Search Results (236)

Background/Objectives: Dementia is a progressive, multifactorial neurodegenerative syndrome that poses a major public health challenge, with an increasing number of cases due to an aging population. Vitamin D (vitD) is crucial not only for bone and calcium homeostasis, but also as a neuroactive steroid that influences brain functions such as neurotransmission, neuroprotection and immunomodulation. Emerging evidence suggests that vitD deficiency may be a modifiable risk factor for the development of dementia. Thus, the aim of this review is to understand the possible role of vitD as a modifiable risk factor in the prevention of dementia. Methods: Research was conducted in the PubMed and Scopus databases using combinations of the MeSH terms ‘calcitriol’, ‘dementia’, ‘vitamin D receptors’, and ‘brain function’ for articles from 2014 until 2026. Results: The analysis of the 30 articles retrieved exhibited a significant association between vitD deficiency and an increased risk of dementia. Longitudinal studies and meta-analyses have indicated an increased risk of dementia and Alzheimer’s disease proportional to the severity of the deficit. A significant association with vascular dementia was also highlighted, with the risk increasing synergistically in the presence of hypertension. Conclusions: The evidence reviewed suggests that both vitD deficiency and insufficiency are strongly associated with increased risk of dementia, particularly Alzheimer’s disease and vascular dementia. Addressing vitD deficiency by maintaining adequate levels is proposed as a potentially effective preventive strategy against cognitive decline and dementia. Full article

With a lack of population-specific reference intervals (RIs) in Bangladesh, this study aimed to determine RIs for complete blood count (CBC) and specific micronutrients, vitamin D (VitD) and zinc, and to assess the possible impact of prior history of SARS-CoV-2 infection on these parameters. Healthy participants (n = 1724) of both sexes aged ≥ 10 years from slum and non-slum areas of Dhaka city were sampled systematically. A total of 26 CBC parameters were determined using an automated hematology analyzer, whereas the micronutrients VitD and zinc were measured using automated immunoassay analyzers and atomic absorption spectrophotometry (AAS), respectively. Multiple regression analysis (MRA) was employed to determine the association of variations in reference values (RVs) of hematological and micronutrient parameters with sex, age, and slum residency of the participants. Practical significance of each factor was judged from partial correlation coefficients (r_p) by setting its minimum effect size at |r_p| = 0.2. The need to partition RVs by sex and age was assessed using the ANOVA-based standard deviation ratio (SDR). RIs were determined by parametric method after Gaussian transformation using the two-parameter Box–Cox formula, with or without the latent abnormal values exclusion (LAVE) method. By MRA, sex and age were significant source of variations for various CBC parameters, whereas slum residence was associated with increased levels of VitD and zinc Using the SDR ≥ 0.35 threshold, RVs were partitioned by sex to derive RIs for hemoglobin, hematocrit, red cell count and indices (MCH, MCHC), and plateletcrit, as well as for VitD and zinc. Comparing these RIs with those from the global collaborative studies indicated significant differences in erythrocyte and leukocyte parameters. These are the first population-specific RIs for urban Dhaka city, underscoring the need for country-specific RIs for accurate clinical use. Full article

The objective of this trial was to evaluate the impact of an α-tocopherol injection on pre-weaning calf performance including markers of growth and behavior. Sixty-one days prior to weaning, both nursing Angus and Hereford steer calves (SC; n = 16) and Angus and Hereford heifer calves (HC; n = 28) were randomly assigned to one of two treatments: (1) no injectable α-tocopherol (CON; n = 23) or (2) 1500 IU of injectable α-tocopherol administered subcutaneously (VitE; n = 21). Average daily gain (ADG), exit velocity (EV), serum urea nitrogen, serum cortisol, and serum α-tocopherol concentrations were evaluated on d 0, 28, and 61 of the trial. Steer calves increased (p = 0.01) ADG compared to HC, with SC gaining about 13% more than HC. There was no impact (p ≥ 0.20) of injectable vitamin E on calf ADG. As the trial progressed, EV slowed (p = 0.0005) in both HC and SC regardless of treatment. Serum α-tocopherol concentrations were influenced (p = 0.04) by an interaction of treatment, sex, and time, with CON-SC being the only group that did not have serum α-tocopherol concentrations decrease throughout the trial. Overall, this trial found that a pre-weaning vitamin E injectable did not improve pre-weaning calf performance, but calf sex did. Full article

