Search Results (266)

Background/Objectives: This review integrates evolutionary, metabolic, genetic, and nutritional perspectives to explain how sterol-derived vitamin D pathways shape human physiology and inter-individual variability in vitamin D status. Methods: The literature on sterol and vitamin D metabolism across animals, plants, fungi, and algae was synthesized with data from metabolomics databases, genome-wide association studies, RNA-seq resources (including GTEx), structural biology, and functional genomics. Results: Vitamin D₂ and vitamin D₃ likely emerged early in evolution as non-enzymatic photochemical sterol derivatives and were later co-opted into a tightly regulated endocrine system in vertebrates. In humans, cytochrome P450 enzymes coordinate vitamin D activation and degradation and intersect with oxysterol production, thereby linking vitamin D signaling to cholesterol and bile acid metabolism. Tissue-specific gene expression and regulatory genetic variants, particularly in the genes DHCR7, CYP2R1, CYP27B1, and CYP27A1, contribute to population-level differences in vitamin D status and metabolic outcomes. Structural analyses reveal selective, high-affinity binding of 1,25-dihydroxyvitamin D₃ to VDR, contrasted with broader, lower-affinity ligand recognition by LXRs. Dietary patterns modulate nuclear receptor signaling through distinct yet convergent ligand sources, including cholesterol-derived oxysterols, oxidized phytosterols, and vitamin D₂ versus vitamin D₃. Conclusions: Sterol and vitamin D metabolism constitute an evolutionarily conserved, adaptable network shaped by UV exposure, enzymatic control, genetic variation, and diet. This framework explains inter-individual variability in vitamin D biology and illustrates how evolutionary and dietary modulation of sterol-derived ligands confers functional flexibility to nuclear receptor signaling in human health. Full article

Background and Objectives: Chronic kidney disease (CKD) increases the risk of coronary artery disease (CAD), and vitamin D deficiency—particularly reduced levels of 1,25-dihydroxyvitamin D [1,25(OH)₂D], the biologically active form of vitamin D that declines early in CKD due to impaired renal conversion—may be a contributing factor. This study aimed to assess the relationship between 1,25(OH)₂D levels and the presence and severity of CAD in CKD patients. Materials and Methods: We retrospectively analyzed 398 non-dialysis CKD patients (eGFR < 60 mL/min/1.73 m²) who underwent elective coronary angiography. Serum 1,25(OH)₂D and 25(OH)D levels were measured, and CAD severity was assessed using the Gensini score. Results: Lower 1,25(OH)₂D levels were independently associated with both the presence and se-verity of CAD. Logistic regression revealed that each 1 pg/mL increase in 1,25(OH)₂D was linked to an 11% reduction in odds of significant CAD (OR: 0.89; 95% CI: 0.86–0.93; p < 0.001). In contrast, 25(OH)D was not significantly related to CAD. Linear regression showed an inverse correlation between 1,25(OH)₂D and Gensini scores (β = −0.329, p < 0.001), indicating reduced disease severity with higher vitamin D levels. Subgroup analyses confirmed consistent associations across age, sex, diabetes, hypertension, and LDL-cholesterol categories. ROC analysis demonstrated that 1,25(OH)₂D alone had good predictive ability for CAD (AUC = 0.818), which improved to 0.925 when combined with traditional risk factors. The optimal cutoff for 1,25(OH)₂D was ≤16.6 pg/mL, yielding 73.3% sensitivity and 83.5% specificity. Conclusions: Serum 1,25(OH)₂D is an independent predictor of both the presence and extent of CAD in CKD patients and may serve as a valuable non-traditional biomarker for cardiovascular risk assessment. Full article

Vitamin D is a steroid hormone whose relevant immunomodulatory role has been widely described. Therefore, its contribution to the pathogenesis of immune-mediated diseases is an important and ongoing matter of research. Specifically, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, through the interaction with its receptor, exerts different activities on the innate and adaptive immune system, among which are suppression of inflammation and promotion of tolerogenic responses. Indeed, vitamin D insufficiency/deficiency has been related to the pathogenesis and/or disease activity of several autoimmune diseases, including, amongst others, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes mellitus. Based on these premises, in this review, we will describe the main molecular mechanisms modulated by vitamin D in the regulation of immune responses, including the induction of immune tolerance. Moreover, we will focus on the current knowledge regarding the contribution of vitamin D depletion to the aforementioned autoimmune diseases, seeking to provide evidence as to why its supplementation in the context of these immune-mediated disorders may potentially ameliorate disease activity and its related clinical manifestations. Full article

