Top

Osteoporosis International

Published in:

Open Access 01-11-2021 | Hyperthyroidism | Original Article

Subclinical hyperthyroidism is associated with increased risk of vertebral fractures in older men

Authors: J. Svensson, C. Ohlsson, M. K. Karlsson, M. Lorentzon, C. Lewerin, D. Mellström

Published in: Osteoporosis International | Issue 11/2021

Abstract

Summary

In elderly men included in MrOS-Sweden, subclinical hyperthyroidism (SHyper) was markedly associated with increased risk of vertebral fractures.

Introduction

Overt hyperthyroidism is associated with increased risk of fractures. However, only a few studies have investigated whether SHyper is associated with fracture risk in elderly men. We therefore investigated if SHyper was a risk factor for fractures in Swedish men.

Methods

We followed (median 9.8 years) elderly men (n = 1856; mean age 75, range 69–81 years) participating in the Gothenburg and Malmö subcohorts of the prospective, population-based MrOS-Sweden study. The statistical analyses included Cox proportional hazards regression. SHyper was defined as serum thyroid-stimulating hormone (TSH) < 0.45 mIU/L (n = 38).

Results

SHyper was associated with increased risk of all fractures [n = 456; hazard ratio (HR) adjusted for age, study center, and levothyroxine treatment = 1.99, 95% confidence interval (CI): 1.20–3.32], major osteoporotic fractures (MOF, n = 338; HR 2.44, 95% CI: 1.42–4.21), and vertebral fractures (n = 176; HR 3.79, 95% CI: 2.02–7.11). These associations remained after full adjustment for covariates including total hip bone mineral density and in subanalyses including only men with serum free thyroxine ≤ the upper normal limit. However, after exclusion of men receiving levothyroxine treatment, the associations with all fractures and MOF lost significance.

Conclusions

In elderly Swedish men, there was a strong association between SHyper and increased risk of vertebral fractures, whereas the associations with all incident fractures and MOF need to be confirmed in further studies.

Bassett J, Williams G (2016) Role of thyroid hormones in skeletal development and bone maintenance. Endocr Rev 37:135–187CrossRef

Mosekilde L, Eriksen E, Charles P (1990) Effects of thyroid hormones on bone and mineral metabolism. Endocrinol Metab Clin N Am 19:35–63CrossRef

Abrahamsen B, Jørgensen H, Laulund A, Nybo M, Bauer D, Brix T, Hegedüs L (2015) The excess risk of major osteoporotic fractures in hypothyroidism is driven by cumulative hyperthyroid as opposed to hypothyroid time: an observational register-based time-resolved cohort analysis. J Bone Miner Res 30:898–905CrossRef

Flynn R, Bonellie S, Jung R, MacDonald T, Morris A, Leese G (2010) Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab 95:186–193CrossRef

Murphy E, Glüer C, Reid D, Felsenberg D, Roux C, Eastell R, Williams G (2010) Thyroid function within the upper normal range is associated with reduced bone mineral density and an increased risk of nonvertebral fractures in healthy euthyroid postmenopausal women. J Clin Endocrinol Metab 95:3173–3181CrossRef

Roef G, Lapauw B, Goemaere S, Zmierczak H, Fiers T, Kaufman J, Taes Y (2011) Thyroid hormone status within the physiological range affects bone mass and density in healthy men at the age of peak bone mass. Eur J Endocrinol 164:1027–1034CrossRef

Abrahamsen B, Jørgensen H, Laulund A, Nybo M, Brix T, Hegedüs L (2014) Low serum thyrotropin level and duration of suppression as a predictor of major osteoporotic fractures-the OPENTHYRO register cohort. J Bone Miner Res 29:2040–2050CrossRef

Taylor P, Razvi S, Pearce S, Dayan C (2013) Clinical review: a review of the clinical consequences of variation in thyroid function within the reference range. J Clin Endocrinol Metab 98:3562–3571CrossRef

Segna D, Bauer D, Feller M, Schneider C, Fink H, Aubert C, Collet T, da Costa B, Fischer K, Peeters R, Cappola A, Blum M, van Dorland H, Robbins J, Naylor K, Eastell R, Uitterlinden A, Rivadeneira Ramirez F, Gogakos A, Gussekloo J, Williams G, Schwartz A, Cauley J, Aujesky D, Bischoff-Ferrari H, Rodondi N, Thyroid Studies Collaboration (2018) Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts. J Intern Med 283:56–72CrossRef

10.

Blum M, Bauer D, Collet T, Fink H, Cappola A, da Costa B, Wirth C, Peeters R, Åsvold B, den Elzen W, Luben R, Imaizumi M, Bremner A, Gogakos A, Eastell R, Kearney P, Strotmeyer E, Wallace E, Hoff M, Ceresini G, Rivadeneira F, Uitterlinden A, Stott D, Westendorp R, Khaw K, Langhammer A, Ferrucci L, Gussekloo J, Williams G, Walsh J, Jüni P, Aujesky D, Rodondi N, Thyroid Studies Collaboration (2015) Subclinical thyroid dysfunction and fracture risk: a meta-analysis. JAMA 313:2055–2065

11.

Zhu H, Zhang J, Wang J, Zhao X, Gu M (2019) Association of subclinical thyroid dysfunction with bone mineral density and fracture: a meta-analysis of prospective cohort studies. Endocrine E67:685–698

12.

Finigan J, Greenfield D, Blumsohn A, Hannon R, Peel N, Jiang G, Eastell R (2008) Risk factors for vertebral and nonvertebral fracture over 10 years: a population-based study in women. J Bone Miner Res 23:75–85CrossRef

13.