Background and Objectives: Urinary tract infections (UTIs) represent one of the most frequently encountered bacterial infections in clinical practice. Although vitamin D (vit D) is recognised for its immunomodulatory properties, its relationship with the spectrum of uropathogens remains unclear. This study investigated the distribution of UTI-causing pathogens in relation to serum vit D status and demographic variables including age, sex, season, and year of presentation at a tertiary hospital in the Eastern Mediterranean. Materials and Methods: A retrospective cross-sectional analysis was conducted on 942 adult patients with culture-confirmed UTIs at a university hospital in Cyprus between January 2019 and December 2024. Serum 25-hydroxyvitamin D [25(OH)D] levels were classified as deficient (≤20 ng/mL), insufficient (20–29.9 ng/mL), or sufficient (≥30 ng/mL) according to Turkish Endocrinology Society (TEMD) guidelines. Pathogen distribution was correlated with vit D category, sex, age group, season, and year using chi-square analysis and multivariable logistic regression. Timing of urine culture collection (at admission vs. more than 48 h after admission), catheter use, upper vs. lower urinary tract classification, and comorbidity data were recorded for each patient. Results: Escherichia coli was the most frequently isolated uropathogen (48.83%), followed by Klebsiella pneumoniae (18.79%) and Enterococcus faecalis (11.89%). No statistically significant association was found between vit D level and uropathogen type (p = 0.504). Infections were more prevalent in females (70.49%) and in patients aged over 70 years (56.26%). Vit D deficiency was present in 47.98% of the cohort. Catheter-derived specimens accounted for 35.1% of cultures. Upper tract infection was diagnosed in 233 patients (24.7%) and lower tract infection in 709 patients (75.3%). The most frequent comorbidities were hypertension (48.4%), diabetes mellitus (33.1%), and chronic kidney disease (21.0%); on multivariable analysis, diabetes mellitus (adjusted OR = 1.4) and chronic kidney disease (adjusted OR = 1.6) were independently associated with K. pneumoniae infection. In vit D-deficient patients, K. pneumoniae infection risk was significantly higher during winter in unadjusted analysis (OR = 1.8; 95% CI: 1.3–2.5) and remained elevated after multivariable adjustment (aOR = 1.6; 95% CI: 1.1–2.3). Vit D levels showed significant seasonal variation (p < 0.001), with lower values in winter (18.6 ng/mL) and higher values in summer (28.4 ng/mL). Conclusions: On multivariable analysis, no statistically significant association was found between vit D level and uropathogen species overall (χ² = 13.291; p = 0.504); a seasonal interaction was observed between vit D deficiency and Klebsiella infections in winter. UTI risk was highest in elderly and female patients. These findings point to the need for considering seasonal and dietary factors in UTI management and call for prospective investigation. Full article

