Front Endocrinol (Lausanne). 2020 Apr 24;11:200. doi: 10.3389/fendo.2020.00200. eCollection 2020.
Excess adiposity in childhood may affect bone development, ultimately leading to bone frailty. Previous reports showing an increased rate of extremity fractures in children with obesity support this fear. On the other hand, there is also evidence suggesting that bone mineral content is higher in obese children than in normal weight peers. Both adipocytes and osteoblasts derive from multipotent mesenchymal stem cells (MSCs) and obesity drives the differentiation of MSCs toward adipocytes at the expense of osteoblast differentiation. Furthermore, adipocytes in bone marrow microenvironment release a number of pro-inflammatory and immunomodulatory molecules that up-regulate formation and activation of osteoclasts, thus favoring bone frailty. On the other hand, body adiposity represents a mechanical load, which is beneficial for bone accrual. In this frame, bone quality, and structure result from the balance of inflammatory and mechanical stimuli. Diet, physical activity and the hormonal milieu at puberty play a pivotal role on this balance. In this review, we will address the question whether the bone of obese children and adolescents is unhealthy in comparison with normal-weight peers and discuss mechanisms underlying the differences in bone quality and structure. We anticipate that many biases and confounders affect the clinical studies conducted so far and preclude us from achieving robust conclusions. Sample-size, lack of adequate controls, heterogeneity of study designs are the major drawbacks of the existing reports. Due to the increased body size of children with obesity, dual energy absorptiometry might overestimate bone mineral density in these individuals. Magnetic resonance imaging, peripheral quantitative CT (pQCT) scanning and high-resolution pQCT are promising techniques for the accurate estimate of bone mineral content in obese children. Moreover, no longitudinal study on the risk of incident osteoporosis in early adulthood of children and adolescents with obesity is available. Finally, we will address emerging dietary issues (i.e., the likely benefits for the bone health of polyunsaturated fatty acids and polyphenols) since an healthy diet (i.e., the Mediterranean diet) with balanced intake of certain nutrients associated with physical activity remain the cornerstones for achieving an adequate bone accrual in young individuals regardless of their adiposity degree.
This review was narrative and highlighted the number of unsolved issues about the effect of excess adiposity on the developing bone. We believe that a systematic review was unfeasible owing to the small number of clinical studies available from the literature and, moreover, to their extreme heterogeneity in the design. No in vivo study provided robust evidence that bone health is impaired in children with obesity enhancing the risk of extremity fractures. In these patients, fractures may occur more frequently due to clumsiness that enhances risk of falls and to excess weight that generates greater mechanical forces trough the extremity bones. On the other hand, some studies found increased bone mass in overweight children. However, technical issues, i.e., the lack of gold standard methodology to estimate BMC in these patients with increased body size, prevented us from suggesting conclusive results. Emerging imaging techniques will be likely helpful to solve the question of whether the bone health is impaired in relation to the increased size, greater fat and lean mass, taller height, and advanced bone age of the obese youth. Experimental evidence in animal and cellular models demonstrates that replacement of BM by adipose tissue alters the bone microenvironment and promotes low-grade inflammation, which in turn result in reduced osteoblast and enhanced osteoclast activities. A rearrangement of the bone microarchitecture and a prevailing bone reabsorption seem to be the net results of these processes. Without any doubt, bone accrual in children with obesity is affected by different humoral stimuli, i.e., inflammatory cytokines, adipokines and myokines. Nevertheless, their bone is also subjected to a mechanical workload that is beneficial for bone accrual and geometry. Finally, there are emerging dietary issues that strongly suggest that the adequate intake of some natural compounds is beneficial for bone health.
In conclusion, in answering the main question addressed in this review, i.e., whether the bone mineral content is higher in children with obesity as compared to normal-weight peers or the bone structure of these individuals is more fragile, larger population studies are needed that will consider not only fatness of participants but also their inflammatory status, lifestyle habits in terms of PA (weight-bearing vs. not wear-bearing), sedentary conducts and dietary intake of macro-and micronutrients.