Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
 
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2016, Vol. 7 Issue (6) : 734-743     DOI: 10.14336/AD.2016.0325
Original Article |
Low Normal TSH levels are Associated with Impaired BMD and Hip Geometry in the Elderly
Lee Su Jin1,2, Kim Kyoung Min3, Lee Eun Young4, Song Mi Kyung5, Kang Dae Ryong6, Kim Hyeon Chang7, Youm Yoosik8, Yun Young Mi5, Park Hyun-Young9, Kim Chang Oh10, Rhee Yumie1,*
1Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea
2Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea
3Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
4Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
5Department of Research Affairs, Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Korea
6Office of Biostatistics, Ajou University School of Medicine, Suwon, Korea
7Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
8Department of Sociology, Yonsei University, Seoul, Korea
9Division of Cardiovascular and Rare Diseases, Korea National Institute of Health, Osong, Korea
10Division of Geriatrics, Department of Internal Medicine, Severance Hospital, Seoul, Korea
Download: PDF(1388 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    
Abstract  

Subclinical hyperthyroidism is known to be associated with the risk of fractures in elderly people. However, there are few studies assessing whether low normal thyroid-stimulating hormone (TSH) levels affect bone density and geometry. Here, we aimed to assess the influence of the TSH level on bone mineral density (BMD) and geometry in elderly euthyroid subjects. This was a cross-sectional cohort study. A total of 343 men and 674 women with euthyroidism were included and analyzed separately. The subjects were divided into tertiles based on the serum TSH level. The BMD and geometry were measured using dual-energy X-ray absorptiometry and a hip structural analysis program. Multiple regression analysis was used to compute the odds ratios of osteoporosis in the lower TSH tertile group and the association between geometry parameters and the TSH level. We found that the femoral neck and total hip BMDs were lower in the lower TSH tertile group. In women, the cross-sectional area and cortical thickness of the femur were negatively associated with the TSH level in all three regions (the narrow neck, intertrochanter, and femoral shaft); however, in men, these geometry parameters were significantly associated with the TSH level only in the intertrochanter region. The buckling ratio, a bone geometry parameter representing cortical instability, was significantly higher in the lower TSH tertile group in all three regions in women, but not in men. Our results indicated that lower TSH levels in the euthyroid range are related to lower BMD and weaker femoral structure in elderly women.

Keywords TSH      euthyroidism      elderly people      bone density      bone geometry     
Corresponding Authors: Rhee Yumie   
About author:

these authors contributed equally to this work.

