Every Move Counts to Improve Bone Health at Clinical Sites in Young Pediatric Cancer Survivors: The iBoneFIT Project.

PURPOSE: We aimed to examine the associations of 24-h movement behaviors (moderate to vigorous physical activity [MVPA], light physical activity [LPA], sedentary behavior [SB], and sleep) with age-, sex-, and race-specific areal bone mineral density (aBMD) z -score parameters at clinical sites in young pediatric cancer survivors. METHODS: This cross-sectional multicenter study was carried out within the iBoneFIT framework in which 116 young pediatric cancer survivors (12.1 ± 3.3 yr old; 42% female) were recruited. We obtained anthropometric and body composition data (i.e., body mass, stature, body mass index, and region-specific lean mass), time spent in movement behaviors over at least seven consecutive 24-h periods (wGT3x-BT accelerometer, ActiGraph), and aBMD z -score parameters (age-, sex-, and race-specific total at the body, total hip, femoral neck and lumbar spine). Survivors were classified according to somatic maturity (pre or peri/postpubertal depending on the estimated years from peak height velocity). The adjusted models' coefficients were used to predict the effect of reallocating time proportionally across behaviors on the outcomes. RESULTS: In prepubertal young pediatric cancer survivors, reallocating time to MVPA from LPA, SB, and sleep was significantly associated with higher aBMD at total body ( B = 1.765, P = 0.005), total hip ( B = 1.709, P = 0.003), and lumbar spine ( B = 2.093, P = 0.001). In peri/postpubertal survivors, reallocating time to LPA from MVPA, SB, and sleep was significantly associated with higher aBMD at all sites ( B = 2.090 to 2.609, P = 0.003 to 0.038). Reallocating time to SB from MVPA or LPA was significantly associated with lower aBMD at most sites in prepubertal and peri/postpubertal survivors, respectively. Finally, reallocating time to sleep from MVPA, LPA, and SB was significantly associated with lower aBMD at total body ( B = -2.572, P = 0.036) and total hip ( B = -3.371, P = 0.015). CONCLUSIONS: These findings suggest that every move counts and underline the benefits of increasing MVPA or LPA, when low MVPA levels are present, for bone regeneration after pediatric cancer treatment completion.

Muscle strength deficits are associated with low bone mineral density in young pediatric cancer survivors: The iBoneFIT project.

BACKGROUND: Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density (aBMD). However, the prevalence of muscle strength deficits is not well documented, and the associations of muscle strength with aBMD are unknown in this population. Therefore, this study aimed to investigate the prevalence of upper- and lower-body muscle strength deficits and to examine the associations of upper- and lower-body muscle strength with age-, sex, and race-specific aBMD Z-scores at the total body, total hip, femoral neck, and lumbar spine. METHODS: This cross-sectional study included 116 pediatric cancer survivors (12.1 ± 3.3 years old, mean ± SD; 42.2% female). Upper- and lower-body muscle strength were assessed by handgrip and standing long jump test, respectively. Dual­energy X­ray absorptiometry was used to measure aBMD (g/cm2). Associations between muscle strength and aBMD were evaluated in multivariable linear regression models. Logistic regression was used to evaluate the contribution of muscle strength (1-decile lower) to the odds of having low aBMD (Z-score ≤ 1.0). All analyses were adjusted for time from treatment completion, radiotherapy exposure, and body mass index. RESULTS: More than one-half of survivors were within the 2 lowest deciles for upper- (56.9%) and lower- body muscle strength (60.0%) in comparison to age- and sex-specific reference values. Muscle strength deficits were associated with lower aBMD Z-scores at all sites (B = 0.133-0.258, p = 0.001-0.032). Each 1-decile lower in upper-body muscle strength was associated with 30%-95% higher odds of having low aBMD Z-scores at all sites. Each 1-decile lower in lower-body muscle strength was associated with 35%-70% higher odds of having low aBMD Z-scores at total body, total hip, and femoral neck. CONCLUSION: Muscle strength deficits are prevalent in young pediatric cancer survivors, and such deficits are associated with lower aBMD Z-scores at all sites. These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added benefit of improving aBMD.