This study aimed to investigate the effects of dietary manganese deficiency and compare the impact of manganese macroparticles (MnCO₃) and nanoparticles (Mn₂O₃NPs) on bone remodeling and metabolism. Twenty-seven male Wistar rats were divided into three groups (n = 9): control (standard MnCO₃, 65 mg Mn/kg), manganese-deficient, and Mn₂O₃NPs-supplemented (65 mg Mn/kg). After a 12-week feeding period, bone-related markers and gene expression were analyzed in the femur and blood. Mn-deficient rats showed reduced plasma levels of bone-specific alkaline phosphatase (BALP), tartrate-resistant acid phosphatase 5b (TRAP5b), interferon-β (IFN-β), RANKL glycoprotein, 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂D₃), vitamin K₂, and collagen turnover markers (PINP, CTX-1, NTX). Femur levels of BALP, TRAP5b, interferon-γ (IFN-γ), osteonectin, calcitonin, PICP, PINP, and CTX-1 were also decreased. Replacing MnCO₃ with Mn₂O₃NPs increased IFN-γ but lowered IFN-β and 1,25-(OH)₂D₃ levels in plasma. This treatment also decreased the femur level of BALP and calcitonin, and the RANKL:OPG ratio, while increasing the expression level of Sp7 and Ctsk genes. To conclude, our results suggest that manganese deficiency is associated with suppressed bone turnover and altered mineral metabolism. Furthermore, replacing MnCO₃ with Mn₂O₃ nanoparticles did not yield the anticipated benefits for bone remodeling, as evidenced by the observed imbalances in osteogenic and resorptive markers, indicating a need for cautious evaluation of nanoparticle-based supplementation. Full article

Background/Objectives: One of the main reasons for discrepancies in the role of vitamin D in ART could be the measurement of the conventional biomarker 25(OH)D₃. It is known that this value is affected by multiple factors, such as tissue origin, assay variability, classification criteria, and potential storage-related degradation. In this study, we investigate 24,25(OH)₂D₃ as a new biomarker to improve vitamin D assessment in women’s reproductive health, particularly regarding oocyte development. Methods: A prospective cohort study including 35 oocyte donors undergoing controlled ovarian stimulation, who were recruited between October and November 2017, was conducted. Vitamin D metabolites were measured at the baseline and after seven months of storage at −80 °C. Paired serum and pooled follicular fluid (FF) samples were collected at oocyte retrieval. 25(OH)D₃ and 24,25(OH)₂D₃ were quantified by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). Statistical analyses included paired tests (serum vs. FF; baseline vs. stored) and Pearson’s correlations (two-sided α = 0.05). Results: At the baseline, the mean serum 25(OH)D₃ concentration was 91.56 ± 39.01 nmol/L and the mean FF concentration was 58.13 ± 19.55 nmol/L (p < 0.0001). Serum 24,25(OH)₂D₃ averaged 15.62 ± 10.99 nmol/L, compared with 11.26 ± 6.09 nmol/L in FF (p = 0.004). In both fluids, 25(OH)D₃ and 24,25(OH)₂D₃ were strongly correlated (serum R² = 0.92; FF R² = 0.91). Across fluids, the serum–FF correlation was stronger for 24,25(OH)₂D₃ (R² = 0.77, p <0.0001) than for 25(OH)D₃ (R² = 0.69, p < 0.0001). After seven months of storage, 25(OH)D₃ concentrations decreased significantly (serum −32%; FF −38%; both p < 0.0001), whereas 24,25(OH)₂D₃ levels remained stable (serum p = 0.24; FF p = 0.36). Conclusions: Serum 24,25(OH)₂D₃ is a more reliable and minimally invasive biomarker for assessing ovarian vitamin D status than the current gold standard, 25(OH)D₃. Incorporating this metabolite into research studies and storage quality control may improve the reliability of retrospective analyses based on cryopreserved material, contributing to a better understanding of the role of vitamin D in human reproduction. Full article