Issue Date: 01 December 2016
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
Lee Su Jin
Kim Kyoung Min
Lee Eun Young
Song Mi Kyung
Kang Dae Ryong
Kim Hyeon Chang
Youm Yoosik
Yun Young Mi
Park Hyun-Young
Kim Chang Oh
Rhee Yumie
Cite this article:   
Lee Su Jin,Kim Kyoung Min,Lee Eun Young, et al. Low Normal TSH levels are Associated with Impaired BMD and Hip Geometry in the Elderly[J]. Aging and disease, 2016, 7(6): 734-743.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2016.0325     OR     http://www.aginganddisease.org/EN/Y2016/V7/I6/734
Figure 1.  The flow chart of the study subjects
Table 1  Clinical characteristics
Table 2  BMD and fracture risk assessment according to the tertiles of TSH
Osteoporosis
WomenMen
OR95% CIp - valueOR95% CIp - value
1st tertile (TSH1)1.86(1.22 - 2.83)< 0.011.72(0.76 - 3.88)0.19
2nd tertile (TSH2)1.3(0.86 - 1.97)0.350.86(0.35 - 2.09)0.86
3rd tertile (TSH3)Ref.Ref.
Table 3  Odds ratios (ORs) for osteoporosis in the tertile groups of thyroid stimulating hormone (TSH) in euthyroid subjects
RegionGeometry
parameters
WomenMen
ßSEp-valueßSEp-value
NNCSA-0.0960.0310.02-0.0620.0560.26
CoTh-0.130.002< 0.01-0.0670.0040.24
BR0.1110.3190.010.1050.4340.08
ITCSA-0.1130.06< 0.01-0.1160.130.04
CoTh-0.140.006< 0.01-0.1180.0110.04
BR0.160.218< 0.010.1140.2540.04
FSCSA-0.0960.040.02-0.040.0780.47
CoTh-0.1380.008< 0.01-0.0320.0140.58
BR0.1420.075< 0.010.0750.0840.22
Table 4  Association between lower TSH tertile and bone geometry parameters in narrow neck, intertrochanter, and femur shaft.
Figure 2.  Bone geometry parameters of the three regions according to the TSH tertiles in women. CSA (A) and CoTh (B) in the NN, IT, and FS were significantly lower in the lower TSH tertile than in the upper TSH tertile. CSMI (C) and Z (D) were not associated with the TSH tertiles, except for Z in IT. BR (E), which indicates cortical instability, showed higher values in the lower TSH tertile. TSH: thyroid-stimulating hormone, CSA: cross-sectional area, CoTh: cortical thickness, CSMI: cross-sectional moment of inertia, Z: section modulus, NN: narrow neck, IT: intertrochanter, FS: femur shaft. Bars indicate the standard deviations. *p < 0.05 by ANOVA
WomenMen
TotalTSH1TSH2TSH3PTotalTSH1TSH2TSH3P
n = 227n = 227n = 220valuen = 112n = 119n = 112value
TSH range(0.36 - 1.17)(1.18 - 1.93)(1.94 - 5.50)(0.36 - 1.05)(1.06 - 1.67)(1.68 - 5.50)
Narrow neck
CSA, cm22.25 ± 0.352.20 ± 0.37†2.24 ± 0.332.31 ± 0.360.012.91 ± 0.482.89 ± 0.492.90 ± 0.442.947 ± 0.520.67
CSMI, cm41.95 ± 0.481.95 ± 0.521.95 ± 0.451.95 ± 0.470.993.29 ± 0.783.26 ± 0.733.29 ± 0.793.312 ± 0.830.89
Z, cm31.07 ± 0.221.06 ± 0.231.08 ± 0.201.08 ± 0.230.611.62 ± 0.331.60 ± 0.311.63 ± 0.311.637 ± 0.360.72
CoTh, cm0.14 ± 0.030.14 ± 0.03†0.14 ± 0.020.15 ± 0.030.000.16 ± 0.030.16 ± 0.030.16 ± 0.030.165 ± 0.030.68
BR13.38 ± 3.4513.99 ± 3.77*†13.15 ± 3.0012.99 ± 3.470.0112.96 ± 3.4313.38 ± 4.4112.84 ± 2.9912.665 ± 2.670.34
Intertrochanter
CSA, cm23.78 ± 0.683.68 ± 0.69†3.77 ± 0.643.89 ± 0.680.015.10 ± 1.094.97 ± 1.185.129 ± 1.105.19 ± 0.990.34
CSMI, cm49.97 ± 2.599.79 ± 2.709.91 ± 2.5110.23 ± 2.570.1916.47 ± 6.0415.82 ± 6.4716.48 ± 5.6817.10 ± 5.960.32
Z, cm33.19 ± 0.743.11 ± 0.76†3.17 ± 0.713.30 ± 0.730.024.79 ± 1.424.63 ± 1.534.81 ± 1.374.93 ± 1.350.32
CoTh, cm0.31 ± 0.060.30 ± 0.07†0.30 ± 0.06†0.32 ± 0.06<0.010.39 ± 0.090.38 ± 0.100.39 ± 0.080.40 ± 0.080.34
BR10.62 ± 2.4711.10 ± 2.70†10.64 ± 2.2110.12 ± 2.38<0.019.13 ± 2.139.40 ± 2.479.05 ± 2.048.95 ± 1.820.30
Femur shaft
CSA, cm23.59 ± 0.473.51 ± 0.47†3.59 ± 0.463.66 ± 0.46<0.014.73 ± 0.664.71 ± 0.694.72 ± 0.634.77 ± 0.660.76
CSMI, cm43.15 ± 0.613.13 ± 0.613.19 ± 0.613.14 ± 0.610.554.70 ± 0.954.68 ± 0.864.68 ± 0.974.73 ± 1.020.90
Z, cm32.07 ± 0.302.04 ± 0.302.08 ± 0.302.08 ± 0.300.412.85 ± 0.432.84 ± 0.402.85 ± 0.432.86 ± 0.460.93
CoTh, cm0.47 ± 0.090.46 ± 0.09†0.47 ± 0.08†0.49 ± 0.09<0.010.60 ± 0.110.60 ± 0.130.60 ± 0.090.60 ± 0.110.80
