The Effect of Recombinant Human TSH on Sclerostin and Other Selected Bone Markers in Patients after Total Thyroidectomy for Differentiated Thyroid Cancer.

Arkadiusz Zygmunt,Elżbieta Skowrońska-Jóźwiak,Andrzej Lewiński,Kinga Krawczyk-Rusiecka,Ewa Głowacka,Zbigniew Adamczewski,Katarzyna Wojciechowska-Durczyńska

doi:10.3390/jcm10214905

Abstract

The direct effect of TSH on bone metabolism in vivo is difficult to capture as the changes of its concentrations are followed by respective alterations of thyroid hormone levels. We evaluated the effect of recombinant human TSH (rhTSH) on sclerostin and other bone markers in 29 patients after total thyroidectomy for differentiated thyroid cancer (DTC), without any signs of disease recurrence, who received L-thyroxine, most at non-suppressive doses. For two consecutive days, the patients were administered a standard dose of 0.9 mg rhTSH, i.m. Concentrations of sclerostin, osteocalcin, β-CrossLaps, PTH, and some other parameters, were measured before and five days after the first rhTSH administration. The greater the increase in TSH concentration (∆TSH), the greater the decrease in: ∆sclerostin (r = −0.672; p < 0.001), ∆β-CrossLaps (r = −0.580; p < 0.001) and ∆osteocalcin (r = −0.405; p = 0.029) levels, were recorded. The degree of TSH increase depended on the baseline PTH (r = 0.651; p < 0.001), age, and creatinine concentrations. rhTSH strongly inhibited bone turnover, thus, TSH—independently of thyroid hormones—exerted a direct protective effect on bone metabolism. Baseline PTH affected the magnitude of TSH increase and the degree of lowering in sclerostin and β-CrossLaps that suggest factors affecting PTH may play a role in the effect of TSH on the bone.

Highlights

Since Inoueet et al [1] and Abe et al [2] have demonstrated the presence of TSH receptors in osteoblasts and osteoclasts, the potential role of TSH in bone remodeling has been considered
TSH receptors are present in chondrocytes [3], but they have not been found on osteocytes, so far
It is postulated that TSH has an inhibitory effect on chondrocytes and osteoblasts, as well [4]

Summary

Introduction

Since Inoueet et al [1] and Abe et al [2] have demonstrated the presence of TSH receptors in osteoblasts and osteoclasts, the potential role of TSH in bone remodeling has been considered. TSH receptors are present in chondrocytes [3], but they have not been found on osteocytes, so far. Most studies indicate that TSH inhibits osteoclast differentiation and function. It is postulated that TSH has an inhibitory effect on chondrocytes and osteoblasts, as well [4]. TSH inhibits bone metabolism and plays a protective role for the bone [1,5]. It has been shown that sclerostin: (1) inhibits proliferation and differentiation of pre-osteoblastic cells, as well as decreases activation of mature osteoblast; (2) stimulates bone resorption and decreases mineralization;

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Methods

Conclusion