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Cited by 10Bone health and osteoporosis researchThyroid Disorders and TreatmentsVitamin D Research Studies

T4 rather than TSH correlates with BMD among euthyroid adults

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Sheng, Ning, Xing, Fei, Wang, Jie, Duan, Xin, Xiang, Zhou·2023·Frontiers in Endocrinology
DOI 10.3389/fendo.2022.1039079PMC PMC9868946
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Abstract

Purpose: The objective of this study was to evaluate the association between thyroid hormone and bone mineral density (BMD) among euthyroid adults. Methods: This cross-sectional study researched the information from the National Health and Nutrition Examination Survey 2007–2010. We included 3,759 euthyroid participants finally. We used multivariate linear regression models to evaluate the linear relationship between the thyroid hormone profile and BMD. Subgroup analyses stratified by gender and age were further performed. Moreover, the nonlinear relationship was characterized by fitted smoothing curves and generalized additive models, and logistic regression models were used to determine the association of thyroid-stimulating hormone (TSH) and thyroxine (T4) with previous fractures. Results: The weighted multivariable linear regression models showed no association between TSH and BMD. Free thyroxine (FT4), T4, free triiodothyronine (FT3), and total triiodothyronine (T3) were negatively associated with the total femur BMD and the total spine BMD after adjusting for all covariates. Subgroup analyses demonstrated that all groups had a negative association between T4 and BMD, even in patients with osteopenia/osteoporosis. The nonlinear relationship characterized by smooth curve fittings and generalized additive models suggested that an obvious U-shaped, an inverted U -shaped, and an L - shaped curve was exhibited between thyroid hormone and BMD in the different subgroups. In addition, normal high-level T4 was associated with an increased prevalence of previous fractures than normal low-level T4. Conclusions: In this sample of euthyroid adults, T4 exhibits a negative correlation with BMD, regardless of age and gender, in subjects with either normal or lowered BMD. Moreover, high-normal FT4 was associated with an increased prevalence of previous fractures. TSH was not associated with variations of BMD and the fracture risk.

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  • TSH and thyroid hormone levels within the normal range are negatively correlated with BMD among euthyroid adults.

    “TSH and thyroid hormone levels within the normal range are negatively correlated with BMD among euthyroid adults [40, 41].”

    From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [41]

    The Discussion reports a negative association between thyroid hormones (FT4, T4, FT3 and T3) and BMD in euthyroid adults. But it does not support the same general claim for TSH: the Results table shows no significant adjusted association with total femur BMD, and the paper distinguishes T4 from TSH in its conclusions. Thus the thyroid-hormone portion is supported, but the TSH portion is overstated. (LLM, conf=0.92)

