Bone remodeling is a lifelong process, due to the balanced activity of the osteoblasts (OBs), the bone-forming cells, and osteoclasts (OCs), the bone-resorbing cells. This equilibrium is mainly regulated by the WNT-ß-cathenin pathway and the RANK-RANKL/OPG system, respectively. Bone ageing is a process which normally occurs during life due to the imbalance between bone formation and bone resorption, potentially leading to osteoporosis. Bone loss associated with bone ageing is determined by oxidative stress, the result of the increasing production of reactive oxygen species (ROS). The promotion of physical exercise during growth increases the chances of accruing bone and delaying the onset of osteoporosis. Several studies demonstrate that physical exercise is associated with higher bone mineral density and lower fracture incidence, and the resulting bone mineral gain is maintained with ageing, despite a reduction of physical activity in adulthood. The benefits of exercise are widely recognized, thus physical activity is considered the best non-pharmacologic treatment for pathologies such as osteoporosis, obesity, diabetes and cardiovascular disease. We reviewed the physiological mechanisms which control bone remodeling, the effects of physical activity on bone health, and studies on the impact of exercise in reducing bone ageing.

Polycystic ovary syndrome (PCOS) represents an endocrine condition affecting 5–18% of adolescents, frequently in association with obesity, metabolic alterations, and liver dysfunction. In this study, we aimed to evaluate the prevalence and risk factors for developing non-alcoholic fatty liver disease (NAFLD) in a cohort of PCOS adolescents. Thirty-two girls were assessed for anthropometric and biochemical markers: total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), glucose, insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (γGT). In addition, LH, FSH, 17β-Estradiol (E2), prolactin, testosterone (T), free testosterone, delta 4-androstenedione (D4 A), dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding protein (SHBG) were also evaluated. All subjects underwent liver ultrasound to detect NAFLD. Our data demonstrated that PCOS adolescents complicated with NAFLD accounted for 37.5%, and those with obesity and lower SHBG were more predisposed to developing NAFLD. Moreover, SHBG showed a negative correlation with several parameters such as blood pressure, body mass index, waist circumference, insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR). Our results demonstrated that the assessment of SHBG may allow the identification of PCOS adolescents at risk for developing NAFLD and metabolic alterations.

Background and Aims: Coronavirus disease 2019 (COVID-19) lockdown has represented an inedited model of increased metabolic risk in all age groups, due to negative changes in dietary habits, physical activity, lifestyle. These effects have been generally explored at a population level in distinct age groups. Potential intra-familial, specific effects in adults and children sharing the same socio-economic, cultural level and living habits have been scarcely explored. We aimed to characterize changes of anthropometric indices in parents and in their children during COVID-19 lockdown. Methods: A cohort of 149 couple parent/children were prospectively enrolled. By a validated questionnaire we explored changes of body mass index (BMI) and individual lifestyle during a 2-month lockdown (May- July 2020). Results: BMI increased in 70.5% of parents and in 67.8% of their children, with a Δ-BMI of 1.44+0.09 kg/ m 2 and 0.36+0.02 Kg/m 2 , respectively. BMI increments, however, were only significant in adults and did not correlate in the couple parents/children. Most adults (80.5%) and children (71.4%) did not perform regular physical activity during the lockdown. Direct correlations between dietary changes and BMI variations became evident in children, mainly in terms of a decreased consumption of fresh fruit, pulses, fish, and an increased consumption of cereals, carbohydrates, dairy products, olive oil. In normal weight, overweight and obese children, but not in adults, the increase in sleep hours increased with BMI. Conclusions: Despite marked lifestyle changes imposed by the COVID-19 lockdown, BMI variations in parents were independent from those observed in their children, pointing to different outcomes in response to the same external, critical event. Thus, primary prevention measures aimed at maintaining a healthy lifestyle require different approaches according to age.

Noonan syndrome (NS) is a genetic disorder characterized by distinctive craniofacial and skeletal features, short stature, mild to moderate developmental impairment, and multisystem involvement, notably affecting the cardiovascular, musculoskeletal, and endocrine systems. Although abnormalities of the bone matrix, as well as osteopenia and osteoporosis, are well recognized in individuals with NS and other RASopathies, the specific impact of RAS/MAPK pathway dysregulation on bone health remains poorly understood. Objectives: The aim of this study was to evaluate bone turnover and bone remodeling markers in a cohort of children with NS, to gain further insights into the bone status of these patients. Methods: In this cross-sectional, case-control study, we analyzed 28 children (20 males) with a molecular diagnosis of NS and 35 healthy subjects (21 males), matched by age and sex. We assessed markers of bone metabolism and bone turnover (calcium, phosphate, PTH, 25(OH)-vitamin D, osteocalcin, procollagen I N-propeptide-P1NP, bone alkaline phosphatase-BALP, C-telopeptides of type I collagen-CTX) and bone remodeling (RANKL, OPG, and sclerostin). Bone mineralization was measured at the lumbar spine (L2–L4) using dual-energy X-ray absorptiometry (DEXA). Results: Serum CTX levels were significantly higher in NS patients compared to controls (1.8 ± 0.7 vs. 1.3 ± 0.5 ng/mL, p = 0.0004). RANKL levels were higher in NS patients, although the difference did not reach statistical significance. No significant differences were found for OPG, sclerostin, or other markers of bone metabolism between patients and controls. Conclusions: Children with NS exhibit increased bone resorption, as indicated by elevated CTX levels, suggesting a potential imbalance in bone remodeling processes. Further studies are warranted to better define the impact of RAS/MAPK pathway dysregulation on bone health in this population.