The role of bone health in low-velocity fractures and the effects of obesity on the growing skeleton

Abstract

Vitamin D insufficiency in pediatric patients is common. Low levels of vitamin D affect bone mineralization, and in growing children, affect bone formation. This effect on overall bone health places children with vitamin D insufficiency and deficiency at risk for low-velocity fractures. Counseling pediatric patients on adequate vitamin D and calcium supplementation can decrease long-term bone health deficits and lead to improved health status as adults. In addition, obesity rates continue to increase in children. Obesity has direct effects on bone metabolism that negatively impact growing skeletons. Refined definitions for obesity will help prevent labeling patients inappropriately as obese but also allow physicians to counsel children and their parents on the long-term risks that obesity plays on both bone health and overall health.

Key concepts: (1)Vitamin D has a strong influence on bone health with low levels of vitamin D being associated with low bone mineralization on DEXA scans.(2)Children with low vitamin D are at risk for low-velocity fractures including the need for surgical intervention for these lower energy injuries.(3)Obesity leads to a chronic inflammatory state that creates a negative overall effect on the growing skeleton.(4)Obesity can be a stigmatizing condition resulting from many factors related to socioecological, environmental, and genetic influences but when appropriately addressed, can lead to improved long-term bone and overall health.

Keywords: Adipocytes; Leptin; Obesity; RANKL; Vitamin-D insufficiency.

Figure 1

Chart showing the effects of the metabolic syndrome on skeletal physiology. Abd C, abdominal circumference; HDL-c, high-density lipoprotein c; IL, interleukin; TNF, tumor necrosis factor. Reproduced with permission from da Silva VN, Fiorelli LNM, da Silva CC, Kurokawa CS, Goldberg TBL: Do metabolic syndrome and its components have an impact on bone mineral density in adolescents? Nutrition Metab. 2017;14:1 .

Figure 2

Bone metabolism regulated by adipocytes, osteoblasts, and osteoclasts. Fat accumulation is closely related to bone formation and resorption. Osteoblasts and adipocytes are derived from a common multipotential mesenchymal stem cell. Osteoclasts are differentiated from monocyte/macrophage precursors of hematopoietic stem cells origin. Adipocytes secrete several cytokines such as TNF-α, IL-1β, IL-6, adiponectin, and leptin which are capable of modulating osteoclastogenesis through RANKL/RANKL/OPG pathway. IL, interleukin; OPG, osteoprotegerin; RANK, receptor activator of nuclear transcription factor κB; RANKL, receptor activator of nuclear transcription factor κB ligand; TNF-α, tumor necrosis alpha. Reproduced with permission from Cao JJ. Effects of obesity on bone metabolism. Journal of Orthopaedic Surgery and Research. 2011;6:30 .

Figure 3

Impact of exercise and high-calorie diet and sedentary lifestyle on bone and fat. Mesenchymal stem cell lineage drives osteogenic differentiation. Exercise plays an important role in bone modeling and remodeling via the osteocyte network while suppressing the accumulation of fat. Sedentary and indoor lifestyles stimulate adipogenic programs accompanied by increased marrow adiposity. With poor mechanical load, osteocytes reduce osteoprotegerin levels inducing RANKL effects resulting in osteoclast-mediated resorption in bone. MCSF, mesenchymal stem cell factor; NOX4, NADPH oxidase 4; PPARγ, peroxisome proliferator-activated receptor gamma; RANKL, receptor activator of nuclear factor-κB ligand; ROS, reactive oxygen species; RUNX2, runt-related transcription factor 2; TGF-β, transforming growth factor-β. Reproduced with permission from Korkmaz HA, Ozkan B. Impact of obesity on bone metabolism in children. J Pediatr Endocrinolo Metab. 2022;35:557-565 .

Figure 4

Illustration showing the mechanism of central and peripheral leptin signaling. ADRB2, B2 adrenergic receptor; BMSCs, bone marrow stromal cells; LEPR, leptin receptor. Reproduced with permission from Macmillan Publishers Ltd, Kawai M, Devlin MJ, Rosen CJ: Fat targets for skeletal health. Nat Rev Rheumatol. 2009;5:365-372 .