Effects of Denosumab on Bone Mineral Density in Women With Anorexia Nervosa: A Pilot Study
Condition: Bone Density; Bone Loss; Anorexia Nervosa; Eating Disorder; Atypical Anorexia Nervosa
MeSH terms: Anorexia; Feeding and Eating Disorders; Anorexia Nervosa
Intervention: Denosumab 60 MG [Prolia]; Placebo Injection; Alendronate 70Mg Tab
Intervention description: Denosumab 60mg injection at baseline and 6 months; Placebo Injection at baseline and 6 months; Alendronate 70mg PO weekly starting at Month 12 through 24 months.
Intervention MeSH terms: Denosumab; Alendronate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking description: Double blind
Enrollment: 30.0
Sex: Female
Minimum age: 20 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      This protocol is a randomized, double-blind, placebo-controlled clinical trial which aims to
      investigate the effect of denosumab on BMD in women with anorexia nervosa. The investigators
      hypothesize that 12 months of denosumab administration will result in an increase in bone
      mineral density, decrease in markers of bone resorption and improvement in bone
      microarchitecture in osteopenic women with anorexia nervosa compared with placebo.

      An optional extension study will offer subjects 12-month administration of open-label
      alendronate (an oral bisphosphonate) after the initial 12 month administration of denosumab
      or placebo. We hypothesize that 12 months of denosumab followed by 12 months of open-label
      alendronate will result in a greater increase in BMD compared to 12 months of placebo
      followed by 12 months of open-label alendronate. Within the group of women who receive
      sequential therapy with 12 months of denosumab followed by 12 months of alendronate, we
      hypothesize that BMD will be maintained between 12 and 24 months while on alendronate.
    

Eligibility criteria:

        Inclusion/Exclusion Criteria:

        Inclusion Criteria:

          -  Female

          -  Age 20-60 years, skeletally mature with closed epiphyses

          -  Anorexia nervosa or atypical anorexia nervosa defined by DSM-V diagnostic criteria

          -  BMD T-score < -1.0

          -  Normal serum 25-OH vitamin D (>30 ng/mL) and calcium levels

          -  For women of reproductive age, agree to use an effective contraceptive method. Highly
             effective methods of birth control include:

               -  Combined (estrogen and progestogen) hormonal methods (pills, vaginal ring, or
                  skin patch)

               -  Intrauterine device (IUD)

               -  Intraduterine hormonal-releasing system (IUS)

               -  Surgery to tie both fallopian tubes (bilateral tubal ligation/occlusion)

               -  Your male partner has had a vasectomy and testing shows there is no sperm in the
                  semen

          -  Dental check up within the past year

        Exclusion Criteria:

          -  Any disease known to affect bone, including untreated thyroid dysfunction, Cushing's
             or renal failure

          -  Subjects with a known esophageal disease cannot participate in the alendronate
             extension study

          -  Any medication known to affect bone metabolism within 3 months of the study, excluding
             oral contraceptives or other forms of estrogen administration. Bisphosphonates must
             have been discontinued for at least one year before participation

          -  Immunodeficiency or taking immunosuppressive therapy

          -  Serum potassium <3.0 meq/L

          -  Serum ALT >3 times upper limit of normal

          -  eGFR of less than 30 ml/min

          -  Hypocalcemia

          -  Diabetes mellitus

          -  Active substance abuse, including alcohol

          -  History of malignancy

          -  Paget disease of bone

          -  Osteomalacia

          -  Osteonecrosis of the jaw (ONJ) or risk factor for ONJ, such as invasive dental
             procedures (eg, tooth extraction, dental implants, oral surgery in the past 6 months),
             poor oral hygiene, periodontal and/or pre-existing dental disease, and current use of
             corticosteroids.

          -  Planned invasive dental procedure over the next 24 months.

          -  Known senstivity to any of the products or components to be administered during dosing
             or known sensitivity to mammalian cell derived drug products

          -  Sensitivity to calcium or vitamin D supplements

          -  Pregnant, planning to become pregnant with 7 months after the end of treatment and/or
             breastfeeding