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References 38 · Cited by 10

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  1. [1]Hong C Choi S Park M Park SM Lee G. Body composition and osteoporotic fracture using anthropometric prediction equations to assess muscle and fat masses. J Cachexia Sarcopenia Muscle (2021) 12: 2247–58. doi: 10.1002/jcsm.12850 PMC8718033 34706399 · DOI
  2. [2]Bonnick SL Shulman L. Monitoring osteoporosis therapy: Bone mineral density, bone turnover markers, or both? Am J Med (2006) 119: S25–31. doi: 10.1016/j.amjmed.2005.12.020 16563938 · DOI
  3. [3]Blake GM Fogelman I. Monitoring treatment for osteoporosis by using bone densitometry. Semin Nucl Med (2001) 31: 212–22. doi: 10.1053/snuc.2001.23528 11430528 · DOI
  4. [4]Yao X Chen L Xu H Zhu Z. The association between serum uric acid and bone mineral density in older adults. Int J Endocrinol (2020) 2020: 3082318. doi: 10.1155/2020/3082318 32676109 PMC7341403 · DOI
  5. [6]Nicholls JJ Brassill MJ Williams GR Bassett JH. The skeletal consequences of thyrotoxicosis. J Endocrinol (2012) 213: 209–21. doi: 10.1530/JOE-12-0059 22454529 · DOI · Paper page
  6. [8]Gogakos AI Duncan Bassett JH Williams GR. Thyroid and bone. Arch Biochem Biophys (2010) 503: 129–36. doi: 10.1016/j.abb.2010.06.021 20599658 · DOI
  7. [9]Abe E Marians RC Yu W Wu XB Ando T Li Y. TSH is a negative regulator of skeletal remodeling. Cell (2003) 115: 151–62. doi: 10.1016/S0092-8674(03)00771-2 14567913 · DOI · Paper page
  8. [10]Morris MS. The association between serum thyroid-stimulating hormone in its reference range and bone status in postmenopausal American women. Bone (2007) 40: 1128–34. doi: 10.1016/j.bone.2006.12.001 17236836 · DOI · Paper page
  9. [11]Svare A Nilsen TI Bjøro T Forsmo S Schei B Langhammer A. Hyperthyroid levels of TSH correlate with low bone mineral density: the HUNT 2 study. Eur J Endocrinol (2009) 161: 779–86. doi: 10.1530/EJE-09-0139 19671706 · DOI
  10. [12]Lin JD Pei D Hsia TL Wu CZ Wang K Chang YL. The relationship between thyroid function and bone mineral density in euthyroid healthy subjects in Taiwan. Endocr Res (2011) 36: 1– 8. doi: 10.3109/07435800.2010.514877 21226562 · DOI · Paper page
  11. [14]Acar B Ozay AC Ozay OE Okyay E Sisman AR Ozaksoy D. Evaluation of thyroid function status among postmenopausal women with and without osteoporosis. Int J Gynaecol Obstet (2016) 134: 53–7. doi: 10.1016/j.ijgo.2015.11.025 27177516 · DOI
  12. [15]Zantut-Wittmann DE Quintino-Moro A Dos Santos PNS Melhado-Kimura V Bahamondes L Fernandes A. Lack of influence of thyroid hormone on bone mineral density and body composition in healthy euthyroid women. Front Endocrinol (Lausanne) (2019) 10: 890. doi: 10.3389/fendo.2019.00890 31998231 PMC6965015 · DOI
  13. [17]Tang Y Wang S Yi Q Xia Y Geng B. High-density lipoprotein cholesterol is negatively correlated with bone mineral density and has potential predictive value for bone loss. Lipids Health Dis (2021) 20: 75. doi: 10.1186/s12944-021-01497-7 34304735 PMC8310606 · DOI
  14. [18]Looker AC Johnston CC Jr. Wahner HW Dunn WL Calvo MS Harris TB. Prevalence of low femoral bone density in older U.S. women from NHANES III. J Bone Miner Res (1995) 10: 796– 802. doi: 10.1002/jbmr.5650100517 7639115 · DOI
  15. [19]Mondal S Raja K Schweizer U Mugesh G. Chemistry and biology in the biosynthesis and action of thyroid hormones. Angew Chem Int Ed Engl (2016) 55: 7606–30. doi: 10.1002/anie.201601116 27226395 · DOI
  16. [21]Inoue M Tawata M Yokomori N Endo T Onaya T. Expression of thyrotropin receptor on clonal osteoblast-like rat osteosarcoma cells. Thyroid (1998) 8: 1059–64. doi: 10.1089/thy.1998.8.1059 9848724 · DOI
  17. [22]Hoermann R Midgley JE Larisch R Dietrich JW. Relational stability in the expression of normality, variation, and control of thyroid function. Front Endocrinol (Lausanne) (2016) 7: 142. doi: 10.3389/fendo.2016.00142 27872610 PMC5098235 · DOI · Paper page
  18. [23]Williams AJ Robson H Kester MHA van Leeuwen J Shalet SM Visser TJ. Iodothyronine deiodinase enzyme activities in bone. Bone (2008) 43: 126–34. doi: 10.1016/j.bone.2008.03.019 PMC2681075 18468505 · DOI
  19. [25]Bours SP van Geel TA Geusens PP Janssen MJ Janzing HM Hoffland GA. Contributors to secondary osteoporosis and metabolic bone diseases in patients presenting with a clinical fracture. J Clin Endocrinol Metab (2011) 96: 1360–7. doi: 10.1210/jc.2010-2135 21411547 · DOI · Paper page
  20. [26]Bassett JH Williams GR. Role of thyroid hormones in skeletal development and bone maintenance. Endocr Rev (2016) 37: 135–87. doi: 10.1210/er.2015-1106 PMC4823381 26862888 · DOI · Paper page
  21. [27]Patel KV Brennan KL Brennan ML Jupiter DC Shar A Davis ML. Association of a modified frailty index with mortality after femoral neck fracture in patients aged 60 years and older. Clin Orthop Relat Res (2014) 472: 1010–7. doi: 10.1007/s11999-013-3334-7 PMC3916591 24166073 · DOI · Paper page
  22. [28]Sahin SB Ayaz T Sumer F İlkkilic K Algun E. Bone mineral density in geriatric patients with toxic nodular goiter. Aging Clin Exp Res (2015) 27: 221–6. doi: 10.1007/s40520-014-0269-0 25161096 · DOI
  23. [29]Vestergaard P Mosekilde L. Hyperthyroidism, bone mineral, and fracture risk–a meta-analysis. Thyroid (2003) 13: 585–93. doi: 10.1089/105072503322238854 12930603 · DOI · Paper page
  24. [30]Appetecchia M. Effects on bone mineral density by treatment of benign nodular goiter with mildly suppressive doses of l-thyroxine in a cohort women study. Horm Res (2005) 64: 293–8. doi: 10.1159/000089489 16269872 · DOI
  25. [31]Reverter JL Holgado S Alonso N Salinas I Granada ML Sanmartí A. Lack of deleterious effect on bone mineral density of long-term thyroxine suppressive therapy for differentiated thyroid carcinoma. Endocr Relat Cancer (2005) 12: 973–81. doi: 10.1677/erc.1.01072 16322336 · DOI
  26. [32]Murphy E Glüer CC Reid DM Felsenberg D Roux C Eastell R. 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 (2010) 95: 3173–81. doi: 10.1210/jc.2009-2630 20410228 · DOI · Paper page
  27. [33]Grimnes G Emaus N Joakimsen RM Figenschau Y Jorde R. The relationship between serum TSH and bone mineral density in men and postmenopausal women: The tromsø study. Thyroid (2008) 18: 1147–55. doi: 10.1089/thy.2008.0158 18925834 · DOI · Paper page
  28. [36]Aubert CE Floriani C Bauer DC da Costa BR Segna D Blum MR. Thyroid function tests in the reference range and fracture: Individual participant analysis of prospective cohorts. J Clin Endocrinol Metab (2017) 102: 2719–28. doi: 10.1210/jc.2017-00294 PMC6283437 28482002 · DOI
  29. [37]van Vliet NA Noordam R van Klinken JB Westendorp RG Bassett JD Williams GR. Thyroid stimulating hormone and bone mineral density: Evidence from a two-sample mendelian randomization study and a candidate gene association study. J Bone Miner Res (2018) 33: 1318–25. doi: 10.1002/jbmr.3426 29544020 · DOI
  30. [38]Lee SJ Kim KM Lee EY Song MK Kang DR Kim HC. Low normal TSH levels are associated with impaired BMD and hip geometry in the elderly. Aging Dis (2016) 7: 734–43. doi: 10.14336/AD.2016.0325 PMC5198865 28053824 · DOI

