Bone Loss in Women With Anorexia Nervosa

August 31, 2020 updated by: Karen Klahr Miller, MD, Massachusetts General Hospital

IGF-1 and Bone Loss in Women Anorexia Nervosa

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

77

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Anorexia Nervosa,
  • Over 18,
  • Female,
  • Decreased bone density

Exclusion Criteria:

  • Medications to increase bone density

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Quadruple

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Center for Research Resources (NCRR)

Investigators

  • Principal Investigator: Anne Klibanski, M.D., Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2003

Primary Completion (Actual)

April 1, 2008

Study Completion (Actual)

April 1, 2008

Study Registration Dates

First Submitted

August 16, 2004

First Submitted That Met QC Criteria

August 16, 2004

First Posted (Estimate)

August 17, 2004

Study Record Updates

Last Update Posted (Actual)

September 2, 2020

Last Update Submitted That Met QC Criteria

August 31, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5 R01 DK052625 (completed)
  • R01DK052625 (U.S. NIH Grant/Contract)
  • 1UL1RR025758 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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