Bone Loss in Women With Anorexia Nervosa

Phase 2

Completed

Conditions: Anorexia Nervosa

Interventions: Drug: Actonel (risedronate)
Drug: Testosterone
Drug: Placebo testosterone
Drug: Placebo Actonel (risedronate)

Registration Number: NCT00089843

Lead Sponsor: Massachusetts General Hospital

Brief 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.

Detailed 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 & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 77

Inclusion Criteria

Anorexia Nervosa,
Over 18,
Female,
Decreased bone density

Exclusion Criteria

Medications to increase bone density

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
4	Actonel (risedronate)	Active Actonel (risedronate) and placebo testosterone
4	Placebo testosterone	Active Actonel (risedronate) and placebo testosterone
2	Placebo Actonel (risedronate)	Placebo Actonel (risedronate) and active testosterone patch
3	Actonel (risedronate)	Active Actonel (risedronate) and active testosterone patch
1	Placebo Actonel (risedronate)	Placebo testosterone patch and placebo Actonel (risedronate)
1	Placebo testosterone	Placebo testosterone patch and placebo Actonel (risedronate)
3	Testosterone	Active Actonel (risedronate) and active testosterone patch
2	Testosterone	Placebo Actonel (risedronate) and active testosterone patch

Primary Outcome Measures

Name	Time	Method
Bone Mineral Density	Baseline and 12 months	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.

Secondary Outcome Measures

Name	Time	Method
Markers of Bone Metabolism	Baseline to 12 months	type 1 collagen C-telopeptide(CTX); The differences in log-transformed values are reported as percent change.