Background: Overt thyroid dysfunction is a risk factor for osteoporosis and fractures. Subclinical hyperthyroidism has been associated with fracture risk. It remains unclear whether variation in thyroid function within the euthyroid range modulates bone health.
Aim: To test the hypothesis that TSH and FT4 are associated with bone turnover markers and predict hip fracture risk in community-dwelling older men without known thyroid disease.
Methods: Prospective cohort study of 4248 men aged 70-89 years. Baseline (2001-04) blood samples were assayed for TSH, FT4, osteocalcin, undercarboxylated osteocalcin (ucOC), N-terminal propeptide of type I collagen (P1NP) and collagen type I C-terminal cross-linked telopeptide (CTX). Incidence of hip fracture events was ascertained to 2012. Associations of TSH and FT4 with bone turnover markers were analysed using linear regression and with incident hip fracture using Cox proportional hazards regression.
Results: After excluding men with pre-existing thyroid or bone disease, there were 3567 men for analysis. Of these, 3140 were euthyroid, 401 had subclinical hypothyroidism and 26 had subclinical hyperthyroidism. Men with subclinical hyperthyroidism were older and had lower creatinine than the other groups (both p <0.001). Subclinical thyroid dysfunction was not associated with bone turnover markers or incident hip fracture. In euthyroid men, cross-sectional analyses revealed inverse associations between TSH and P1NP (r = -0.053, p = 0.04) and TSH and CTX (r = -0.039, p = 0.01) after adjusting for age, BMI, waist-hip ratio, smoking, alcohol, physical activity, hypertension, dyslipidaemia, frailty, diabetes, cancer, CVD, creatinine and vitamin D. Neither TSH nor FT4 were predictive of incident hip fracture in euthyroid men.
Conclusions: In euthyroid older men higher TSH was independently associated with lower bone formation and bone resorption markers. Variation in thyroid function within the euthyroid range may influence bone metabolism during ageing. Further investigation is needed to determine the effect on fracture risk.