Background/Objectives: Vitamin D in its active form, 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], plays a critical role in immune regulation, gut barrier function, and systemic inflammation. Its deficiency is frequent in Inflammatory Bowel Disease (IBD), but the clinical implications remain uncertain. The aim of the study is to assess the prevalence of vitamin D deficiency in a well-characterized IBD cohort in Western Greece, and explore its associations with clinical features, laboratory biomarkers, and treatment intensity. Methods: In this cross-sectional study, 184 consecutive, well-characterized IBD outpatients followed at a tertiary referral center in Western Greece underwent clinical evaluation and laboratory testing between January 2023 and December 2024. Vitamin D is determined by measuring 25-hydroxyvitamin D [25(OH)D], which reflects the body’s vitamin D stores due to its longer half-life compared with the biologically active form. Deficiency was defined as serum 25(OH)D < 20 ng/mL. Associations with disease type, clinical and laboratory biomarkers, severity indices, and treatment were analyzed using multivariate logistic regression. Results: Vitamin D deficiency was identified in 67 patients (36.4%). Although unrelated to disease type, hospitalization, surgery, or disease activity indices, deficiency correlated with systemic inflammation, nutrition/metabolic markers, and treatment intensity. More specifically, vitamin D-deficient patients exhibited higher platelet counts (p = 0.005) and erythrocyte sedimentation rate (ESR) (p = 0.014), lower hemoglobin (p = 0.005), albumin (p = 0.011), and serum glutamic-oxaloacetic transaminase (SGOT) (p = 0.009) levels and more frequent use of biologic therapy (p = 0.009). In multivariate analysis, vitamin D deficiency remained independently associated with biologic therapy (aOR = 0.374; 95% CI: 0.148–0.946), platelet count (aOR = 0.996, 95% CI: 0.992–0.999), and SGOT (aOR = 1.05, 95% CI: 1.00–1.10), indicating consistent links between vitamin D deficiency and treatment intensity, systemic inflammation, and nutritional or metabolic status. Conclusions: Vitamin D deficiency is common among IBD patients and independently associates with systemic inflammation, metabolic impairment, and intensified treatment requirement, supporting its potential role as a marker of disease burden. Full article

Background: Vitamin D is increasingly recognized as a key immunomodulatory nutrient, influencing innate and adaptive immune responses. While 25-hydroxyvitamin D [25(OH)D] is widely used to assess vitamin D status, the active form, 1,25-dihydroxyvitamin D [1,25(OH)₂D], may exert distinct effects on immune function. This study investigates the concentration-dependent and sex-specific relationships of both vitamin D metabolites with systemic inflammatory markers in a large clinical cohort. Objectives: To characterize the associations of 25(OH)D and 1,25(OH)₂D with total white blood cell (WBC) count and leukocyte subtypes, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Methods: We conducted a retrospective cross-sectional analysis of 125,537 adults (37.9% male; age 18–89 years) from routine laboratory diagnostics collected between 2014 and 2020 in Germany. Serum 25(OH)D and 1,25(OH)₂D were measured using standardized chemiluminescent immunoassays. Inflammatory markers were assessed via automated hematology. Multivariable-adjusted linear and non-linear regression models were used to assess associations, adjusting for age, sex, and season. Results: Neutrophils and Monocytes: Displayed U-shaped associations with both 25(OH)D and 1,25(OH)₂D. Neutrophil counts were lowest at 25(OH)D levels of ~40–60 nmol/L and increased significantly at both lower and higher extremes (p < 0.001). Lymphocytes: Inverse relationship with 25(OH)D (p < 0.001), and an inverse U-shaped relationship with 1,25(OH)₂D, peaking at ~90 pmol/L, with counts decreasing at both lower and higher levels (p < 0.001). Sex-specific analysis revealed that the relationship between 1,25(OH)₂D and lymphocyte count remained independent only in men, Eosinophils and Basophils: Demonstrated consistently negative correlations with both forms of vitamin D across all concentration ranges (p < 0.001). Conclusions: Our findings reveal distinct, concentration-dependent associations between vitamin D metabolites and leukocyte profiles, with evidence for nonlinear and sex-specific immunological effects. Both low and high levels of 25(OH)D and 1,25(OH)₂D were linked to increased neutrophil and monocyte counts, suggesting that vitamin D excess, like deficiency, may be linked to low-grade inflammation. These data are hypothesis-generating and suggest that personalized monitoring of vitamin D status may be relevant for future research on immune health, particularly in populations at risk for inflammatory or metabolic disease, but they do not provide a basis for clinical decision-making. Full article

