Decreased bone mineral density in Costello syndrome.

INTRODUCTION: Costello syndrome (CS) is a multisystemic disorder characterized by postnatal reduced growth, facial dysmorphism, cardiac defects, cognitive impairment, skin and musculo-skeletal anomalies, and predisposition to certain cancers. CS is caused by activating germline mutations in the HRAS proto-oncogene. Similar to what is observed in other RASopathies, CS causative HRAS mutations promote enhanced signal flow through the RAF-MEK-ERK and PI3K-AKT signaling cascades. While decreased bone mineralization has been documented in other RASopathies, such as neurofibromatosis type 1 and Noonan syndrome, systematic studies investigating bone mineral density (BMD) are lacking in CS. MATERIALS AND METHODS: Dual-energy X-ray absorptiometry (DXA) was utilized to assess BMD and body composition (fat and fat-free mass) in a cohort of subjects with molecularly confirmed diagnosis of CS (n = 9) and age-matched control individuals (n = 29). Using general linear regression, subtotal body (total body less head), lumbar, femoral neck and femur BMD parameters were compared considering age, sex, body mass index (BMI) and Tanner stage. Blood and urine biomarkers of bone metabolism were also assessed. RESULTS: All individuals with CS showed significantly lower mean values of subtotal, lumbar and femoral neck BMD compared to the control group (p ≤ 0.01). Similarly, mean total body mass and fat-free mass parameters were lower among the CS patients than in controls (p < 0.01). Low 25-OH vitamin D concentration was documented in all individuals with CS, with values below the reference range in two patients. No significant correlation between vitamin D levels and BMD parameters was observed. DISCUSSION: CS belongs to a family of developmental disorders, the RASopathies, that share skeletal defects as a common feature. The present data provide evidence that, similar to what is recently seen in NF1 and NS, bone homeostasis is impaired in CS. The significant decrease in BMD and low levels of vitamin D documented in the present cohort, along with the risk for pathologic fractures reported in adult individuals with CS, testifies the requirement for a preventive treatment to alleviate evolutive complications resulting from dysregulated bone metabolism.

Association of the visceral adiposity index with femur bone mineral density and osteoporosis among the U.S. older adults from NHANES 2005-2020: a cross-sectional study.

Background: The visceral adiposity index (VAI) is a marker of abdominal fat distribution and adipose tissue function. However, the association between VAI and femur bone mineral density (BMD) and osteoporosis is unclear among the U.S. older adults. Methods: Cross-sectional data for adults aged 60 years and older from the 2007-2020 National Health and Nutrition Examination Survey (NHANES) were included. Multivariable linear and logistic regression were used to evaluate the association between VAI and femur BMD and osteoporosis. We used the smooth curve fitting to address nonlinearity. Moreover, a two-piecewise linear regression model was used to explain the nonlinearity further. Results: The findings of the multivariable logistic regression models showed that as the VAI value increased by one unit, the prevalence of osteoporosis decreased by 1.2% after adjusting for covariates associated with osteoporosis. The multivariable linear regression models demonstrated that VAI was positively correlated with femur BMD. Further analysis revealed an inverted L-shaped and inverted U-shaped relationship between VAI and femur BMD at different sites. Conclusions: Our findings indicated that an increased VAI is independently linked to a higher prevalence of osteoporosis among the U.S. older adults. Further analysis reveals that once VAI reaches a certain threshold, femur BMD no longer increases and may even decrease. This suggests that a moderate accumulation of visceral fat may be beneficial for bone health, while excessive visceral fat could potentially have detrimental effects.

Bone mineral density in lifelong trained male football players compared with young and elderly untrained men.

PURPOSE: The purpose of the present controlled cross-sectional study was to investigate proximal femur and whole-body bone mineral density (BMD), as well as bone turnover profile, in lifelong trained elderly male football players and young elite football players compared with untrained age-matched men. METHODS: One hundred and forty healthy, non-smoking men participated in the study, including lifelong trained football players (FTE, n = 35) aged 65-80 years, elite football players (FTY, n = 35) aged 18-30 years, as well as untrained age-matched elderly (UE, n = 35) and young (UY, n = 35) men. All participants underwent a regional dual-energy X-ray Absorptiometry (DXA) scan of the proximal femur and a whole-body DXA scan to determine BMD. From a resting blood sample, the bone turnover markers (BTMs) osteocalcin, carboxy-terminal type-1 collagen crosslinks (CTX-1), procollagen type-1 amino-terminal propeptide (P1NP), and sclerostin were measured. RESULTS: FTE had 7.3%-12.9% higher (p < 0.05) BMD of the femoral neck, wards, shaft, and total proximal femur in both legs compared to UE, and 9.3%-9.7% higher (p < 0.05) BMD in femoral trochanter in both legs compared to UY. FTY had 24.3%-37.4% higher (p < 0.001) BMD in all femoral regions and total proximal femur in both legs compared to UY. The whole-body DXA scan confirmed these results, with FTE showing similar whole-body BMD and 7.9% higher (p < 0.05) leg BMD compared to UY, and with FTY having 9.6% higher (p < 0.001) whole-body BMD and 18.2% higher (p < 0.001) leg BMD compared to UY. The plasma concentration of osteocalcin, CTX-1, and P1NP were 29%, 53%, and 52% higher (p < 0.01), respectively, in FTY compared to UY. CONCLUSION: BMD of the proximal femur and whole-body BMD are markedly higher in lifelong trained male football players aged 65-80 years and young elite football players aged 18-30 years compared to age-matched untrained men. Elderly football players even show higher BMD in femoral trochanter and leg BMD than untrained young despite an age difference of 47 years.

Association of sarcopenia and physical activity with femur bone mineral density in elderly women.

PURPOSE: This study examined the association of femur bone mineral density (BMD) with body composition and physical activity in elderly women. METHODS: This was a cross sectional study involving 119 women with mean age of 73.1±5.5 years. Body composition parameters including body mass index (BMI), percent of body fat (%BF), appendicular skeletal muscle mass (ASM) index and femur BMD was measured by dual-energy X-ray absorptiometry (DXA). Physical activity was assessed by the uniaxial accelerometer for 7 consecutive days including weekends. Based on femur BMD T-scores, subjects were classified as optimal group, osteopenia group, and osteoporosis group. Based on ASM index, subjects were classified as normal group and sarcopenia group. According to WHO recommendations of physical activity for elderly, the subjects were classified as active group or inactive group. Logistic regression analyses were used to determine the odds ratio (OR) for osteopenia and osteoporosis. RESULTS: There were linear decreases for body composition parameters including weight (P=.023), BMI (P=.039), lean mass (P=.032), ASM index (P=.007) and physical activity parameters including daily of step (P<.001), low intensity physical activity (P<.001), moderate intensity physical activity (P=.001) across femur BMD levels. Compared to the normal group (OR=1), the sarcopenia group had a significantly higher OR (OR=4.823; P=.042), and the inactive group had a significantly higher OR (OR=5.478; P=.005) having osteopenia and osteoporosis when compared to the active group (OR=1). CONCLUSION: The findings of this study suggested that physical activity along with a healthy nutrition should be promoted as a preventive strategy against osteopenia and osteoporosis in elderly women.