Which indices of cardiorespiratory fitness are more strongly associated with brain health in children with overweight/obesity?

PURPOSE: To compare the strength of associations between different indices of cardiorespiratory fitness (CRF) and brain health outcomes in children with overweight/obesity. METHODS: Participants were 100 children aged 8-11 years. CRF was assessed using treadmill exercise test (peak oxygen uptake [V̇O2peak ], treadmill time, and V̇O2 at ventilatory threshold) and 20-metre shuttle run test (20mSRT, laps, running speed, estimated V̇O2peak using the equations by Léger et al., Mahar et al., and Matsuzaka et al.). Intelligence, executive functions, and academic performance were assessed using validated methods. Total gray matter and hippocampal volumes were assessed using structural MRI. RESULTS: V̇O2peak /body mass (ß = 0.18, 95% CI = 0.01-0.35) and treadmill time (ß = 0.18-0.21, 95% CI = 0.01-0.39) were positively associated with gray matter volume. 20mSRT laps were positively associated with executive functions (ß = 0.255, 95% CI = 0.089-0.421) and academic performance (ß = 0.199-0.255, 95% CI = 0.006-0.421), and the running speed was positively associated with executive functions (ß = 0.203, 95% CI = 0.039-0.367). Estimated V̇O2peak/Léger et al. was positively associated with intelligence, executive functions, academic performance, and gray matter volume (ß = 0.205-0.282, 95% CI = 0.013-0.500). Estimated V̇O2peak/Mahar et al. and V̇O2peak/Matsuzaka et al. (speed) were positively associated with executive functions (ß = 0.204-0.256, 95% CI = 0.031-0.436). CONCLUSION: Although V̇O2peak is considered the gold standard indicator of CRF in children, peak performance (laps or running speed) and estimated V̇O2peak/Léger et al. derived from 20mSRT had stronger and more consistent associations with brain health outcomes than other indices of CRF in children with overweight/obesity.

A 20-week exercise program improved total body and legs bone mineral density in children with overweight or obesity: The ActiveBrains randomized controlled trial.

OBJECTIVES: The aim of this study was to investigate the effect of a 20-week exercise program on bone mineral parameters in children with overweight or obesity. DESIGN: Randomized controlled trial. METHODS: This study took part from November 21, 2014, to June 30, 2016, in Granada, Spain. A secondary analysis of this parallel-group randomized controlled trial was performed with 77 children with overweight or obesity (9.9 ±â€¯1.2, 65 % boys) who were randomly allocated to exercise or control group. All participants received lifestyle recommendations. The control group continued their usual routines, whereas the exercise group attended a minimum of 3 supervised 90-minute sessions/week of aerobic plus resistance training for 20 weeks. A whole-body scan by dual-energy X-ray absorptiometry was carried out to obtain body composition at total body less head, arms, lumbar spine, pelvis, and legs. RESULTS: Participants in the exercise group acquired significantly higher total body aBMD (mean z-score [95 % confidence intervals, CI], 0.607 [0.522-0.692]) compared with the participants in the control group (mean z-score, 0.472 [0.388-0.556]); difference between groups, 0.135 standard deviations [95 % CI 0.015-0.255], and legs aBMD (mean z-score, 0.629 [0.550-0.708]); control group (mean z-score, 0.518 [0.440-0.596]); difference between groups, 0.111 [0.001-0.222]; all p < 0.05. There were no significant differences between exercise group and control group at the remaining evaluated regions (p > 0.05). CONCLUSIONS: A 20-week non-specifically bone-targeted exercise program induced a small, yet significant, improvement on total body and legs aBMD in children with overweight or obesity. Future studies should investigate the interaction of weight status in the bone response to exercise programs. TRIAL REGISTRATION: Prospectively registered in ClinicalTrials.gov Identifier: NCT02295072.

Determinants of bone parameters in young paediatric cancer survivors: the iBoneFIT project.

