Diana Jecan-Toader

Background: Vitamin D, through its role in antimicrobial peptide (AMP) expression, may influence innate immunity and inflammation in urinary tract infections (UTIs). This study evaluated its role in patients with vesicoureteral reflux (VUR) and its contribution to the pathophysiology of reflux nephropathy (RN). Methods: We conducted a cross-sectional observational study of 25 pediatric patients with VUR, representing a subgroup analysis of a larger cohort examined in a previous study. We determined patients’ vitamin D status, correlated it with recurrent UTIs and RS, and explored its relationship with urinary LL-37, NGAL, and IL-6 levels as markers of innate immune function. Results: Serum vitamin D levels ranged from 10.7 to 123.2 ng/mL (mean 39.5 ng/mL); 12% had deficiency and 20% had insufficient levels. Low vitamin D levels were detected in patients with more than five acute pyelonephritis (APNs), with a mean value classified as insufficient (27.3 ng/mL). Patients with RS had a lower mean vitamin D level compared to those without (30.51 ng/mL vs. 41.23 ng/mL), though the difference was not statistically significant (p = 0.39). No significant associations were found between vitamin D and urinary IL-6 or NGAL levels. A strong positive correlation was observed between vitamin D and urinary LL-37/creatinine (r = 0.78, r² = 0.61). Conclusions: Vitamin D appears to influence the frequency of UTIs and the development of RS, primarily by modulating LL-37 secretion, suggesting a possible role in the pathophysiology of RN.

Background: Vitamin K2 (menaquinone) has been studied as a molecule with important effects on bone metabolism and has been proposed as a potential adjuvant in fracture healing, particularly under osteoporotic conditions. However, its functional impact on osteoporotic fracture healing remains largely undefined. The aim of this study was to evaluate the effects of vitamin K2 supplementation, in the form of menaquinone-4 (MK-4) and menaquinone-7 (MK-7), on fracture healing in an ovariectomized rat model of osteoporosis. Methods: Forty Wistar rats were included in this study and allocated to four equal groups: Sham control, ovariectomized control, MK-4, and MK-7. Osteoporosis was induced by bilateral ovariectomy, and 12 weeks after ovariectomy, a femoral fracture was produced and fixed by intramedullary nailing. Starting on postoperative day 2, the MK-4 group received 5 mg/kg/day of MK-4, while the MK-7 group received MK-7 at a dose of 0.05 mg/kg/day. Fracture healing was assessed primarily by biomechanical testing using a three-point bending test and was further analyzed by histological and biochemical parameters, including CTXI, PINP, ucOC, BALP, and ALT. Results: Vitamin K2 supplementation did not improve functional fracture healing. In both treatment groups, fractures showed nonunion-like mechanical behavior, precluding meaningful quantitative biomechanical comparison. Although histological and biochemical findings, particularly in the MK-4 group, showed some degree of biological activity, these changes did not translate into mechanically competent bone union. Both treatment groups showed a tendency toward impaired healing, with progression toward nonunion-like behavior under the present experimental conditions. No significant hepatic toxicity was observed. Conclusions: In this ovariectomized rat femoral fracture model, vitamin K2 supplementation with either MK-4 or MK-7 did not enhance functional fracture healing despite evidence of biological activity of the treatment. These findings suggest a discrepancy between molecular or histological effects and biomechanical outcomes, indicating that, under the conditions tested, vitamin K2 is insufficient to overcome impaired healing in osteoporotic bone and may adversely influence fracture repair under these experimental conditions, although the mechanism remains uncertain.

Background: Osteoporosis is a major skeletal disorder, particularly affecting postmenopausal women. Young ovariectomized rat models are commonly used to investigate estrogen deficiency-related skeletal changes, although they do not fully reproduce osteoporosis in a mature postmenopausal skeleton. Established pharmacological therapies remain the cornerstone of osteoporosis management, while nutritional factors continue to be investigated for their potential supportive role in bone metabolism. Menaquinone-7 (MK-7), a form of vitamin K2, has been investigated for potential skeletal effects through vitamin k-dependent mechanisms, particularly osteocalcin carboxylation. The aim of this study was to evaluate the dose-dependent effects of MK-7 on bone turnover markers, femoral mechanical resistance, qualitative histological findings, and hepatic safety in a young ovariectomized rat model. Methods: Forty female Wistar rats that were 8 weeks old, and thus still undergoing skeletal maturation, were assigned to four groups: sham-operated controls, ovariectomized controls, ovariectomized rats treated with low-dose MK-7, and ovariectomized rats treated with high-dose MK-7. Treatment was administered every 48 h for 12 weeks. At study completion, 35 rats survived; standardized analysis included eight animals per group. Plasma bone turnover markers (BTMs) and alanine aminotransferase were measured, femoral strength was assessed by the three-point bending test, and bone and liver histology was analyzed. Results: Biomechanical testing showed that high-dose MK-7 was associated with greater femoral mechanical resistance compared with untreated ovariectomized rats, while qualitative histology suggested differences in cortical architecture among groups. Biochemically, MK-7 treatment reduced undercarboxylated osteocalcin, suggesting vitamin K-dependent target engagement, whereas conventional turnover markers showed discordant findings. Overall, hepatic architecture was preserved, although mild hepatocellular apoptosis was observed. Conclusions: In this young OVX rat model, high-dose MK-7 was associated with improved femoral mechanical resistance compared with untreated OVX controls. However, because ovariectomy was performed during skeletal maturation, these findings should be interpreted as preliminary and cannot be directly extrapolated to established postmenopausal osteoporosis in a mature skeleton, and further studies are needed to clarify its activity pathways and safety profile.

Background and Objectives: Distal radius fractures (DRFs) represent the most common fracture in the elderly population and are typically the first fractures to occur in the sequence of fragility fractures. Although fracture instability is an important criteria for guiding treatment, there is no universal consensus on how to define an unstable DRF. Given the demonstrated influence of bone quality on fracture stability, it has been hypothesized that second metacarpal index (2MCI) may also serve as a predictor of instability in DRFs. This study aimed to evaluate the predictive value of 2MCI for fracture instability and to determine its threshold value beyond which surgical management should be considered. Materials and Methods: A retrospective study was conducted between January 2023 and May 2025 investigating conservatively treated DRFs. Radiographic parameters including 2MCI, volar inclination, radial inclination, and ulnar variance were obtained at three time points: pre-reduction, post-reduction, and at 6 weeks of follow-up time. Univariate and multivariate linear regression analysis and receiver operating characteristic (ROC) analysis were conducted to determine the optimal 2MCI threshold for predicting clinically significant displacement. Results: A strong correlation was found between 2MCI and the changes (∆) in volar inclination (p < 0.001), radial inclination (p < 0.001), and ulnar variance (p < 0.001) in univariate regression analysis. In multivariate regression analysis, 2MCI was an independent predictor of ∆ volar inclination (p < 0.001) and ∆ radial inclination (p = 0.004). For ∆ ulnar variance, both 2MCI (p = 0.003) and initial displacement (p = 0.049) were statistically significant predictors. A 2MCI cut-off value of 0.412 predicted a ∆ volar inclination greater than 10° (sensitivity 80.9% and specificity 74.1%, p < 0.001). Conclusions: The results of this study reveal the potential of the 2MCI as a quantitative marker of both fracture instability and bone fragility. Further prospective validation may demonstrate its role as a standard radiographic parameter in DRFs, as well as in guiding treatment selection.