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The Impact of Thyroid Hormone Levels on Metabolism: Especially in Bone Homeostasis

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A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 8361

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Special Issue Editors

Prof. Dr. Tatijana Zemunik

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Guest Editor

School of Medicine, University of Split, 21000 Split, Croatia
Interests: genetics; thyroid hormones and antibodies; parameters of calcium homeostasos; GWAS; prediction analysis

Dr. Mirjana Babić Leko

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Guest Editor

School of Medicine, University of Split, 21000 Split, Croatia
Interests: genetics; molecular biology; neurobiology; thyroid; Alzheimer’s disease

Dr. Ivana Gunjača

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Guest Editor

School of Medicine, University of Split, 21000 Split, Croatia
Interests: genetics; molecular biology; thyroid hormones; GWAS; immunofluorescence

Special Issue Information

Dear Colleagues,

Thyroid hormones are important in bone development, maturation and bone maintenance in adulthood. Thyroid dysfunction in childhood affects bone mineralization and growth. In adulthood, thyroid dysfunction can increase the risk of bone fracture due to disturbed bone remodelling. There are several types of thyroid hormone receptors in human osteoblasts, while almost all thyroid hormone receptors are expressed in osteoclasts. However, the mechanism of thyroid hormones’ activity in bones has yet to be elucidated. In recent years, several studies have linked the activity of thyroid hormone in bone with bone turnover markers. On the other hand, a recent study defined that the specific transporter proteins at the plasma membrane are essential for thyroid hormone bioavailability in the cells and consequently influence bone mass. Since this scientific area is broad and insufficiently defined, this Special Issue of Metabolites aims to publish papers with new information in this field. Other interesting and innovative topics related to thyroid hormones and metabolism are also welcome for this Special Issue.

Prof. Dr. Tatijana Zemunik
Dr. Mirjana Babić Leko
Dr. Ivana Gunjača
Guest Editors

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Keywords

thyroid hormones
bone homeostasis
trabecular bone changes
osteoblasts
osteoclast
osteoporosis
osteocalcin
bone turnover markers
thyroid hormone transporter

Published Papers (5 papers)

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Research

14 pages, 1684 KiB

Open AccessArticle

A Causality between Thyroid Function and Bone Mineral Density in Childhood: Abnormal Thyrotropin May Be Another Pediatric Predictor of Bone Fragility

by Dongjin Lee and Moon Bae Ahn

Metabolites 2023, 13(3), 372; https://doi.org/10.3390/metabo13030372 - 2 Mar 2023

Viewed by 1145

Abstract

Low bone mass can occur in children and adolescents with numerous chronic conditions; however, the influence of abnormal thyroid hormone and thyroid-stimulating hormone (TSH) levels on low bone mineral density (BMD) in children and adolescents remains controversial. Investigating the effects of excessive or deficient thyroid hormone and TSH levels on the risk of childhood bone fragility may provide a better understanding of the role of thyroid function on bone density in the pediatric population. The triiodothyronine (T3), thyroxine (T4), and TSH levels and BMD of 619 children diagnosed with various underlying conditions and whose treatment was completed were simultaneously assessed. The T3, free thyroxine (FT4), and TSH levels were subcategorized based on the age-matched reference range, and the lumbar spine BMD (LSBMD) data were compared. The mean LSBMD z-score was 0.49 ± 1.28, while T3, FT4, and TSH levels were 1.25 ± 0.29 ng/mL, 1.28 ± 0.19 ng/dL, and 2.76 ± 1.87 µU/mL, respectively. Both lumbar and femoral BMD z-scores were lower in children with abnormal TSH levels. TSH abnormality was the strongest risk factor for decreased LSBMD z-scores, and thus could be an early indicator of low BMD in children and adolescents with various underlying conditions. Full article

(This article belongs to the Special Issue The Impact of Thyroid Hormone Levels on Metabolism: Especially in Bone Homeostasis)

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9 pages, 1580 KiB

Open AccessArticle

Effect of Suppressive Levothyroxine Therapy on Bone Mineral Density in Young Patients with Differentiated Thyroid Carcinoma

by André Borsatto Zanella, Laura Marmitt, Tayane Muniz Fighera, Rafael Selbach Scheffel, Poli Mara Spritzer, José Miguel Dora and Ana Luiza Maia