BACKGROUND: Bone health is remarkably affected by endocrine side effects due to paediatric cancer treatments and the disease itself. We aimed to provide novel insights into the contribution of independent predictors of bone health in young paediatric cancer survivors. METHODS: This cross-sectional multicentre study was carried out within the iBoneFIT framework in which 116 young paediatric cancer survivors (12.1 ± 3.3 years old; 43% female) were recruited. The independent predictors were sex, years from peak height velocity (PHV), time from treatment completion, radiotherapy exposure, region-specific lean and fat mass, musculoskeletal fitness, moderate-vigorous physical activity and past bone-specific physical activity. RESULTS: Region-specific lean mass was the strongest significant predictor of most areal bone mineral density (aBMD), all hip geometry parameters and Trabecular Bone Score (ß = 0.400-0.775, p ≤ 0.05). Years from PHV was positively associated with total body less head, legs and arms aBMD, and time from treatment completion was also positively associated with total hip and femoral neck aBMD parameters and narrow neck cross-sectional area (ß = 0.327-0.398, p ≤ 0.05; ß = 0.135-0.221, p ≤ 0.05), respectively. CONCLUSION: Region-specific lean mass was consistently the most important positive determinant of all bone parameters, except for total hip aBMD, all Hip Structural Analysis parameters and Trabecular Bone Score. IMPACT: The findings of this study indicate that region-specific lean mass is consistently the most important positive determinant of bone health in young paediatric cancer survivors. Randomised clinical trials focused on improving bone parameters of this population should target at region-specific lean mass due to the site-specific adaptations of the skeleton to external loading following paediatric cancer treatment. After paediatric cancer diagnosis, years from peak height velocity (somatic maturity) is critical for bone development.

Effect of exercise on bone health in children and adolescents with cancer during and after oncological treatment: A systematic review and meta-analysis.

Background: Although regular physical activity and exercise programs might improve bone health caused by oncological treatment and the disease itself, it remains unknown the pooled effect of exercise interventions following frequency, intensity, time and type prescriptions. Objective: This systematic review and meta-analysis aimed to synthesise evidence regarding the effectiveness of exercise interventions on bone health in children and adolescents with cancer during and after oncological treatment. Methods: A systematic search was conducted in the MEDLINE (via PubMed), Web of Science and Scopus databases from November 2021 to January 2022. Randomised controlled trials (RCTs) and non-RCTs reporting pre-post changes of the effectiveness of exercise interventions on DXA-measured bone parameters in young population (1-19 years) during or after oncological treatment were included. Pooled (ESs) and 95% confidence intervals (95%CIs) were calculated. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Results: A total of eight trials with 341 participants were included. The meta-analyses did not reveal a statistically significant increase in whole body areal bone mineral density (ES = 0.10; 95%CI: -0.14, 0.34), lumbar spine (ES = 0.03; 95%CI: -0.21, 0.26) or femoral neck (ES = 0.10; 95%CI: -0.37, 0.56). Similarly, during the oncological treatment phase the ES was 0.04 (95%CI: -0.17, 0.25) and after the ES was 0.07 (95%CI: -0.20, 0.33). Conclusion: To date, exercise interventions have been inappropriate and therefore, ineffective to illustrate any beneficial effect on bone health in children and adolescents with cancer during and after oncological treatment. Systematic Review Registration: PROSPERO registration number: CRD42022310876.

Speed, agility, and musculoskeletal fitness are independently associated with areal bone mineral density in children.

Background: There is still little understanding of the associations between physical fitness variables and bone health in children taking into account key confounders. Aim: The aim of this study was to analyze the associations between performance in tests of speed, agility, and musculoskeletal fitness (power of the upper and lower limbs) with bone mass of different regions in children, considering the adjustment to maturity-offset, lean percentage, and sex. Methods: Cross-sectional study design: the sample consisted of 160 children aged 6-11 years. The physical fitness variables tested were 1) speed, assessed with the running test at a maximum speed of 20 m; 2) agility, assessed through the 4×4-m square test; 3) lower limb power, assessed using the standing long jump test, and 4) upper limb power, assessed using the 2-kg medicine ball throw test. Areal bone mineral density (aBMD) was obtained from the analysis of body composition by dual-energy X-ray absorptiometry (DXA). Simple and multiple linear regression models were performed using the SPSS software. Results: In the crude regression analyses, the results indicated a linear relationship between all the physical fitness variables and aBMD in all body segments, but maturity-offset, sex, and lean mass percentage seemed to have an effect on these relationships. Except for the upper limb power, the other physical capacities (speed, agility, and lower limb power) were associated with aBMD in at least three body regions in the adjusted analyses. These associations occurred in the spine, hip, and leg regions, and the aBMD of the legs presented the best association magnitude (R 2). Conclusion: There is a significant association between speed, agility, and musculoskeletal fitness, specifically the lower limb power and aBMD. That is, the aBMD is a good indicator of the relationship between fitness and bone mass in children, but it is essential to consider specific fitness variables and skeletal regions.

