined using DXA and pQCT. Total and free thyroid hormones, TBG and TSH were determined using immunoassays. Results: Free and total thyroid hormone concentrations were inversely associated with BMD and BMC at the hip and total body (FT3, TT3, TT4) and at the spine (FT3). TBG was negatively associated with BMC and aBMD at all sites. At the radius, cortical bone area was inversely associated with TT3, TT4 and TBG and trabecular bone density was inversely associated with FT4, TT4 and TBG. We observed inverse associations between cortical bone area at the mid-tibia and FT3, TT3, TT4 and TBG. No associations between TSH and DXAor pQCT-measurements were found. Conclusion: In healthy men at age of peak bone mass, between-subject variation in thyroid hormone concentrations affects bone density, with higher levels of FT3, TT3, TT4 and TBG being associated with less favourable bone density and content. Abbreviations: DXA, dual-energy X-ray absorptiometry; FT3, free triiodothyronine; FT4, free thyroxine; TT3, total triiodothyronine; TT4, total thyroxine; TSH, thyroid-stimulating hormone; TBG, thyroid binding globulin; pQCT, peripheral quantitative computed tomography; aBMD, areal bone