Acute myeloid leukemia (AML) is an aggressive and often fatal hematopoietic malignancy, diagnosed predominantly in the elderly. The five-year survival of patients with AML is as low as 30%. Differentiation therapy of a subtype of AML, named acute promyelocytic leukemia (APL), using all-trans retinoic acid (ATRA) was the most successful example of a targeted therapy against AML. Epigenetic-based differentiation therapies for other subtypes of AML are also showing improvements in response and in survival rates. Thus, in this study, we investigated a potential differentiation therapy with a combination of 1,25-dihydroxyvitamin D (1,25D) analog (named PRI5202) and low concentration of Fludarabine. We show that such a combination elicits immunostimulatory and pro-differentiation effects in AML cells, specifically in those with activating mutations in fibroblast growth factor receptor (FGFR) and Janus kinase (JAK) pathways. We show here that both PRI5202 and Fludarabine are potent activators of the transcription of many innate immunity-related genes, and that, in combination, their effects are in many aspects synergistic. We propose that such a low-intensity regimen may be suitable for older patients with AML, who are unfit for intensive chemotherapy. We also present data indicating that PRI5202 induces myeloid differentiation in blasts from patients with myelodysplastic syndrome (MDS), and we propose to further investigate PRI5202 as a differentiation therapy for patients suffering from MDS. Full article

Corneal fibrosis, a significant source of visual impairment, can result from keratocyte-to-myofibroblast transdifferentiation during wound healing. This study investigated the antifibrotic role of 1,25-dihydroxyvitamin D₃ (1,25 Vit D) and the lesser-known vitamin D, 24,25-dihydroxyvitamin D₃ (24,25 Vit D), in human and mouse corneal stromal cells (HSCs and MSCs) and in a Vit D receptor knockout (VDR KO) mouse model. Cells were treated with TGF-β1 ± Vit D metabolites and the expression of fibrotic and antifibrotic genes and proteins was evaluated. Both metabolites significantly reduced α-smooth muscle actin levels in HSCs, MSCs and organ-cultured mouse corneas (p < 0.05). They also upregulated the mRNA expression of BMP2, BMP6, BMPR2, and TGF-β3, as well as the protein expression of BMP6 and TGF-β3. VDR KO corneas subjected to alkali injury exhibited increased fibrotic responses and reduced CD45+ immune cell infiltration compared to wild-type controls. Notably, 24,25 Vit D exerted antifibrotic effects even in VDR KO cells, and the alternative 24,25 Vit D receptor FAM57B was expressed in all corneal cell layers. These results reveal consistent antifibrotic effects of both 1,25 and 24,25 Vit D across species, support the existence of VDR-independent mechanisms in the cornea, and offer new insights into potential therapeutic strategies for preventing corneal fibrosis. Full article

Background/Objectives: Vitamin D deficiency is common in the Middle East, where it affects about 90% of the population. 25-hydroxyvitamin D [25(OH)D]. plays a key role in immune function and antimicrobial defense. Its deficiency has been implicated in surgical site infections (SSIs) also, which lead to increased healthcare costs and morbidity. Around 60% SSIs are preventable by addressing factors like 25(OH)D levels among others. In Qatar, 55.8% of the population is 25(OH)D deficient, but no direct link has been established between 25(OH)D deficiency and SSI risk. This study aims to investigate the relationship between deficient 25(OH)D levels and SSI development in surgical patients at Hamad Medical Corporation (HMC), Qatar. Methods: A retrospective chart review was conducted on adult patients who underwent surgery at HMC, Qatar, between January 2021 and December 2023, with known 25(OH)D levels measured within three months before surgery. A multivariate logistic regression analysis was conducted to evaluate the relationship between 25(OH)D levels and SSIs. Results: This retrospective chart review included 24,097 patients, with 3818 (15.8%) being 25(OH)D deficient. The mean age of the patients was 45 years, and 55% of them were female. The proportion of SSIs was highest in the 25(OH)D deficient group (2.7%) compared to the insufficient (1.8%) and sufficient (1.9%) groups, with a p-value of <0.01. The mean 25(OH)D level was 23 ng/mL in the SSI group, compared to 25 ng/mL in the no SSI group, with a p-value of <0.01. Multivariate logistic regression analysis identified several independent risk factors for SSIs, including 25(OH)D deficiency, male gender, intermediate and major case levels, longer operative times, lower preoperative serum albumin, and contaminated and dirty wounds, all with p-values of <0.05. Conclusions: Preoperative lower 25(OH)D levels increase the risk of SSIs. This study emphasizes the importance of optimizing 25(OH)D levels before surgery to reduce the occurrence of SSIs. Full article