Metabolites 2022, 12(9), 842; https://doi.org/10.3390/metabo12090842 - 7 Sep 2022

Viewed by 1577

Abstract

Suppressive levothyroxine therapy (sT4) is a cornerstone in the management of differentiated thyroid cancer (DTC). Long-term sT4 may affect bone mineral density (BMD). We evaluated the effect of sT4 on the bone mass of young DTC patients. In this cross-sectional study, BMD was evaluated via dual-energy X-ray absorptiometry in DTC patients younger than 25 years at diagnosis and undergoing sT4 for ≥1 year. The two control groups comprised patients matched for sex, age, and body-mass-index who were thyroidectomized for indications other than DTC and undergoing L-T4-replacement therapy, and healthy individuals with no prior known thyroid disease. Ninety-three participants were included (thirty-one in each group). There were no differences in the mean age, female sex (77.4% in all groups), or BMI between the sT4 group and each control group. The median TSH level was lower (0.4 [0.04–6.5] vs. 2.7 [0.8–8.5] mIU/mL, p = 0.01) and the mean L-T4 mcg/Kg levels were higher (2.4 ± 0.6 vs. 1.6 ± 0.3, p = 0.01) in the sT4 group compared to the L-T4-replacement therapy group. Lumbar spine, femoral neck, and total femur BMD were all similar among the groups. sT4 does not impact BMD in young DTC patients after a median time of suppression of 8 years. These findings may help in the decision-making and risk/benefit evaluation of sT4 for this population. Full article

(This article belongs to the Special Issue The Impact of Thyroid Hormone Levels on Metabolism: Especially in Bone Homeostasis)

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11 pages, 1355 KiB

Open AccessArticle

Thyroid Hormones Are Not Associated with Plasma Osteocalcin Levels in Adult Population with Normal Thyroid Function

by Nikolina Pleić, Dubravka Brdar, Ivana Gunjača, Mirjana Babić Leko, Vesela Torlak, Ante Punda, Ozren Polašek, Caroline Hayward and Tatijana Zemunik

Metabolites 2022, 12(8), 719; https://doi.org/10.3390/metabo12080719 - 4 Aug 2022

Viewed by 1587

Abstract

Thyroid hormones (THs) play an indispensable role in skeletal development and bone remodeling. Some studies have reported associations of THs with serum osteocalcin (OC) levels, but the results are quite inconsistent and the molecular mechanism of their simultaneous or interdependent activity on bone is almost unknown. Therefore, the aim of this study was to determine the possible associations of plasma THs with plasma OC levels and the possible mediating effect of OC on the relationship between THs and bone mineral density (BMD). For this purpose, out of the initial 1981 participants, we selected healthy euthyroid participants controlled for available confounding factors that can affect thyroid function and bone metabolism (N = 694). Given our results, we could not confirm any associations of THs with plasma OC levels nor the mediating effect of OC on the relationship between THs and BMD in euthyroid population. In the group of women controlled for menopause status (N = 396), we found a significant negative association of body mass index (BMI) with OC levels (β = −0.14, p = 0.03). We also found a negative association of free triiodothyronine (fT3) (β = −0.01, p = 0.02) and age (β = −0.003, p < 0.001) with BMD, and a positive association of BMI (β = 0.004, p < 0.001) and male gender (β = 0.1, p < 0.001) with BMD. In addition, we found significantly higher plasma OC levels and lower values of BMD in postmenopausal euthyroid women compared with premenopausal euthyroid women. In our opinion, the results of previous studies suggesting an association between circulating THs and serum OC levels may be influenced by an inconsistent selection of participants and the influence of confounding factors. Full article

(This article belongs to the Special Issue The Impact of Thyroid Hormone Levels on Metabolism: Especially in Bone Homeostasis)

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12 pages, 287 KiB

Open AccessArticle

Wnt Inhibitors and Bone Mineral Density in Patients with Graves’ Disease Treated with Antithyroid Drugs: A Preliminary Prospective Study

by Dunja Mudri, Tomislav Kizivat, Ivica Mihaljević and Ines Bilić Ćurčić

Metabolites 2022, 12(8), 711; https://doi.org/10.3390/metabo12080711 - 29 Jul 2022

