Journal of Osh State University. Medicine
Journal of Osh State University. Medicine
e-ISSN 1694-8831
DOI: 10.52754/16948831
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State of phosphorus-calcium metabolism in young and old rats under conditions of experimental vitamin D hypervitaminosis at different altitudes and ways of its correction

Aiperi Keneshbek kyzy, Zhyldyz Makhmudova, Zhanyl Sapakunova

Received 22.05.2025, Revised 20.10.2025, Accepted 17.12.2025

Abstract

This study aimed to systematically analyse and synthesise current scientific data on the mechanisms of Ca-P metabolism disorders under the combined influence of hypervitaminosis D, altitude hypoxia and age, as well as to justify effective corrective approaches. Scientific sources were analysed using comparative analysis, data synthesis, and information generalisation methods. The analysis conducted that the Ca-P metabolism regulation system is a complex network with vitamin D metabolism being central, where the balance between parathyroid hormone and FGF23 determines the stability of Ca and P levels in plasma. Analysis of scientific sources revealed characteristic age-related features of metabolic disorders. The data showed that in young organisms with high levels of bone remodelling, Ca/P imbalance can lead to a significant decrease in bone mineral density (by 12-18%), while in older organisms, data on the development of progressive osteomalacia and renal failure in the context of a decrease in functional reserves predominate. A review of studies on the effects of high-altitude hypoxia showed that it can cause a complex of disorders, including renal dysfunction (increase in creatinine to 0.81 ± 0.04 mg/dL), electrolyte imbalance (decrease in calcium to 8.1 ± 0.6 mg/dL with an increase in phosphorus to 7.1 ± 0.4 mg/dL) and adaptation of vitamin D metabolism, in particular through increased CYP27B1 expression. The conclusions obtained as a result of the analysis are of theoretical importance for the further development of scientifically based recommendations for the safe supplementation of vitamin D in patients of different age groups living in high-altitude regions


Keywords:

parathyroid hormone; osteomalacia; high altitude hypoxia; age-related characteristics; renal failure

