Endocrine DOI 10.1007/s12020-013-0147-0

ORIGINAL ARTICLE

Association between calcaneus quantitative ultrasound (QUS) parameters and thyroid status in middle-aged and elderly Chinese men with euthyroidism: a population-based cross-sectional study Yun Shi • Min Sun • Zhixiao Wang • Qi Fu • Mengdie Cao • Zhenxin Zhu Chuchen Meng • Jia Mao • Yu Duan • Wei Tang • Xiaoping Huang • Jieli Lu • Yufang Bi • Guang Ning • Wei He • Tao Yang



Received: 15 August 2013 / Accepted: 12 December 2013 Ó Springer Science+Business Media New York 2014

Abstract Although it is generally accepted that thyroid hormones affect bone metabolism, there is little data on the association of thyroid antibodies with bone status. We aimed to investigate the association between thyroid hormones or antibodies and quantitative ultrasound (QUS) parameters. This was a cross-sectional, population-based study conducted in Nanjing, China. A total of 1,001 Chinese men over 40 years were enrolled. We measured free triiodothyronine, free thyroxin (fT4), thyroid-stimulating hormone, anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin, 25-hydroxyvitamin D, and QUS parameters. After adjusting for potential confounders, QUS values decreased from the lowest to highest tertiles of fT4 in euthyroid men [quantitative ultrasound index (QUI) p = 0.002, broadband

ultrasound attenuation (BUA) p = 0.000, speed of sound (SOS) p = 0.009, respectively]. Men with high anti-TPO levels (C200 IU/ml) were found to have lower QUI (p = 0.030), BUA (p = 0.034), and SOS (p = 0.041) values than controls (\200 IU/ml). The prevalence of vitamin D deficiency was significantly higher in individuals with high anti-TPO than those in lower levels (87.5 vs. 59.5 %, p = 0.001). Our results suggest that high fT4 or anti-TPO values are associated with lower QUS parameters. Prospective studies are needed to confirm the precise relationship between thyroid status and osteoporosis.

Yun Shi and Min Sun have contributed equally to this study.

Introduction

Electronic supplementary material The online version of this article (doi:10.1007/s12020-013-0147-0) contains supplementary material, which is available to authorized users.

Osteoporosis is currently a serious public health issue with increasing prevalence among the aging population, particularly in developing countries such as China [1]. It can result in pain, disability, decreased quality of life, increased risk of fracture, and mortality. Although it is well established that thyroid hormones affect bone metabolism, abnormalities in thyroid function may cause osteoporosis or even increased susceptibility to osteoporotic fracture [2]. There is little data on the association of thyroid autoimmune antibodies with bone mineral density (BMD). This is important because hormones and antibodies offer information on different aspects of thyroid status and may represent different mechanisms of bone loss. The thyroid gland is susceptible to autoimmune responses that lead to autoimmune thyroid diseases (AITD) such as Graves’s disease and Hashimoto thyroiditis (HT). AITD is characterized by elevated thyroid-stimulating

Y. Shi  M. Sun  Z. Wang  Q. Fu  M. Cao  Z. Zhu  C. Meng  J. Mao  Y. Duan  X. Huang  W. He (&)  T. Yang (&) Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu, China e-mail: [email protected] T. Yang e-mail: [email protected] W. Tang Department of Endocrinology, Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin 214400, Jiangsu, China J. Lu  Y. Bi  G. Ning Department of Endocrinology, Rui-jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Keywords Thyroid antibody  Thyroid hormones  Osteoporosis  Calcaneus quantitative ultrasound

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hormone receptor antibody (TRAb), anti-thyroid peroxidase (anti-TPO), or anti-thyroglobulin (anti-Tg) levels. As observed in AITD, dysregulation of the immune system indirectly influences bone loss [3]. Nevertheless, the mechanisms leading to bone loss are poorly understood. Majima et al. [4] had reported that BMD measured by dualenergy X-ray absorptiometry (DXA) correlated negatively with TRAb in males with Graves’s disease; however, no significant correlation was observed with regard to antiTPO and anti-Tg. Moreover, previous studies examining the relationship between thyroid status and bone metabolism were based on BMD measurements obtained by DXA; however, QUS parameters are directly related to BMD assessed by DXA (r = 0.82–0.85) [5]. In contrast, QUS is inexpensive, easyto-use, and radiation-free. It also provides information on bone density, architecture, elasticity, and fragility [6]. Thus, QUS is an alternative approach to assess BMD, particularly in population-based studies. Until now, only few studies have identified the relationship between thyroid hormones and QUS parameters and the association of thyroid autoimmune antibodies with QUS parameters is not yet clear. The purpose of our study was to determine (1) whether an association existed between thyroid hormones (fT3 and fT4), thyroid-stimulating hormone (TSH), and QUS and (2) whether QUS parameters decreased in middle-aged and elderly Chinese men with elevated anti-TPO or anti-Tg levels.

