Background: Low bone mineral density (BMD) is the most important risk factor for fragility fracture. Body weight is the most consistent predictor of difference in BMD between individuals. However, it is unclear which component of weight – lean mass (LM) or fat mass (FM) – is associated with BMD. People with the genetic disorder of Prader-Willi syndrome (PWS) have increased FM but reduced LM. In this study, we sought to define the impact of LM and FM on BMD by studying individuals with PWS in comparison to carefully matched controls.
Methods: The study involved 11 adults with PWS, who were age- and sex-matched with 13 obese individuals and 10 lean individuals. Whole body BMD was measured by dual-energy X-ray absorptiometry. Total body FM and LM were derived from the whole body scan. Differences in BMD between groups were analysed by analysis of covariance, adjusting for the effects of LM and FM.
Results: There was no significant difference in FM between the obese and PWS groups or in LM between the lean and PWS groups. BMD in lean individuals was significantly lower than PWS individuals. After adjusting for LM and FM, there was no significant difference in BMD between groups, and the only significant predictor of BMD was LM.
Discussion: Human obesity is generally accompanied by increased LM, making it difficult to dissect the effects of adipose tissue and muscle. PWS is an ideal human model in which to study the relative importance of LM versus FM because of the unique body composition phenotype: low LM despite increased FM. This study demonstrated that in adults with wide-ranging body composition, BMD was more strongly related to LM than to FM, suggesting that lean tissue may be the most important determinant of BMD.