Is higher physical fitness associated with better psychological health in young pediatric cancer survivors? A cross-sectional study from the iBoneFIT project.

OBJECTIVE: To examine the associations of self-perceived and objectively-measured physical fitness with psychological well-being and distress indicators in young pediatric cancer survivors. MATERIALS AND METHODS: A total of 116 participants (12.1 ± 3.3 years, 56.9% boys) from the iBoneFIT project participated in this cross-sectional study. Objectively-measured physical fitness (muscular fitness) was obtained by handgrip strength and standing long jump tests for the upper and lower body, respectively. Self-perceived physical fitness was obtained by the International Fitness Scale (IFIS). Positive and negative affect were assessed by the positive affect schedule for children (PANAS-C), happiness by Subjective Happiness Scale (SHS), optimism by Life Orientation Test-Revised (LOT-R), self-esteem by the Rosenberg Self-Esteem Scale (RSE), anxiety by State-Trait Anxiety Inventory for Children (STAIC-R), and depression by Children Depression Inventory (CDI). Multiple linear regressions adjusted by key covariates were performed to analyze associations. RESULTS: No associations were found between objectively-measured muscular fitness and any of the psychological well-being and distress indicators (p > 0.05). Self-perceived overall fitness and flexibility were positively associated with positive affect (ß ≥ 0.258, p < 0.05). Self-perceived cardiorespiratory fitness, speed/agility, and flexibility were negatively associated with depression (ß ≥ -0.222, p < 0.05). Finally, self-perceived cardiorespiratory fitness was also negatively associated with anxiety and negative affect (ß ≥ -0.264, p < 0.05). CONCLUSIONS: Perceived physical fitness, but not objectively physical fitness, seems to be inversely related to psychological distress variables and to less extent positively related to psychological well-being. The findings from this study highlight the importance of promoting self-perceived fitness in the pediatric oncology population.

Comparative effects of different types of exercise on health-related quality of life during and after active cancer treatment: A systematic review and network meta-analysis.

BACKGROUND: The positive influence of most types of exercise has been reported repeatedly, but what the most effective exercise approaches are for improving health-related quality of life (HRQoL) in people with cancer remains unknown. The aim of this systematic review and network meta-analysis was to synthesize the evidence from intervention studies to assess the effects of different types of exercise on HRQoL during and after cancer treatment. METHODS: MEDLINE, SPORTDiscus, the Cochrane Library, Web of Science, and Scopus were searched for randomized controlled trials aimed at testing the effects of exercise interventions meant to improve HRQoL in people with cancer. Separate analyses were conducted for HRQoL as measured by general and cancer-specific questionnaires. We also evaluated whether the effects of exercise were different during and after cancer treatment in both the physical and mental HRQoL domains. RESULTS: In total, 93 studies involving 7435 people with cancer were included. Network effect size estimates comparing exercise intervention vs. usual care were significant for combined exercise (0.35, 95% confidence interval (95%CI): 0.14-0.56) for HRQoL as measured by general questionnaires, and for combined (0.31, 95%CI: 0.13-0.48), mind-body exercise (0.54, 95%CI: 0.18-0.89), and walking (0.39, 95%CI: 0.04-0.74) for HRQoL as measured by cancer-specific questionnaires. CONCLUSION: Exercise programs combining aerobic and resistance training can be recommended to improve HRQoL during and after cancer treatment. The scarcity and heterogeneity of these studies prevents us from making recommendations about other exercise modalities due to insufficient evidence.

