Bone health in children with overweight/obesityThe role of systemic chronic inflammation, vitamin D and muscular fitness

Resumen

Background Previous research suggests a link between obesity and bone morphogenesis which may be explained by inflammatory markers and adipokines. It is known that bone development is regulated by modelling and remodelling processes that depend on the mechanical forces applied by the muscles to the skeleton. Furthermore, the relationships of vitamin D and muscular strength with bone have been described, but no study has jointly examined the association of these predictors with bone. Objectives The present Doctoral Thesis aimed to study which inflammatory markers and adipokines are associated with bone health and whether these associations are modified by muscular fitness levels in children with overweight/obesity (study 1 and study 2). In addition, this Thesis examined whether the relationship between vitamin D (i.e., plasma calcidiol) and bone health was mediated by muscular fitness (study 3). Methods To address these aims, we used baseline data from the ActiveBrains project. Plasma interleukin (IL)-1β, IL-6, tumour necrosis factor-α (TNF-α), epidermal growth factor, vascular endothelial growth factor A (VEGF), C-reactive protein, leptin, adiponectin and calcidiol were analysed. Muscular fitness was assessed in laboratory (through determining each participant’s 1 repetition maximum at bench and leg press) and in field-based conditions (handgrip strength and standing long jump). Bone outcomes, fat and lean mass were assessed by dual-energy x-ray absorptiometry. For study 1 and study 2, the association between these biochemical markers and bone outcomes was tested with multiple regression analyses controlling for sex, somatic maturation and lean mass. Additionally, the muscular fitness interaction was examined in the associations of inflammatory markers and adipokines with bone outcomes. For study 3, the mediator role of muscular fitness was examined in the association between calcidiol and bone outcomes controlling for sex, somatic maturation, lean mass and season. Results and main findings In study 1, IL-6 and VEGF levels were negatively associated with bone mineral content at the total body, whereas TNF-α (negatively) and IL-1β (positively) levels were associated with bone mineral content at the lumbar spine. In study 2, no association was found between leptin or adiponectin levels and bone outcomes. Furthermore, high levels of objectively measured muscular fitness may attenuate the adverse effects of VEGF and TNF-α on bone mineral content at the total body and lumbar spine, respectively (study 1). In addition, a negative association between leptin and bone mineral content at the lumbar spine was observed in the low lower-body muscular fitness group, whereas no significant association was found in the high lower-body muscular fitness group (study 2). In study 3, calcidiol was indirectly associated with areal bone mineral density at the total body, arms and legs through relative muscular fitness. Overall conclusions The results of this Thesis suggest that IL-1β, IL-6, TNF-α, VEGF and leptin (to a lesser extent) could be contributing factors explaining the link between obesity and bone health in children with overweight/obesity. Optimal muscular fitness levels may attenuate the adverse effects of TNF-α, VEGF and leptin on bone. Moreover, muscular fitness seems to play a key role in the relationship of calcidiol levels and bone outcomes in this population. Altogether, appropriate levels of vitamin D and muscular fitness may preserve normal bone accretion in children with overweight/obesity.