Correlation between serum SOST，CHI3L1 and CYR61 levels and bone metabolism in patients with hyperthyroidism

doi:10.3969/j.issn.1673-8640.2026.07.006

Abstract

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

CLC Number:

R446.1

ZHANG Xue, LI Yue, CHE Yongjun, ZHOU Xiaohong. Correlation between serum SOST，CHI3L1 and CYR61 levels and bone metabolism in patients with hyperthyroidism[J]. Laboratory Medicine, 2026, 41(7): 650-656.

Figures/Tables 8

References 20

[1]	Chaker L, Cooper D S, Walsh J P, et al. Hyperthyroidism[J]. Lancet, 2024, 403(10428):768-780. DOI URL
[2]	Alam A, Sofi G, Quamri A. The perspective of unani medicine in understanding hyperthyroidism[J]. Altern Ther Health Med, 2023, 29(7):262-267.
[3]	Branstetter R M 4th, Islam R K, Toups C A, et al. Mechanisms and treatment options for hyperthyroid-induced osteoporosis:a narrative review[J]. Cureus, 2023, 15(11):e48798.
[4]	Jin J, Huang R, Chang Y, et al. Roles and mechanisms of optineurin in bone metabolism[J]. Biomed Pharmacother, 2024, 172:116258. DOI URL
[5]	Wu D, Li L, Wen Z, et al. Romosozumab in osteoporosis:yesterday,today and tomorrow[J]. J Transl Med, 2023, 21(1):668. DOI
[6]	Park K R, Park J I, Lee S, et al. Chi3L1 is a therapeutic target in bone metabolism and a potential clinical marker in patients with osteoporosis[J]. Pharmacol Res, 2022, 184:106423. DOI URL
[7]	Lang A, Eastburn E A, Younesi M, et al. CYR61 delivery promotes angiogenesis during bone fracture repair[J]. NPJ Regen Med, 2025, 10(1):20. DOI PMID
[8]	卢秀波, 田文, 姜可伟, 等. 甲状腺功能亢进症外科治疗中国专家共识(2020版)[J]. 中国实用外科杂志, 2020, 40(11):1229-1233. DOI
[9]	中华医学会骨质疏松和骨矿盐疾病分会, 章振林, 夏维波, 等. 原发性骨质疏松症诊疗指南(2022)[J]. 中华内分泌代谢杂志, 2023, 39(5):377-406.
[10]	宋云霄, 童巍, 张海晨, 等. 系统性炎症指标与老年骨质疏松症患者骨折发生的相关性[J]. 检验医学, 2022, 37(3):235-239. DOI
[11]	Marini F, Giusti F, Palmini G, et al. Role of Wnt signaling and sclerostin in bone and as therapeutic targets in skeletal disorders[J]. Osteoporos Int, 2023, 34(2):213-238. DOI
[12]	Sheng R, Cao M, Song M, et al. Muscle-bone crosstalk via endocrine signals and potential targets for osteosarcopenia-related fracture[J]. J Orthop Translat, 2023, 43:36-46. DOI URL
[13]	任艳霞, 李军, 李思源, 等. 绝经后2型糖尿病患者血清骨硬化蛋白表达与骨密度关系的研究[J]. 中国糖尿病杂志, 2021, 29(9):683-687.
[14]	Gao J, Xiang S, Wei X, et al. Icariin promotes the osteogenesis of bone marrow mesenchymal stem cells through regulating sclerostin and activating the Wnt/β-Catenin signaling pathway[J]. Biomed Res Int, 2021, 2021:6666836. DOI URL
[15]	Xu W, Chao R, Xie X, et al. IL13Rα2 as a crucial receptor for Chi3l1 in osteoclast differentiation and bone resorption through the MAPK/AKT pathway[J]. Cell Commun Signal, 2024, 22(1):81. DOI PMID
[16]	朱瑞, 马洪川, 陈华玲, 等. 2型糖尿病合并骨质疏松症患者血清Chi3L1 NEFAs与糖脂代谢及骨密度的相关性[J]. 河北医学, 2024, 30(3):448-453.
[17]	Hsu G C, Marini S, Negri S, et al. Endogenous CCN family member WISP1 inhibits trauma-induced heterotopic ossification[J]. JCI Insight, 2020, 5(13):e135432. DOI URL
[18]	杜娟, 卢晓丽, 张雪, 等. 弥漫性毒性甲状腺肿患者血清高半胱氨酸蛋白61及Fractalkine水平的表达及其临床意义[J]. 现代生物医学进展, 2022, 22(20):3987-3990.
[19]	Marinkovic M, Dai Q, Gonzalez A O, et al. Matrix-bound Cyr61/CCN1 is required to retain the properties of the bone marrow mesenchymal stem cell niche but is depleted with aging[J]. Matrix Biol, 2022, 111:108-132. DOI PMID
[20]	王方, 张欢, 付志远, 等. 血清CYR61、IL-17、Klotho蛋白对Graves眼病病情的评估价值[J]. 分子诊断与治疗杂志, 2024, 16(6):1165-1168.