Subjects and methods Study population A total of 10,027 individuals [40-year old who lived in Gulou, Nanjing, China, were recruited to a population-based cross-sectional study from June to December 2011. The present study used a subsample including 6,180 individuals collected from September to November 2011, and a total of 1,149 males were randomly selected to measure thyroid function, thyroid antibody, and serum 25-hydroxyvitamin D (25-OHD). After exclusion of subjects with overt hypothyroidism (TSH [5.29 uIU/ml, fT4 \8.5 pmol/l) or overt hyperthyroidism (TSH \0.35 uIU/ml, fT4 [22.5 pmol/l) and subjects with a history of cancer, thyroid, liver, or renal disease, autoimmune disease, on drugs that interfere with bone metabolism such as vitamin D, calcium, and bisphosphonate, corticosteroids, or on hormone replacement therapy (HRT), 1,001 males were included in the final analysis. All participants provided written informed consent. The protocol was approved by the Institutional Review Board of Jiangsu Province Hospital affiliated with Nanjing Medical University.

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Data collection A detailed questionnaire was completed with assistance from physicians for each subject, including age, sex, current smoking status and alcohol consumption, physical activity, and medical history. Weight, height, waist circumference (WC), and hip circumference (HC) were measured according to a standard protocol. Venous blood samples were drawn after an overnight fast and stored at -80 °C. Body mass index (BMI) was calculated as weight (kg) divided by height squared (m2). Quantitative ultrasound (QUS) of the right mid-calcaneus was performed with the Sahara Clinical Sonometer (Hologic, Bedford, MA, USA). The QUS device measures broadband ultrasound attenuation (BUA, dB/MHz) and speed of sound (SOS, m/s). Quantitative ultrasound index (QUI) was calculated from BUA and SOS, and then derived BMD, T score, and Z score. Calibration was performed before daily measurement according to the manufacturer’s instructions. Fasting serum-free thyroxine (fT4, reference interval: 8.5–22.5 pmol/l), serum-free triiodothyronine (fT3, reference interval: 3.5–6.5 pmol/l), serum thyroid-stimulating hormone (TSH, reference interval: 0.35–5.29 uIU/ml), anti-thyroglobulin (anti-Tg, reference interval: 0–110 IU/ml), and anti-thyroid peroxidase (anti-TPO, reference interval: 0–40 IU/ml) were measured by chemiluminescent immunoassay (AutoBio Co., Ltd., Zhengzhou, China). Coefficients of variation for the assays were all \15 %. Serum anti-TPO and anti-Tg were defined as positive and negative if the value of the antibody was higher than the upper reference or lower than the upper reference, respectively. Serum anti-TPO and anti-Tg levels that were higher than fivefold increase refer to high level [7]. An enzyme immunoassay (IDS, UK) was used to quantify serum 25-OHD. The intra- and inter-assay coefficients of variation were \8 and \10 %, respectively. Vitamin D deficiency was defined as 25-OHD of \50 nmol/l [8]. Statistical analysis All analyses were performed with SPSS 17.0 for Windows (Chicago, IL, USA). Continuous variables were presented as mean ± SD or medians (inter-quartile ranges). Categorical variables were presented as proportions. To compare the QUS parameters in relation to tertiles of thyroid hormones and antibodies adjusted for covariates, including age, BMI, current smoking and current alcohol consumption, physical activity, 25-OHD, and thyroid hormones, covariance analyses were conducted. The statistical tests were two-sided, and a p value of \0.05 was considered statistically significant.