Cardiorespiratory Fitness and Bone Turnover Markers in Adults With Metabolic Syndrome: The Mediator Role of Inflammation.

The relationship between inflammatory markers and bone turnover in adults is well known, and a negative association between cardiorespiratory fitness (CRF) and inflammatory markers has also been described. Hence, we tested whether the association between CRF and bone turnover markers is mediated by inflammatory markers in adults with metabolic syndrome. A total of 81 adults (58.5 ± 5.0 years, 62.7% women) were included in the analysis. CRF was measured by the 6-min walking test. Serum interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor alpha, high-sensitivity c-reactive protein (hsCRP) and vascular endothelial growth factor, collagen type I cross-linked C-telopeptide, procollagen type I N-terminal propeptide (P1NP), and total osteocalcin were assessed using a sensitive ELISA kit. Body composition was assessed by dual-energy X-ray absorptiometry. Partial correlation was used to test the relationship between CRF, inflammatory markers, and bone turnover markers, controlling for sex, lean mass, and fat mass. Boot-strapped mediation procedures were performed, and indirect effects with confidence intervals not including zero were interpreted as statistically significant. CRF was positively correlated with P1NP levels (r = .228, p = .044) and osteocalcin levels (r = .296, p = .009). Furthermore, CRF was positively correlated with IL-1ß levels (r = .340, p = .002) and negatively correlated with hsCRP levels (r = -.335, p = .003), whereas IL-1ß levels were positively correlated with P1NP levels (r = .245, p = .030), and hsCRP levels were negatively correlated with P1NP levels (r = -.319, p = .004). Finally, the association between CRF and P1NP levels was totally mediated by hsCRP (percentage of mediation = 39.9). Therefore, CRF benefits on bone formation could be dependent on hsCRP concentrations in this population.

Leptin levels were negatively associated with lumbar spine bone mineral content in children with overweight or obesity.

AIM: Adipokines seem to play a role in bone morphogenesis, although this also depends on the mechanical forces applied to the skeleton. The aim was to assess the relationships of resting leptin and adiponectin with bone parameters and whether high muscular fitness levels affect these relationships in children with overweight or obesity. METHODS: This cross-sectional study took part from 2014 to 2016 in Granada, Spain. Participants were recruited from University Hospitals, and we also used advertisements in local media and school contacts in the city. Adipokines were analysed in plasma. Muscular fitness was assessed by one repetition maximum in bench and leg press tests. Dual-energy X-ray absorptiometry was used to measure bone parameters. RESULTS: We included 84 children (10.0 ± 1.2y; 63% boys) in this analysis. Leptin was negatively associated with lumbar spine bone mineral content (ß = -0.162, p = 0.053). No significant interaction was found for muscular fitness. Simple slope estimates suggested that children performing more than 133.3 kg in leg press test ameliorated the negative association between leptin and lumbar spine bone mineral content. CONCLUSION: Leptin levels were negatively associated with lumbar spine bone mineral content in children with overweight or obesity. A high muscular fitness at the lower body could counteract this association.

Improving cardiorespiratory fitness protects against inflammation in children: the IDEFICS study.

BACKGROUND: Muscular and cardiorespiratory fitness (MF and CRF) have been related to inflammation. Thus, the aim of this study was to assess the relationship between fitness and high-sensitivity C-reactive protein (hs-CRP) in European children both in the cross-sectional and longitudinal analysis. METHODS: Three hundred and fifty-seven children (46.2% males) aged 2-9 years with hs-CRP measured, data from MF and CRF, diet quality, objectively measured physical activity (PA) and screen time at baseline and follow-up after 2 years were included. Body mass index z-score (zBMI), waist circumference (WC) and fat mass index (FMI) were assessed. MF and CRF were also dichotomized as follows: low-medium quartiles (Q1-Q3) and highest quartile (Q4). RESULTS: At follow-up, children with the highest CRF (Q4) showed a lower probability of having high hs-CRP. In the longitudinal analysis, children who improved their CRF over time showed a significantly lower probability (p < 0.05) of being in the highest hs-CRP category at follow-up, independently of the body composition index considered: odds ratio (OR) = 0.22 for zBMI, OR = 0.17 for WC, and OR = 0.21 for FMI. CONCLUSIONS: Improving CRF during childhood reduces the odds of an inflammatory profile, independently of body composition and lifestyle behaviours. These highlight the importance of enhancing fitness, especially CRF, to avoid an inflammatory state in children. IMPACT: Improvements in the cardiorespiratory profile during childhood could reverse an unfavourable inflammatory status. There is a longitudinal and inverse association between CRF and inflammation in children. This is the first longitudinal study assessing the relationship between fitness and inflammation during childhood that takes also into account the lifestyle behaviours. Results from the present study suggest a protective role of fitness already in childhood. Efforts to improve fitness in children should be aimed at as inflammation could trigger future cardiovascular disease.

