The prevalence of obesity is increasing throughout the world [1
]. Among many effects, obesity is a risk factor for bone fracture [2
]; however, the risk of fracture is a complex one that changes over the lifetime of the individual. Obese children and adolescents tend to have an increased fracture risk [3
]; non-diabetic obese adults, conversely, show the reverse trend [5
]. In adults, an increased bone mineral density has been associated with obesity [5
], and this is often cited as the primary reason for the observed reduction in fractures. In children and adolescents, however, the mechanistic picture is less clear as there are developmental consequences of obesity, such as changes in muscle development and posture control [10
], which could markedly affect fracture risk. Additionally, activity levels may be a confounding issue, where adolescents are more likely to participate in group sports which can lead to falls and injury while adults are generally less active and may not be exposed to similar falling risks. Obesity also promotes diseases such as diabetes; indeed, fracture risk is elevated in adults with type 2 diabetes [4
]. Although corresponding fracture rates for diabetic children have not been reported, reduced bone mineral content and bone size have been observed in type 1 diabetic adolescents, which implies an increased fracture risk [13
These observations suggest an age-dependent response of bone to obesity, which are considered here by studying two groups of wild-type mice: a young group and an adult group. Fracture risk findings [3
] would imply that adult cortical bone tends to have a more favorable response to increasing obesity than young cortical bone, although as noted, complicating factors, e.g., diabetes, activity levels, etc., may change the overall fracture risks reported by these studies.
Studies into changes in bone mineral density and content address an important aspect of bone fracture risk, but further investigation into microstructural quality and mechanical behavior, in addition to quantitative measures such as bone size and amount of mineral, may provide some insight into the changes in fracture risk throughout a lifetime. Prior work with animal models has been conducted into the question of how mechanical properties of bone are affected by both diabetic and non-diabetic obesity [14
], but this work primarily investigated size-dependent mechanical properties (i.e., load, deflection, total energy absorbed in bend), which do not permit mechanistic delineation between the issues of the quantity vs. mechanical quality of the bone. In general, a decrease in quality of bone (i.e., reduced mechanical properties) and an increase in quantity (i.e., larger bone dimensions and bone mineral content) have been reported. To further characterize how the mechanical integrity of the tissue changes with obesity, size-independent measures such as strength, bending modulus, and toughness must also be determined [18
Many physiologic systems are affected by obesity and are important to consider in such a study. Obesity affects leptin, insulin-like growth factor I (IGF-I), and advanced glycation end-product (AGE) concentrations [7
]. Leptin and IGF-I are both important to consider in obesity studies because they affect, and are affected by, both obesity and bone [20
], as is non-enzymatic glycation (NEG) which can affect fracture toughness through collagen cross-linking [23
]. Higher AGEs would also be a logical consequence of a high-fat diet, which should increase blood glucose levels, to subsequently increase the rate of NEG.
Structural changes, such as larger bone size, have been observed with obesity in both adolescents and adults [26
], and are an important characteristic to evaluate in investigating the effects of obesity on bone fracture risk. To provide further insight, macroscopic changes such as femoral length, circumference at the midshaft, and bone growth rates were performed in addition to qualitative imaging, which is a valuable tool to show bone structure changes and has been done in a prior study performed by this group [19
]. By combining mechanical testing, analysis of biological factors, and structural evaluation, this study was aimed at addressing how obesity affects cortical bone at two stages in life, adolescence and adulthood, in an effort to further understand what factors influence fracture risk throughout life.