Endocrine Table 1 Baseline ultrasound measurements and demographic characteristics of the study population

Lower QUS parameters in men with a high anti-TPO level

Men

BMI body mass index, WC waist circumference, HC hip circumference, fT3 free triiodothyronine, fT4 free thyroxin, TSH thyroid-stimulating hormone, anti-TPO anti-thyroid peroxidase, anti-Tg antithyroglobulin, QUI/sti quantitative ultrasound index, BUA broadband ultrasound attenuation, SOS speed of sound, 25-OHD 25-hydroxyvitamin D

There were no differences in QUS parameters between negative control and positive group according to the reference interval of anti-TPO level (40 IU/ml) (data not shown). However, when we divided the group into low and high anti-TPO group according to the fivefold increase(200 IU/ml) in order to ensure that only true cases of thyroid autoimmunity were studied [7], we found that after adjusting for age, BMI, smoking status, alcohol consumption, physical activity, 25-OHD, and fT4 level, subjects with high anti-TPO levels (C200 IU/ml) showed lower QUS parameter values compared with the control (antiTPO \200 IU/ml) (Table 3). In addition, we also observed serum fT4 to be an independent influencing factor (p = 0.013, p = 0.003, p = 0.029, respectively). Following measurement of 25-OHD in all subjects, no linear correlation was found between anti-TPO and 25-OHD levels (r = 0.050, p = 0.117). Individuals with high antiTPO have lower 25-OHD levels (42.59 ± 9.46 vs. 47.47 ± 15.07 nmol/l, p = 0.008). The prevalence of vitamin D deficiency was significantly higher in individuals with high anti-TPO than those in lower levels (87.5 vs. 59.5 %, p = 0.001). There was no association between anti-Tg levels and QUS parameters (supplement Table 1).

Results

Discussion

Baseline characteristics and laboratory parameters

To the best of our knowledge, this is a large, populationbased investigation to include men aged over 40 years. Furthermore, our study was not restricted to thyroid hormones; it also included thyroid autoimmune antibodies, unlike previous studies that rarely measured fT3, anti-TPO, and anti-Tg levels. The present study demonstrated that not only thyroid hormones but also antibody was associated with QUS parameters. A point of interest was that this study demonstrated for the first time the inverse correlation between anti-TPO and QUS parameters in men. Moreover, this association was independent of other potential conventional risk factors. The present study showed a decrease in QUS parameter values with an increase in fT4 concentrations in men. While there was no study describing the association between fT4 levels and QUS parameters, Tauchmanova` et al. [9] found a negative correlation between QUS parameters (SOS) and fT3 in 30 premenopausal and 30 early postmenopausal women with subclinical hyperthyroidism. Because circulatory TT4 is derived from the thyroid gland and the majority of TT3 is produced by

N

1,001

Age (years)

58.59 ± 8.87

BMI (kg/m2)

24.90 ± 3.10

WC (cm)

88.60 ± 8.62

HC (cm)

97.46 ± 6.52

25-OHD (nmol/l)

47.32 ± 14.94

Current smoking (%) Current alcohol (%)

28.5 52.7

Physical activity (%)

71.8

fT3 (pmol/l)

4.45 ± 1.16

fT4 (pmol/l)

15.34 ± 3.77

TSH (uIU/ml)

2.20 (1.36, 3.59)

QUI

93.2 ± 18.2

BUA (dB/MHz)

77.3 ± 16.7

SOS (m/s)

1,542.6 ± 29.7

Data are mean ± SD, medians (inter-quartile ranges), or numbers (proportions)

Table 1 lists the clinical characteristics. Among 1,001 males, the positivities of anti-Tg and anti-TPO were 5.39 and 8.09 %, respectively. The prevalence of high levels of anti-Tg and anti-TPO was 2.00 and 3.20 %, respectively. Lower QUS parameter values in men with a higher fT4 level Men were divided into tertiles based on serum fT4, fT3, and TSH levels, respectively, and covariance analyses were performed to examine the association between QUS parameters and thyroid hormones (Table 2). In the unadjusted model, fT4 was significantly associated with decrease in all the QUS parameters in males. In the fully adjusted model (i.e., after adjusting for age, BMI, smoking status, alcohol consumption, physical activity, 25-OHD, fT3, and TSH levels), the association remained significant. However, we did not find a significant relationship between fT3 or TSH and QUS parameters.

