Low serum thyrotropin level and duration of suppression as a predictor of major osteoporotic fractures - The OPENTHYRO register cohort

The relationship between thyrotoxicosis and osteoporotic fractures remains controversial, particularly in men. Register-based cohort study including all patients with a serum thyrotropin (TSH) measurement in the region of Funen 1996-2010. All TSH determinations were done in the same lab, which served all hospitals and General Practice (GP) practices in the region. Persons with raised TSH or a history of thyroid/pituitary disease or use of thyroid medications were excluded. The study population consisted of 222,138 (96%) persons with normal and 9217 (4%) with low TSH (<0.3 mIU/L). A single low TSH at baseline was associated with increased risk of hip fractures (adj HR 1.16, 95% CI 1.07-1.26, p<0.001) but not major osteoporotic fractures (MOF, adj HR 1.06, 95% CI 0.99-1.12, p=0.058) over a median follow-up of 7.5 years. When men were analyzed separately, results did not reach statistical significance. We found a significant association between duration of thyrotoxicosis and fracture. For each 6 months in which the mean TSH value was decreased (<0.3 mIU/L), hip fracture risk increased by a factor 1.07 (adj HR, 95% CI 1.04-1.10, p<0.001) and MOF by 1.05 (adj HR, 95% CI 1.03-1.07, p<0.001). Overt thyrotoxicosis was associated with an increased risk of hip fractures but not MOF. In euthyroid patients, the risk of fractures increased significantly with each SD unit of TSH decrease: Hip fracture (HR 1.45, 95% CI 1.22-1.71, p<0.001) and MOF (HR 1.32, 95% CI 1.19-1.46, p<0.001). In a population-based cohort, a single, first measurement of decreased TSH in patients without known thyroid disease was associated with an increased long-term risk of hip fracture, which remained significant in women but not in men after adjusting for confounders. Moreover, the risk of both hip fracture and MOF increased exponentially by the length of time during which TSH had remained low.