Effects of Anorexia Nervosa on Bone Mass in Adolescents

Phase 2

Completed

Conditions: Anorexia Nervosa

Interventions: Drug: Physiologic Estrogen/progesterone
Other: Placebo

Registration Number: NCT00088153

Lead Sponsor: Massachusetts General Hospital

Brief Summary: 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.

Detailed 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 110

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Physiologic estrogen replacement	Physiologic Estrogen/progesterone	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
Placebo	Placebo	Placebo patches or pills

Primary Outcome Measures

Name	Time	Method
Percent Change in Spine Bone Density Over the Study Duration (18 Months)	Baseline and 18 months	Bone density at the spine (lumbar 1-4 vertebrae) was measured using dual energy x-ray absorptiometry (DXA) at baseline, 6 months, 12 months and 18 months. The primary outcome was the percent change in bone density at the spine from baseline to 18 months. Areal bone density is measured as g/cm2. The unit of measure for the percent change in bone density is 'percent' Percent change in bone density= \[\[Bone density at 18 months- Bone density at baseline)\*100/Bone density at baseline\]%
Change in Spine Bone Mineral Density Z-scores Over the Study Duration (18 Months)	Baseline and 18 months	Bone density at the spine (lumbar 1-4 vertebrae) was measured using dual energy x-ray absorptiometry (DXA) at baseline, 6 months, 12 months and 18 months. The other primary outcome was the change in spine bone density Z-score from baseline to 18 months. The bone density Z-score is a standard deviation score that compares one's bone density to the mean for age and gender, and the Z-score, therefore, does not have any units. It is simply referred to as a Z-score. Change in bone density Z-score= \[Bone density Z-score at 18 months- Bone density Z-score at baseline\]

Secondary Outcome Measures

Name	Time	Method
Change in N-terminal Propeptide of Type 1 Procollagen (P1NP) Over the Study Duration (18 Months)	Baseline and 18 months	P1NP is a surrogate marker of bone formation that is measured in serum. P1NP levels were measured at baseline, 6, 12 and 18 months. A secondary outcome was the change in P1NP levels from baseline to 18 months: \[P1NP at 18 months - P1NP at baseline). The unit is ng/ml