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Endocrine Table 2 Relationship between tertiles of fT4 and QUS parameters in men Thyroid hormone Tert 1

Tert 2

Unadjusted

Model 1

Model 2

Model 3

Tert 3

fT4

B13.56

13.57–17.00

C17.01

N

334

334

333

QUI

95.6 ± 19.6

92.7 ± 16.9

91.3 ± 17.9**

0.009

0.004

0.005

0.002

BUA

79.9 ± 17.0

76.7 ± 16.1*

75.3 ± 16.7**

0.001

0.001

0.001

0.000

SOS

1,545.8 ± 32.1

1,541.9 ± 27.5

1,540.0 ± 28.9*

0.040

0.018

0.019

0.009

fT3

B4.05

4.06–4.60

C4.61

N QUI

337 93.6 ± 19.8

331 93.2 ± 18.2

333 92.8 ± 16.6

0.862

0.636

0.638

0.861

BUA

77.8 ± 17.9

77.2 ± 16.9

76.9 ± 15.1

0.777

0.539

0.557

0.852

SOS

1,542.9 ± 32.2

1,542.7 ± 29.6

1,542.1 ± 27.1

0.944

0.788

0.785

0.533

TSH

B1.62

1.63–3.01

C3.02

N

338

330

333

QUI

92.6 ± 17.5

93.2 ± 18.6

93.8 ± 18.6

0.683

0.491

0.487

0.433

BUA

76.8 ± 16.0

76.8 ± 17.5

78.2 ± 16.5

0.450

0.372

0.384

0.339

SOS

1,541.7 ± 28.7

1,542.8 ± 30.1

1,543.2 ± 30.3

0.786

0.599

0.597

0.536

Model 1 was adjusted for age and BMI. Model 2 was adjusted for age, BMI, smoking status, alcohol consumption, physical activity, and 25-OHD. Model 3 was adjusted for age, BMI, smoking status, alcohol consumption, physical activity, 25-OHD, fT3, fT4, and TSH BMI body mass index, 25-OHD 25-hydroxyvitamin D, fT3 free triiodothyronine, fT4 free thyroxin, TSH thyroid-stimulating hormone, QUI/sti quantitative ultrasound index, BUA broadband ultrasound attenuation, SOS speed of sound p values for comparisons between individuals in Tert 1 of fT4 and those in Tert 2 or Tert 3:* p \ 0.05, ** p \ 0.01 Table 3 Relationship between QUS parameters and anti-TPO in men

N

anti-TPO (\200) Mean ± SD

anti-TPO (C200) Mean ± SD

969

32

Unadjusted

p value Model 1

Model 2

QUI

93.3 ± 18.2

86.3 ± 17.3

0.028

0.031

0.030

BUA

77.5 ± 16.7

71.3 ± 14.5

0.039

0.043

0.034

SOS

1,542.9 ± 29.6

1,531.7 ± 29.3

0.036

0.038

0.041

Model 1 was adjusted for age and BMI. Model 2 was adjusted for age, BMI, smoking status, alcohol consumption, physical activity, 25-OHD, and fT4 BMI body mass index, QUI/sti quantitative ultrasound index, BUA broadband ultrasound attenuation, SOS speed of sound, 25-OHD 25-hydroxyvitamin D, fT4 free thyroxin

deiodination of TT4 [10], results from this study were consistent with our finding that thyroid status at ‘‘hyperthyroid’’ correlated with lower QUS parameter values. The inverse correlation between fT4 and QUS parameters reported herein was similar to that reported in studies which measured BMD by DXA. Lin et al. [11] described a weak negative correlation between T4 and BMD in postmenopausal women and young men; however, they did not identify a significant relationship between TSH and BMD in 2,957 men and women with normal thyroid function in Taiwan. Van der Deure et al. [12] observed a negative association between serum fT4 and several bone parameters in 1,151 men and women aged C55 years.