Cited by 1 | Viewed by 1614

Abstract

This study aimed to investigate the association of Wnt inhibitors with thyroid hormones, bone turnover markers, and bone mineral density (BMD) in patients with newly diagnosed Graves’ disease (GD) at the beginning of the antithyroid treatment and after a follow-up period of one year. The study included 37 patients with newly diagnosed GD who were treated with antithyroid drugs (ATD). At baseline and after one year, thyroid hormones and thyroid-stimulating hormone (TSH), serum concentrations of sclerostin, and Dickkopf-1 (DKK1) were measured by an enzyme-linked immunosorbent assay (ELISA). In addition, BMD was measured by dual-energy X-ray absorptiometry (DXA), and markers of bone turnover including osteocalcin (OC), beta-cross laps (β-CTX), and deoxypyridinoline (DPD) were determined. After one year of ATD therapy sclerostin levels were significantly decreased (p < 0.001), whereas DKK1 levels were significantly increased (p = 0.01). In addition, BMD of the lumbar spine, total hip, and femoral neck was significantly improved (p < 0.001), accompanied by an increase in OC, β-CTX, and DPD concentrations (p < 0.001). At baseline, sclerostin levels were positively associated with free triiodothyronine (FT3). Following ATD therapy, a positive correlation was observed between FT3 and DKK1 (p = 0.003), whereas a negative correlation was found between TSH and DKK1 (p = 0.04). Correlation analysis demonstrated no association of the sclerostin and DKK1 with other bone remodeling biomarkers OC, β-CTX, or DPD. Also, no significant correlation between sclerostin or DKK1 and T-score or BMD of the lumbar spine, hip, and femoral neck was observed at both time points. Conclusion: Observed differences in sclerostin and DKK1 serum following GD treatment indicate involvement of Wnt inhibitors in the etiopathogenesis of bone loss associated with hyperthyroidism. Furthermore, both sclerostin and DKK1 are involved in the reversal of changes in bone metabolism following ATD therapy, thus presenting potentially valuable bone remodeling markers worth further investigation. Full article

(This article belongs to the Special Issue The Impact of Thyroid Hormone Levels on Metabolism: Especially in Bone Homeostasis)

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13 pages, 2823 KiB

Open AccessArticle

Maternal Hyperthyroidism in Rats Alters the Composition and Gene Expression of the Matrix Produced In Vitro by Chondrocytes from Offspring with Intrauterine Growth Restriction

by Fabiana R. Araújo, Bruno M. Bertassoli, Natália M. Ocarino, Amanda M. S. Reis, Juneo F. Silva, Lorena G. R. Ribeiro and Rogéria Serakides

Metabolites 2022, 12(4), 292; https://doi.org/10.3390/metabo12040292 - 26 Mar 2022

Cited by 1 | Viewed by 1652

Abstract

Herein, we aimed to evaluate cultures of femoral chondrocytes from offspring of rats with intrauterine growth restriction (IUGR) induced by maternal hyperthyroidism. Fourteen adult female Wistar rats were divided into two groups, a control group and a group treated with daily L-thyroxine administration using an orogastric tube (50 µg/animal/day) during pregnancy. Three days after birth, the offspring were euthanized for chondrocyte extraction. At 7, 14, and 21 days, viability and alkaline-phosphatase (ALP) activity were assessed using the MTT assay and BCIP/NBT method, respectively, in a 2D culture. Pellets (3D cultures) were stained with periodic acid Schiff (PAS) to assess the morphology and percentage of PAS+ areas. The gene transcripts for Col2, Col10, Acan, Sox9, and Runx2 were evaluated by qRT-PCR. The MTT and ALP-assay results showed no significant differences between the groups. Maternal hyperthyroidism did not alter the chondrocyte morphology, but significantly reduced the percentage of PAS+ areas, decreased the expression of the gene transcripts of Col2 and Acan, and increased Sox9 expression. Maternal hyperthyroidism in rats alters the composition and gene expression of the matrix produced by chondrocytes from offspring with IUGR. This may be one of the mechanisms through which excess maternal thyroid hormones reduce offspring bone growth. Full article

(This article belongs to the Special Issue The Impact of Thyroid Hormone Levels on Metabolism: Especially in Bone Homeostasis)

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