Do patients with type 2 diabetes have impaired hip bone microstructure? A study using 3D modeling of hip dual-energy X-ray absorptiometry.

Aim: Patients with type 2 diabetes (T2DM) have more risk of bone fractures. However, areal bone mineral density (aBMD) by conventional dual-energy x-ray absorptiometry (DXA) is not useful for identifying this risk. This study aims to evaluate 3D-DXA parameters determining the cortical and trabecular compartments in patients with T2DM compared to non-diabetic subjects and to identify their determinants. Materials and methods: Case-control study in 111 T2DM patients (65.4 ± 7.6 years old) and 134 non-diabetic controls (64.7 ± 8.6-year-old). DXA, 3D-DXA modelling via 3D-Shaper software and trabecular bone score (TBS) were used to obtain aBMD, cortical and trabecular parameters, and lumbar spine microarchitecture, respectively. In addition, biochemical markers as 25-hydroxyvitamin d, type I procollagen N-terminal propeptide (P1NP), C-terminal telopeptide of type I collagen (CTX), and glycated haemoglobin (HbA1c) were analysed. Results: Mean-adjusted values showed higher aBMD (5.4%-7.7%, ES: 0.33-0.53) and 3D-DXA parameters (4.1%-10.3%, ES: 0.42-0.68) in the T2DM group compared with the control group. However, TBS was lower in the T2DM group compared to the control group (-14.7%, ES: 1.18). In addition, sex (ß = 0.272 to 0.316) and body mass index (BMI) (ß = 0.236 to 0.455) were the most consistent and positive predictors of aBMD (p ≤ 0.01). BMI and P1NP were negative predictors of TBS (ß = -0.530 and -0.254, respectively, p ≤ 0.01), while CTX was a positive one (ß = 0.226, p=0.02). Finally, BMI was consistently the strongest positive predictor of 3D-DXA parameters (ß = 0.240 to 0.442, p<0.05). Conclusion: Patients with T2DM present higher bone mass measured both by conventional DXA and 3D-DXA, suggesting that 3D-DXA technology is not capable of identifying alterations in bone structure in this population. Moreover, BMI was the most consistent determinant in all bone outcomes.

Prospective physical fitness status and development of cardiometabolic risk in children according to body fat and lifestyle behaviours: The IDEFICS study.

BACKGROUND: Elevated cardiometabolic risk (CMR) is an important factor for cardiovascular diseases later in life while physical fitness seems to decrease CMR. OBJECTIVE: Thus, the aim of the present study is to assess the association between muscular fitness (MF) and cardiorespiratory fitness (CRF) on CMR in European children, both cross-sectional and longitudinally. METHODS: A total of 289 children (49.5% males) from eight European countries, aged 6 to 9, with longitudinal information on blood pressure, triglycerides, total cholesterol, HDL-cholesterol, homoeostasis model assessment, body mass index, data on fitness level, objectively measured physical activity (PA), diet quality, and total screen time were included. A CMR score was calculated and dichotomized. MF and CRF were also dichotomized. Cross-sectional and longitudinal multilevel logistic regressions adjusting for lifestyle behaviours were performed. RESULTS: Reaching a high level of MF during childhood as well as remaining in that level over-time were associated with an 82% and 62% lower probability of high CMR at follow-up, respectively. Also, children who became top CRF over time, showed a 77% lower probability (P < 0.05) of being in the highest CMR quartile at follow-up, independently of sociodemographic and lifestyle indicators. CONCLUSIONS: A high MF at early childhood and during childhood reduces the odds of having CMR. Same occurs with the improvement of CRF during childhood. These findings highlight the importance of enhancing fitness to avoid CMR already in children.

