CALCIUM-PHOSPHATE HOMEOSTASIS DISTURBANCES IN PEDIATRIC PATIENTS WITH CHRONIC GASTROINTESTINAL DISORDERS: CLINICAL MANIFESTATIONS AND PATHOGENETIC MECHANISMS
DOI:
https://doi.org/10.37547/Keywords:
calcium-phosphate metabolism, chronic gastrointestinal diseases, children, malabsorption, inflammatory bowel disease, chronic gastroduodenitis, vitamin D, parathyroid hormone, osteopenia, pediatric gastroenterology, bone mineral density.Abstract
Disturbances of calcium-phosphate metabolism represent a clinically significant and frequently underrecognized complication of chronic gastrointestinal (GI) diseases in children; however, the pathogenetic mechanisms underlying these disturbances across different nosological entities remain incompletely characterized. The present prospective comparative study examined clinical manifestations and laboratory markers of calcium-phosphate homeostasis in 72 children with chronic GI diseases admitted to the National Children's Medical Center (NCMC, Tashkent, Uzbekistan). Patients were stratified into three groups according to their primary diagnosis: chronic gastroduodenitis (CGD), inflammatory bowel disease (IBD), and malabsorption syndrome (MAS). The severity of calcium-phosphate homeostasis disturbances was found to increase progressively in the sequence CGD → IBD → MAS and was determined both by the degree of mucosal inflammatory involvement and by the depth of nutrient absorption impairment. Vitamin D deficiency was documented in 17.9%, 54.2%, and 80.0% of patients in the CGD, IBD, and MAS groups, respectively. Secondary hyperparathyroidism was identified in 7.1%, 41.7%, and 65.0% of patients, while reduced bone mineral density (BMD) was detected in 10.7%, 37.5%, and 70.0% of cases. The strongest predictors of BMD reduction were serum 25(OH)D (r = 0.72), parathyroid hormone (r = −0.68), and ionized calcium (r = 0.64). The identified clinicopathogenetic patterns provide a scientific basis for developing differentiated approaches to the diagnosis and correction of mineral metabolism disturbances in this patient population.
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1. Benchimol E.I., Fortinsky K.J., Gozdyra P., Van den Heuvel M., Van Limbergen J., Griffiths A.M. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends // Inflammatory Bowel Diseases — 2011. — Vol. 17, № 1. — P. 423–439. https://doi.org/10.1002/ibd.21349
2. Christakos S., Dhawan P., Verstuyf A., Verlinden L., Carmeliet G. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects // Physiological Reviews — 2016. — Vol. 96, № 1. — P. 365–408. https://doi.org/10.1152/physrev.00014.2015
3. de Bie C.I., Paerregaard A., Kolacek S., Ruemmele F.M., Koletzko S., Fell J.M., Escher J.C. Disease phenotype at diagnosis in pediatric Crohn's disease: 5-year analyses of the EUROKIDS Registry // Inflammatory Bowel Diseases — 2013. — Vol. 19, № 2. — P. 378–385. https://doi.org/10.1002/ibd.22834
4. Fabri M., Stenger S., Shin D.M., Yuk J.M., Liu P.T., Realegeno S., Jo E.K., Krutzik S.R., Modlin R.L. Vitamin D is required for IFN-γ-mediated antimicrobial activity of human macrophages // Science Translational Medicine — 2011. — Vol. 3, № 104. — P. 104ra102. https://doi.org/10.1126/scitranslmed.3003045
5. Guarino A., Ashkenazi S., Gendrel D., Lo Vecchio A., Shamir R., Szajewska H. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe // *Journal of Pediatric Gastroenterology and Nutrition*. — 2014. — Vol. 59, № 1. — P. 132–152. https://doi.org/10.1097/MPG.0000000000000375
6. Holick M.F., Binkley N.C., Bischoff-Ferrari H.A., Gordon C.M., Hanley D.A., Heaney R.P., Murad M.H., Weaver C.M. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline // *Journal of Clinical Endocrinology & Metabolism*. — 2011. — Vol. 96, № 7. — P. 1911–1930. https://doi.org/10.1210/jc.2011-0385
7. Huybers S., Naber T.H., Bindels R.J., Hoenderop J.G. Prednisolone-induced Ca²⁺ malabsorption is caused by diminished expression of the epithelial Ca²⁺ channel TRPV6 // *American Journal of Physiology — Gastrointestinal and Liver Physiology*. — 2007. — Vol. 292, № 1. — P. G92–G97. https://doi.org/10.1152/ajpgi.00317.2006
8. Laass M.W., Schmitz R., Uhlig H.H., Zimmer K.P., Koletzko S., Posovszky C. The prevalence of celiac disease in children and adolescents in Germany // *Deutsches Ärzteblatt International*. — 2015. — Vol. 112, № 33–34. — P. 553–560. https://doi.org/10.3238/arztebl.2015.0553
9. Levin A.D., Wadhera V., Leach S.T., Woodhead H.J., Lemberg D.A., Mendoza-Cruz A.C., Day A.S. Vitamin D deficiency in children with inflammatory bowel disease // *Digestive Diseases and Sciences*. — 2011. — Vol. 56, № 3. — P. 830–836. https://doi.org/10.1007/s10620-010-1544-3
10. Lionetti E., Catassi C. New clues in celiac disease epidemiology, pathogenesis, clinical manifestations, and treatment // *International Reviews of Immunology*. — 2011. — Vol. 30, № 4. — P. 219–231. https://doi.org/10.3109/08830185.2011.602443
11. Pappa H.M., Grand R.J., Gordon C.M. Report on the vitamin D status of adult and pediatric patients with inflammatory bowel disease and its significance for bone health and disease // *Inflammatory Bowel Diseases*. — 2006. — Vol. 12, № 12. — P. 1162–1174. https://doi.org/10.1097/01.mib.0000236929.74040.b0
12. Shamir R., Phillip M., Levine A. Growth retardation in pediatric Crohn's disease: pathogenesis and interventions // *Inflammatory Bowel Diseases*. — 2007. — Vol. 13, № 5. — P. 620–628. https://doi.org/10.1002/ibd.20115
13. Sylvester F.A., Wyzga N., Hyams J.S., Davis P.M., Lerer T., Vance K., Hawker G., Griffiths A.M. Natural history of bone metabolism and bone mineral density in children with inflammatory bowel disease // *Inflammatory Bowel Diseases*. — 2007. — Vol. 13, № 1. — P. 42–50. https://doi.org/10.1002/ibd.20006
14. Turner D., Ruemmele F.M., Orlanski-Meyer E., Griffiths A.M., de Carpi J.M., Bronsky J., Veres G., Aloi M., Strisciuglio C., Braegger C.P., Assa A. Management of paediatric ulcerative colitis, part 1: ambulatory care // Journal of Pediatric Gastroenterology and Nutrition — 2018. — Vol. 67, № 2. — P. 257–291. https://doi.org/10.1097/MPG.0000000000002035
15. Zanchetta M.B., Longobardi V., Bai J.C. Bone and celiac disease // Current Osteoporosis Reports — 2016. — Vol. 14, № 2. — P. 43–48. https://doi.org/10.1007/s11914-016-0304-5