https://doi.org/10.52754/16948645_2025_4(2)_50

Retrieved from Vol. 4, No. 2, 2025

Pages 50-61

References Suggested citation

References

  1. Kolosovych IV, Hanol IV. The role of phosphorus-calcium homeostasis and vitamin D in the pathogenesis of acute pancreatitis and assessment of its severity. Physiol J. 2022;68(3):61–7. DOI: 10.15407/fz68.03.061
  2. Sun M, Wu X, Yu Y, Wang L, Xie D, Zhang Z, et al. Disorders of calcium and phosphorus metabolism and the proteomics/Metabolomics-based research. Front Cell Dev Biol. 2020;8:576110. DOI: 10.3389/fcell.2020.576110
  3. Çaykara B, Öztürk G, Mutlu HH, Arslan E. Relationship between vitamin D, calcium, and phosphorus levels. J Acad Res Med. 2020;10(3):252–7. DOI: 10.4274/jarem.galenos.2020.3351
  4. Bikle DD. Vitamin D: Newer concepts of its metabolism and function at the basic and clinical level. J Endocr Soc. 2020;4(2):bvz038. DOI: 10.1210/jendso/bvz038
  5. Bikle D, Christakos S. New aspects of vitamin D metabolism and action – addressing the skin as source and target. Nat Rev Endocrinol. 2020;16:234–52. DOI: 10.1038/s41574-019-0312-5
  6. Saponaro F, Saba A, Zucchi R. An update on vitamin D metabolism. Int J Mol Sci. 2020;21(18):6573. DOI: 10.3390/ijms21186573
  7. Papadopoulou A, Bountouvi E, Karachaliou FE. The molecular basis of calcium and phosphorus inherited metabolic disorders. Genes. 2021;12(5):734. DOI: 10.3390/genes12050734
  8. Shaikh NA, Chen JR, Baylink DJ, Tang X. Vitamin D-mediated regulation of intestinal stem cells 2297. J Immunol. 2025;214(1):vkaf283.232. DOI: 10.1093/jimmun/vkaf283.232
  9. Hossain A. Hypovitaminosis D: A modifiable risk factor for noncommunicable diseases [Master’s thesis]. Dhaka: BRAC University; 2022.
  10. Noonan ML. Linking osteocyte oxygen sensing and biomineralization via FGF23: Implications for chronic kidney disease [Doctoral dissertation]. Indianapolis: Indiana University-Purdue University Indianapolis; 2022.
  11. Zhang B, Podolskiy DI, Mariotti M, Seravalli J, Gladyshev VN. Systematic age‐, organ‐, and diet‐associated ionome remodeling and the development of ionomic aging clocks. Aging Cell. 2020;19(5):e13119. DOI: 10.1111/acel.13119
  12. Areco VA, Kohan R, Talamoni G, de Talamoni NGT, López MEP. Intestinal Ca2+ absorption revisited: A molecular and clinical approach. World J Gastroenterol. 2020;26(24):3344–64. DOI: 10.3748/wjg.v26.i24.3344
  13. Miller WL, Imel EA. Rickets, vitamin D, and Ca/P metabolism. Horm Res Paediatr. 2022;95(6):579–92. DOI: 10.1159/000527011
  14. Bellavia D, Costa V, De Luca A, Maglio M, Pagani S, Fini M, et al. Vitamin D level between calcium-phosphorus homeostasis and immune system: New perspective in osteoporosis. Curr Osteoporos Rep. 2024;22(6):599–610. DOI: 10.1007/s11914-016-0331-2
  15. Gutiérrez OM, Porter AK, Viggeswarapu M, Roberts JL, Beck GR. Effects of phosphorus and calcium to phosphorus consumption ratio on mineral metabolism and cardiometabolic health. J Nutr Biochem. 2020;80:108374. DOI: 10.1016/j.jnutbio.2020.108374
  16. De Vincentis S, Del Sindaco G, Pagnano A, Brigante G, Moretti A, Zirilli L, et al. Application of calcium-to-phosphorus (Ca/P) ratio in the diagnosis of pseudohypoparathyroidism: Another piece in the puzzle of diagnosis of Ca-P metabolism disorders. Front Endocrinol. 2023;14:1268704. DOI: 10.3389/fendo.2023.1268704
  17. El‐Boshy M, Refaat B, Almaimani RA, Abdelghany AH, Ahmad J, Idris S, et al. Vitamin D3 and calcium cosupplementation alleviates cadmium hepatotoxicity in the rat: Enhanced antioxidative and anti‐inflammatory actions by remodeling cellular calcium pathways. J Biochem Mol Toxicol. 2020;34(3):e22440. DOI: 10.1002/jbt.22440.