Serum sclerostin concentration is associated with specific adipose, muscle and bone tissue markers in lean adolescent females with increased physical activity.

OBJECTIVES: Sclerostin is an important regulator of bone mass involving the Wnt/ß-catenin signalling pathway. Relatively few studies have investigated the relationships of circulating sclerostin levels with adiposity-related and muscle-related biochemical factors in individuals with increased energy metabolism. The aim of this study was to investigate the associations of circulating sclerostin with adipokines, myokines, osteokines and body composition values in lean adolescent females with increased physical activity. METHODS: A total of 73 adolescent females who were physically active and aged 14-18 years old participated in the study. Sclerostin, leptin, resistin, tumour necrosis factor (TNF)-α, interleukin (IL)-6, irisin, osteocalcin, C-terminal telopeptide of type I collagen (CTx), insulin-like growth factor (IGF)-1 and insulin were obtained from fasting blood samples. Body composition was measured by dual-energy X-ray absorptiometry (DXA) and analyzed for body fat mass, lean body mass, bone mineral content and muscle mass. RESULTS: Serum sclerostin (117.9 ± 60.3 pg/mL) was correlated with age, age at menarche, body fat, muscle mass, training activity, leptin, TNF-α, irisin, osteocalcin, CTx and IGF-1. Multivariate linear regression analysis demonstrated that fat mass (ß = 0.434; p = 0.001), leptin (ß = -0.308; p = 0.015), irisin (ß = 0.227; p = 0.024) and CTx (ß = 0.290; p = 0.031) were the most important predictors of serum sclerostin concentration. CONCLUSIONS: Bone-derived sclerostin is associated with specific adipokine, myokine and osteokine values in lean adolescent females with increased physical activity. These results suggest that the interactions between bone, adipose and muscle tissues could also be associated with circulating sclerostin concentrations.

Testing the Functional Model of Bone Development: Direct and Mediating Role of Muscle Strength on Bone Properties in Growing Youth.

This study examines the functional model of bone development in peri-pubertal boys and girls. Specifically, we implemented a mixed-longitudinal design and hierarchical structural models to provide experimental evidence in support of the conceptual functional model of bone development, postulating that the primary mechanical stimulus of bone strength development is muscle force. To this end, we measured radial and tibial bone properties (speed of sound, SOS), isometric grip and knee extensors strength, bone resorption (urinary NTX concentration), body mass index (BMI), somatic maturity (years from peak height velocity) and skeletal maturity (bone age) in 180 children aged 8-16 years. Measurements were repeated 2-4 times over a period of 3 years. The multilevel structural equation modeling of 406 participant-session observations revealed similar results for radial and tibial SOS. Muscle strength (i.e., grip strength for the radial and knee extension for tibial model) and NTX have a significant direct effect on bone SOS (ß = 0.29 and -0.18, respectively). Somatic maturity had a direct impact on muscle strength (ß = 0.24) and both a direct and indirect effect on bone SOS (total effect, ß = 0.30). Physical activity and BMI also had a significant direct impact on bone properties, (ß = 0.06 and -0.18, respectively), and an additional significant indirect effect through muscle strength (ß = 0.01 and 0.05, respectively) with small differences per bone site and sex. Muscle strength fully mediated the impact of bone age (ß = 0.14) while there was no significant effect of energy intake on either muscle strength or bone SOS. In conclusion, our results support the functional model of bone development in that muscle strength and bone metabolism directly affect bone development while the contribution of maturity, physical activity, and other modulators such as BMI, on bone development is additionally modulated through their effect on muscle strength.

The Mediating Role of Lean Soft Tissue in the Relationship between Somatic Maturation and Bone Density in Adolescent Practitioners and Non-Practitioners of Sports.

