This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: [10.1002/jbmr.2244]
Low Serum Thyrotropin Level and Duration of Suppression as a Predictor of Major Osteoporotic Fractures – The OPENTHYRO Register Cohort
© 2014 American Society for Bone and Mineral Research
Preliminary findings were presented as an abstract at the annual meeting of the American Society for Bone and Mineral Research, Baltimore October 2013
- Accepted manuscript online: 9 APR 2014 05:59AM EST
- Manuscript Accepted: 25 MAR 2014
- Manuscript Revised: 21 MAR 2014
- Manuscript Received: 14 JAN 2014
- Novartis, Nycomed/Takeda and Amgen
- Novo Nordisk Foundation
- Cited By
- Health Services Research;
- Fracture risk assessment;
- Endocrine pathways;
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 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 9,217 (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 analysed separately, results did not reach statistical significance. We found a significant association between duration of thyrotoxicosis and fracture. For each six 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. © 2014 American Society for Bone and Mineral Research