  18. Gurudatta M. An evaluation of role of Vitamin D in the pathophysiology of streptozotocin induced type-ii diabetes mellitus in rats and its impact on oral hypoglycemic/antidiabetic agents [Doctoral thesis]. Vijayapur: BLDE; 2022.
  19. Nowacka A, Śniegocki M, Bożiłow D, Ziółkowska EA. CYP24A1 in small intestinal Vitamin D metabolism and clinical implications. Nutrients. 2025;17(21):3348. DOI: 10.3390/nu17213348
  20. Durup D, Diaz-delCastillo M, Morgenlykke J, Jensen LT, Frandsen E, Abelson KS, et al. Hypophosphatemic hypovitaminosis D Induces osteomalacia in the adult female rat. Endocrinology. 2020;161(8):bqaa100. DOI: 10.1210/endocr/bqaa100
  21. Argano C, Torres A, Orlando V, Cangialosi V, Maggio D, Pollicino C, et al. Molecular insight into the role of vitamin D in immune-mediated inflammatory diseases. Int J Mol Sci. 2025;26(10):4798. DOI: 10.3390/ijms26104798
  22. Devi S. A review on Klotho: FGF23 mediated pathway integration and aging. J Gerontol Geriatr. 2025;73(3):92–108. DOI: 10.36150/2499-6564-n819
  23. Wang S, Xu Q, Zhang Y, Jiang X, Wang N, Hu Y, et al. The FGF23-Klotho axis promotes microinflammation in chronic kidney disease. Cytokine. 2024;184:156781. DOI: 10.1016/j.cyto.2024.156781
  24. Huang DX, Kang X, Jiang LJ, Zhu DL, Yang L, Luo JY, et al. Exploring the impact of high-altitude de-acclimatization on renal function: The roles of oxidative and endoplasmic reticulum stress in rat models. Biochem Biophys Res Commun. 2024;708:149770. DOI: 10.1016/j.bbrc.2024.149770
  25. Kirk B, Lombardi G, Duque G. Bone and muscle crosstalk in ageing and disease. Nat Rev Endocrinol. 2025;21:375–90. DOI: 10.1038/s41574-025-01088-X
  26. Li T, Xing G, Shao Y, Zhang L, Li S, Lu L, et al. Dietary calcium or phosphorus deficiency impairs the bone development by regulating related calcium or phosphorus metabolic utilization parameters of broilers. Poult Sci. 2020;99(6):3207–14. DOI: 10.1016/j.psj.2020.01.028
  27. Jiampochaman S, Chuengsaman P, Kanjanabuch T, Susantitaphong P, Sriudom K, Katesomboon S, et al. A comparison between severity-dependent protocol and fixed-dose regimen of oral vitamin D supplementation on correction of hypovitaminosis D among dialysis patients. J Ren Nutr. 2025;35(2):353–63. DOI: 10.1053/j.jrn.2024.11.002
  28. Palubiski LM, O’Halloran KD, O’Neill J. Renal physiological adaptation to high altitude: A systematic review. Front Physiol. 2020;11:756. DOI: 10.3389/fphys.2020.00756
  29. Wang SY, Gao J, Zhao JH. Effects of high altitude on renal physiology and kidney diseases. Front Physiol. 2022;13:969456. DOI: 10.3389/fphys.2022.969456
  30. Yan C, Tian D, Zhang C, Zhang Q, Sun Y. Evaluation of blood cellular and biochemical parameters in rats under a chronic hypoxic environment at high altitude. Ann Med. 2023;55(1):898–907. DOI: 10.1080/07853890.2023.2184859
  31. Chen X, An Z, Wei L, Zhang J, Li J, Wang Z, et al. Vitamin D3 metabolic enzymes in plateau Zokor (Myospalax baileyi) and plateau Pika (Ochotona curzoniae): Expression and response to hypoxia. Animals. 2022;12(18):2371. DOI: 10.3390/ani12182371
  32. Almanzar G, Alarcon JC, Garzon R, Navarro AM, Ondo-Méndez A, Prelog M. Hypoxia and activation of hypoxia inducible factor alpha as influencers of inflammatory helper T cells in autoimmune disease – a link between cancer and autoimmunity. Front Immunol. 2025;16:1633845. DOI: 10.3389/fimmu.2025.1633845
  33. Liu BH, Chong FL, Yuan CC, Liu YL, Yang HM, Wang WW, et al. Fucoidan ameliorates renal injury-related calcium-phosphorus metabolic disorder and bone abnormality in the CKD-MBD model rats by targeting FGF23-klotho signaling axis. Front Pharmacol. 2021;11:586725. DOI: 10.3389/fphar.2020.586725
  34. Zhang J, Cao ZB. Exercise: A possibly effective way to improve vitamin D nutritional status. Nutrients. 2022;14(13):2652. DOI: 10.3390/nu14132652