组别	例数	SOST/（ng·mL^-1）	CHI3L1/（ng·mL^-1）	CYR61/（ng·mL^-1）	每日平均膳食维生素D摄入量/（IU·d^-1）
正常对照组	162	1.25±0.24	0.91±0.18	2.14±0.51	118.95±29.63
甲亢组	162	2.96±0.53	0.56±0.12	3.75±0.67	125.64±35.31
t值		37.409	20.592	24.337	1.847
P值		<0.001	<0.001	<0.001	0.066

组别	例数	SOST/（ng·mL^-1）	CHI3L1/（ng·mL^-1）	CYR61/（ng·mL^-1）	每日平均膳食维生素D摄入量/（IU·d^-1）
正常对照组	162	1.25±0.24	0.91±0.18	2.14±0.51	118.95±29.63
甲亢组	162	2.96±0.53	0.56±0.12	3.75±0.67	125.64±35.31
t值		37.409	20.592	24.337	1.847
P值		<0.001	<0.001	<0.001	0.066

组别	例数	血磷/（mmol·L^-1）	血钙/（mmol·L^-1）	25（OH）D/（ng·mL^-1）	PTH/（pg·mL^-1）	B-ALP/（μg·L^-1）	P1NP/（pg·mL^-1）	β-CTX/（ng·mL^-1）
正常对照组	162	1.15±0.16	2.37±0.32	22.34±4.39	22.51±6.31	1.68±0.32	47.52±12.57	0.51±0.11
甲亢组	162	1.34±0.24	2.63±0.45	16.51±3.57	39.84±7.58	3.84±1.15	115.36±31.25	0.94±0.23
t值		8.384	5.993	13.114	22.365	23.031	25.635	21.467
P值		<0.001	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001

组别	例数	血磷/（mmol·L^-1）	血钙/（mmol·L^-1）	25（OH）D/（ng·mL^-1）	PTH/（pg·mL^-1）	B-ALP/（μg·L^-1）	P1NP/（pg·mL^-1）	β-CTX/（ng·mL^-1）
正常对照组	162	1.15±0.16	2.37±0.32	22.34±4.39	22.51±6.31	1.68±0.32	47.52±12.57	0.51±0.11
甲亢组	162	1.34±0.24	2.63±0.45	16.51±3.57	39.84±7.58	3.84±1.15	115.36±31.25	0.94±0.23
t值		8.384	5.993	13.114	22.365	23.031	25.635	21.467
P值		<0.001	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001

项目	SOST		CHI3L1		CYR61
项目	r值	P值	r值	P值	r值	P值
血磷	0.516	0.003	-0.511	0.006	0.528	0.001
血钙	0.504	0.005	-0.521	0.002	0.497	0.032
25（OH）D	-0.527	0.001	0.532	0.008	-0.503	0.002
PTH	0.523	0.007	-0.694	<0.001	0.522	0.002
B-ALP	0.605	<0.001	-0.517	0.002	0.504	0.008
P1NP	0.543	0.001	-0.498	0.031	0.621	<0.001
β-CTX	0.501	0.001	-0.509	0.004	0.613	<0.001