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How does Hashimoto’s thyroiditis affect bone metabolism?

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Abstract

Bone marrow contains resident cellular components that are not only involved in bone maintenance but also regulate hematopoiesis and immune responses. The immune system and bone interact with each other, coined osteoimmunology. Hashimoto’s thyroiditis (HT) is one of the most common chronic autoimmune diseases which is accompanied by lymphocytic infiltration. It shows elevating thyroid autoantibody levels at an early stage and progresses to thyroid dysfunction ultimately. Different effects exert on bone metabolism during different phases of HT. In this review, we summarized the mechanisms of the long-term effects of HT on bone and the relationship between thyroid autoimmunity and osteoimmunology. For patients with HT, the bone is affected not only by thyroid function and the value of TSH, but also by the setting of the autoimmune background. The autoimmune background implies a breakdown of the mechanisms that control self-reactive system, featuring abnormal immune activation and presence of autoantibodies. The etiology of thyroid autoimmunity and osteoimmunology is complex and involves a number of immune cells, cytokines and chemokines, which regulate the pathogenesis of HT and osteoporosis at the same time, and have potential to affect each other. In addition, vitamin D works as a potent immunomodulator to influence both thyroid immunity and osteoimmunology. We conclude that HT affects bone metabolism at least through endocrine and immune pathways.

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Abbreviations

HT:

Hashimoto’s thyroiditis

RANK:

receptor activator of nuclear factor-kappaB

RANKL:

receptor activator of nuclear factor-kappaB ligand

AIT:

autoimmune thyroiditis

TH:

thyroid hormones

TSH:

thyroid stimulating hormone

T4:

thyroxine

T3:

triiodothyronine

OATP:

organic anion transporting polypeptide

MCT:

monocarboxylate transporter

SLC:

solute carriers

DIO1:

type 1 iodothyronine deiodinase

DIO2:

type 2 iodothyronine deiodinase

DIO3:

type 3 iodothyronine deiodinase

GWA:

genome-wide association

HPT:

hypothalamic-pituitary-thyroid

TR:

thyroid hormone nuclear receptor

IGF-1:

insulin-like growth factor-1

OPG:

osteoprotegerin

LT4:

levothyroxine

NK:

natural killer

TgAb:

antibodies against thyroglobulin

TPOAb:

antibodies against thyroid peroxidase

CDC:

complement-dependent cytotoxicity

ADCC:

antibody-dependent cell-mediated cytotoxicity

FRAX:

Fracture Risk Assessment Tool

1,25(OH)2D:

1,25-dihydroxyvitamin D

VDR:

vitamin D receptor

IL:

interleukin

ST2:

suppression of tumorigenicity 2 protein

TNF-α:

tumor necrosis factor- alpha

IFN-γ:

interferon-gamma

L-SAT:

lymphocytic- spontaneous autoimmune thyroiditis

TRAF6:

tumor necrosis factor receptor associated factor 6

RUNX2:

runt-related transcription factor 2

Se:

selenium

SeNPs:

Se nanoparticles

ALP:

alkaline phosphatase

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Authors and Affiliations

  1. Laboratory of Endocrinology and Metabolism/Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, 37 Guoxue Lane, 610041, Chengdu, P.R. China

    Jialu Wu & Xijie Yu

  2. Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, 37 Guoxue Lane, 610041, Chengdu, P.R. China

    Hui Huang

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This work was supported by grants from the National Natural Science Foundation of China [No. 82273294]; the Science and Technology Department of Sichuan Province (2022YFS0136); the Chengdu Bureau of Science and Technology (2022-YF05-01316-SN); the Sichuan University [No. 2018SCUH0093]; and the 1.3.5 project for discipline of excellence, West China Hospital, Sichuan University [No. 2020HXFH008, No. ZYJC18003].

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Wu, J., Huang, H. & Yu, X. How does Hashimoto’s thyroiditis affect bone metabolism?. Rev Endocr Metab Disord 24, 191–205 (2023). https://doi.org/10.1007/s11154-022-09778-x

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