Bone Loss in Women With Anorexia Nervosa

NCT ID: NCT00089843

Last Updated: 2020-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2008-04-30

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

Conditions

Anorexia Nervosa

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

2

Placebo Actonel (risedronate) and active testosterone patch

Group Type: ACTIVE_COMPARATOR

Testosterone

Intervention Type: DRUG

Testosterone patch 150mcg daily

Placebo Actonel (risedronate)

Intervention Type: DRUG

Placebo tablet identical in appearance to active Actonel (risedronate) tablet

3

Active Actonel (risedronate) and active testosterone patch

Group Type: ACTIVE_COMPARATOR

Testosterone

Intervention Type: DRUG

Testosterone patch 150mcg daily

Actonel (risedronate)

Intervention Type: DRUG

Actonel (risedronate) 35mg PO one time weekly

4

Active Actonel (risedronate) and placebo testosterone

Group Type: ACTIVE_COMPARATOR

Actonel (risedronate)

Intervention Type: DRUG

Actonel (risedronate) 35mg PO one time weekly

Placebo testosterone

Intervention Type: DRUG

Placebo patch identical in appearance to testosterone patch

1

Placebo testosterone patch and placebo Actonel (risedronate)

Group Type: PLACEBO_COMPARATOR

Placebo Actonel (risedronate)

Intervention Type: DRUG

Placebo tablet identical in appearance to active Actonel (risedronate) tablet

Placebo testosterone

Intervention Type: DRUG

Placebo patch identical in appearance to testosterone patch

Interventions

Testosterone

Testosterone patch 150mcg daily

Intervention Type: DRUG

Actonel (risedronate)

Actonel (risedronate) 35mg PO one time weekly

Intervention Type: DRUG

Placebo Actonel (risedronate)

Placebo tablet identical in appearance to active Actonel (risedronate) tablet

Intervention Type: DRUG

Placebo testosterone

Placebo patch identical in appearance to testosterone patch

Intervention Type: DRUG

Other Intervention Names

Intrinsa; Actonel

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• Medications to increase bone density

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Karen Klahr Miller, MD

Chief, Neuroendocrine Unit

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anne Klibanski, M.D.

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

Miller KK, Wexler TL, Zha AM, Lawson EA, Meenaghan EM, Misra M, Binstock AB, Herzog DB, Klibanski A. Androgen deficiency: association with increased anxiety and depression symptom severity in anorexia nervosa. J Clin Psychiatry. 2007 Jun;68(6):959-65. doi: 10.4088/jcp.v68n0621.

Reference Type: DERIVED

PMID: 17592924 (View on PubMed)

Other Identifiers

R01DK052625

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1UL1RR025758

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5 R01 DK052625 (completed)

Identifier Type: -

Identifier Source: org_study_id