Abstract

Vitamin D and calcium metabolism are central to skeletal growth, mineralisation, and metabolic bone homeostasis in childhood, making laboratory assessment of these nutrients critical in pediatric bone disorders such as nutritional rickets, osteomalacia, metabolic bone disease of prematurity, chronic kidney diseaserelated mineral bone disorder, and selected inherited or malabsorptive conditions. Interpretation of laboratory markers in children is more difficult than in adults because normal values vary with age, growth velocity, pubertal stage, dietary intake, sun exposure, and underlying disease, while available diagnostic thresholds are not uniformly standardized across pediatric populations. Serum 25-hydroxyvitamin D is the preferred marker of vitamin D status. Still, its clinical meaning depends on simultaneous interpretation of calcium, phosphate, alkaline phosphatase, parathyroid hormone, renal function, and radiologic findings, particularly when bone disease is suspected. Additional complexity arises from assay variability, age-specific differences in reference intervals, and the overlap between calciopenic and phosphopenic disorders. This review summarizes the physiology of vitamin D-calcium-phosphate regulation, outlines key biochemical patterns in common pediatric bone disorders, analyzes major laboratory interpretation pitfalls, and summarizes practical strategies for more accurate diagnosis and monitoring in children.

• 1.   Moon, R. J., Harvey, N. C., Davies, J. H., & Cooper, C. (2014). Vitamin D and skeletal health in infancy and childhood. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 25(12), 2673–2684. https://doi.org/10.1007/s00198- 014-2783-5
• 2.   Palacios, C., & Gonzalez, L. (2014). Is vitamin D deficiency a major global public health problem?. The Journal of steroid biochemistry and molecular biology, 144 Pt A, 138–145. https://doi.org/10.1016/j.jsbmb.2013.11.003
• 3.   Gupta, P., Dabas, A., Seth, A., Bhatia, V. L., Khadgawat, R., Kumar, P., Balasubramanian, S., Khadilkar, V., Mallikarjuna, H. B., Godbole, T., Krishnamurthy, S., Goyal, J. P., Bhakhri, B. K., Ahmad, A., Angadi, K., Basavaraj, G. V., Parekh, B. J., Kurpad, A., Marwaha, R. K., Shah, D., … Sachdev, H. P. S. (2022). Indian Academy of Pediatrics Revised (2021) Guidelines on Prevention and Treatment of Vitamin D Deficiency and Rickets. Indian pediatrics, 59(2), 142–158.
• 4.   Kamboj, P., Dwivedi, S., & Toteja, G. S. (2018). Prevalence of hypovitaminosis D in India & way forward. The Indian journal of medical research, 148(5), 548–556. https://doi. org/10.4103/ijmr.IJMR_1807_18
• 5.   Munns, C. F., Shaw, N., Kiely, M., Specker, B. L., Thacher, T. D., Ozono, K., Michigami, T., Tiosano, D., Mughal, M. Z., Mäkitie, O., RamosAbad, L., Ward, L., DiMeglio, L. A., Atapattu, N., Cassinelli, H., Braegger, C., Pettifor, J. M., Seth, A., Idris, H. W., Bhatia, V., … Högler, W. (2016). Global Consensus Recommendations on Prevention and Management of Nutritional Rickets. Hormone research in paediatrics, 85(2), 83–106. https://doi.org/10.1159/000443136
• 6.   Vitamin D deficiency in children: An update on its prevalence, therapeutics and knowledge gaps. (n.d.). https://www. opensciencepublications.com/fulltextarticles/ IJN-2395-2326-4-167.pdf
• 7.   Pettifor J. M. (2014). Calcium and vitamin D metabolism in children in developing countries. Annals of nutrition & metabolism, 64 Suppl 2, 15–22. https://doi.org/10.1159/000365124
• 8.   Allgrove, J. (2015). Calcium and bone disorders in children and adolescents. In Endocrine development. https://doi.org/10.1159/ isbn.978-3-318-05467-5
• 9.   Uday, S., & Högler, W. (2020). Nutritional rickets & osteomalacia: A practical approach to management. The Indian journal of medical research, 152(4), 356–367. https://doi. org/10.4103/ijmr.IJMR_1961_19
• 10.   Rustico, S. E., Calabria, A. C., & Garber, S. J. (2014). Metabolic bone disease of prematurity. Journal of clinical & translational endocrinology, 1(3), 85–91. https://doi. org/10.1016/j.jcte.2014.06.004