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However, the result of this study does not exclude that TSH may have a direct effect on bone in humans [13–16], such as already demonstrated in mice [17]. The lack of statistical association between low TSH and QUS parameters could be explained by the following possible reasons. First, our study analyzed only QUS parameters without considering other features of skeletal fragility (i.e., BMD data, fractures). Second, thyroid autoimmunity underlying the high serum TSH values [18, 19] may have mitigated the potential association between low TSH values and skeletal fragility. Third, the respective effect of high thyroid hormones and low TSH in the skeleton cannot be discriminated in population studies because of the physiological

Endocrine

reciprocal relationship between thyroid hormones and TSH [20]. Previous studies by Majima et al. [4] and Jo´dar et al. [21], which focused on the association of TRAb with BMD, showed a significantly negative relationship between TRAb and BMD in hyperthyroid patients. However, there is little information on the association of antiTPO or anti-Tg with BMD. In our study, when the negative control was compared with positive group, no difference was observed. In contrast, when subjects were divided into high and low levels, a significant difference was observed. There are several plausible explanations for these data. First, as observed in other autoimmune diseases such as type 1 diabetes, high levels of antibodies predict severe target cell dysfunction compared with antibodies positivity in lower levels or antibodies negativity [22]. Furthermore, Strieder et al. [23] showed a relationship between a high anti-TPO titer and an increasing TSH level, which signified thyroid failure. Evidence also shows anti-TPO titer to be correlated with the degree of lymphocytic infiltration of the thyroid gland [24]. Second, a lower anti-TPO level may partly be explained by non-autoimmune thyroid damage. Third, low autoantibody levels may result from falsepositive laboratory results that are not related to disease but caused by random assay variations. Thus, we concluded that a high anti-TPO level is an indicator of severe lymphocytic infiltration and subsequent thyroid failure. As shown in our study, men with anti-TPO levels of C200 IU/ml had significantly lower QUS parameters. The prevalence of vitamin D deficiency was significantly higher in individuals with high anti-TPO than those in lower levels. The pathophysiological mechanisms linking anti-TPO to QUS parameters have not been well ascertained, and it is possible that multiple factors are involved. First, bone interacts with the immune system at anatomical, vascular, cellular, and molecular levels as described in osteoimmunology [25]. Local inflammatory and proinflammatory cytokines produced by the thyroid gland can affect skeletal growth, development, and bone turnover by indirectly inducing bone destruction, osteoporosis, and osteoporotic fractures [26]. Many human and animal studies have identified critical inflammatory cytokines involved in the pathogenesis of bone loss or osteoporosis during autoimmune disease [27, 28]. In addition, an activation of peripheral lymphocytes in thyroid autoimmune disease may lead to bone loss [29]. Second, low 25-OHD levels in subjects with high anti-TPO levels may be an underlying cause linking AITD to osteoporosis. Vitamin D3 obtained from sunlight or diet is converted to 25-hydroxy vitamin D3 (25(OH)D3) in the liver and further converted to 1,25dihydroxy vitamin D (1,25(OH)2D3) in the kidney, the biologically active form [8]. Vitamin D, which is essential

for bone and mineral homeostasis, is an immune modulator with anti-inflammatory properties [30]. Several researches reported a relationship between hypovitaminosis D and thyroid autoimmunity. Yasuda et al. [31] demonstrated that lower vitamin D levels and a higher prevalence of vitamin D deficiency in Graves’ disease compared to healthy controls. This finding was in line with the observation by Kivity et al. [32] who identified that the prevalence of vitamin D deficiency was significantly higher in individuals with AITDs as opposed to healthy controls. Besides human studies, in vitro vitamin D promotes a Th2 phenotype while inhibiting the production of Th1 and Th17 cell cytokines [33]. Furthermore, CXCL10, a Th1 chemokine, which plays an important role in AITD, is inhibited by vitamin D analogy in human thyroid cells [34]. In addition, some studies demonstrated a correlation between polymorphism of vitamin D-related genes (e.g., vitamin D3 receptor (VDR) [35], vitamin D-binding protein [36]) and AITD. Thus, Rotondi commented that vitamin D deficiency in AITD may be something more than a causal association [37]. Third, the effects of thyroid hormones should not be ignored, even though the association between anti-TPO levels and QUS parameters remained significant after adjusting for thyroid hormones. In contrast, we did not find an association between antiTg levels and QUS parameters. Although Tg is a thyroidspecific antigen and anti-Tg is an index of AITD, there is no information available to show that anti-Tg results in tissue or cell damage during AITD [38]. While a study by Rebuffat et al. [39] demonstrated anti-TPO to mediate the destruction of thyroid cells and possibly to play a pathogenic role in AITD, differences between thyroid antibodies and QUS parameters may explain this discrepancy in data. Although our study was large, several limitations were presented. First, DXA, the golden diagnostic criteria for osteoporosis, was not provided for our subjects. QUS, which measures bone mass, was not sensitive enough because mineral content and other materials and structural properties can affect ultrasound propagation in bone [40]. Regardless, QUS has several advantages and directly relates to heel BMD using DXA. Second, individuals were community-dwelling Chinese men aged over 40 years; therefore, these results were not generalized to other ethnic groups. Third, a causal association could not be addressed due to the cross-sectional nature of this study, and large prospective studies are needed to understand this relationship better. In conclusion, fT4 levels were negatively associated with QUS parameters. Our findings demonstrated that high anti-TPO levels may confer lower QUS parameters in middle-aged and elderly Chinese men. If this finding is validated by prospective studies, high fT4 or anti-TPO levels should be taken into account during osteoporosis

