Anorexia nervosa (AN) is a lethal psychiatric disorder associated with serious medical sequelae sceondary to malnutrition. The most effective treatment to improve pubertal and cardiac function, bone health and cognition in AN is full restoration of weight and endogenous gonadal function. Effective psychosocial treatments for adolescents with AN and other restrictive eating disorders focus on early and complete weight restoration. Although research has shown that faster rates of weight gain and higher fat mass (FM) early in AN treatment are associated with greater psychiatric recovery; the impact of the rate of weight restoration on metabolic function, body composition, adipose distribution and bone health has not been addressed - and is the focus of this proposal. The proposed study will characterize changes in bone health, body composition, and fat distribution after weight restoration from AN, and will help to determine the relationship between changes in body composition and recovery of bone density and structure. The study has two primary components. The first component will examine participants who achieve a healthy goal weight in the first year of AN treatment to determine if earlier weight gain during the first year f AN treatment is associated with greater increases in percent body fat, visceral adiposity, IMAT, insulin resistance and inflammatory cytokines over the 24 month interval. The second component seeks to identify if changes in body composition, fat distribution and inflammatory cytokines are associated with changes in trabecular and cortical bone mineral density (BMD) and cortical dimensions over 2 years of treatment in children and adolescents with AN. The applicant has collected preliminary data in a prevalent sample of adolescents with AN that suggests that weight gain is associated with relatively greater recovery of fat mass, compared with lean body mass (LBM), and AN was associated with decreased trabecular bone mineral density and cortical dimensions. This data was used to inform the study design. The proposed study will identify important areas of intervention in adolescents with AN which will help to drive future interventions to reduce future complications, such as impaired bone accrual, early onset of osteoporosis, and fracture, as well as form the basis for the applicant's future R01 proposal. The candidate, Dr. Rebecka Peebles, is a rising expert in the field of eating disorders and their medical complications associated with bone health and body composition. She has extensive clinical training and a strong research background that will help her succeed in her career as an independent researcher in adolescent medicine focusing on eating disorder research and improving the bone health and better understanding the body composition of patients with AN. The candidate proposes a comprehensive interdisciplinary career development plan that will provide her with the skills and experience for her development into an independent clinical investigator. Since her previous submission, Dr. Virginia Stallings has assumed the position of primary mentor, due to the move of Dr. Mary Leonard to Stanford University to start a bone research program. Dr. Leonard will continue to serve as co-mentor in conjunction with Dr. James Lock. Her co-mentors are both recipients of an NIH K24 award. With the addition of Dr. Stallings to Dr. Peebles' career development mentoring team; she has excellent guidance from two top leaders in the field of bone health and body composition in varied chronic diseases, in addition to a leading investigator in adolescent eating disorders. Her multidisciplinary advisory committee also includes NIH-funded leaders in biostatistics, epidemiology, bone metabolism, body composition, weight regulation, and eating disorders. She will draw on outstanding resources available through CHOP, including the CTSA supported Center for Clinical and Translational Research (CTA), and the Center for Clinical Epidemiology and Biostatistics (CCEB). She will also complete additional formal didactic training in biostatistics, epidemiology, and skeletal biology relevant to this proposal. The proposed project will build on her prior training and research experience to promote her transition to independence. The career development goals outlined in the application will serve as the basis for future investigations. Her long-term goals are to conduct clinical trials to improve body composition, bone health, and related outcomes in eating disorders. The study proposed here is the necessary first step to advance her career in eating disorders, body composition, and bone health research.
Full restoration of weight and endogenous gonadal function in adolescents with anorexia nervosa (AN) is an important predictor of treatment success and is associated with improved pubertal and cardiac function, bone health, and cognition. Adolescence is an important period of growth and change in musculoskeletal development which can be disrupted by AN; this can place patients at risk for impaired bone accrual, early onset of osteoporosis, and fracture. Although faster rates of weight gain and higher fat mass (FM) early in AN treatment are associated with greater psychiatric recovery, the impact of the rate of weight restoration on body composition, adipose distribution, metabolic markers, and bone health has not been addressed, and is the focus of this proposal.
