Bone Loss in Women With Anorexia Nervosa

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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IGF-1 and Bone Loss in Women Anorexia Nervosa

Conditions
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Anorexia Nervosa

Intervention / Treatment
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* Drug: Testosterone
* Drug: Actonel (risedronate)
* Drug: Placebo Actonel (risedronate)
* Drug: Placebo testosterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Anorexia Nervosa, Over 18, Female, Decreased bone density Exclusion Criteria: Medications to increase bone density

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 2<br>Placebo Actonel (risedronate) and active testosterone patch | Drug: Testosterone<br>* Testosterone patch 150mcg daily<br>* Other names: Intrinsa;Drug: Placebo Actonel (risedronate)<br>* Placebo tablet identical in appearance to active Actonel (risedronate) tablet<br>|
| Active Comparator: 3<br>Active Actonel (risedronate) and active testosterone patch | Drug: Testosterone<br>* Testosterone patch 150mcg daily<br>* Other names: Intrinsa;Drug: Actonel (risedronate)<br>* Actonel (risedronate) 35mg PO one time weekly<br>* Other names: Actonel;|
| Active Comparator: 4<br>Active Actonel (risedronate) and placebo testosterone | Drug: Actonel (risedronate)<br>* Actonel (risedronate) 35mg PO one time weekly<br>* Other names: Actonel;Drug: Placebo testosterone<br>* Placebo patch identical in appearance to testosterone patch<br>|
| Placebo Comparator: 1<br>Placebo testosterone patch and placebo Actonel (risedronate) | Drug: Placebo Actonel (risedronate)<br>* Placebo tablet identical in appearance to active Actonel (risedronate) tablet<br>Drug: Placebo testosterone<br>* Placebo patch identical in appearance to testosterone patch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eating Disorders, Osteopenia