Authors
Sheng, N., Xing, F., Wang, J., Duan, X., & Xiang, Z.
Affiliations
Sichuan University (CN)
Corresponding author
  • Duan, Xin
  • Xiang, Zhou
ORCID
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2023-01-09
Volume
13
Pages
1039079-1039079
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2022.1039079
PMC
PMC9868946
OpenAlex
W4315480342
Cited by
10
References
38
Citations by year
2026: 3 · 2025: 1 · 2024: 5 · 2023: 1
FWCI
2.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (31870961, 82202705)
  • Department of Science and Technology of Sichuan Province (2023NSFSC1738, 2020YFS0140)
  • Sichuan University (2019HXFH041)
  • West China Hospital, Sichuan University (2023NSFSC1738, 2019HXFH041, 82202705)
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
Keywords
thyroxine, thyroid-stimulating hormone, bone mineral density, euthyroid adults, free thyroxine, free triiodothyronine, total triiodothyronine, osteoporosis, osteopenia, previous fractures, fracture risk, nonlinear dose-response relationship, sex differences, age differences
MeSH terms
Adult, Cross-Sectional Studies, Humans, Hypothyroidism, Nutrition Surveys, Thyroid Hormones, Thyrotropin, Thyroxine, Triiodothyronine, Bone Density, Fractures, Bone

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