This study aimed to identify the mediating effect of lean soft tissue (LST) in the association between somatic maturation and areal bone mineral density (aBMD) in adolescents by sex and sport participation. The sample included 558 adolescents (401 males, mean age of 14.0 years) that were practitioners of sports (11 sport modalities, n = 402) and a non-sport group (n = 157). Somatic maturation was assessed by using a validated peak height velocity prediction equation. Dual-energy X-ray absorptiometry (DXA) was used to assess aBMD (upper and lower limbs, spine and total body less head-TBLH) and LST. For both sexes, LST mediated the association between somatic maturation and aBMD at all skeletal sites (mediation percentage ranging from 36.3% to 75.4%). For sport and non-sport groups, the LST also mediated the association between somatic maturation and aBMD at all skeletal sites (mediation percentage ranging from 51.6% to 85.6%). The direct effect was observed in all groups, except for lower limbs and TBLH in the non-sport group. The association between somatic maturation and aBMD was mediated by LST in adolescents of both sexes and regardless of involvement in organized sports. Our findings highlighted the role of improving LST to mitigate the association of somatic maturation with aBMD.

The "Fat but Fit" Paradigm and Bone Health in Young Adults: A Cluster Analysis.

The fat but fit paradox has suggested that obese individuals with good fitness levels have lower cardiometabolic risk compared to individuals with normal weight but lower fitness levels. This paradigm has not been explored in the context of bone health. The aim of this study was to test whether categories of fat but fit paradigm assessed by body fat percentage and handgrip strength holds up in young adults and to analyze the relationship between fat but fit categories and bone outcomes. Cluster cross-sectional analyses of data from 499 young adults aged 18 to 30 from Toledo and Cuenca, Spain were conducted. Body fat percentage, handgrip strength, bone mineral content (BMC), bone mineral density (BMD), and dietary nutrients such as, proteins, magnesium, calcium, phosphorus, potassium, and vitamin D were assessed. Cluster analysis of body fat percentage and handgrip z scores resulted in a classification of four clusters that could be interpreted according to Fat Unfit (FU), Unfat Unfit (UU), Fat Fit (FF) and Unfat Fit (UF) categories. ANCOVA models showed that young adults in clusters with higher handgrip strength levels (FF, UF) and with higher key bone nutrients levels (UF) had significantly higher total BMC values than their peers in the UU and FU cluster categories, after controlling for sex, age and height. This study provides two novel conclusions in relation to the fat but fit paradigm: first, it confirms the construct of the four clusters of body fat percentage and handgrip strength, and second, it reinforces the predictive validity of the fat but fit paradigm categories, indicating the positive effect, although it may not just be a causal relationship, of muscular strength and key bone nutrients on counteracting the negative effect of obesity on bone health.

3D DXA Hip Differences in Patients with Acromegaly or Adult Growth Hormone Deficiency.

The skeleton is regulated by and responds to pituitary hormones, especially when the circulating levels are perturbed in disease. This study aims to analyse the between-group differences in 3D dual-energy X-ray absorptiometry (DXA) parameters at the hip site among patients with acromegaly or adult growth hormone deficiency (AGHD) and a healthy control group. The current cross-sectional study includes data for 67 adults, 20 with acromegaly, 14 with AGHD and 33 healthy controls. We obtained the areal bone mineral density (aBMD) outcomes using DXA and cortical and trabecular parameters using 3D-DXA software (3D-SHAPER). The mean-adjusted 3D-DXA parameters did not differ between acromegaly patients and the controls (p > 0.05); however, we found cortical bone impairment (-7.3% to -8.4%; effect size (ES) = 0.78) in AGHD patients (p < 0.05). Differences in the cortical bone parameters were more evident when comparing AGHD patients (-8.5% to -16.2%; ES = 1.22 to 1.24) with acromegaly patients (p < 0.05). In brief, the 3D mapping highlighted the trochanter as the site with greater cortical bone differences between acromegaly patients and the controls. Overall, AGHD patients displayed lower cortical parameters at the trochanter, femoral neck and intertrochanter compared to the controls and acromegaly patients. To sum up, 3D-DXA provided useful information about the characteristics of bone involvement in growth hormone (GH)-related disorders. Patients with AGHD showed distinct involvement of the cortical structure.