Background: Gefitinib is a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeting EGFR-mutated non-small cell lung cancer (NSCLC) and is a current first-line treatment for NSCLC. However, acquired resistance leads to the failure of treatment and remains a challenge. Therefore, identifying novel therapeutic approaches to combat EGFR-TKI resistance is crucial. Methods: The Cancer Genome Atlas (TCGA) database analysis and gefitinib-resistant cell lines were used to analyze VDR expression in NSCLC. Cell proliferation and apoptosis were assessed via MTT assay, colony formation assay, and flow cytometry. Immunofluorescence, qPCR, and Western blotting were used to measure mRNA and protein expression levels of VDR and other related molecules. Xenograft tumors in BALB/c nude mice were employed to investigate the effects of VDR and 1,25-dihydroxyvitamin D3 (1,25(OH)₂D₃) on gefitinib-resistant tumors in vivo. Results: We found that VDR was significantly upregulated in EGFR-TKI-resistant NSCLC cells. Patients with high VDR expression exhibited poor prognosis. VDR knockdown significantly inhibited cell proliferation, tumor growth, and reduced gefitinib resistance, whereas VDR overexpression enhanced resistance. VDR knockdown downregulated EGFR and FASN expression. Silencing either EGFR or FASN confirmed the existence of a positive feedback regulatory loop involving VDR, EGFR, and FASN. Treatment with 1,25(OH)₂D₃ increased VDR levels but decreased EGFR and FASN expression. VDR knockdown significantly enhanced the inhibitory effect of 1,25(OH)₂D₃ on gefitinib resistance. The combination of VDR knockdown and 1,25(OH)₂D₃ treatment was more effective than either treatment alone in suppressing EGFR and FASN expression. Conclusions: VDR promotes NSCLC resistance to EGFR-TKIs by regulating EGFR and FASN expression through a positive feedback loop. Knocking down VDR effectively enhances the ability of 1,25(OH)₂D₃ to overcome gefitinib resistance, mediated by the synergistic downregulation of EGFR and FASN expression. Targeting VDR represents a potential strategy to enhance the efficacy of 1,25(OH)₂D₃ in overcoming EGFR-TKI resistance. Full article

Paraoxonase 1 (PON1) is an antioxidant enzyme that plays physio-pathological roles. Prior in silico analysis revealed the presence of response elements of the nuclear receptor superfamily in the PON1 promoter, comparable to glucocorticoid receptors (GR), the vitamin D receptor (VDR), and the pregnenolone X receptor (PXR). The aim of this study was to evaluate the effects of 1α,25-dihydroxyvitamin D₃, a ligand specific to VDR, on the expression and activity of PON1 in hepatocarcinoma cells (HepG2 cells). PON1 activities (arylesterase/AREase and lactonase/LACase) were determined by spectrophotometry. Quantitative real-time PCR was used to evaluate the effect of VDR and PXR on the mRNA levels of PON1 and CYP3A4 genes. Molecular models and dynamics simulations were built using specialized software. Treatments with 1α,25-dyhydroxyvitamin D₃ (calcitriol), its active hormonal form, resulted in an induction of PON1 mRNA and AREase activity compared to control cultures. These results suggest that calcitriol plays a role in the regulation of PON1 transcription and provide evidence that this hormone increases PON1 levels in HepG2 cells. In addition, the molecular modeling suggests that calcitriol enhances PON1 activity and this increase could be caused by direct interaction on the PON1 protein. This study shows the effects of calcitriol on PON1 expression, proposing a new molecular mechanism for the transcriptional regulation of PON1 through a process linked to VDR activation and direct interaction of calcitriol on the PON1 protein. Full article

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the etiologic agent that causes the coronavirus disease (COVID-19) identified in Wuhan, in 2019. Men are more prone to developing severe manifestations than women, suggesting a possible crucial role of sex hormones. 17,β-Estradiol (E2) and 1,25 α dihydroxyvitamin D₃ (calcitriol) act upon gene pathways as immunomodulators in several infectious respiratory diseases. In this study, we aimed to evaluate the influence of E2 and calcitriol on the VSV-based pseudovirus SARS-CoV-2 and SARS-CoV-2 infection in vitro. We infected Vero E6 cells with the recombinant VSV-based pseudovirus SARS-CoV-2 and the SARS-CoV-2 viruses according to the pre-treatment and pre–post-treatment models. The Angiotensin-Converting Enzyme 2 (ACE2) and Vitamin D Receptor (VDR) gene expression did not change under different treatments. The VSV-based pseudovirus SARS-CoV-2 infection showed a significant decrease in the focus-forming unit count in the presence of E2 and calcitriol (either alone or in combination) in the pre-treatment model, while in the pre–post-treatment model, the infection was inhibited only in the presence of E2. Th SARS-CoV-2 infection highlighted a decrease in viral titres in the presence of E2 and calcitriol only in the pre–post-treatment model. 17,β-Estradiol and calcitriol can exert an inhibitory effect on SARS-CoV-2 infections, demonstrating their protective role against viral infections. Full article