  35. Beck WR, Scariot PP, Papoti M, Pejon TM, Polisel EEC, Manchado-Gobatto FB, et al. Living high-training low on mice bone parameters analyzed through complex network approach. Int J Sports Med. 2025;46(1):32–40. DOI: 10.1055/a-2361-2840
  36. Melnyk O, Chendey I, Zukow W, Plyska O, Popovych I. The features of reactions to acute stress of neuro-endocrine-immune complex, metabolome, ECG and gastric mucosa in rats with various state of innate muscular endurance and resistance to hypoxia. J Educ Health Sport. 2023;38(1):96–128. DOI: 10.12775/jehs.2023.38.01.007
  37. Sivertsson E, Friederich-Persson M, Persson P, Nangaku M, Hansell P, Palm F. Thyroid hormone increases oxygen metabolism causing intrarenal tissue hypoxia; A pathway to kidney disease. PLoS One. 2022;17(3):e0264524. DOI: 10.1371/journal.pone.0264524
  38. Du Y, Qi M, Wang W, Chen B. Effect of high-altitude hypoxia environment on uric acid excretion, desmin protein level in podocytes, and Na+-K+-ATPase activity. Cell Mol Biol. 2022;68(6):84–91. DOI: 10.14715/cmb/2022.68.6.14
  39. Chang D, Kong F, Jiang W, Li F, Zhang C, Ding H, et al. Effects of L-carnitine administration on sperm and sex hormone levels in a male Wistar rat reproductive system injury model in a high-altitude hypobaric hypoxic environment. Reprod Sci. 2023;30(7):2231–47. DOI: 10.1007/s43032-022-00948-5
  40. Soliman MM, Aldhahrani A, Althobaiti F, Ahmed MM, Sayed S, Alotaibi S, et al. Characterization of the impacts of living at high altitude in Taif: Oxidative stress biomarker alterations and immunohistochemical changes. Curr Issues Mol Biol. 2022;44(4):1610–25. DOI: 10.3390/cimb44040110
  41. Ahmed AE, Alsamghan A, Momenah MA, Alqhtani HA, Aldawood NA, Alshehri MA, et al. Metabolic syndrome and cardiometabolic risk factors in the mixed hypercholesterolemic populations with respect to gender, age, and obesity in Asir, Saudi Arabia. Int J Environ Res Public Health. 2022;19(22):14985. DOI: 10.3390/ijerph192214985
  42. Jie L, Ma Z, Gao Y, Shi X, Yu L, Mao J, et al. The mechanism of palmatine-mediated intestinal flora and host metabolism intervention in OA-OP comorbidity rats. Front Med. 2023;10:1153360. DOI: 10.3389/fmed.2023.1153360
  43. Tocados JMD, Gómez AP, Coral JDD, Valdivielso JM. The multiple functions of insulin-like growth factor 1 in kidney disease. Nephrology. 2025;45(7):501337. DOI: 10.1016/j.nefro.2025.501337
  44. Dastghaib S, Koohpeyma F, Shams M, Saki F, Alizadeh A. New concepts in regulation and function of the FGF23. Clin Exp Med. 2023;23(4):1055–66. DOI: 10.1007/s10238-022-00844-X
  45. Morsanuto V. Biological effects of Vitamin D3 mediated by the interaction with VDR in different tissues [Doctoral thesis]. Vercelli: University of Eastern Piedmont; 2020. DOI: 10.20373/Uniupo/openthesis/115021
  46. Dai C, Lin X, Qi Y, Wang Y, Lv Z, Zhao F, et al. Vitamin D3 improved hypoxia-induced lung injury by inhibiting the complement and coagulation cascade and autophagy pathway. BMC Pulm Med. 2024;24:9. DOI: 10.1186/s12890-023-02784-Y

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APA
Keneshbek kyzy, A., Makhmudova, Zh., & Sapakunova, Zh. (2025). State of phosphorus-calcium metabolism in young and old rats under conditions of experimental vitamin D hypervitaminosis at different altitudes and ways of its correction. Journal of Osh State University. Medicine, 4(2), 50-61. https://doi.org/10.52754/16948645_2025_4(2)_50
Vancouver
Keneshbek kyzy A, Makhmudova Zh, Sapakunova Zh. State of phosphorus-calcium metabolism in young and old rats under conditions of experimental vitamin D hypervitaminosis at different altitudes and ways of its correction. J Osh State Univ Med. 2025;4(2):50–61. doi:10.52754/16948645_2025_4(2)_50