Background

Based on the positive association which we previously found between total body fat mass and bone mass as measured in ALSPAC children at age 10, we postulated that fat mass exerts a positive influence on bone mass accrual in childhood (1). A subsequent mendelian randomisation study in which genetic markers of obesity were used as instrumental variables supported a causal relationship between fat mass and bone mass accrual (2). In a recent study where we examined the relationship between fat mass and cortical bone geometry by pQCT, higher fat mass was associated with a greater overall cross section of bone, but reduced expansion of the inner surface, of which the latter effect was particularly marked in females (A Sayers et al, submitted for publication).

The biological pathways by which fat mass stimulates bone mass accrual in childhood are currently unclear, but may involve factors related to insulin resistance (3). For example, adiponectin is thought to be inversely related to insulin resistance, fat mass and BMD. However, in a recent study based on ALSPAC, whereas adiponectin was inversely related to a range of measures of skeletal development, this association only explained a relatively small proportion of the relationship between fat mass and bone development (A Sayers et al, submitted for publication). In terms of alternative pathways by which fat mass stimulates bone mass accrual in childhood, the insulin/IGF1 axis is another good candidate. IGF1 is known to increase overall bone cross section by stimulating periosteal bone growth in animal models (4). We also previously observed a positive relationship between IGF-1 and BMD measures at age 10 in the children in focus subgroup (J Tobias unpublished observations).

Aims and methods

We aim to establish whether insulin levels, as measured in children at age 16 (TF3) are related to bone mass accrual and cortical geometry as assessed at the same age. If a positive association is observed as expected, we will go on to determine whether this relationship helps to explain associations between the same skeletal parameters and fat mass and adiponectin as previously described. Insulin levels at age 16 will be analysed in relation to bone mass as measured by total body DXA scans at the same age, as will related factors such as fasting blood sugar and lipid levels measured at the same time. We will analyse relationships between total body less head bone mineral content, bone area, bone mineral density and bone mineral content adjusted for bone area. We will also investigate associations with indices of cortical geometry derived from pQCT scans of the mid tibia. Assuming positive associations are observed, we will then examine whether associations between fat mass and bone mass can be explained by those with insulin, by comparing fat-bone mass associations with or without adjustment for insulin. Equivalent analyses will be performed for adiponectin, with the exception that for these analyses, adiponectin levels will consist of those measured at age 10.