Alzheimer’s disease (AD) is characterized by impaired neurotrophic support, oxidative stress, and metabolic dysfunction. Using the intracerebroventricular streptozotocin (ICV-STZ) rat model of sporadic AD, we investigated whether vitamin D₃ (VitD₃) and dimethyl fumarate (DMF), administered alone or in combination, modulate hippocampal neurotrophin-related signaling and redox balance. Animals were assigned to SHAM, STZ, VITD, DMF, and COMBO groups, representing control, ICV-STZ, VitD₃-treated ICV-STZ, DMF-treated ICV-STZ, and combined VitD₃ + DMF-treated ICV-STZ animals, respectively. Hippocampal neurotrophin processing (proBDNF and mature BDNF), downstream signaling (Akt and pAkt), IGF-1 content, mitochondrial oxoglutarate dehydrogenase (OGDH) content, citrate synthase (CS) activity, and glutathione peroxidase (GPx) activity were assessed. STZ administration showed a trend toward reduced mature BDNF content compared with the SHAM group (p = 0.07), whereas combined VitD₃ and DMF treatment significantly increased mature BDNF content compared with the STZ group. The mature BDNF/proBDNF ratio was reduced in the STZ group compared with the SHAM group and tended to be higher in the COMBO group compared with the STZ group (p = 0.09). proBDNF content remained unchanged. IGF-1, pTrkB, total Akt, and pAkt content did not differ significantly between groups. The pAkt/Akt ratio showed a trend toward reduction in the STZ group compared with SHAM group (p = 0.09). GPx activity increased in the STZ group, while CS activity and OGDH content were not significantly altered. These findings indicate that STZ-induced neurodegeneration is characterized by redox-associated uncoupling of neurotrophic signaling rather than mitochondrial disruption. Combined VitD₃ and DMF treatment partially modulated neurotrophic signaling, supporting a limited but measurable neuroprotective effect. Full article

Introduction: Intermittent fasting (IF) is becoming increasingly popular as a method of weight management, but it is unknown whether it affects plasticiser intake with resultant changes in glycaemic control in diabetes and vitamin D (VitD) levels; therefore, this study was undertaken in a cohort of control and type-2 diabetic (T2D) subjects during Ramadan time-restricted feeding (TRF). Methods: In T2D subjects (n = 19) and controls (n = 31) undertaking TRF, 24 h urinary levels of phthalate metabolites, bisphenols and serum VitD were determined pre- and post-TRF by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Anthropometric data and glycosylated haemoglobin (HbA1c) were measured. Results: T2D subjects were older (52 versus 36.73 years, p < 0.001), and had higher BMI (36.54 versus 27.67 kg/m², p < 0.001), body weight (101.77 versus 80.36 kg, p < 0.001), and HbA1c (8.38 versus 5.46%, p < 0.001) compared to controls, while VitD levels did not differ (60.43 versus 63.95 nmol/L, p > 0.05). Post-TRF, HbA1c was unchanged in T2D subjects and there was no difference in weight, BMI or VitD. Increased mono-iso-butyl phthalate (MiBP) in T2D subjects (10 versus 6.1 ng/mL, p = 0.001) and mono-n-butyl phthalate (MnBP) in T2D subjects (37 versus 13 ng/mL, p = 0.018) and controls (8.3 versus 5.4 ng/mL, p = 0.007) were observed post-TRF; however, significance was lost after adjusting for baseline differences in age, BMI, and HbA1c using a general linear model (GLM) repeated-measures ANOVA. Despite having no median differences in DEHP (di-2-ethylhexyl phthalate) metabolites pre- and post-TRF, analyses revealed a significant time × HbA1c interaction for [mono(2-ethyl-5-carboxypentyl) phthalate, MECPP: F(1,42) = 4.79, p = 0.03, mono(2-ethyl-5-hydroxyhexyl) phthalate, MEHHP: F(1,42) = 8.56, p = 0.006, mono(2-ethylhexyl) phthalate, MEHP: F(1,42) = 4.64, p = 0.03 and mono(2-ethyl-5-oxohexyl) phthalate, MEOHP: F(1,42) = 8.19, p = 0.007] and time × group interactions [MEHHP: F(1,42) = 14.27, p < 0.001, MEHP: F(1,42) = 6.35, p = 0.01 and MEOHP: F(1,42) = 10.30, p = 0.003]. Estimated marginal means (adjusted for age, BMI, HbA1c, and VitD) further confirmed higher concentrations of DEHP metabolites [MECPP, MEHHP, MEHP, and MEOHP] in T2D participants over time compared with controls. Additionally, monomethyl phthalate (MMP) trajectories were significantly influenced by the time × group interaction (F(1,42) = 4.28, p = 0.04), with post-TRF elevations observed in T2D subjects. Vitamin D status was observed to modify mono(3-carboxypropyl) phthalate (MCPP) and MEP trajectories over time. Conclusion: Ramadan TRF is associated with changes in plasticiser metabolite levels, with estimated increased levels in T2D subjects versus healthy controls. Metabolite levels were influenced by HbA1c and vitamin D, though BMI was not observed to be a contributing factor. Full article

