Correction of vitamin D deficiency and the role of BsmI (rs1544410) VDR gene polymorphism in mineral metabolism related to cartilage regeneration in osteoarthritis
Authors:   Bukovinian State Medical University, Chernivtsi, Ukraine, Sokolova I. , Berbets A. , Fediv O. , Sokolov B. 
Published: December 2024

Mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts maintain the physiological stability of bone tissue. Their activity is regulated by numerous molecular factors, among which vitamin D plays a crucial role. Vitamin D influences the functional interactions between bone cells and their niche through autocrine and paracrine effects, as well as by regulating calcium-phosphorus homeostasis. However, the role of vitamin D deficiency in mineral metabolism in patients with osteoarthritis (OA) and the approaches to the treatment of such patients based on the genotype of the BsmI (rs1544410) VDR gene polymorphism remain inconclusive.
The aim of the study was to correct vitamin D deficiency and disturbances in calcium-phosphorus homeostasis, and to clarify the pathogenetic role of the BsmI (rs1544410) VDR gene polymorphism in mineral metabolism in patients with osteoarthritis (OA).
Material and methods. 60 patients with acute knee OA, Kellgren-Lawrence stages I–III, and vitamin D deficiency were examined. Vitamin D and parathyroid hormone levels in peripheral blood were measured using enzyme immunoassay, total calcium and phosphorus concentrations by biochemical analysis, ionized calcium by ion-selective method, and calcitonin by immunochemiluminescence. Measurements were taken before the treatment and after 3 months of cholecalciferol supplementation at a dose of 6000 IU. Additionally, the genotypes of the BsmI (rs1544410) polymorphism of the VDR gene were analyzed using PCR-RFLP.
Results. Among the participants, 44 patients (73.3 %) were carriers of the unfavorable A allele of the BsmI polymorphism. Specifically, 38.3 % had the GA genotype, and 35.0 % had the AA genotype. The unfavorable AA genotype was associated with significantly lower levels of key mineral metabolism indicators: total calcium was 10.0 % lower, ionized calcium was 16.0 % lower, and phosphorus was 20.0 % lower compared to the GG genotype. Calcitonin levels were also significantly reduced in the context of vitamin D deficiency. Compared to the physiological norm, calcitonin levels were lower, with a decrease of 28.5 % in patients with the GG genotype, 50.5 % in those with the GA genotype, and 36.9 % in patients with the AA genotype, compared to their respective control groups.
In patients with the GG genotype, the parathyroid hormone level was significantly 2.2 times higher than in the control group. In those with the AA genotype, the level was 30.9 % higher than in the GG genotype and 3.2 times higher than in the control group. Similarly, in patients with the GA genotype, the level was 20.0 % higher than in the GG genotype and 3 times higher than in the control group.
After treatment with cholecalciferol, optimal vitamin D levels were achieved and increased by 39.8 % in patients with the GG genotype or by 30.0 % in those with the pathological A allele. In patients with the GG genotype, indicators of mineral metabolism significantly improved and normalized. Patients with the GA and AA genotypes reached reference values for ionized calcium and parathyroid hormone. However, despite positive changes in dynamics, total calcium, phosphorus, and calcitonin levels in patients carrying the A allele did not normalize in response to the treatment.
Conclusions. When correcting vitamin D deficiency and calcium-phosphorus homeostasis disorders with cholecalciferol, patients with the GG genotype of the BsmI polymorphism of the VDR gene exhibited significantly higher levels of vitamin D, calcium-phosphorus homeostasis markers, and calcitonin, as well as significantly lower levels of parathyroid hormone compared to the patients with the pathological A allele.