Bone Loss in Women With Anorexia Nervosa

Overview

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.

Full Title of Study: “IGF-1 and Bone Loss in Women Anorexia Nervosa”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Factorial Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: April 2008

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

Interventions

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

Arms, Groups and Cohorts

  • Active Comparator: 2
    • Placebo Actonel (risedronate) and active testosterone patch
  • Active Comparator: 3
    • Active Actonel (risedronate) and active testosterone patch
  • Active Comparator: 4
    • Active Actonel (risedronate) and placebo testosterone
  • Placebo Comparator: 1
    • Placebo testosterone patch and placebo Actonel (risedronate)

Clinical Trial Outcome Measures

Primary Measures

  • Bone Mineral Density
    • Time Frame: 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 Measures

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

Participating in This Clinical Trial

Inclusion Criteria

  • Anorexia Nervosa, – Over 18, – Female, – Decreased bone density Exclusion Criteria:

  • Medications to increase bone density

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 45 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Massachusetts General Hospital
  • Collaborator
    • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Provider of Information About this Clinical Study
    • Principal Investigator: Karen Klahr Miller, MD, Chief, Neuroendocrine Unit – Massachusetts General Hospital
  • Overall Official(s)
    • Anne Klibanski, M.D., Principal Investigator, Massachusetts General Hospital

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.