Background: Ulcerative colitis (UC) is a multifactorial disease characterized by aberrant mucosal immune activation in response to intestinal dysbiosis. Contemporary management strategies aim to target inflammation and microbiome alterations while reducing relapse risk. A multidimensional assessment integrating clinical, inflammatory, immune, and microbial endpoints may better capture therapeutic effects beyond symptom control. Aims: To evaluate whether supplementation with Lactobacillus rhamnosus GG co-formulated with vitamin D3 (Dicoflor IBD Immuno) as an adjunct to optimized mesalamine (5-ASA) is associated with coordinated changes across clinical and biological domains in mild-to-moderate UC, using a multidimensional assessment framework. Methods: This single-center, randomized, double-blind, placebo-controlled pilot trial was conducted at Fondazione Ca’ Granda IRCCS Policlinico di Milano between May 2022 and May 2024. Thirty-six patients with mild-to-moderate UC receiving optimized 5-ASA were randomized to LGG+VitD3 (ALD3) or placebo (AP) for 4 weeks. Clinical activity, health-related quality of life (HRQoL), fecal calprotectin, peripheral immune cell subsets, and gut microbiota composition were assessed at baseline and week 4. Results: Both 5-ASA-LGG+VitD3 (ALD3)- and 5-ASA-placebo (AP)-treated patients showed significant improvement in clinical activity and HRQoL, without between-group differences. A higher proportion of clinical responders was observed in the ALD3 group, although this was not statistically significant. LGG+VitD3-supplemented patients showed reduced fecal calprotectin levels and increased frequencies of IL-22-producing CD4⁺ T cells. Microbiome analysis revealed enrichment of short-chain fatty acid-producing taxa, including Coprococcus and Fusicatenibacter, in ALD3-treated patients. Conclusions: In patients with mild UC receiving optimized 5-ASA, LGG+VitD3 supplementation does not improve short-term clinical outcomes beyond placebo but is associated with favorable modulation of inflammatory, immune, and microbial parameters, supporting the relevance of multidimensional biological endpoints in adjunctive UC management. Full article

Background/Objectives: Vitamin D (Vit-D) and magnesium (Mg) levels have been associated with an increased risk of developing functional thyroid disorders or autoimmune thyroid diseases (AITD). In this study, our objective was to evaluate if 25-hydroxyvitamin D (25OH Vit-D) and/or Mg levels are associated with an increased risk of functional thyroid disorders and/or AITD. Methods: A population-based case-control study was conducted, with a total of 1028 participants (514 cases and 514 controls). Blood concentrations of 25OH Vit-D, Mg, TSH, FT4, FT3, and thyroid autoantibodies (TPOAb, TgAb, and TRAb) were determined in the study participants. Results: Among the cases (in women), the prevalence of goiter, hypothyroidism, and thyroid autoantibody positivity was significantly higher. No differences were found in the prevalence of functional thyroid disorders or in thyroid antibody positivity (among cases) according to sex or age. The prevalence of thyroid antibody positivity (specifically TPOAb and/or TgAb) was significantly higher in cases with 25OH Vit-D and/or Mg deficiency. The 25OH Vit-D level that best discriminated the highest frequency of AITD was 23.5 ng/mL [AUC: 0.665 (95% CI: 0.636–0.694, p < 0.001)]; while for Mg it was 1.8 mg/dL [AUC: 0.697 (95% CI: 0.668–0.725, p < 0.001)], indicating that the model has weak discrimination (although better than chance), with good sensitivity and low specificity, being able to identify the vast majority of positive cases (with AITDs), at the cost of including a significant proportion of false positives. Conclusions: Overall, we found that low serum levels of 25OH Vit-D and/or Mg appear to be associated with a significantly increased risk of goiter, functional thyroid disorders (specifically hypothyroidism), and with greater positivity of thyroid antibodies. Full article

