Abstract
Summary
Thyroid dysfunction is associated with the loss of bone density (osteoporosis). However, the connection between subclinical thyroid dysfunction and osteoporosis remains controversial. This study found no apparent association between subclinical hypothyroidism or subclinical hyperthyroidism and bone mineral density (BMD) in the lumbar spine and femur.
Introduction
The present study examined the relationship between subclinical thyroid dysfunction and BMD in healthy middle-aged adults.
Methods
A total of 25,510 healthy Koreans with normal free thyroxine levels were enrolled from January 2011 to December 2016, and 91% of subjects visited only once. The average age of the 15,761 women was 45, and the average age of the 9749 men was 48. Levels of thyroid-stimulating hormone (TSH) and BMD were recorded in all subjects. BMD was measured using dual-energy X-ray absorptiometry.
Results
No apparent association was found between subclinical thyroid dysfunction and BMD in the lumbar spine, femur-neck, and proximal femur sites compared with a euthyroid group. Age, body mass index (BMI), and postmenopausal status affected BMD in women, and only BMI affected BMD in men. Subclinical hypothyroidism was independently associated with a lower risk of osteoporosis (odds ratio 0.657, 95% confidence interval 0.464–0.930) in 4710 postmenopausal women.
Conclusions
No apparent association was found between subclinical hypothyroidism or subclinical hyperthyroidism defined on single TSH measurement and BMD at the lumbar spine and femur in a large cohort of middle-aged men and women. Subclinical hypothyroidism was independently associated with a lower risk of osteoporosis in postmenopausal women.
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References
Wilson GR, Curry RW Jr (2005) Subclinical thyroid disease. Am Fam Physician 72:1517–1524
Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall I, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN, American Thyroid Association, American Association of Clinical Endocrinologists (2011) Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 21:593–646
Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, Pessah-Pollack R, Singer PA, Woeber KA, American Association Of Clinical Endocrinologists And American Thyroid Association Taskforce On Hypothyroidism In Adults (2012) Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid 22:1200–1235
Garmendia Madariaga A, Santos Palacios S, Guillén-Grima F, Galofré JC (2014) The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab 99:923–931
Foldes J, Tarjan G, Szathmari M et al (1993) Bone mineral density in patients with endogenous subclinical hyperthyroidism: is this thyroid status a risk factor for osteoporosis? Clin Endocrinol 39:521–527
Vestergaard P, Mosekilde L (2002) Fractures in patients with hyperthyroidism and hypothyroidism: a nationwide follow-up study in 16,249 patients. Thyroid 12:411–419
Gogakos AI, Duncan Bassett JH, Williams GR (2010) Thyroid and bone. Arch Biochem Biophys 503:129–136
Lee WY, Oh KW, Rhee EJ, Jung CH, Kim SW, Yun EJ, Tae HJ, Baek KH, Kang MI, Choi MG, Yoo HJ, Park SW (2006) Relationship between subclinical thyroid dysfunction and femoral neck bone mineral density in women. Arch Med Res 37:511–516
Garin MC, Arnold AM, Lee JS, Robbins J, Cappola AR (2014) Subclinical thyroid dysfunction and hip fracture and bone mineral density in older adults: the cardiovascular health study. J Clin Endocrinol Metab 99:2657–2664
Yang R, Yao L, Fang Y, Sun J, Guo T, Yang K, Tian L (2018) The relationship between subclinical thyroid dysfunction and the risk of fracture or low bone mineral density: a systematic review and meta-analysis of cohort studies. J Bone Miner Metab 36:209–220
Vadiveloo T, Donnan PT, Cochrane L, Leese GP (2011) The thyroid epidemiology, audit, and research study (TEARS): morbidity in patients with endogenous subclinical hyperthyroidism. J Clin Endocrinol Metab 96:1344–1351
Svare A, Nilsen TI, Asvold BO, 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 169:845–852
Kim M, Kim TY, Kim SH, Lee Y, Park SY, Kim HD, Kwon H, Choi YM, Jang EK, Jeon MJ, Kim WG, Shong YK, Kim WB (2015) Reference interval for thyrotropin in a ultrasonography screened Korean population. Korean J Intern Med 30:335–344
Park SY, Kim HI, Oh HK et al (2018) Age- and gender-specific reference intervals of TSH and free T4 in an iodine-replete area: Data from Korean National Health and Nutrition Examination Survey IV (2013-2015). PLoS One 13:e0190738
