Effects of Romosozumab on Bone Density in Women With Anorexia Nervosa

NCT04779216 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 2020P000329
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This protocol is a randomized, double-blind, placebo-controlled clinical trial which aims to investigate the effect of romosozumab on BMD in women with anorexia nervosa. The investigators will also investigate the safety of romosozumab in women with anorexia nervosa. The investigators hypothesize that 12 months of romosozumab administration will result in an increase in bone mineral density, increase in markers of bone formation and decrease in markers of bone resorption, and improvement in bone microarchitecture in osteopenic women with anorexia nervosa compared with placebo. In Phase 2, participants will receive a single infusion of open-label zoledronic acid (an intravenous bisphosphonate) 5 mg after the initial 12-month administration of romosozumab or placebo. The investigators hypothesize that 12 months of romosozumab followed by a single intravenous infusion of open-label zoledronic acid will result in a greater increase in BMD compared to 12 months of placebo followed by a single intravenous infusion of open-label zoledronic acid. Within the group of women who receive sequential therapy with 12 months of romosozumab followed by a single intravenous infusion of zoledronic acid, the investigators hypothesize BMD will be maintained between 12 and 24 months following administration of zoledronic acid.

Conditions

Bone Density, Low; Bone Loss; Anorexia Nervosa; Eating Disorders

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline to 12 Months in Postero-anterior Lumbar Spine Bone Mineral Density by Dual Energy X-ray Absorptiometry (DXA).

  Percent change from baseline to 12 months in postero-anterior lumbar spine bone mineral density by dual energy x-ray absorptiometry (DXA).

  Baseline to 12 Months

Secondary Outcomes (1)

• Percent Change From Baseline to 24 Months in Postero-anterior Lumbar Spine BMD.

  Baseline to 24 Months

Study Arms (2)

Active Romosozumab 210mg Injection

EXPERIMENTAL

Romosozumab 210mg injection monthly for 12 months. A single infusion of open-label zoledronic acid 5 mg after the initial 12-month administration of romosozumab.

Drug: Romosozumab Prefilled Syringe; Drug: Zoledronic acid 5 mg

Placebo

PLACEBO COMPARATOR

Placebo injection monthly for 12 months. A single infusion of open-label zoledronic acid 5 mg after the initial 12-month administration of placebo.

Drug: Placebo; Drug: Zoledronic acid 5 mg

Interventions

Romosozumab Prefilled Syringe DRUG

Romosozumab 210mg Injection monthly for 12 months

Active Romosozumab 210mg Injection

Placebo DRUG

Placebo Injection monthly for 12 months

Placebo

Zoledronic acid 5 mg DRUG

A single infusion of open-label zoledronic acid 5 mg after the initial 12-month administration of romosozumab or placebo

Also known as: Zoledronate, Reclast

Active Romosozumab 210mg Injection; Placebo

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female
• Age 20-60 years, skeletally mature with closed epiphyses
• Body mass index (BMI) ≥ 16.5 kg/m2
• Anorexia nervosa or atypical anorexia nervosa defined by DSM-V diagnostic criteria
• BMD Z-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); Intrauterine hormonal-releasing system (IUS); Surgery to tie both fallopian tubes (bilateral tubal ligation/occlusion); Woman's male partner has had a vasectomy and testing shows there is no sperm in the semen
• Dental check-up within the past year

You may not qualify if:

• Hospitalization within 3 months of baseline study visit, including inpatient eating disorder treatment facility; participating in a residential eating disorder treatment program within 3 months of study participation is permitted
• Myocardial infarction or stroke within 1 year preceding enrollment
• History of hypertension or use of anti-hypertensive medications within the past 6 months
• Any disease known to affect bone, including untreated thyroid dysfunction, Cushing's or renal failure
• 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 25-OH vitamin D level \<30 ng/mL
• Serum potassium \<3.0 meq/L
• Serum magnesium \<1.5 meq/L
• Serum ALT \>3 times upper limit of normal
• eGFR of less than 30 ml/min
• LDL \> 190 mg/dL
• Hypocalcemia
• Diabetes mellitus
• Active substance abuse, including alcohol

Sponsors & Collaborators

• Karen Klahr Miller, MD: lead
• Amgen: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Bone Diseases, Metabolic; Anorexia Nervosa; Feeding and Eating Disorders

Interventions

Zoledronic Acid

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Mental Disorders; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Karen Miller, MD
• Organization: Massachusetts General Hospital

kkmiller@mgh.harvard.edu

6177263870

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 26, 2021
• First Posted: March 3, 2021
• Study Start: September 20, 2021
• Primary Completion: October 24, 2024
• Study Completion: November 17, 2025
• Last Updated: December 16, 2025
• Results First Posted: December 16, 2025

Record last verified: 2025-11

Locations

US (1)