Bone Loss in Women With Anorexia Nervosa

Anorexia Nervosa Clinical Trial

Official title:

IGF-1 and Bone Loss in Women Anorexia Nervosa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00089843
• Other study ID #: 5 R01 DK052625 (completed)
• Secondary ID: R01DK0526251UL1R
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: June 2003
• Est. completion date: April 2008

Study information

• Verified date: August 2020
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Women with Anorexia Nervosa have been found to have low bone density. The study will determine whether administration of low doses of a natural hormone, testosterone and/or risedronate, a medication to help prevent bone breakdown will improve or prevent bone loss in this condition.

Description:

II. SPECIFIC AIMS

Severe osteopenia is a prevalent complication of anorexia nervosa (AN), affecting over half of all women with this disease. Loss of 25-50% of total bone mass occurs frequently and is often permanent. Although anorexia nervosa affects from 0.5-1.0% of college age women, no successful therapeutic interventions have been developed for osteoporosis in this population. Bone loss in anorexia nervosa is characterized by reduced bone formation coupled with increased bone resorption. Anorexia nervosa results in a deficiency of testosterone. Testosterone administration reduces bone resorption and data suggest that low-dose testosterone replacement therapy can increase surrogate markers of bone formation. Bisphosphonates are now well established to decrease bone resorption and improve bone density in severely osteopenic postmenopausal women. However, there are few data regarding the use of this antiresorptive therapy in women with severe pre-menopausal bone loss. Our preliminary data demonstrate that administration of a bisphosphonate decreases bone resorption and increases bone mass in women with AN after 6 and 9 months. These are the first data to demonstrate a striking increase in bone density in such women. We will test the hypothesis that a combined strategy to increase bone formation and decrease bone resorption by combining testosterone with a bisphosphonate will increase bone mass in anorexia nervosa.

The following hypotheses will be tested:

Specific Aim 1. Testosterone, a nutritionally dependent bone trophic factor, is a critical determinant of decreased bone formation in anorexia nervosa, and administration of physiologic testosterone will increase bone formation and lean body mass in this disease

We will investigate in women with anorexia nervosa whether:

A. Bone formation is reduced in association with low serum testosterone B. Testosterone deficiency is due to a combination of ovarian and adrenal defects resulting from undernutrition C. Testosterone administration reverses testosterone deficiency leading to an acute and sustained increase in bone formation and a decrease in bone resorption D. Administration of physiologic testosterone replacement stimulates increases in IGF-I levels in women with anorexia nervosa, a mechanism for increased bone formation and bone density E. Administration of physiologic testosterone replacement increases lean body mass, a major determinant of bone density

Specific Aim 2. Long-term (12 months) physiologic testosterone administration combined with a bisphosphonate increases bone density by a dual anabolic and anti-resorptive strategy

We will investigate in women with anorexia nervosa whether:

A. Physiologic testosterone administration increases bone density B. Administration of a bisphosphonate decreases the excessive state of bone resorption and increases bone density C. Co-administration of physiologic testosterone replacement and a bisphosphonate increases bone density to a greater degree than testosterone or a bisphosphonate alone by increasing bone formation and decreasing bone resorption

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: April 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Anorexia Nervosa,

• Over 18,

• Female,

• Decreased bone density

Exclusion Criteria:

• Medications to increase bone density

Related Conditions & MeSH terms

• Anorexia
• Anorexia Nervosa

Intervention

Drug:
• Testosterone
Testosterone patch 150mcg daily
• Actonel (risedronate)
Actonel (risedronate) 35mg PO one time weekly
• Placebo Actonel (risedronate)
Placebo tablet identical in appearance to active Actonel (risedronate) tablet
• Placebo testosterone
Placebo patch identical in appearance to testosterone patch

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Center for Research Resources (NCRR), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone Mineral Density	Percent change in postero-anterior (PA) spine bone mineral density as measured by dual energy x-ray absorptiometry (DXA)over a 12-month period. The differences in log-transformed values are reported as percent change.	Baseline and 12 months
Secondary	Markers of Bone Metabolism	type 1 collagen C-telopeptide(CTX); The differences in log-transformed values are reported as percent change.	Baseline to 12 months