Abstract
Background:
Hyperthyroidism disrupts bone metabolism, leading to increased bone turnover and potential loss of bone mineral density. Sclerostin, a key regulator of bone formation, may serve as a useful biomarker reflecting skeletal changes in thyroid dysfunction.
Objective:
To evaluate serum sclerostin levels in patients with hyperthyroidism and examine their correlation with thyroid hormone parameters—free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH).
Methods:
A case–control study was conducted at ACPM Medical College and Hospital, enrolling 30 hyperthyroid patients (including subclinical cases) and 30 age- and sex-matched healthy controls. Serum levels of sclerostin and thyroid hormones were measured using electrochemiluminescence immunoassay. Analysis of variance was used to compare sclerostin levels between groups, and Pearson correlation analysis assessed relationships between sclerostin and thyroid hormones.
Results:
Hyperthyroid patients exhibited lower mean serum sclerostin levels (1.2 ng/mL) compared to healthy controls (1.5 ng/mL), although the difference was not statistically significant (P = 0.48). Sclerostin showed a significant negative correlation with fT₃ (r = −0.45, P < 0.001) and fT₄ (r = −0.38, P = 0.002), and a positive correlation with TSH (r = 0.50, P < 0.001).
Conclusion:
Serum sclerostin levels are significantly associated with thyroid hormone status in hyperthyroid individuals. These findings suggest that sclerostin may serve as a potential biomarker for monitoring bone health in thyroid dysfunction. Further large-scale, longitudinal studies are warranted to confirm its diagnostic and prognostic utility.
Keywords: Biomarkers, bone metabolism, fT3, fT4, hyperthyroidism, sclerostin, thyroid hormones, TSH
INTRODUCTION
Thyroid disorders, particularly hypothyroidism and hyperthyroidism, adversely affect a variety of physiological systems, with bone metabolism emerging as a significant area of concern. Hyperthyroidism leads to augmented bone turnover, placing patients at an increased risk for fractures due to declining bone mineral density.[1] The synthesis and activity of thyroid hormones, chiefly thyroxine (T4) and triiodothyronine (T3), are fundamental to the modulation of various metabolic processes, including those governing bone health.[2]
Sclerostin plays a pivotal role in regulating bone remodeling by inhibiting Wnt signaling, which promotes osteoblast differentiation and bone formation. Thus, alterations in sclerostin levels may serve as a biomarker for disruptions in bone metabolism, particularly in individuals with thyroid dysfunction.[3] Research has demonstrated that sclerostin expression is significantly influenced by thyroid hormone levels; hence, understanding these interactions can illuminate the pathophysiology of hyperthyroidism-induced bone changes.[4]
Given the profound implications of thyroid dysfunction globally, with millions affected, our study aims to explore serum sclerostin levels in patients with hyperthyroidism. Furthermore, we seek to investigate the relationship between these levels and thyroid hormones (thyroid-stimulating hormone [TSH], free triiodothyronine [fT3], free thyroxine [fT4]), thereby evaluating their potential as diagnostic markers in the context of thyroid-related bone disorders.
MATERIALS AND METHODS
Study design and population
This study is a case–control investigation conducted at ACPM Medical College and Hospital in Dhule, Maharashtra, India. A total of 60 participants were recruited, comprising two groups:
Group 1: 30 patients diagnosed with hyperthyroidism or subclinical hyperthyroidism
Group 2: 30 age- and sex-matched healthy controls.
Data collection
Blood samples were collected to assess serum levels of thyroid hormones (TSH, fT3, and fT4) and sclerostin, utilizing electrochemiluminescence immunoassay (ECLIA) methodology. The patients underwent thorough clinical evaluations, including a comprehensive medical history to ascertain the duration of hyperthyroidism and any comorbid conditions.
Statistical analysis
Data were analyzed using analysis of variance (ANOVA) to compare biomarker levels between hyperthyroid patients and healthy controls. To explore the relationship between serum sclerostin and thyroid hormones, Pearson or Spearman correlation coefficients were employed, depending on the normal distribution of the data.
RESULTS
This study aimed to assess serum sclerostin levels in individuals with hyperthyroidism and investigate their correlation with thyroid hormone parameters (fT3, fT4, and TSH).