Background: Zika virus (ZIKV), a mosquito-borne flavivirus, is associated with congenital malformations and neuroinflammatory disorders, highlighting the need to identify host factors that shape infection outcomes. Macrophages, key targets and reservoirs of ZIKV, orchestrate both antiviral and inflammatory responses. Methods: Vitamin D (VitD) has emerged as a potent immunomodulator that enhances macrophage antimicrobial activity and regulates inflammation. To investigate how VitD shapes macrophage responses to ZIKV, we reanalyzed publicly available RNA-seq and miRNA-seq datasets from monocyte-derived macrophages (MDMs) of four donors, differentiated with or without VitD and subsequently infected with ZIKV. Results: Differential expression analysis identified long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs integrated into competing endogenous RNA (ceRNA) networks. In VitD-conditioned and ZIKV-infected MDMs, 65 lncRNAs and 23 miRNAs were significantly modulated. Notably, lncRNAs such as HSD11B1-AS1, Lnc-FOSL2, SPIRE-AS1, and PCAT7 were predicted to regulate immune and metabolic genes, including G0S2, FOSL2, PRELID3A, and FBP1. Among the miRNAs, let-7a and miR-494 were downregulated, while miR-146a, miR-708, and miR-378 were upregulated, all of which have been previously implicated in antiviral immunity. Functional enrichment analysis revealed pathways linked to metabolism, stress responses, and cell migration. ceRNA network analysis suggested that SOX2-OT and SLC9A3-AS1 may act as molecular sponges, modulating regulatory axes relevant to immune control and viral response. Conclusions: Despite limitations in sample size and experimental validation, this study provides an exploratory map of ncRNA–mRNA networks shaped by VitD during ZIKV infection, highlighting candidate molecules and pathways for further studies on host–virus interactions and VitD-mediated immune regulation. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease with early-age onset. While vitamin D (VitD) has been associated with AD alleviation, geographical factors should be considered as VitD synthesis depends on sunlight exposure and dietary intake. We conducted a mapping review to identify geography-related evidence gaps in interventional and observational studies on the VitD-AD inverse association. We analyzed latitude and the Human Development Index (HDI) as background geographical factors. The review identified 38 studies (17 interventional, 21 observational), of which 26 confirmed the inverse VitD-AD association. Of all reviewed studies, 73% were from latitudes above 35° N, and 70.3% were from developed countries. The median latitude and HDI were 37.5° N and 0.915, respectively. Conversely, only 5.4% of studies were from Africa and 8.1% from Latin America. Studies that did not confirm the inverse VitD-AD association tended to be concentrated in developed countries at higher latitudes (median latitude 42.4° N, median HDI 0.937). Only 8.1% of all studies were from low-latitude developed countries, and among interventional studies this share was even lower (6.3%). In addition, 52.6% of studies lacked data on baseline VitD variability and 13.2% had no baseline VitD data at all. More thorough data reporting and additional clinical studies from countries that do not follow the high latitude/high HDI overlap pattern would facilitate future meta-analyses aimed at clarifying the role of VitD in AD treatment. Full article

