Thyrotropin, Hyperthyroidism, and Bone Mass

Abstract

Thyrotropin, traditionally seen as a pituitary hormone that regulates thyroid glands, has additional roles in physiology including skeletal remodeling. Population-based observations in subjects with euthyroidism or subclinical hyperthyroidism indicated a negative association between bone mass and low-normalTSH. The findings of correlative studies were supported by small intervention trials using recombinant human TSH (rhTSH) injection, and genetic and case-based evidence. Genetically-modified mouse models, which disrupt the reciprocal relationship between TSH and thyroid hormone, have allowed us to examine an independent role of TSH. Since the first description of osteoporotic phenotype in haploinsufficient Tshr +/- mice with normal thyroid hormone levels, the anti–osteoclastic effect of TSH has been documented in in vitro and in vivo studies. Further studies showed that increased osteoclastogenesis in Tshr–deficient mice was mediated by TNFα. Low TSH not only increased osteoclastogenesis, but also decreased osteoblastogenesis in bone marrow–derived primary osteoblast cultures. However, later in vivo studies using small and intermittent dose of rhTSH showed pro-anabolic effect, which suggests that its action might be dose- and frequency-dependent. TSHR was shown to interact with IGF1R, and VEGF and Wnt pathway might play a role in TSH effect on osteoblasts. The expression and direct skeletal effect of a biologically active splice variant of TSHβ subunit (TSHβv) in bone-marrow-derived macrophage and other immune cells suggest local skeletal effect of TSHR. Further studies of how locally secreted TSHβv and systemic TSHβ interact in skeletal remodeling through the endocrine, immune and skeletal system will help us better understand the hyperthyroidism-induced bone disease.

Bone circuitry and interorgan skeletal crosstalk

“…Furthermore, induction of an iatrogenic hyperthyroid state in mice supplementing T4 caused profoundly higher bone loss in mice without the TSHR compared with wild type mice ( Baliram et al, 2012 ). This preclinical data is consistent with strong negative correlations between low serum TSH levels and bone turnover markers, bone mineral density and fracture risk from several population-based observational studies ( Aubert et al, 2017 ; Kim et al, 2006 ; Kim et al, 2021 ; Morris, 2007 ).…”

Biofortification: Effect of Iodine Fortified Food in the Healthy Population, Double-Arm Nutritional Study

“…Thus, vitamin D, calcium, and potassium are involved in the action mechanism that improves bone turnover ( 36 , 37 ). In addition, it is known that thyroid hormones have a strong effect on bone metabolism and osteoporosis ( 38 ).…”

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study of Jianyao Migu Granules in the Treatment of Osteopenic Low Back Pain

“…The present study found that the TSH levels were significantly higher in the JYMGG group than the placebo group. Population-based observations show that bone mass is correlated with the TSH level 30 and TSH receptors are expressed in a large number of osteoblast precursor cells and osteoclasts; thus, TSH regulates osteoblast bone formation and osteoclast bone absorption through different intracellular signals. 31 , 32 TSH promotes the proliferation and differentiation of osteoblasts.…”