• 11.   Patel P, Hashmi MF. Chronic Kidney DiseaseMineral Bone Disorder (CKD-MBD) [Updated 2024 Apr 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih. gov/books/NBK560742/
• 12.   Abseyi, S. N., & Şıklar, Z. (2023). Approach to Rickets: Is It Calciopenic or Phosphopenic?. Turkish archives of pediatrics, 58(5), 458–466. https://doi.org/10.5152/TurkArchPediatr. 2023.23050
• 13.   Alsaif, S., Aljarbou, T., Alrahili, M., Alsherbini, L., Maghoula, M., Alluwaymi, A., Alsenani, M., Altuwaym, A., Alamer, F., Mandurah, A., Baylon, B., Alsehli, F., Ali, I., & Ali, K. (2025). Biochemical markers for metabolic bone disease in preterm infants: insights from a structured Bone Health Programme in the Middle East. BMJ paediatrics open, 9(1), e003927. https:// doi.org/10.1136/bmjpo-2025-003927.
• 14.   Corsello, A., Spolidoro, G. C. I., Milani, G. P., & Agostoni, C. (2023). Vitamin D in pediatric age: Current evidence, recommendations, and misunderstandings. Frontiers in medicine, 10, 1107855. https://doi.org/10.3389/ fmed.2023.1107855.
• 15.   Liju Yang, Vijaylaxmi Grey, Pediatric reference intervals for bone markers, Clinical Biochemistry, Volume 39, Issue 6, 2006, Pages 561-568, ISSN 0009-9120, https://doi. org/10.1016/j.clinbiochem.2005.11.015.
• 16.   Shao, J., Zhou, S. S., Qu, Y., Liang, B. B., Yu, Q. H., & Wu, J. (2020). Correlation between bone turnover and metabolic markers with age and gender: a cross-sectional study of hospital information system data. BMC musculoskeletal disorders, 21(1), 603. https://doi.org/10.1186/ s12891-020-03610-w
• 17.   Weitzmann, M. N., & Ofotokun, I. (2016). Physiological and pathophysiological bone turnover - role of the immune system. Nature reviews. Endocrinology, 12(9), 518–532. https://doi.org/10.1038/nrendo.2016.91
• 18.   Sempos, C. T., & Binkley, N. (2020). 25-Hydroxyvitamin D assay standardisation and vitamin D guidelines paralysis. Public health nutrition, 23(7), 1153–1164. https://doi. org/10.1017/S1368980019005251
• 19.   Hu, Z. D., Huang, Y. L., Wang, M. Y., Hu, G. J., & Han, Y. Q. (2018). Predictive accuracy of serum total calcium for both critically high and critically low ionized calcium in critical illness. Journal of clinical laboratory analysis, 32(9), e22589. https://doi.org/10.1002/jcla.22589
• 20.   Binkovitz, L. A., & Henwood, M. J. (2007). Pediatric DXA: technique and interpretation. Pediatric radiology, 37(1), 21–31. https://doi. org/10.1007/s00247-006-0153-y
• 21.   Jacqueline-Michéle Strauch, Mandy Vogel, Christof Meigen, Uta Ceglarek, Jürgen Kratzsch, Anja Willenberg, Wieland Kiess, Pediatric reference values of alkaline phosphatase: Analysis from a German population-based cohort and influence of anthropometric and blood parameters, Bone, Volume 174, 2023, 116809, ISSN 8756-3282, https://doi.org/10.1016/j.bone.2023.116809.
• 22.   Bharill, S., & Wu, M. (2023). Hypocalcemia and Hypercalcemia in Children. Pediatrics in review, 44(9), 533–536. https://doi. org/10.1542/pir.2022-005578
• 23.   Singh, R. J., Taylor, R. L., Reddy, G. S., & Grebe, S. K. (2006). C-3 epimers can account for a significant proportion of total circulating 25-hydroxyvitamin D in infants, complicating accurate measurement and interpretation of vitamin D status. The Journal of clinical endocrinology and metabolism, 91(8), 3055– 3061. https://doi.org/10.1210/jc.2006-0710
• 24.   ICMR-NIN Expert Committee, Dietary Guidelines for Indians-2024.
• 25.   Prevention and treatment of vitamin D and calcium deficiency in children and adolescents: Indian Academy of Pediatrics (IAP) guidelines. (n.d.). https://www.indianpediatrics.net/ july2017/july-567-573.htm
• 26.   Event. (2026, May 22). Early signs of rare bone conditions in children and adults. Dr. Umesh Jadhav. https://drumeshjadhav.com/earlysigns-of-rare-bone-conditions-in-childrenand-adults/
• 27.   Rodd, C., Kirouac, N., Orkin, J., & Grimes, R. (2022). Evaluating and optimizing bone health in children with chronic health conditions. Paediatrics & child health, 27(4), 232–242. https://doi.org/10.1093/pch/pxac036

Data Sharing Statement

Funding