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management. Additional experimental and prospective studies are needed to determine the precise relationship between thyroid status and osteoporosis.

13.

Acknowledgments The authors thank Prof. Rongbing Yu, Nanjing Medical University, for statistical advice. 14. Conflict of interest There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. 15.

References 1. D.C. Bauer, D.C. Bauer, L. Palermo, D. Black, J.A. Cauley, Study of Osteoporotic Fractures Research Group: Universities of California (San Francisco), Pittsburgh, Minnesota (Minneapolis), and Kaiser Center for Health Research, Portland, Quantitative ultrasound and mortality: a prospective study. Osteoporos. Int. 13(8), 606–612 (2002) 2. P. Vestergaard, L. Mosekilde, Fractures in patients with hyperthyroidism and hypothyroidism: a nationwide follow-up study in 16249 patients. Thyroid 12(5), 411–419 (2002) 3. G. Schett, J.P. David, The multiple faces of autoimmune-mediated bone loss. Nat. Rev. Endocrinol. 6(12), 698–706 (2010) 4. T. Majima, Y. Komatsu, K. Doi, C. Takagi, M. Shigemoto, A. Fukao, T. Morimoto, J. Corners, K. Nakao, Negative correlation between bone mineral density and TSH receptor antibodies in male patients with untreated Graves’ disease. Osteoporos. Int. 17(7), 1103–1110 (2006) 5. S. Grampp, H.K. Genant, A. Mathur, P. Lang, M. Jergas, M. Takada, C.C. Glu¨er, Y. Lu, M. Chavez, Comparisons of noninvasive bone mineral measurements in assessing age-related loss, fracture discrimination, and diagnostic classification. J. Bone Miner. Res. 12(5), 697–711 (1997) 6. M.A. Krieg, R. Barkmann, S. Gonnelli, A. Stewart, D.C. Bauer, L. Del Rio Barquero, J.J. Kaufman, R. Lorenc, P.D. Miller, W.P. Olszynski, C. Poiana, A.M. Schott, E.M. Lewiecki, D. Hans, Quantitative ultrasound in the management of osteoporosis: the 2007 ISCD official positions. J. Clin. Densitom. 11(1), 163–187 (2008) 7. K.S. Stamatelopoulos, K. Kyrkou, E. Chrysochoou, H. Karga, S. Chatzidou, G. Georgiopoulos, S. Georgiou, K. Xiromeritis, C.M. Papamichael, M. Alevizaki, Arterial stiffness but not intimamedia thickness is increased in euthyroid patients with Hashimoto’s thyroiditis: the effect of menopausal status. Thyroid 19(8), 857–862 (2009) 8. M.F. Hollick, Vitamin D deficiency. N. Engl. J. Med. 357(3), 266–281 (2007) 9. L. Tauchmanova`, V. Nuzzo, A. Del Puente, F. Fonderico, A. Esposito-Del Puente, S. Padulla, A. Rossi, G. Bifulco, G. Lupoli, G. Lombardi, Reduced bone mass detected by bone quantitative ultrasonometry and DEXA in pre- and postmenopausal women with endogenous subclinical hyperthyroidism. Maturitas 48(3), 299–306 (2004) 10. A. Wojcicka, J.H. Bassett, G.R. Williams, Mechanisms of action of thyroid hormones in the skeleton. Biochim. Biophys. Acta 1830(7), 3979–3986 (2013) 11. J.D. Lin, D. Pei, T.L. Hsia, C.Z. Wu, K. Wang, Y.L. Chang, C.H. Hsu, Y.L. Chen, K.W. Chen, S.H. Tang, The relationship between thyroid function and bone mineral density in euthyroid healthy subjects in Taiwan. Endocr. Res. 36(1), 1–8 (2011) 12. W.M. van der Deure, A.G. Uitterlinden, A. Hofman, F. Rivadeneira, H.A. Pols, R.P. Peeters, T.J. Visser, Effects of serum TSH

