Effects of Anorexia Nervosa on Bone Mass in Adolescents

Mass General Brigham

Status and phase: Completed; Phase 3; Phase 2

Conditions: Anorexia Nervosa

Treatments: Drug: Physiologic Estrogen/progesterone; Other: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00088153

R01DK062249 (U.S. NIH Grant/Contract)

DK062249

Details and patient eligibility

About

This study is to determine the effects of anorexia nervosa on bone mass and hormone levels in adolescents. Whether administration of estrogen, a normal hormone present during puberty, can help maintain bone development in girls with anorexia nervosa will be determined.

Full description

Adolescence is a critical time for bone mineral accretion as between 60-90% of peak bone mass is established during this period, and peak bone mass is a major determinant of bone density and osteoporosis risk during adulthood. Anorexia nervosa (AN) is the third most common chronic illness among adolescent girls, with a prevalence of 0.2-1.0%. Therefore, AN occurs at a time during which patients are the most vulnerable to disruption of bone mineral accretion. Osteopenia is a major co-morbid complication of AN in 50-75% of female adolescents and adult women with this eating disorder. Women with the onset of the disorder during adolescence have more severe osteopenia than women with onset during adulthood. Little is known about the pathogenesis of osteopenia in this adolescent population and there are no established therapies. Improved understanding of bone mineral metabolism and factors which predict recovery of bone mineral accretion are critical in the development of therapeutic strategies to preserve and maximize bone mass in girls with the onset of AN during adolescence. Estrogen is known to be a critical factor in the development of peak bone mass. Although AN is associated with profound estrogen deficiency, there are no controlled studies investigating the effects of estrogen administration in this population.

This research proposal will address critical unanswered questions regarding bone abnormalities in adolescents with anorexia nervosa. Defining changes in bone formation with weight recuperation and hormonal variables would provide insight into the factors essential for bone mineral accretion during adolescence, as well as those that predict recovery. Determination of dose-dependent estrogen effects in this population will be key in targeting interventions during the time of active disease, with the long-term goal of preserving peak bone mass accretion in this vulnerable group of patients. Data obtained from women with post-menopausal osteoporosis or from women with AN cannot be extrapolated to adolescent patients who are in an active period of bone growth and mineralization as well as remodeling. Given the increasing prevalence of AN and its profound consequences on bone health, these studies will provide much needed data to enable treatment strategies for this severe co-morbid disease.

Enrollment: 110 patients

Sex: Female

Ages: 12 to 18 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Females Only with Anorexia Nervosa and Amenorrhea 12-18 years
• Normal-weight girls 12-18 years with no past or present history of an eating disorder

Exclusion criteria

• Diseases affecting bone metabolism (including untreated thyroid disease, premature ovarian failure, diabetes, cancer, pituitary, renal disease or bone fracture within the past six months)
• Use of prescription medications affecting bone metabolism within three months
• Suicidality
• Psychosis
• Substance abuse
• Hematocrit <30 %
• Potassium <3.0 mmol/L
• Glucose <50 mg/dl.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

110 participants in 2 patient groups, including a placebo group

Physiologic estrogen replacement

Experimental group

Description:

Mature girls with anorexia nervosa (AN) (bone age 15 or greater): Transdermal estradiol (100 mcg) with cyclic progesterone (days 1-10 of each month). Immature girls with AN (bone age less than 15 years): Ethinyl estradiol (3.75 mcg daily for the first 6 months, 7.5 mcg daily for the next 6 months, and 11.25 mcg daily for the final 6 months of the study

Treatment:

Drug: Physiologic Estrogen/progesterone

Placebo

Placebo Comparator group

Description:

Placebo patches or pills

Treatment:

Other: Placebo