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CompletedNCT03292146Updated Nov 4, 2025Results posted

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

A Phase 3 interventional study of Denosumab 60 MG [Prolia] and Placebo Injection in Bone Density, Bone Loss and Anorexia Nervosa, sponsored by Massachusetts General Hospital. Completed at 1 site in United States. Open to female participants aged 20 Years to 60 Years. Per ClinicalTrials.gov, last updated 2025-11-04.

Sponsored by Massachusetts General Hospital · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
30
Allocation
Randomized
Ages
20 Years to 60 Years
Sex
Female
01

Study 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.

02

Conditions studied

  • Bone Density
  • Bone Loss
  • Anorexia Nervosa
  • Eating Disorder
  • Atypical Anorexia Nervosa
03

Who can participate

Ages eligible
20 Years to 60 Years
Sexes eligible
Female
Accepts healthy volunteers
No

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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
30 participants (actual)

Study arms

  • 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] · Drug: Alendronate 70Mg Tab

  • 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: Placebo Injection · Drug: Alendronate 70Mg Tab

Interventions

  • DrugDenosumab 60 MG [Prolia]

    Denosumab 60mg injection at baseline and 6 months

  • DrugPlacebo Injection

    Placebo Injection at baseline and 6 months

  • DrugAlendronate 70Mg Tab

    Alendronate 70mg PO weekly starting at Month 12 through 24 months.

05

What researchers measure

Primary outcomes

  1. 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).

    Time frame: 12 months (Period 1)

Secondary outcomes

  1. Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA

    Time frame: Baseline to 24 months

  2. Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA

    Time frame: 12 months to 24 months (Period 2)

06

Results

Posted Oct 12, 2022

Participant flow

Women, age 20-60 years, with anorexia nervosa or atypical anorexia nervosa and BMD T-score \< -1.0

Baseline to 12 months
Participant flow — Baseline to 12 months
MilestoneDenosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)
Started2010
Completed189
Not completed21
Withdrew: Relocation10
Withdrew: Seeking higher level of care for eating disorder10
Withdrew: Seeking treatment for chronic fatigue syndrome01
12 months to 24 months
Participant flow — 12 months to 24 months
MilestoneDenosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)
Started189
Completed156
Not completed33
Withdrew: Planning pregnancy22
Withdrew: Personal reasons10
Withdrew: Lost to follow-up01

Outcome measures

PrimaryPostero-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).

Time frame:
12 months (Period 1)
Reported as:
Least squares mean · g/cm^2
Postero-anterior (PA) Lumbar Spine Bone Mineral Density by Dual-energy X-ray Absorptiometry (DXA)
g/cm^2Denosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)
Postero-anterior (PA) Lumbar Spine Bone Mineral Density by Dual-energy X-ray Absorptiometry (DXA)0.90 ± 0.030.87 ± 0.04
Statistical analysis
  • Denosumab (0-12 months) followed by alendronate (12-24 months) vs Placebo (0-12 months) followed by alendronate (12-24 months) · Mixed Models Analysis · p = 0.009
SecondaryPercent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA
Time frame:
Baseline to 24 months
Reported as:
Mean · % change
Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA
% changeDenosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)
Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA3.9 ± 4.35.8 ± 5.3
Statistical analysis
  • Denosumab (0-12 months) followed by alendronate (12-24 months) vs Placebo (0-12 months) followed by alendronate (12-24 months) · t-test, 2 sided · p = 0.41
SecondaryPercent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA
Time frame:
12 months to 24 months (Period 2)
Reported as:
Mean · % change
Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA
% changeDenosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)
Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA-2.0 ± 3.74.6 ± 3.2
Statistical analysis
  • Denosumab (0-12 months) followed by alendronate (12-24 months) · Matched pairs · p = 0.06
  • Placebo (0-12 months) followed by alendronate (12-24 months) · Matched pairs · p = 0.01

Adverse events

Collected over Baseline to 24 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Denosumab (0-12 months) followed by alendronate (12-24 months)0/20 (0%)0/20 (0%)6/20 (30%)
Placebo (0-12 months) followed by alendronate (12-24 months)0/10 (0%)0/10 (0%)3/10 (30%)
Most frequent other events
Most frequent other events
EventDenosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)
constipationGastrointestinal disorders3/200/10
COVID-19Infections and infestations1/201/10
bone fractureInjury, poisoning and procedural complications1/201/10
Gallbladder biliary dyskinesiaGastrointestinal disorders0/201/10
nausea/stomach pain/bloatingGastrointestinal disorders1/200/10
KeratitisInfections and infestations1/200/10
C. difficileInfections and infestations1/200/10
Disc degeneration and herniationInjury, poisoning and procedural complications1/200/10

Baseline characteristics

Women, age 20-60 years, with anorexia nervosa or atypical anorexia nervosa and BMD T-score \< -1.0

Age, Categorical
Age, Categorical(Participants)Denosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)Total
<=18 years000
Between 18 and 65 years201030
>=65 years000
Age, Continuous
Age, Continuous(years)Denosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)Total
Mean29.2 ± 8.029.4 ± 6.829.3 ± 7.5
Sex: Female, Male
Sex: Female, Male(Participants)Denosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)Total
Female201030
Male000
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Denosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)Total
Hispanic or Latino000
Not Hispanic or Latino201030
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Denosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)Total
American Indian or Alaska Native000
Asian101
Native Hawaiian or Other Pacific Islander000
Black or African American000
White191029
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Denosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)Total
United States201030
Body mass index (BMI)
Body mass index (BMI)(kg / m^2)Denosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)Total
Mean19.0 ± 1.718.0 ± 2.018.7 ± 1.9
Postero-anterior (PA) lumbar spine areal bone mineral density (aBMD) Z-score
Postero-anterior (PA) lumbar spine areal bone mineral density (aBMD) Z-score(Z-score)Denosumab (0-12 months) followed by alendronate (12-24 months)Placebo (0-12 months) followed by alendronate (12-24 months)Total
Mean-1.6 ± 0.9-1.7 ± 1.4-1.6 ± 1.1

1 further baseline measures are reported on the registry.

07

Study locations

1 site
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
08

References and documents

Study documents

  • Study protocol · Mar 2, 2021
  • Statistical analysis plan · Jul 13, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03292146
Lead sponsor
Massachusetts General Hospital
Collaborators
Amgen
Responsible party
Karen Klahr Miller, MD (Professor of Medicine, Massachusetts General Hospital) — Principal investigator
First posted
Sep 25, 2017
Start date
Oct 25, 2017
Primary completion
Jul 22, 2021
Completion
Jul 22, 2021
Results posted
Oct 12, 2022
Last update
Nov 4, 2025

Study contacts

Karen K Miller, MD
principal investigator · Massachusetts General Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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