Effects of Denosumab on Bone Mineral Density in Women With Anorexia Nervosa: A Pilot Study

Phase 3

Completed

Conditions: Bone Density
Bone Loss
Anorexia Nervosa
Eating Disorder
Atypical Anorexia Nervosa

Interventions: Drug: Denosumab 60 MG [Prolia]
Drug: Placebo Injection
Drug: Alendronate 70Mg Tab

Brief 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Active Denosumab 60mg Injection	Denosumab 60 MG [Prolia]	Denosumab 60mg injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.
Placebo	Placebo Injection	Placebo injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.
Placebo	Alendronate 70Mg Tab	Placebo injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.
Active Denosumab 60mg Injection	Alendronate 70Mg Tab	Denosumab 60mg injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.

Primary Outcome Measures

Name	Time	Method
Postero-anterior (PA) Lumbar Spine Bone Mineral Density by Dual-energy X-ray Absorptiometry (DXA)	12 months (Period 1)	Postero-anterior (PA) lumbar spine bone mineral density was assessed by dual-energy x-ray absorptiometry (DXA). The DXA scanner used was a Hologic Horizon A (Hologic, Inc., Waltham, MA).

Secondary Outcome Measures