123

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26. 27.

and FT4 levels and the TSHR-Asp727Glu polymorphism on bone: the Rotterdam Study. Clin. Endocrinol. 68(2), 175–181 (2008) G. Mazziotti, T. Porcelli, I. Patelli, P.P. Vescovi, A. Giustina, Serum TSH values and risk of vertebral fractures in euthyroid post-menopausal women with low bone mineral density. Bone 46(3), 747–751 (2010) K.Y. Chin, S. Ima-Nirwana, I.N. Mohamed, A. Aminuddin, M.H. Johari, W.Z. Ngah, Thyroid-stimulating hormone is significantly associated with bone health status in men. Int. J. Med. Sci. 10(7), 857–863 (2013) G. Martini, L. Gennari, V. De Paola, T. Pilli, S. Salvadori, D. Merlotti, F. Valleggi, S. Campagna, B. Franci, A. Avanzati, R. Nuti, F. Pacini, The effects of recombinant TSH on bone turnover markers and serum osteoprotegerin and RANKL levels. Thyroid 18(4), 455–460 (2008) G. Mazziotti, F. Sorvillo, M. Piscopo, M. Cioffi, P. Pilla, B. Biondi, S. Iorio, A. Giustina, G. Amato, C. Carella, 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 (2005) E. Abe, R.C. Marians, W. Yu, X.B. Wu, T. Ando, Y. Li, J. Iqbal, L. Eldeiry, G. Rajendren, H.C. Blair, T.F. Davies, M. Zaidi, TSH is a negative regulator of skeletal remodeling. Cell 115(2), 151–162 (2003) T.E. Hamilton, S. Davis, L. Onstad, K.J. Kopecky, Thyrotropin levels in a population with no clinical, autoantibody, or ultrasonographic evidence of thyroid disease: implications for the diagnosis of subclinical hypothyroidism. J. Clin. Endocrinol. Metab. 93(4), 1224–1230 (2008) P. Vejbjerg, N. Knudsen, H. Perrild, P. Laurberg, I.B. Pedersen, L.B. Rasmussen, The association between hypoechogenicity or irregular echo pattern at thyroid ultrasonography and thyroid function in the general population. Eur. J. Endocrinol. 155(4), 547–552 (2006) J.H. Bassett, G.R. Williams, Critical role of the hypothalamicpituitary-thyroid axis in bone. Bone 43(3), 418–426 (2008). doi:10.1016/j.bone.2008.05.007 E. Jo´dar, M. Mun˜oz-Torres, F. Escobar-Jime´nez, M. QuesadaCharneco, J.D. Lund del Castillo, Bone loss in hyperthyroid patients and in former hyperthyroid patients controlled on medical therapy: influence of aetiology and menopause. Clin. Endocrinol. (Oxf.) 47(3), 279–285 (1997) A.W. van Deutekom, R.J. Heine, S. Simsek, The islet autoantibody titres: their clinical relevance in latent autoimmune diabetes in adults (LADA) and the classification of diabetes mellitus. Diabet. Med. 25(2), 117–125 (2008) T.G. Strieder, M.F. Prummel, J.G. Tijssen, E. Endert, W.M. Wiersinga, Risk factors for and prevalence of thyroid disorders in a cross-sectional study among healthy female relatives of patients with autoimmune thyroid disease. Clin. Endocrinol. 59(3), 396–401 (2003) H. Yoshida, N. Amino, K. Yagawa, K. Uemura, M. Satoh, K. Miyai, Y. Kumahara, Association of serum antithyroid antibodies with lymphocytic infiltration of the thyroid gland: studies of seventy autopsied cases. J. Clin. Endocrinol. Metab. 46(6), 859–862 (1978) H. Takayanagi, Osteoimmunology and the effects of the immune system on bone. Nat. Rev. Rheumatol. 5(12), 667–676 (2009). doi:10.1038/nrrheum.2009.217 I.B. McInnes, G. Schett, Cytokines in the pathogenesis of rheumatoid arthritis. Nat. Rev. Immunol. 7(6), 429–442 (2007) M. Kunz, S.M. Ibrahim, Cytokines and cytokine profiles in human autoimmune diseases and animal models of autoimmunity. Mediators Inflamm. 2009, 979258 (2009). doi: 10.1155/2009/979258