Background and Objectives: Reduced bone quality due to osteoporosis significantly complicates oral rehabilitation and bone regeneration therapies. While Vitamin D (Vit. D3) is crucial for osteogenesis, systemic administration often lacks local efficacy. This study aimed to evaluate the osteoregenerative potential of a novel Chitosan-based nanostructured scaffold (NS) loaded with Vit. D3, underlining its efficacy in vitro and in an ovariectomized (OVX) rat model of osteoporosis. Materials and Methods: Chitosan NSs were fabricated with varying Vit. D3 concentrations. In vitro assessments included cytotoxicity (MTT assay), cell viability (Alamar Blue), and mineralization (Alizarin Red) using human dental follicle stem cells. In vivo, 30 Wistar rats were ovariectomized to induce osteoporosis (confirmed by biomarkers Osteocalcin and β-CTX) and were divided into three groups (n = 10). Bilateral maxillary bone defects were treated with (1) a Control (clot only), (2) a Hemostatic Sponge with Vit. D3 (HS/Vit. D3), or (3) an NS loaded with Vit. D3 (NS/Vit. D3-6.25 ng/mL). Histological and morphometric analyses were performed at 4 and 8 weeks. Results: In vitro, the NS loaded with 6.25 ng/mL Vit. D3 demonstrated superior cytocompatibility, achieving a cell viability of 117.77% at 72 h and significantly enhanced calcium nodule deposition compared to controls. In vivo, a total of 44 defect sites were analyzed following the exclusion of compromised samples (Control: 16 sites; HS/Vit. D3: 16 sites; NS/Vit. D3: 12 sites). The NS/Vit. D3-6.25 ng/mL group exhibited the highest degree of mature bone formation and vascularization (p < 0.05) compared to the Control and HS/Vit. D3 groups. While cellular activity (osteoblasts/osteocytes) was initially higher in the HS/Vit. D3 group, the NS/Vit. D3-6.25 ng/mL group achieved superior structural integration and scaffold replacement by mature bone tissue over time. Conclusions: The novel Vit. D3-loaded Chitosan NS effectively promotes bone regeneration in osteoporotic conditions. It supports osteogenic differentiation in vitro and enhances bone matrix maturation in vivo, suggesting its potential as a bioactive scaffold for regenerative dentistry. Full article

Background/aim: Vitamin D (VitD) has been implicated in neuroprotection, yet its role in Parkinson’s disease (PD) remains unclear. This systematic review and meta-analysis aimed to evaluate the association between VitD status, supplementation, and vitamin D receptor (VDR) gene polymorphisms with PD risk and outcomes. Methodology: Following PRISMA guidelines, we searched PubMed, Scopus, and Google Scholar through August 2025 for observational studies, clinical trials, and genetic association studies. Primary outcomes included serum VitD levels in PD versus healthy controls (HCs), prevalence of VitD insufficiency/deficiency, and effects of VitD supplementation on motor symptoms. Secondary outcomes assessed associations between VDR polymorphisms and PD susceptibility. Data were synthesized using random- and fixed-effects models, with heterogeneity and publication bias evaluated. PROSPERO (CRD420251133875). Results: Sixty-three studies (n ≈ 10,700 participants) met inclusion criteria. PD patients exhibited significantly lower VitD levels (SMD = −0.46; 95% CI: −0.51 to −0.41) and higher odds of insufficiency (OR = 1.52) and deficiency (OR = 2.20) compared to HC. Cohort data suggested sufficient VitD may reduce PD risk (HR = 0.83). Supplementation yielded modest, non-significant improvements in motor outcomes. Among 20 genetic studies, FokI (rs2228570) was most consistently associated with PD, while other VDR SNPs showed variable or null associations. Conclusions: VitD deficiency is common in PD and may influence disease risk and motor function. Current evidence indicates limited benefit of supplementation for motor outcomes, and genetic associations remain inconsistent. Full article

Background/Objectives: Postpartum depression (PPD) represents a major public health issue, with a direct impact on the quality of life of the mother–infant dyad. 25-hydroxyvitamin D (25(OH)D), hereafter referred to as VitD, has been suggested to exert protective effects on mood regulation. However, current findings remain inconsistent. This study aimed to assess the association between gestational VitD deficiency (≤19.9 µg/mL) and the diagnosis of PPD three months after delivery. Methods: This longitudinal study followed mother–child dyads in the city of Pelotas, RS, Brazil. A total of 983 pregnant women were initially recruited, of whom 713 had complete data available for this analysis. Blood samples were collected up to 24 weeks of gestation for subsequent measurement of serum VitD levels using chemiluminescence, and PPD diagnosis was established using the Mini International Neuropsychiatric Interview (M.I.N.I. Plus). Logistic regression models were applied and adjusted for potential confounders, such as maternal age, socioeconomic status, and history of depression during pregnancy. Results: In the adjusted model, deficient serum VitD levels were associated with a two-fold-higher likelihood of PPD diagnosis compared to insufficient/sufficient VitD levels (≥20 µg/mL) (OR = 2.0; 95% CI 1.0–4.2; p = 0.049). Conclusions: These findings highlight the potential role of VitD in maternal mental health and support the importance of monitoring VitD status during pregnancy. From a public health standpoint, ensuring adequate vitamin D levels in prenatal care may contribute to reducing the burden of postpartum depression. Full article