Bauer D, Ettinger B, Nevitt M, Stone K, Study of Osteoporotic Fractures Research Group (2001) Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med 134:561–568CrossRef

14.

Garin M, Arnold A, Lee J, Robbins J, Cappola A (2014) Subclinical thyroid dysfunction and hip fracture and bone mineral density in older adults: the cardiovascular health study. J Clin Endocrinol Metab 99:2657–2664CrossRef

15.

Lee J, Buzková P, Fink H, Vu J, Carbone L, Chen Z, Cauley J, Bauer D, Cappola A, Robbins J (2010) Subclinical thyroid dysfunction and incident hip fracture in older adults. Arch Intern Med 170:1876–1883CrossRef

16.

Svare A, Nilsen T, Asvold B, Forsmo S, Schei B, Bjøro T, Langhammer A (2013) Does thyroid function influence fracture risk? Prospective data from the HUNT2 study, Norway. Eur J Endocrinol 169:845–852CrossRef

17.

Vadiveloo T, Donnan P, Cochrane L, Leese G (2011) The Thyroid Epidemiology, Audit, and Research Study (TEARS): morbidity in patients with endogenous subclinical hyperthyroidism. J Clin Endocrinol Metab 96:1344–1351CrossRef

18.

Waring A, Harrison S, Fink H, Samuels M, Cawthon P, Zmuda J, Orwoll E, Bauer D, Osteoporotic Fractures in Men (MrOS) Study (2013) A prospective study of thyroid function, bone loss, and fractures in older men: the MrOS study. J Bone Miner Res 28:472–479CrossRef

19.

Siru R, Alfonso H, Chubb S, Golledge J, Flicker L, Yeap B (2018) Subclinical thyroid dysfunction and circulating thyroid hormones are not associated with bone turnover markers or incident hip fracture in older men. Clin Endocrinol 89:93–99CrossRef

20.

Mellstrom D, Johnell O, Ljunggren O, Eriksson AL, Lorentzon M, Mallmin H, Holmberg A, Redlund-Johnell I, Orwoll E, Ohlsson C (2006) Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden. J Bone Miner Res 21:529–535CrossRef

21.

Aubert C, Floriani C, Bauer D, da Costa B, Segna D, Blum M, Collet T, Fink H, Cappola A, Syrogiannouli L, Peeters R, Åsvold B, den Elzen W, Luben R, Bremner A, Gogakos A, Eastell R, Kearney P, Hoff M, Le Blanc E, Ceresini G, Rivadeneira F, Uitterlinden A, Khaw K, Langhammer A, Stott D, Westendorp R, Ferrucci L, Williams G, Gussekloo J, Walsh J, Aujesky D, Rodondi N, Thyroid Studies Collaboration (2017) Thyroid function tests in the reference range and fracture: individual participant analysis of prospective cohorts. J Clin Endocrinol Metab 102:2719–2728CrossRef

22.

Floriani C, Feller M, Aubert C, M'Rabet-Bensalah K, Collet T, den Elzen W, Bauer D, Angelillo-Scherrer A, Aujesky D, Rodondi N (2018) Thyroid dysfunction and anemia: a prospective cohort study and a systematic review. Thyroid 28:575–582CrossRef

23.

Karlsson M, Ribom E, Nilsson J, Ljunggren Ö, Ohlsson C, Mellström D, Lorentzon M, Mallmin H, Stefanick M, Lapidus J, Leung P, Kwok A, Barrett-Connor E, Orwoll E, Rosengren B (2012) Inferior physical performance tests in 10,998 men in the MrOS study is associated with recurrent falls. Age Ageing 41:740–746CrossRef

24.

Lewerin C, Nilsson-Ehle H, Jacobsson S, Johansson H, Sundh V, Karlsson M, Lorentzon M, Barrett-Connor E, Vandenput L, Ohlsson C, Mellström D (2014) Serum estradiol associates with blood hemoglobin in elderly men: the MrOS Sweden study. J Clin Endocrinol Metab 99:2549–2556CrossRef

25.

Boekholdt S, Titan S, Wiersinga W, Chatterjee K, Basart D, Luben R, Wareham N, Khaw K (2010) Initial thyroid status and cardiovascular risk factors: the EPIC-Norfolk prospective population study. Clin Endocrinol 72:404–410CrossRef

26.

Wang L, Smith A, Palmer F, Tuttle R, Mahrous A, Nixon I, Patel S, Ganly I, Fagin J, Boucai L (2015) Thyrotropin suppression increases the risk of osteoporosis without decreasing recurrence in ATA low- and intermediate-risk patients with differentiated thyroid carcinoma. Thyroid 25:300–307CrossRef

Title: Subclinical hyperthyroidism is associated with increased risk of vertebral fractures in older men
Authors: J. Svensson
C. Ohlsson
M. K. Karlsson
M. Lorentzon
C. Lewerin
D. Mellström
Publication date: 01-11-2021
Publisher: Springer London
Keywords: Hyperthyroidism
Levothyroxine
Published in: Osteoporosis International / Issue 11/2021
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-021-05964-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Subclinical hyperthyroidism is associated with increased risk of vertebral fractures in older men

Abstract

Summary

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 11/2021

One-year outcomes of an osteoporosis liaison services program initiated within a healthcare system

Bone biomechanical properties and tissue-scale bone quality in a genetic mouse model of familial dysautonomia

Fracture-induced pain-like behaviours in a femoral fracture mouse model

Fracture risk in hypoparathyroidism: a systematic review and meta-analysis

Orthogeriatric co-management reduces incidence of delirium in hip fracture patients

A 1:1 matched case-control study on dietary protein intakes and hip fracture risk in Chinese elderly men and women