Objectives

1)To determine the impact of adolescent disordered eating behaviours on bone accrual and bone development throughout adolescence and young adulthood.

2) To determine the role of factors such as caloric restriction, delayed puberty, excessive exercise, gender in explaining the effect of disordered eating on bone health in adolescence.

3) To determine the impact of adolescent disordered eating behaviours on stress fractures in young adulthood.

Background

Eating disorders (ED) are chronic disorders and affect about 5-10% of the population (Hoek and Van Hoeken, 2003).

Adolescent ED and bone development: ED have a peak incidence in adolescence, a crucial time for physical and skeletal development. Pubertal years are the period in the life course 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 life (Ott, 1991).

Past research focusing on bone density in ED has shown that restrictive ED (such as anorexia nervosa (AN) and atypical anorexia nervosa/ Eating Disorder not otherwise specified-EDNOS) are associated with reduced bone mass. This is probably secondary to low weight, reduced fat mass and hormonal abnormalities secondary to poor nutrition (Misra, 2008; Mehler et al, 2011). Whilst recovery from the ED has been shown to lead to improvements in bone density, several studies show that bone density remains lower than in individuals who have not experienced an ED, particularly in cases where the ED onset was in adolescent years (Biller et al., 1989; Hartman et al., 2000; Wentz et al., 2007; Bolton et al., 2005).

Binge- type ED (such as bulimia nervosa and binge eating disorder) have been less well studied, and appear not to affect bone density to the same extent as restrictive ED, particularly if normal weight is maintained (Misra, 2008). However, higher fracture risk was also shown in these women compared to controls (Vestergaard et al., 2003).

Studies investigating bone density in adolescents with restrictive ED as measured by dual energy X-ray absorptiometry (DXA) have shown low bone density at the spine, hip and femoral neck (Misra, 2008); as well as reduced bone turnover. These effects are apparent in both girls and boys (Castro et al., 2002). Follow-up studies of adolescents have reported some improvement in bone density with nutritional restoration, mainly in areas of trabecular bone, such as the spine. Several studies, however, have shown fewer improvements in bone density at cortical sites despite recovery from the ED ((Herzog et al., 1993; Mika et. al, 2007). Given that the adolescent years provide a narrow window of opportunity in which to optimize bone mass accrual, disruption during these years might lead to permanent deficits.

Stress fractures:Although stress fractures are relatively uncommon, they affect as many as 15% of young women athletes and military recruits. Among females, other suspected risk factors for developing a stress fracture include disordered eating (Rosen et al, 1986) and irregular menstrual cycles, both which may result in a deficient estrogen status that can counteract the beneficial effects of exercise on bone density (Wolman et al., 1990; Lloyd et al. 2000; Bass et al.,1998).The combination of disordered eating, amenorrhea, and low bone density is characterized as the Female Athlete Triad. The recognition of the triad has served to increase awareness of bone health concerns among young female athletes (Yeager et al., 1993; Otis et al., 1997). Thus, it is extremely important to identify modifiable predictors of stress fracture so that prevention programs could be developed for high-risk populations.

Gaps in the literature:Most studies in the field to date rely on small clinical samples, and are likely to represent more severely ill subjects attending in- or out-patient services and not be generalisable to all ED. Length of follow-up has often been limited to 1-2 years. Moreover, DXA provides an overall estimate of bone mass but does not directly measure aspects like cortical thickness and cross sectional area that determine overall bone strength. Techniques like peripheral quantitative computed tomography (pQCT) can provide detailed information about cortical bone geometry and strength, but only one study to date has used this method to study bone changes in adolescents with ED (Milos et al.,2007). In light of recent finding that fat mass is an important positive determinant of cortical bone size and thickness (Sayers & Tobias, 2009), we are particularly interested in examining whether adolescent ED predicts weaker cortical bones due to reduced fat mass. More than half of adult bone calcium is acquired during adolescence and a woman's peak bone mineral density, a major determinant of her long-term risk of osteoporosis, is thought to be achieved by early adulthood. Therefore assessing bone density in young adulthood, as well as throughout adolescence, allows a better assessment of peak bone density. This additional investigation will allow a better understanding of the longitudinal effects of adolescent ED behaviours on bone development.

To our knowledge there are: no studies on a general population sample of adolescents/young adults able to link temporal relationships between disordered eating behaviours and bone development. Both would allow a clear identification of causal biological mechanisms, and take into account the role of confounders. The current lack of evidence impacts on available prevention and early treatment for patients with ED.

This study is unique in that data have already been collected prospectively and independently on bone density and ED behaviours in about 6,000 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC). This longitudinal prospective study will allow: (1) determining precise temporal relationships between predictor (ED behaviours) and outcomes (bone density, cortical bone size and thickness, peak bone mass, and stress fractures); (2) focusing on causal biological mechanism taking into account the role of confounders (thanks to the wealth of data available in ALSPAC).

Methodology

Theoretical/conceptual framework: This is a longitudinal study, which will rely on data prospectively collected as part of the ALSPAC study. The ALSPAC study is a longitudinal prospective cohort of 14,000 mothers and their children. Women were enrolled in the study in pregnancy. Children have been followed up at regular intervals from birth up to age 18.

Research questions:do adolescent disordered eating behaviours (not only clinical ED) negatively affect bone accrual and bone development during puberty and into young adulthood, including individuals with subclinical disorders not currently viewed as being at risk? Do reductions in fat mass contribute to these deleterious effects of ED behaviours on bone development particularly those on cortical bone? This being the case, are reductions in fat mass in the context of ED behaviours particularly harmful, reflecting the fact that they are achieved by dietary restriction as opposed to by increased physical activity? What is the impact of disordered eating behaviours on peak bone mass?

Methods:

Outcomes:

1) Total DXA scans have been performed on the children/adolescents at ages: 11.5 (n = 7159), age 13.5 (n = 6147), age 15.5 (n= 5509) and age 17.5 (approximately 4000). In addition, hip DXA scans have been performed at age 13.5 and 17.5, and pQCT scans of the mid tibia at 15.5 and 17.5. Standard DXA and pQCT parameters related to bone development have been derived and will serve as the main outcomes. Data on fractures has also been collected at regular intervals.

We are seeking funding for a new wave of data collection to collect:

1. a 1-page questionnaire on stress fractures;

2. a two page questionnaire (or computerised assessment) on disordered eating behaviours and participation in exercise

3. DXA (hip and total body) and pQCT (tibia plus radius)

4. objective measurement of weight and height

Predictors:

1) Data on adolescent ED behaviours have been collected at age 13, 14, 16, and 18 adolescents

Other explanatory variables (mediators and/or confounders):

1)- Data are also available on pubertal timing and anthropometric measures at all the above ages on ~6,000 adolescents.

-Total body fat and lean mass as measured by total body DXA

-Physical activity as measured in the children by accelerometry at multiple time points

-Detailed information on adolescent diet using a combination of diet diaries and food frequency questionnaires

-Extensive information on socio economic status

Data collection: we envisage the new data collection can be part of an ALSPAC clinic, alternatively we will select individuals on the basis of their exposure (any disordered eating in adolescence, N=600-800) and unexposed individuals (no disordered eating in adolescence, N=600-800) to assess.

Analyses: Univariate and multivariate logistic models will be used to determine the effect of relevant predictors on outcomes. Longitudinal modelling will be used for longitudinal repeated data and to model hypothesised relationships.