关键词: 骨硬化蛋白, 壳多糖酶3样蛋白1, 高半胱氨酸蛋白61, 骨代谢, 甲状腺功能亢进, 骨质疏松症

Abstract:

Objective To investigate the clinical value of serum sclerostin（SOST），chitinase-3-like protein 1（CHI3L1）and cysteine-rich protein 61（CYR61）levels in patients with hyperthyroidism（HT）secondary to osteoporosis（OP）. Methods A total of 162 HT patients（HT group）and 162 healthy subjects（healthy control group）were enrolled from Handan Central Hospital from January 2022 to July 2024. Based on bone density measurements，HT patients were classified into 3 groups：normal bone mass（55 cases），low bone mass（50 cases）and OP（57 cases）. The clinical data，thyroid function indicators and lipid profiles were collected. Serum SOST，CHI3L1，CYR61 levels and bone metabolism markers，including 25-hydroxyvitamin D [25（OH）D]，parathyroid hormone （PTH），type Ⅰ procollagen N-terminal propeptide（P1NP），beta-collagen crosslaps（β-CTX）and bone-derived alkaline phosphatase（B-ALP），were determined. Pearson correlation analysis was used to assess the correlations between serum SOST，CHI3L1，CYR61 levels and bone metabolism markers. Multivariate Logistic regression analysis was performed to identify risk factors for OP in HT patients. Receiver operating characteristic（ROC）curves were used to evaluate the diagnostic performance of each marker for HT secondary to OP. Results Compared with healthy control group，the HT group showed higher serum levels of SOST，CYR61，blood phosphorus，calcium，PTH，B-ALP，P1NP and β-CTX（P<0.001），and lower levels of CHI3L1 and 25（OH）D（P<0.001）. Blood phosphorus，calcium，PTH，B-ALP，P1NP and β-CTX were positively correlated with serum SOST and CYR61（P<0.05）but negatively correlated with CHI3L1（P<0.05）. 25（OH）D was negatively correlated with SOST and CYR61（P<0.05），but positively correlated with CHI3L1（P<0.05）. Serum levels of SOST，CYR61，blood phosphorus，calcium，PTH，B-ALP，P1NP，β-CTX，free triiodothyronine（FT₃），free thyroxine（FT₄）and thyrotropin receptor antibody（TRAb）increased in turn among normal bone mass，low bone mass and OP groups（P<0.001），while CHI3L1 and 25（OH）D levels decreased in turn（P<0.001）. No statistical significance were observed among the 3 groups regarding other clinical parameters（P>0.05）. After adjusting for FT₃，FT₄ and TRAb，increased SOST and CYR61 levels and decreased CHI3L1 level were independent risk factors for OP in HT patients（P<0.01）. The areas under curves（AUC）for single and combined determinations of serum SOST，CHI3L1 and CYR61 in diagnosing HT secondary to OP were 0.826，0.831，0.805 and 0.961，respectively. Conclusions Serum levels of SOST，CHI3L1 and CYR61 are correlated with bone metabolism markers in HT patients，and their combined determination offers high diagnostic efficacy for HT secondary to OP.

Key words: Sclerostin, Chitinase-3-like protein 1, Cysteine-rich protein 61, Bone metabolism, Hyperthyroidism, Osteoporosis