Effects of Anorexia Nervosa on Bone Mass in Adolescents

Anorexia Nervosa Clinical Trial

Official title:

Effects of Anorexia Nervosa on Peak Bone Mass

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00088153
• Other study ID #: DK062249
• Secondary ID: R01DK062249
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 2003
• Est. completion date: June 2011

Study information

• Verified date: October 2021
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: June 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 12 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anorexia
• Anorexia Nervosa

Intervention

Drug:
• Physiologic Estrogen/progesterone
Vivelle Dot patch 100 mcg twice weekly; Provera 2.5 mg daily for the first 10 days of the month

Other:
• Placebo
Placebo patches twice weekly; Placebo pills daily for the first 10 days of every month

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), The Hospital for Sick Children

Country where clinical trial is conducted

United States, 

References & Publications (1)

Misra M, Katzman D, Miller KK, Mendes N, Snelgrove D, Russell M, Goldstein MA, Ebrahimi S, Clauss L, Weigel T, Mickley D, Schoenfeld DA, Herzog DB, Klibanski A. Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nerv — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change in Spine Bone Density Over the Study Duration (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]%	Baseline and 18 months
Primary	Change in Spine Bone Mineral Density Z-scores Over the Study Duration (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]	Baseline and 18 months
Secondary	Change in N-terminal Propeptide of Type 1 Procollagen (P1NP) Over the Study Duration (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	Baseline and 18 months