Bone Loss in Women With Anorexia Nervosa
Condition: Anorexia Nervosa
MeSH terms: Anorexia; Anorexia Nervosa
Study type: Interventional
Phase: Phase 2/Phase 3

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
    

Intervention name(s): Testosterone; Actonel (risedronate); Placebo Actonel (risedronate); Placebo testosterone
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Testosterone patch 150mcg daily; Actonel (risedronate) 35mg PO one time weekly; Placebo tablet identical in appearance to active Actonel (risedronate) tablet; Placebo patch identical in appearance to testosterone patch
Other intervention name(s): Intrinsa; Actonel
Intervention MeSH terms: Risedronic Acid; Etidronic Acid; Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Eating Disorders; Osteopenia