Background/Objectives: Vitamin D₃ is predominantly sequestered in adipose tissue, where it is slowly mobilized under conditions of deficiency in vivo. However, the kinetics of its uptake, release, and interaction with its major metabolites, 25(OH)D₃ and 1,25(OH)₂D₃, remain poorly understood. Given the close relationship between obesity, low-grade chronic inflammation, and disrupted vitamin D metabolism, a clearer understanding of these dynamics in adipocytes is essential. Thus, we sought to characterize time-dependent uptake and metabolites in differentiated human adipocytes. Methods: Human pre-adipocytes were differentiated in vitro and exposed to either vitamin D₃ and 1,25(OH)₂D₃ or the combination of vitamin D₃, 25(OH)D₃ and 1,25(OH)₂D₃. Intracellular concentrations were quantified through HPLC at various time points. A separate efflux experiment assessed vitamin D₃ release under basal and isoproterenol-stimulated conditions using ³H-vitamin D₃ and scintillation counting. Results: Vitamin D₃ uptake showed a gradual and sustained increase over 96 h, suggesting ongoing accumulation within lipid-rich compartments. In contrast, 25(OH)D₃ and 1,25(OH)₂D₃ peaked rapidly within the first hour and declined sharply. Isoproterenol stimulation significantly enhanced vitamin D₃ release into the extracellular medium from the adipocytes, indicating increased efflux during lipolytic activation. Conclusions: Adipocytes selectively retain vitamin D₃ while rapidly clearing its hydroxylated forms. These findings highlight the distinct intracellular handling of vitamin D metabolites and suggest that tailored supplementation strategies—particularly in individuals with excess adiposity—may improve bioavailability and metabolic efficacy. Full article

Osteogenesis imperfecta (OI) is a rare bone dysplasia that occurs with a frequency of 1/15,000–20,000 live births. It is characterized by increased susceptibility of bone fractures, skeletal deformities, low stature, and low bone mass. It results in impaired production of type I collagen. About 90% of people with OI have heterozygous mutations in the COL1A1 and COL1A2 genes. Fibroblast growth factor 23 (FGF23) is a protein involved in the regulation of phosphate and 1,25-dihydroxyvitamin D₃ metabolism on a negative feedback basis. FGF23 is secreted by osteocytes in response to increased serum calcitriol and phosphorus. The purpose of this study was to evaluate the concentration of FGF23 among children with osteogenesis imperfecta and the differences in reference values in a healthy population of children and adolescents. Then, this study sought to evaluate how the course of osteogenesis imperfecta, including type of disease, number of bone fractures, and bone mineral density, are related to FGF23 concentration. The study included 47 children aged 3 to 17 years with a diagnosis of osteogenesis imperfecta, confirmed by genetic tests. The patients were hospitalized at the Department from August 2019 to September 2020 and were treated with intravenous infusions of sodium pamidronate. The course of the disease was analyzed, including the number of bone fractures, clinical symptoms, and anthropometric parameters, and bone densitometry was performed by dual X-ray absorptiometry (DXA) in Total Body Less Head (TBLH) and Spine options with Z-score evaluation. FGF23 concentration was determined by the ELISA method. The study was prospective in nature. Results: The mean level of FGF23 in the study group of patients was 645.09 pg/mL and was within the reference values for the developmental age population. There was no significant correlation between FGF23 concentration and anthropometric measurements: body weight (p = 0.267), height (p = 0.429), gender (p = 0.291), or pubertal stage (p = 0.223) in the study group of patients. FGF23 levels were not related to the number of fractures (p = 0.749), the number of sodium pamidronate cycles administered (p = 0.580), bone mineral density parameters (Z-score), the form of osteogenesis imperfecta (p = 0.156), or the genetic test result (p = 0.573). FGF23 levels decrease with age (r = −0.32, p = 0.030) and BMI (r = −0.34, p = 0.020). The level of FGF23 in patients with osteogenesis imperfecta is lower among older children and those having a higher BMI. This index cannot be a diagnostic tool in this group of patients, for no differences were found between the concentrations in patients with osteogenesis imperfecta and the developmental age population. Full article