The effect of eating disorders on bone health and development

Supervisors: Dr Nadia Micali and Dr Jonathan Tobias

Hypothesis:
1) Overall ED behaviours across adolescence will be associated with lower Bone Mass Density at age 17.5.
2) Cortical circumference of the bone, bone thickness and density will also be affected. Excessive exercise for weight loss might be protective against low Bone Mass Density in some adolescents. Gender differences will be highlighted. Caloric restriction, fat mass, pubertal timing and genetic factors will be investigated as potential mediators or moderators.

Aims and methods:
Eating disorders have a peak incidence in adolescence1, a crucial time for physical and skeletal development; when bone mass reaches its highest level. The level of bone mass attained at this age is a key determinant of long-term bone health and risk of osteoporotic fractures in later life2. There is some evidence that eating disorders have negative effects on bone development, especially if they onset in adolescence3. The current lack of evidence impacts on available prevention and early treatment for adolescents with eating disorders, this study will allow clear identification of causal biological mechanisms that could help preventative and therapeutic efforts.

Aims:

1) To determine the impact of adolescent ED/ED behaviours (measured at age 13, 14 and 16) on bone density at age 17.5 (focusing on hip BMD) and fractures;
2) To determine: a) whether associations found with hip BMD reflect an influence on cortical circumference, thickness or density (based on tibial pQCT); b)the role of factors such as caloric restriction, fat mass, pubertal timing, bone turnover, excessive exercise, gender and genetic factors (polymorphisms of RANKL) in explaining the effect of ED on bone health.

Methods:
This is a longitudinal study, based on data prospectively collected as part of the Avon Longitudinal Study of Parents and Children (ALSPAC): a cohort of 14,000 mothers and their children enrolled in pregnancy. Children have been followed up at regular intervals from birth onwards (N=10,000).

Data collected at ages 13,14 and 16 on eating disorders behaviours will be used to predict bone development. The main outcome measure will be Bone Mass Density at age 17; fractures at age 15 and at age 21, and other bone characteristics (such as cortical geometry and strength of the mid-tibia) will be investigated. Collected data will be extracted; new data will be collected at age 20/21 on fractures. Univariate and multivariate logistic/linear models will be used to determine the effect of relevant predictors on outcomes. Risk mechanisms will be investigated using multivariate regression models and where necessary structural equation modelling, in order to develop risk models.

References:
1) Hoek HW, van Hoeken D. Review of the prevalence and incidence of eating disorders. Int J Eat Disord. 2003 Dec;34(4):383-96. Review.
2) Ott, SM. 1991 Bone density in adolescents NEJM 325: 1646-1647.
3) Misra M. Long Term Skeletal Effects of Eating Disorders and Onset in Adolescence. Ann NY Acad Sci 1135: 212-218; 2008.