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

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

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.

Study Overview

• Status: Completed
• Conditions: Anorexia Nervosa; Bone Loss; Eating Disorder; Bone Density; Atypical Anorexia Nervosa
• Intervention / Treatment: Drug: Denosumab 60 MG [Prolia]; Drug: Alendronate 70Mg Tab; Drug: Placebo Injection

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 56 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Denosumab 60mg Injection; 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]; Denosumab 60mg injection at baseline and 6 months; Drug: Alendronate 70Mg Tab; Alendronate 70mg PO weekly starting at Month 12 through 24 months.
Placebo Comparator: Placebo; Placebo injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.	Drug: Alendronate 70Mg Tab; Alendronate 70mg PO weekly starting at Month 12 through 24 months.; Drug: Placebo Injection; Placebo Injection at baseline and 6 months

What is the study measuring?

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	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)

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Amgen
• Investigators: Principal Investigator: Karen K Miller, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2017
• Primary Completion (Actual): July 22, 2021
• Study Completion (Actual): July 22, 2021

Study Registration Dates

• First Submitted: September 21, 2017
• First Submitted That Met QC Criteria: September 21, 2017
• First Posted (Actual): September 25, 2017

Study Record Updates

• Last Update Posted (Estimated): November 4, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Mental Disorders; Metabolic Diseases; Signs and Symptoms, Digestive; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Bone Diseases, Metabolic; Feeding and Eating Disorders; Anorexia Nervosa; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Organophosphorus Compounds; Organophosphonates; Diphosphonates; Denosumab; Alendronate
• Other Study ID Numbers: 2017P000529

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No