Introduction: Metabolic syndrome (MS) is associated with increased carbonyl stress, accumulation of advanced glycation end products (AGE), and induction of arterial calcifications (AC) through the osteoblastic transdifferentiation of vascular smooth muscle cells (VSMC). Metformin (MET) inhibits this transdifferentiation in vitro. We evaluated whether oral MET can prevent AC in an experimental model of MS. Materials and Methods: Young adult male Wistar rats were divided into two groups: one received water as the drinking source (C) and the other a 20% fructose solution (F). After two weeks, and for an additional four weeks, each group was subdivided, and MET (100 mg/kg/day) was added to the drinking water of one half (thus, M and FM). Metabolic and body parameters were measured. The aorta was dissected for histomorphometric and immunohistochemical analyses. Aortic VSMC were isolated to assess alkaline phosphatase (ALP) activity, collagen production, extracellular matrix mineralization, and gene expression of Runx2 and the receptor for AGE (RAGE). Results: Group F developed features consistent with MS, including increased adiposity, non-fasting hyperglycemia, dyslipidemia, and elevated serum fructosamine. Aortas from F animals showed a reduced elastic-to-muscular ratio, increased collagen content, AGE accumulation, and RAGE overexpression. VSMC from F rats displayed higher ALP activity, increased collagen production and mineralization, and elevated expression of Runx2 and RAGE. Cotreatment with MET prevented all these MS-induced alterations. In vitro, MET blocked AGE-induced RAGE upregulation by VSMC, an effect abolished by an AMP-activated protein kinase (AMPK) inhibitor. Conclusion: These findings indicate that oral MET treatment attenuates extracellular glycation, AGE/RAGE activation, and vascular remodeling associated with experimental MS.
Introduction: bone mass undergoes dynamic changes throughout growth. The objective was to evaluate variations in bone remodeling markers, trabecular microarchitecture, and densitometric and biomechanical properties of the femur in female Wistar rats. Materials and methods: six age groups were studied (newborn, 21, 45, 90, 105, and 180 days; n=6/group). Serum levels of calcium (Ca), phosphorus (Pi), osteocalcin (OCN), and C-terminal telopeptide of type I collagen (CTX) were determined. Bone structure was evaluated by histomorphometry (BV/TV), density (BMDft), and femoral bone mineral content (BMOft) by densitometry (DXA), and biomechanics (CSMI, stiffness, fracture strength, Young's modulus) by three-point bending test. Results: the results showed that Ca was highest at 21 and 180 days, and the lowest Pi value was observed at 90 days (p<0.05). OCN decreased and CTX increased from 21 to 180 days of age. BV/TV increased significantly from birth to 45 days. DMOft and CMOft increased up to 180 days. Biomechanical properties reached their maximum values in early adulthood. Discussion: taken together, these findings describe the physiological sequence of bone maturation, where bone turnover initially predominates, followed by a phase of structural gain and, finally, mechanical consolidation of the bone. Conclusions: these data may serve as a reference for experimental studies evaluating interventions on bone health during growth.
Introduction: Angular deformities around the knee, i.e., genu varum and genu valgum, are common in children and can arise from various underlying conditions. Surgical treatment options include temporary hemiepiphysiodesis (guided growth), which is less invasive and carries fewer risks compared to traditional osteotomies. While effective for coronal deformities, the impact of this technique on persistent torsional deformities remains underexplored. Objectives: This study aims to assess the persistent torsional deformity following complete correction of varus coronal deformity in pediatric patients treated with 8-plate hemiepiphysiodesis. Methods: A retrospective case series study was conducted in a tertiary center from March 2023 to January 2025. The study included skeletally immature patients aged 2.5 to 12 years with genu varum deformity who underwent 8-plate hemi-epiphysiodesis for varus deformity correction. Clinical and radiological assessments-including foot progression angle, thigh-foot angle and heel bisector line-were used to evaluate rotational deformities after varus correction. Results: A total of 26 limbs of 14 patients with mean age 4.54 years were analyzed. The mean duration of epiphysiodesis was 10.46 months. Despite successful correction of coronal deformities, 61.5% of patients exhibited persistent intoeing. The persistent torsion was of tibial source which was manifested in the foot progression angle and the thigh-foot angle. Conclusion: While 8-plate is effective for coronal deformity correction in pediatric genu varum, a significant proportion of patients retain persistent torsional deformities.
Introduction: Fragility fractures in older adults often coexist with comorbidities, affecting their location and severity. Objective: To analyze whether the number of comorbidities acts as a mediator in the association between hypertension and fragility fracture type in older adults. Materials and methods: A cross-sectional study based on secondary data from 719 adults aged >= 50 years with non-vertebral fragility fractures. Hayes' PROCESS model 4 was used to assess whether the total number of comorbidities mediated the association between hypertension and fracture type (upper vs. lower limb). Linear and logistic regressions were adjusted for age, sex, diabetes, dyslipidemia, smoking, and calcium/vitamin D supplementation. Bootstrap resampling with 5000 iterations was applied. Results were illustrated in a mediation model diagram to represent the theoretical analytical framework. Results: Hypertension (B=1.35; p<0.001), diabetes mellitus (B=1.09; p<0.001), dyslipidemia (B=1.36; p<0.001), and vitamin D use (B=0.73; p<0.001) were associated with a higher number of comorbidities. In the logistic regression, a direct positive association between hypertension and upperlimb fractures was observed (B=0.43; p=0.042), along with a significant indirect association mediated by comorbidities (B=-0.48; 95% CI: -0.73 to-0.28). A higher number of comorbidities was associated with lower limb fractures (B=-0.36; p<0.001). Sex (B=-0.50; p=0.012), dyslipidemia (B=0.82; p<0.001), smoking (B=0.42; p=0.033), and low calcium intake (B=-0.71; p=0.008) were also significant. Conclusions: Hypertension was associated with upper limb fractures; however, this association was attenuated or reversed in the presence of multiple comorbidities, favoring lower limb fractures.
Introduction: medical history increases the risk of fragility fractures, predisposing to more vulnerable areas according to the type of history. Objective: to determine the most vulnerable areas of fragility fractures according to clinical history. Materials and method: analytical and crosssectional study of a secondary database of 719 adults. The variables were the presence of shoulder, wrist, hip and ankle fractures, age, sex, diabetes mellitus, hypertension, obesity, smoking, reduced mobility, dyslipidemia, osteoporosis, age, arthritis, renal, cardiovascular and thyroid disease, cancer and number of comorbidities. The automatic detection tree of chi-square interactions and Cramer's V were used. Results: the decision tree identified key variables of fragility fracture areas, age group, diabetes and comorbidities. Ankle fractures were associated primarily with individuals aged 50 to 65 years with diabetes (V=0.181; p<0.001). Hip fractures with individuals aged 84 years or older (V=0.332; p<0.001). Shoulder and wrist fractures with individuals aged 66 to 83 years with two or fewer comorbidities (V=0.216; p<0.001). Conclusions: fragility fractures are significantly associated with age and the presence of comorbidities, especially diabetes. People older than 84 years have a greater propensity for hip fractures, those between 50 and 65 years with diabetes are more prone to ankle fractures. Shoulder and wrist fractures are more common in individuals aged 66 to 83 years with few comorbidities.
