Effects of Anorexia Nervosa on Peak Bone Mass

Given the increasing prevalence of AN, its profound consequences on bone health, and lack of optimal treatment interventions, these studies will provide critical data needed to identify optimal treatment strategies for this severe co-morbid disease using state- of- the- art endpoints of BMD, bone microarchitecture and strength. Although both low IGF-1 and hypogonadism are associated with increased skeletal fragility in AN, the mechanisms by which these factors interact are incompletely understood. Specifically, the increased skeletal fragility that is associated with AN is poorly reflected by DXA-derived BMD. Furthermore, the magnitude and mechanisms by which IGF-1 deficiency and hypogonadism influence bone microarchitecture are not defined. The growing incidence of eating disorders in adolescent girls and their long-term effects on skeletal health provide strong rationale for studies that will provide a better understanding of these issues and the evaluation of rational therapeutic approaches. The studies described in this proposal utilize both cross-sectional and RCT approaches to achieve this goal. Additionally, our utilization of sophisticated techniques such as high resolution peripheral QCT (HR-pQCT) will improve our understanding of the relationship between IGF-1, gonadal steroids and bone quality and will aid in the development of effective therapies in the treatment of skeletal fragility in Anorexia Nervosa.

Inclusion criteria

AN:

• Age: 14-22 years old
• Bone age (BA): ≥14 years
• Should meet DSM IV criteria for AN
• Subjects at MGH will be evaluated by co-investigator Dr. David Herzog, Director of the Harris Center for Eating Disorders, at MGH, and by Dr. Debra Katzman, co-investigator, and the Hospital for Sick Children, Toronto who directs their Eating Disorders Program, respectively, before enrollment.

Inclusion criteria

Controls:

• Healthy adolescent girls 14-22 years
• BA of ≥14 years
• BMI between the 10th-90th percentiles for age
• Regular menstrual periods every 28-35 days for subjects ≥ 2 years post-menarche.

Exclusion criteria

• Diseases known to affect bone metabolism including untreated thyroid disease, Cushing's syndrome, diabetes, pituitary disease, renal failure and prior bone fracture within six months of the study.
• Medications known to affect bone metabolism, including gonadal steroids, within three months.
• Evidence of suicidality, psychosis, or substance abuse.
• Premature ovarian failure, as demonstrated by an elevated FSH.
• Abnormal TSH.
• Hematocrit <30%, Potassium <3.0 mmol/L, Glucose <50 mg/dl
• Pregnancy
• History of malignancy
• Contraindications to estrogen therapy (for girls with AN)