Fat mass is a positive predictor of bone mass in adolescents

Abstract

We read the recent paper by Hong and colleagues (1) with interest because the title of this original article suggests an inverse association between fat mass and bone mass on hip geometry in adolescents. This is in direct contradiction to three large studies we have carried out on the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort using different methods to examine the association between fat and bone in adolescents. First, we used combined cross-sectional and prospective analyses of 3503 children from the United Kingdom and reported a clear and independent positive association between fat mass and bone mass or size measured by dual-energy X-ray absorptiometry (DXA). (2) Second, we used peripheral quantitative computed tomography (pQCT) to estimate cortical bone mass on the same cohort and again reported an independent positive association between fat mass and cortical bone mass (greater in girls than in boys). (3) Third, we used a Mendelian randomization approach to further categorize the association between fat and bone in childhood and again reported an independent positive association. (4) We are therefore surprised by the title of the article by Hong and colleagues. However, we believe that it is misleading and that their conclusion is erroneous. When analyzing relationships between body composition variables, one has to account for the fact that important relationships exist between fat and lean mass and that the latter has a very strong positive relationship with bone mass. Therefore, when exploring associations between fat mass and bone mass specifically, it is essential that the term for fat mass is independent of lean mass. We achieved this is our previous studies by analyzing associations between fat mass and bone mass after adjusting for lean mass. Unfortunately, Hong and colleagues analyzed associations between bone mass and percentage of fat adjusted for body weight, which does not allow the effects of fat mass to be analyzed independent of lean mass because those with a higher percentage of fat adjusted for body weight of necessity will have a lower percentage of lean mass. Therefore, their observation of an inverse association between percentage of fat adjusted for body weight and bone mass is likely to be driven by the strong positive association between lean mass and bone mass that is well described. We believe that Hong and colleagues should reanalyze their data using percentage of fat mass adjusted for lean mass or height, not body weight.

Increased bone mass in a mouse model with low fat mass

“…Furthermore, the higher bone mass in these RID tg mice is even higher than one would expect given the reported positive correlation between measures of weight load, such as body weight or body mass index, and bone mass (5,28). However, the low fat mass and high bone mass in RID tg mice are in line with several studies showing that fat mass is negatively associated with bone mass, although this negative association is under debate (2,3,6,10,20,42). The mechanism behind a negative association between fat and bone mass is thought to be due to the ability of adipose tissue to secrete, for example, inflammatory cytokines known to stimulate osteoclastogenesis and inhibit osteoblastogenesis (9,13,14,16,17,19,23,37).…”

Prenatal concentrations of perfluoroalkyl substances and bone health in British girls at age 17

“…Measures of body size including fat mass, lean mass, and height, have been found to be associated with bone mineral density [23,14]. Our results suggest that the effect of prenatal PFAS exposure on body size may influence the effect of PFAS exposure on bone health measures, given the attenuation of the associations we observed by height adjustment.…”

“…Our primary objective was to examine associations between maternal exposure to PFAS during pregnancy and their daughters’ bone health at 17 years of age using data from mothers and daughters in the Avon Longitudinal Study of Parents and Children (ALSPAC). Given the close dependency of bone mass acquisition on growth and body composition [14], we were also keen to establish whether any observed associations between prenatal PFAS and measures of bone health could be explained by height, fat or lean mass.…”