BR3.38 ± 0.813.50 ± 0.84†3.42 ± 0.79†3.21 ± 0.76<0.012.85 ± 0.652.91 ± 0.772.83 ± 0.572.81 ± 0.610.51
Supplemental Table 1  Bone geometry parameters according to the thyroid-stimulating hormone (TSH) tertile groups
[1] Gogakos AI, Duncan Bassett JH, Williams GR (2010). Thyroid and bone. Arch Biochem Biophys, 503(1): 129-136.
[2] Svare A, Nilsen TI, Bjoro T, Forsmo S, Schei B, Langhammer A (2009). Hyperthyroid levels of TSH correlate with low bone mineral density: the HUNT 2 study. Eur J Endocrinol, 161(5): 779-786.
[3] Nicholls JJ, Brassill MJ, Williams GR, Bassett JH (2012). The skeletal consequences of thyrotoxicosis. J Endocrinol, 213(3): 209-221.
[4] Waung JA, Bassett JH, Williams GR (2012). Thyroid hormone metabolism in skeletal development and adult bone maintenance. Trends Endocrinol Metab, 23(4): 155-162.
[5] Abrahamsen B, Jorgensen HL, Laulund AS, Nybo M, Brix TH, Hegedus 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(9): 2040-2050.
[6] Bauer DC, Ettinger B, Nevitt MC, Stone KL, Study of Osteoporotic Fractures Research G (2001). Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med, 134(7): 561-568.
[7] Blum MR, Bauer DC, Collet TH, Fink HA, Cappola AR, da Costa BR, et al. (2015). Subclinical thyroid dysfunction and fracture risk: a meta-analysis. JAMA, 313(20): 2055-2065.
[8] Murphy E, Gluer CC, Reid DM, Felsenberg D, Roux C, Eastell R, 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(7): 3173-3181.
[9] Leader A, Ayzenfeld RH, Lishner M, Cohen E, Segev D, Hermoni D (2014). Thyrotropin levels within the lower normal range are associated with an increased risk of hip fractures in euthyroid women, but not men, over the age of 65 years. J Clin Endocrinol Metab, 99(8): 2665-2673.
[10] Greenspan SL, Greenspan FS (1999). The effect of thyroid hormone on skeletal integrity. Ann Intern Med, 130(9): 750-758.
[11] Tournis S, Antoniou JD, Liakou CG, Christodoulou J, Papakitsou E, Galanos A, et al. (2015). Volumetric bone mineral density and bone geometry assessed by peripheral quantitative computed tomography in women with differentiated thyroid cancer under TSH suppression. Clin Endocrinol (Oxf), 82(2): 197-204.
[12] LaCroix AZ, Beck TJ, Cauley JA, Lewis CE, Bassford T, Jackson R, et al. (2010). Hip structural geometry and incidence of hip fracture in postmenopausal women: what does it add to conventional bone mineral density? Osteoporos Int, 21(6): 919-929.
[13] Lee EY, Kim HC, Rhee Y, Youm Y, Kim KM, Lee JM, et al. (2014). The Korean urban rural elderly cohort study: study design and protocol. BMC Geriatr, 14: 33.
[14] Binkley N, Krueger D, Gangnon R, Genant HK, Drezner MK (2005). Lateral vertebral assessment: a valuable technique to detect clinically significant vertebral fractures. Osteoporos Int, 16(12): 1513-1518.
[15] Beck TJ, Looker AC, Ruff CB, Sievanen H, Wahner HW (2000). Structural trends in the aging femoral neck and proximal shaft: analysis of the Third National Health and Nutrition Examination Survey Dual-Energy X-Ray Absorptiometry Data. J Bone Miner Res, 15(12): 2297-2304.
[16] Beck T (2007). Extending DXA beyond bone mineral density: Understanding hip structure analysis. Curr Osteoporos Rep, 5(2): 49-55.
[17] Kim JW, Jeon YJ, Baek DH, Kim TN, Chang JS (2014). Percentage of the population at high risk of osteoporotic fracture in South Korea: analysis of the 2010 Fifth Korean National Health and Nutrition Examination survey data. Osteoporos Int, 25(4): 1313-1319.
[18] European Prospective Osteoporosis Study (EPOS) Group (2002). Incidence of vertebral fracture in europe: results from the European Prospective Osteoporosis Study (EPOS). J Bone Miner Res, 17(4): 716-724.
[19] Abe E, Marians RC, Yu W, Wu XB, Ando T, Li Y, et al. (2003). TSH is a negative regulator of skeletal remodeling. Cell, 115(2): 151-162.
