Journal of Pediatric Perspectives

Journal of Pediatric Perspectives

Relationship between Levels of Inflammatory Markers NLR, PLR, and MLR with Bone Mineral Density in Children with Thyroid Disorders

Document Type : original article

Authors
1 Department of Pediatrics, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
2 Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
3 Department of Biostatistics, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
10.22038/jpp.2026.95970.5669
Abstract
Background: Thyroid disorders affect bone metabolism and reduce bone mineral density (BMD) in children. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are simple inflammatory markers, but their association with BMD in children with thyroid disorders is unclear. This study assessed the relationship between NLR, PLR, MLR, and BMD in affected children.
Materials and Methods: This retrospective cross-sectional study included 128 children (63 hypothyroid, 30 hyperthyroid, 35 controls) who had undergone DXA scanning. Thyroid function tests, complete blood count, calcium, phosphorus, and alkaline phosphatase were extracted from records. NLR, PLR, and MLR were calculated from complete blood count (CBC). BMD was measured by DXA and reported as Z-scores. Statistical analysis used ANOVA, correlation, and linear regression with adjustment for confounders.
Results: Mean BMD Z-scores in the hypothyroid group were significantly lower than controls at the lumbar spine (-0.70 ± 0.73 vs. -0.27 ± 0.77, P = 0.001) and femoral neck (-0.74 ± 0.74 vs. -0.35 ± 0.77, P = 0.003). In hypothyroid children, significant positive correlations were observed between all three indices and BMD Z-scores (NLR: r = 0.508, PLR: r = 0.575, MLR: r = 0.660; all P < 0.001). No significant correlations were found in hyperthyroid or control groups. In multiple regression adjusted for age, sex, and thyroid hormones, MLR was the strongest independent predictor of lumbar spine BMD (Beta = 0.357, P = 0.002), followed by NLR (Beta = 0.312, P = 0.003) and PLR (Beta = 0.228, P = 0.048). The model explained 41.8% of BMD variance (R² = 0.418, P < 0.001).
Conclusion: These findings demonstrate an association between systemic inflammation and reduced BMD in hypothyroid children, though the positive correlation direction requires further investigation. NLR, PLR, and MLR, easily calculated from routine CBC, are inexpensive tools for assessing bone health. Regular BMD screening is recommended for hypothyroid children, especially those with elevated inflammatory markers.
Key Words: Bone mineral density, children, Monocyte-to-lymphocyte ratio, Neutrophil-to-lymphocyte ratio, Platelet-to-lymphocyte ratio, Thyroid disorders.
Keywords

1. Bassett JD, Williams GR. Role of thyroid hormones in skeletal development and bone maintenance. Endocrine reviews. 2016 Apr 1;37(2):135-87.
2. Williams GR, Bassett JD. Thyroid diseases and bone health. Journal of endocrinological investigation. 2018 Jan;41(1):99-109.
3. Zhu S, Pang Y, Xu J, Chen X, Zhang C, Wu B, et al. Endocrine regulation on bone by thyroid. Frontiers in endocrinology. 2022 Apr 5;13:873820.
4. Mundy GR. Osteoporosis and inflammation. Nutrition reviews. 2007 Dec 1;65(suppl_3):S147-51.
5. Chen S, Sun X, Jin J, Zhou G, Li Z. Association between inflammatory markers and bone mineral density: a cross-sectional study from NHANES 2007–2010. Journal of Orthopaedic Surgery and Research. 2023 Apr 17;18(1):305.
6. Barbour KE, Boudreau R, Danielson ME, Youk AO, Wactawski‐Wende J, Greep NC, et al. Inflammatory markers and the risk of hip fracture: the Women's Health Initiative. Journal of bone and mineral research. 2012 May 1;27(5):1167-76.
7. Williams GR. Neurodevelopmental and neurophysiological actions of thyroid hormone. Journal of neuroendocrinology. 2008 Jun;20(6):784-94.
8. Bala MM, Bala KA. Bone mineral density (BMD) and neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) in childhood thyroid diseases. Eur Rev Med Pharmacol Sci. 2022 Mar 1;26(6):1945-51.
9. Lee D, Ahn MB. A causality between thyroid function and bone mineral density in childhood: Abnormal thyrotropin may be another pediatric predictor of bone fragility. Metabolites. 2023 Mar 2;13(3):372.
10. Öztürk ZA, Yesil Y, Kuyumcu ME, Bilici M, Öztürk N, Yeşil NK, et al. Inverse relationship between neutrophil lymphocyte ratio (NLR) and bone mineral density (BMD) in elderly people. Archives of gerontology and geriatrics. 2013 Jul 1;57(1):81-5.
11. Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiological reviews. 2014 Apr;94(2):355-82.
12. Fu Q, Zhang C, Yang Y, Teng R, Liu F, Liu P, et al. Correlation study of multiple inflammatory indices and vertebral compression fracture: a cross-sectional study. Journal of Clinical & Translational Endocrinology. 2024 Sep 1;37:100369.
13. Zhang XJ, Zhao H, Zhang D, Ye DD, Qin J, Zhou YR, et al. Blood cell count-derived inflammation indices as predictors of the osteoporotic risk of postmenopausal women. European Review for Medical & Pharmacological Sciences. 2024 Mar 15;28(6).
14. Xue Y, Bao W, Huang W, Zou X, Guo Y. Relationship between neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio and osteoporosis in postmenopausal type 2 diabetic patients: a retrospective study. Medicine. 2024 Dec 13;103(50):e40869.
15. Turkmen K, Erdur FM, Ozcicek F, Ozcicek A, Akbas EM, Ozbicer A, et al. Platelet‐to‐lymphocyte ratio better predicts inflammation than neutrophil‐to‐lymphocyte ratio in end‐stage renal disease patients. Hemodialysis International. 2013 Jul;17(3):391-6.
16. Al Salmani A, Al Shidhani A, Al-Alawi NM, Al Sulaimi AA, Al-Hashemi MA. Inflammatory markers as a predictor of postmenopausal osteoporosis: cross-sectional study from sultan qaboos university hospital. Sultan Qaboos University Medical Journal. 2022 Nov 7;22(4):508.

Articles in Press, Accepted Manuscript
Available Online from 02 August 2026