Endocrine 28. L. van der Heul-Nieuwenhuijsen, R.C. Padmos, R.C. Drexhage, H. de Wit, A. Berghout, H.A. Drexhage, An inflammatory geneexpression fingerprint in monocytes of autoimmune thyroid disease patients. J. Clin. Endocrinol. Metab. 95(4), 1962–1971 (2010) 29. R. Pacifici, Role of T cells in the modulation of PTH action: physiological and clinical significance. Endocrine 44(3), 576–582 (2013) 30. E. van Etten, C. Mathieu, Immunoregulation by 1, 25-dihydroxyvitamin D3: basic concepts. J. Steroid Biochem. Mol. Biol. 97(1–2), 93–101 (2005) 31. T. Yasuda, Y. Okamoto, N. Hamada, K. Miyashita, M. Takahara, F. Sakamoto, T. Miyatsuka, T. Kitamura, N. Katakami, D. Kawamori, M. Otsuki, T.A. Matsuoka, H. Kaneto, I. Shimomura, Serum vitamin D levels are decreased in patients without remission of Graves’ disease. Endocrine 43(1), 230–232 (2013) 32. S. Kivity, N. Agmon-Levin, M. Zisappl, Y. Shapira, E.V. Nagy, K. Danko´, Z. Szekanecz, P. Langevitz, Y. Shoenfeld, Vitamin D and autoimmune thyroid diseases. Cell Mol. Immunol. 8(3), 243–247 (2011) 33. M. Rotondi, L. Chiovato, The chemokine system as a therapeutic target in autoimmune thyroid diseases: a focus on the interferon-c inducible chemokines and their receptor. Curr. Pharm. Des. 17(29), 3202–3216 (2011)

34. E. Borgogni, E. Sarchielli, M. Sottili, V. Santarlasci, L. Cosmi, S. Gelmini, A. Lombardi, G. Cantini, G. Perigli, M. Luconi, G.B. Vannelli, F. Annunziato, L. Adorini, M. Serio, C. Crescioli, Elocalcitol inhibits inflammatory responses in human thyroid cells and T cells. Endocrinology 149(7), 3626–3634 (2008) 35. M. Feng, H. Li, S.F. Chen, W.F. Li, F.B. Zhang, Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis. Endocrine 43(2), 318–326 (2013) 36. A. Kurylowicz, E. Ramos-Lopez, T. Bednarczuk, K. Badenhoop, Vitamin D-binding protein (DBP) gene polymorphism is associated with Graves’ disease and the vitamin D status in a Polish population study. Exp. Clin. Endocrinol. Diabetes 114(6), 329–335 (2006) 37. M. Rotondi, L. Chiovato, Vitamin D deficiency in patients with Graves’ disease: probably something more than a casual association. Endocrine 43(1), 3–5 (2013) 38. A.P. Weetman, Autoimmune thyroid disease. Autoimmunity 37(4), 337–340 (2004) 39. S.A. Rebuffat, B. Nguyen, B. Robert, F. Castex, S. Peraldi-Roux, Antithyroperoxidase antibody-dependent cytotoxicity in autoimmune thyroid Disease. J. Clin. Endocrinol. Metab. 93(3), 929–934 (2008) 40. C.C. Glu¨er, Quantitative ultrasound techniques for the assessment of osteoporosis: expert agreement on current status. J. Bone Miner. Res. 12(8), 1280–1288 (1997)

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Association between calcaneus quantitative ultrasound (QUS) parameters and thyroid status in middle-aged and elderly Chinese men with euthyroidism: a population-based cross-sectional study.

Although it is generally accepted that thyroid hormones affect bone metabolism, there is little data on the association of thyroid antibodies with bon...
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