Effects of Anorexia Nervosa on Peak Bone Mass

• Status: Completed
• Trial end date: 2020-03-01
• Target enrollment: 0
• Participant gender: Female

Summary

Teenage girls with anorexia nervosa (AN) are at risk for low bone density and low rates of bone accrual, raising concerns regarding acquisition of peak bone mass, an important determinant of future bone health and fracture risk. Important factors contributing to low bone density in AN include low levels of estrogen and insulin like growth factor-1 (IGF-1). While estrogen is important for preventing bone loss, IGF-1 is important for optimizing bone formation. We have shown in a previous study that replacement of estrogen is effective in increasing bone density in teenage girls with AN; however, this increase in bone density remains lower than that seen in normal-weight controls over the same duration, and residual deficits persist. Importantly, the impact of administering replacement doses of IGF-1 with estrogen replacement has not been studied in teenagers with AN.

This study will examine the impact of administering recombinant human (rh) insulin like growth factor-1 (rhIGF-1) with estrogen (to mimic pubertal levels of these hormones) versus administration of estrogen alone on bone metabolism in adolescent girls with anorexia nervosa (AN).

One aim of this proposal is to investigate whether co-administration of insulin like growth factor-1 (rhIGF-1) with physiologic estradiol replacement to adolescent girls with AN will increase BMD (bone mineral density) more than estrogen monotherapy, and whether bone mass will approach that seen in healthy adolescent girls. An additional aim is to determine whether co-administration of rhIGF-1 with estradiol to mimic the normal pubertal milieu stimulates bone formation through an IGF-1 mediated anabolic effect, increases bone density to a greater extent than estrogen monotherapy, and improves bone mass accrual to approach that in healthy controls. The impact of rhIGF-1 +estradiol versus estradiol alone on bone microarchitecture will also be assessed.

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Massachusetts General Hospital
• Treatments: Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol valerate; Mecasermin; Polyestradiol phosphate

Criteria

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)