(1) Background: this study aimed to determine whether a serum parathyroid hormone (PTH) threshold of 40 pg/mL represents a clinically relevant risk factor for vitamin D (VitD) deficiency and reduced bone mineral density (BMD). It also investigated potential genetic interactions influencing PTH regulation and skeletal health in patients with periodontitis. (2) Methods: a cross-sectional analysis was conducted on 1038 periodontitis patients (35–75 years). Serum PTH, VitD, calcium (Ca), phosphate (P), and urinary parameters were assessed. Dual-energy X-ray absorptiometry (DXA) was used to evaluate BMD in 261 subjects. Vitamin D Receptor (VDR) and estrogen receptor alpha (ERα) polymorphisms were genotyped, and composite genetic risk scores were calculated. Statistical analyses included correlation tests, subgroup comparisons, and regression models. (3) Results: sixty-two percent of individuals had PTH > 40 pg/mL, which was associated with significantly lower 25(OH)D and Ca levels and reduced T-scores (p < 0.05). PTH levels negatively correlated with BMD (Pearson’s r = –0.159, p = 0.0105). Patients with higher ERα polymorphism scores showed increased PTH values (p < 0.05), while VDR variants demonstrated a positive but no significant trend. (4) Conclusions: a PTH threshold of 40 pg/mL identifies individuals at higher risk of VitD deficiency and skeletal fragility, even without overt hypercalcemia. Genetic factors, particularly ERα variants, may contribute to elevated PTH levels, suggesting value in integrating biochemical, densitometric, and genetic screening for early bone health risk stratification. Full article

Background/Objectives: Vitamin D deficiency contributes to pathological vertebral fragility (path-VF), including fragility fractures and early pedicle screw loosening after posterior instrumented spinal fusion (PISF). Supplementation practices remain inconsistent. This retrospective study evaluated whether patients with path-VF receive appropriate vitamin D3 (Vit.D3) supplementation and assessed the dose–response relationship between daily intake and path-VF risk, particularly in older adults. Methods: A total of 210 patients treated with kyphoplasty or PISF (2022–2023) were classified into a path-VF or control group. Daily oral Vit.D3 intake was categorised as Zero- (0 IU), Low- (<2000 IU), or High-Dose (≥2000 IU). Statistical analyses were performed for each dosage group, including subgroup analyses for patients aged ≥67.5 years. Vertebral BMD was estimated using mean Hounsfield Units (HU) from T11–L5. Results: Patients in the path-VF group received significantly lower Vit.D3 doses than controls (1431.4 ± 1055.7 vs. 2366.7 ± 1186.7 IU/day, p < 0.001). Low-dose supplementation was associated with a markedly increased risk of path-VF compared with high-dose in the overall cohort (OR = 6.5, p = 0.003) and in patients aged ≥67.5 years (OR = 8.6, p = 0.008). Logistic regression identified a threshold of 1900 IU/day (AUC = 0.805). Mean vertebral HU values were significantly lower in the path-VF group than in controls (71.9 ± 29.1 vs. 133.5 ± 52.6, p < 0.001), and no consistent HU gains were observed with increasing Vit.D3 dosage. Conclusions: Low-dose Vit.D3 supplementation was associated with increased path-VF risk, especially in patients aged >67.5 years. Patients without path-VF had received significantly higher doses, suggesting broader benefits of adequate Vit.D3 beyond bone density. A daily intake above 1900 IU may serve as a practical threshold for at-risk elderly patients. Full article