Chang Y, Kim BK, Yun KE, Cho J, Zhang Y, Rampal S, Zhao D, Jung HS, Choi Y, Ahn J, Lima JA, Shin H, Guallar E, Ryu S (2014) Metabolically-healthy obesity and coronary artery calcification. J Am Coll Cardiol 63:2679–2686
Kim MK, Lee WY, Kang JH et al (2014) 2014 clinical practice guidelines for overweight and obesity in Korea. Endocrinol Metab (Seoul) 29:405–409
Kanis JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 4:368–381
Lewiecki EM, Gordon CM, Baim S, Leonard MB, Bishop NJ, Bianchi ML, Kalkwarf HJ, Langman CB, Plotkin H, Rauch F, Zemel BS, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Silverman S (2008) International Society for Clinical Densitometry 2007 Adult and Pediatric Official Positions. Bone 43:1115–1121
Kim TH, Joung JY, Kang M et al (2015) A modest protective effect of thyrotropin against bone loss is associated with plasma triiodothyronine levels. PLoS One 10:e0145292
Blum MR, Bauer DC, Collet TH, Fink HA, Cappola AR, da Costa BR, Wirth CD, Peeters RP, Åsvold BO, den Elzen W, Luben RN, Imaizumi M, Bremner AP, Gogakos A, Eastell R, Kearney PM, Strotmeyer ES, Wallace ER, Hoff M, Ceresini G, Rivadeneira F, Uitterlinden AG, Stott DJ, Westendorp RG, Khaw KT, Langhammer A, Ferrucci L, Gussekloo J, Williams GR, Walsh JP, Jüni P, Aujesky D, Rodondi N, Thyroid Studies Collaboration (2015) Subclinical thyroid dysfunction and fracture risk: a meta-analysis. JAMA 313:2055–2065
Wartofsky L (2014) Subclinical hyperthyroidism and fracture risk in women. J Clin Endocrinol Metab 99:2654–2656
Kim DJ, Khang YH, Koh JM et al (2006) Low normal TSH levels are associated with low bone mineral density in healthy postmenopausal women. Clin Endocrinol 64:86–90
Ding B, Zhang Y, Li Q, Hu Y, Tao XJ, Liu BL, Ma JH, Li DM (2016) Low thyroid stimulating hormone levels are associated with low bone mineral density in femoral neck in elderly women. Arch Med Res 47:310–314
Morris MS (2007) The association between serum thyroid-stimulating hormone in its reference range and bone status in postmenopausal American women. Bone 40:1128–1134
Kim BJ, Lee SH, Bae SJ, Kim HK, Choe JW, Kim HY, Koh JM, Kim GS (2010) The association between serum thyrotropin (TSH) levels and bone mineral density in healthy euthyroid men. Clin Endocrinol 73:396–403
Murphy E, Gluer CC, Reid DM et al (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 95:3173–3181
Saler T, Ahbab S, Saglam ZA et al (2014) Endogenous subclinical hyperthyroidism may not lead to bone loss in premenopausal women. Hippokratia 18:240–244
Abrahamsen B, Jorgensen HL, Laulund AS et al (2014) Low serum thyrotropin level and duration of suppression as a predictor of major osteoporotic fractures-the OPENTHYRO register cohort. J Bone Miner Res 29:2040–2050
Abrahamsen B, Jorgensen HL, Laulund AS et al (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 30:898–905
Schneider C, Feller M, Bauer DC et al. (2018) Initial evaluation of thyroid dysfunction—are simultaneous TSH and fT4 tests necessary? PLoS One 13:e0196631
Kim WG, Kim WB, Woo G et al (2017) Thyroid stimulating hormone reference range and prevalence of thyroid dysfunction in the Korean population: Korea National Health and Nutrition Examination Survey 2013 to 2015. Endocrinol Metab 32:106–114
Biondi B (2012) Natural history, diagnosis and management of subclinical thyroid dysfunction. Best Pract Res Clin Endocrinol Metab 26:431–446
Cheserek MJ, Wu GR, Ntazinda A, Shi YH, Shen LY, le GW (2015) Association between thyroid hormones, lipids and oxidative stress markers in subclinical hypothyroidism. J Med Biochem 34:323–331
Erdogan M, Kosenli A, Ganidagli S et al (2012) Characteristics of anemia in subclinical and overt hypothyroid patients. Endocr J 59:213–220
Sengul E, Cetinarslan B, Tarkun I et al (2004) Homocysteine concentrations in subclinical hypothyroidism. Endocr Res 30:351–359
Acknowledgments
We would like to thank the staff of the Kangbuk Samsung Cohort Study for their hard work, dedication and continuing support.
Funding
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2017R1D1A1B03036425).
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Lee, K., Lim, S., Park, H. et al. Subclinical thyroid dysfunction, bone mineral density, and osteoporosis in a middle-aged Korean population. Osteoporos Int 31, 547–555 (2020). https://doi.org/10.1007/s00198-019-05205-1
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DOI: https://doi.org/10.1007/s00198-019-05205-1