Comparison of serum sclerostin levels between study groups
ANOVA was conducted to compare mean serum sclerostin levels among three groups: patients with overt hyperthyroidism, patients with subclinical hyperthyroidism, and healthy controls. As presented in Table 1, the mean sclerostin concentration was lower in hyperthyroid (1.2 ng/mL) and subclinical hyperthyroid patients (1.3 ng/mL) compared to healthy controls (1.5 ng/mL). However, these differences were not statistically significant. The mean difference in sclerostin levels between hyperthyroid patients and controls was -0.3 ng/mL (95% confidence interval [CI]: −1.2 to 0.6; P = 0.48), and −0.2 ng/mL (95% CI: −1.0 to 0.6; P = 0.72) for subclinical hyperthyroidism versus controls.
Table 1.
Comparison of mean serum sclerostin levels between groups (analysis of variance test)
| Group | Mean sclerostin (ng/mL) | Mean difference versus controls (ng/mL) | 95% confidence interval | P |
|---|---|---|---|---|
| Healthy controls | 1.5 | – | – | – |
| Hyperthyroidism | 1.2 | −0.3 | −1.2-0.6 | 0.48 |
| Subclinical hyperthyroidism | 1.3 | −0.2 | −1.0-0.6 | 0.72 |
Correlation between sclerostin and thyroid hormone levels
Pearson correlation analysis was performed to explore the relationship between serum sclerostin concentrations and thyroid hormone levels. As detailed in Table 2, serum sclerostin levels showed a moderate negative correlation with free triiodothyronine (fT3) (r = −0.45, P < 0.001) and a weak-to-moderate negative correlation with free thyroxine (fT4) (r = −0.38, P = 0.002). In contrast, a moderate positive correlation was observed between sclerostin and TSH (r = 0.50, P < 0.001). These findings suggest that sclerostin levels are inversely associated with active thyroid hormones and directly associated with TSH levels.
Table 2.
Correlation between serum sclerostin and thyroid hormone levels
| Thyroid hormone | Pearson correlation (r) | P | Interpretatison |
|---|---|---|---|
| fT₃ | −0.45 | <0.001 | Moderate negative correlation |
| fT₄ | −0.38 | 0.002 | Weak-to-moderate negative correlation |
| TSH | 0.5 | <0.001 | Moderate positive correlation |
fT₃ = Free triiodothyronine, fT4=Free thyroxine, TSH=Thyroid-stimulating hormone
Figure 1 illustrates the scatter plots with regression lines depicting the correlations between serum sclerostin levels and thyroid hormones. The visual trends support the statistical findings: A negative correlation is observed between sclerostin and both fT3 and fT4. A positive correlation is noted between sclerostin and TSH.
Figure 1.
Correlation between serum sclerostin levels and thyroid hormones (fT3, fT4, and TSH) in study participants. fT₃ = Free triiodothyronine, fT4 = Free thyroxine, TSH = Thyroid-stimulating hormone
DISCUSSION
Our findings reveal important associations between serum sclerostin levels and thyroid function markers in hyperthyroid patients. In comparison with healthy controls, hyperthyroid patients exhibited lower serum sclerostin levels, aligning with prior studies that suggest hyperthyroidism is characterized by increased bone remodeling and, consequently, diminished sclerostin expression.[5]
The interplay between thyroid hormones and bone metabolism is critical, given the global rise in thyroid disorders. This study examined serum sclerostin levels in hyperthyroidism, evaluating their potential as diagnostic markers and their associations with thyroid hormones.[6]
Sclerostin levels across groups of patients with hyperthyroidism exhibited lower sclerostin levels compared to controls, consistent with increased bone turnover and resorption in hyperthyroidism. This reduction may enhance osteoblastic activity, contributing to bone mass loss and elevated fracture risk.[7] The findings align with studies, showing that high thyroid hormone levels suppress sclerostin expression.[8]
Understanding the relationship between thyroid hormone levels and sclerostin could provide valuable insights into developing targeted therapeutic strategies for managing hyperthyroid patients and preventing associated bone loss. Given that our study indicates significant correlations between serum sclerostin and thyroid hormones, future research with larger sample sizes may yield clearer implications for clinical practice and monitoring bone health in patients with thyroid dysfunction.
CONCLUSION
Our study establishes a significant association between serum sclerostin levels and thyroid hormones, highlighting sclerostin’s potential as a biomarker for assessing skeletal health in hyperthyroid patients.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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