[20] Lee YK, Jang S, Jang S, Lee HJ, Park C, Ha YC, et al. (2012). Mortality after vertebral fracture in Korea: analysis of the National Claim Registry. Osteoporos Int, 23(7): 1859-1865.
[21] Yoon HK, Park C, Jang S, Jang S, Lee YK, Ha YC (2011). Incidence and mortality following hip fracture in Korea. J Korean Med Sci, 26(8): 1087-1092.
[22] Kang HY, Yang KH, Kim YN, Moon SH, Choi WJ, Kang DR, et al. (2010). Incidence and mortality of hip fracture among the elderly population in South Korea: a population-based study using the national health insurance claims data. BMC Public Health, 10: 230.
[23] Abrahamsen B, van Staa T, Ariely R, Olson M, Cooper C (2009). Excess mortality following hip fracture: a systematic epidemiological review. Osteoporos Int, 20(10): 1633-1650.
[24] Fransen M, Woodward M, Norton R, Robinson E, Butler M, Campbell A (2002). Excess mortality or institutionalization after hip fracture: men are at greater risk than women. J Am Geriatr Soc, 50: 685-690.
[25] Vestergaard P, Mosekilde L (2003). Hyperthyroidism, bone mineral, and fracture risk - a meta-analysis. Thyroid, 13(6): 585-593.
[26] Dumic-Cule I, Draca N, Luetic AT, Jezek D, Rogic D, Grgurevic L, et al. (2014). TSH prevents bone resorption and with calcitriol synergistically stimulates bone formation in rats with low levels of calciotropic hormones. Horm Metab Res, 46(05): 305-312.
[27] Morris MS (2007). The association between serum thyroid-stimulating hormone in its reference range and bone status in postmenopausal American women. Bone, 40(4): 1128-1134.
[28] Feitosa Dda S, Bezerra Bde B, Ambrosano GM, Nociti FH, Casati MZ, Sallum EA, et al. (2008). Thyroid hormones may influence cortical bone healing around titanium implants: a histometric study in rats. J Periodontol, 79(5): 881-887.
[29] Roef G, Lapauw B, Goemaere S, Zmierczak H, Fiers T, Kaufman JM, et al. (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(6): 1027-1034.
[30] Kim DJ, Khang YH, Koh JM, Shong YK, Kim GS (2006). Low normal TSH levels are associated with low bone mineral density in healthy postmenopausal women. Clin Endocrinol (Oxf), 64(1): 86-90.
[31] Mazziotti G, Porcelli T, Patelli I, Vescovi PP, Giustina A (2010). Serum TSH values and risk of vertebral fractures in euthyroid post-menopausal women with low bone mineral density. Bone, 46(3): 747-751.
[32] Lin JD, Pei D, Hsia TL, Wu CZ, Wang K, Chang YL, et al. (2011). The relationship between thyroid function and bone mineral density in euthyroid healthy subjects in Taiwan. Endocr Res, 36(1): 1-8.
[33] van Rijn LE, Pop VJ, Williams GR (2014). Low bone mineral density is related to high physiological levels of free thyroxine in peri-menopausal women. Eur J Endocrinol, 170(3): 461-468.
[34] Bassett JH, Williams GR (2003). The molecular actions of thyroid hormone in bone. Trends Endocrinol Metab, 14(8): 356-364.
[35] Mazziotti G, Sorvillo F, Piscopo M, Cioffi M, Pilla P, Biondi B, et al. (2005). Recombinant human TSH modulates in vivo C-telopeptides of type-1 collagen and bone alkaline phosphatase, but not osteoprotegerin production in postmenopausal women monitored for differentiated thyroid carcinoma. J Bone Miner Res, 20(3): 480-486.
[36] Johannesdottir F, Aspelund T, Reeve J, Poole KE, Sigurdsson S, Harris TB, et al. (2013). Similarities and differences between sexes in regional loss of cortical and trabecular bone in the mid-femoral neck: the AGES-Reykjavik longitudinal study. J Bone Miner Res, 28(10): 2165-2176.
[37] Power J, Loveridge N, Lyon A, Rushton N, Parker M, Reeve J (2003). Bone remodeling at the endocortical surface of the human femoral neck: a mechanism for regional cortical thinning in cases of hip fracture. J Bone Miner Res, 18(10): 1775-1780.
No related articles found!
Viewed
Full text


Abstract

Cited

  Shared   
Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail: editorial@aginganddisease.org
Powered by Beijing Magtech Co. Ltd