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

Study Overview
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Brief Summary
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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.

Official Title
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Effects of Denosumab on Bone Mineral Density, Markers of Bone Metabolism and Bone Microarchitecture in Women With Anorexia Nervosa: A Pilot Study

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

Intervention / Treatment
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* Drug: Denosumab 60 MG [Prolia]
* Drug: Placebo Injection
* Drug: Alendronate 70Mg Tab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Denosumab 60mg Injection<br>Denosumab 60mg injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months. | Drug: Denosumab 60 MG [Prolia]<br>* Denosumab 60mg injection at baseline and 6 months<br>Drug: Alendronate 70Mg Tab<br>* Alendronate 70mg PO weekly starting at Month 12 through 24 months.<br>|
| Placebo Comparator: Placebo<br>Placebo injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months. | Drug: Placebo Injection<br>* Placebo Injection at baseline and 6 months<br>Drug: Alendronate 70Mg Tab<br>* Alendronate 70mg PO weekly starting at Month 12 through 24 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postero-anterior (PA) Lumbar Spine Bone Mineral Density by Dual-energy X-ray Absorptiometry (DXA) | 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). | 12 months (Period 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA |  | Baseline to 24 months | 
| Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA |  | 12 months to 24 months (Period 2) |