Skeletal Health and Bone Marrow Composition in Adolescents With Cystic Fibrosis

October 28, 2025 updated by: Rebecca Gordon, MD, Massachusetts General Hospital
The investigators will be evaluating bone marrow composition via magnetic resonance imaging in adolescents diagnosed with cystic fibrosis (CF) compared to healthy, matched controls. The investigators will also be assessing their bone mineral density via other imaging modalities, including dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). This longitudinal project will focus on abnormalities in bone marrow composition, and specifically whether adolescents with diagnosed with CF exhibit increased bone marrow fat, its association with bone mineral density (BMD) and the underlying pathophysiology, including glycemic control, inflammation, and bone turnover markers.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Less than optimal bone health has been seen in children that have cystic fibrosis (CF). This can present as low bone density or altered bone structure, weakening the bones and increasing fragility and fracture risk. As adolescence is especially important in bone development, conditions such as CF during this time can lead to long term bone issues. The underlying mechanisms are not well understood, but what is known is that red bone marrow converts to fat-rich yellow marrow. This study aims to focus on abnormalities in bone marrow, and specifically whether adolescents who have been diagnosed with CF have more bone marrow fat.

The primary hypothesis is that patients with CF will have associated increased fat levels in bone marrow, which will be associated with decreased bone formation and suboptimal bone health. The central objective is to obtain longitudinal data on the differences in bone marrow between patients with CF versus healthy adolescents. Long term, the investigators want to study how abnormal marrow fat and suboptimal bone health relate to one another.

The study involves 36 adolescents diagnosed with CF and 36 matched healthy controls. Eligibility criteria include no other chronic diseases that affect bone health and limited use of bone altering medications in the prior three months. The adolescents with CF will be matched with healthy adolescents based on sex, ancestry, age, and pubertal stage. Additional data on participants with CF will be collected via a chart review that will enable us to more fully characterize their CF.

Imaging will include: MRI of the knee with quantitative marrow fat assessment; dual-energy X-ray absorptiometry (DXA); and peripheral quantitative computed tomography (pQCT). All scans will be for research purposes only. The MRIs will be evaluated for any incidental findings, and if any identified, it will be reported to their primary care physician.

Additionally, blood draws will be used to assess markers of bone formation/resorption and inflammation. In participants with CF, they will have a continuous glucose monitor to assess dysglycemia. All participants will also complete questionnaires.

There will be a baseline visit, and then a follow up visit 1 year later, with identical study procedures at both visits.

Study Type

Observational

Enrollment (Estimated)

36

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The experimental group will be adolescents aged 13-20 with CF.

The control group will be matched for sex, ancestry, age (within 2 years), and pubertal stage (based on Tanner staging, ± 1 Tanner stage).

Description

Inclusion Criteria:

  • 13-20 years old
  • Cystic fibrosis with pancreatic insufficiency
  • Must have a stable treatment regimen, including CFTR modulator usage unchanged for the prior three months
  • Liver transplant recipients will be eligible, as long as they are at least 1 year post-transplant and are no longer on Prednisone for immunosuppressive therapy

Exclusion Criteria:

  • Diagnosis of other chronic disease affecting bone health
  • Active use (within the past 3 months) of medications that are known to affect skeletal metabolism
  • CF exacerbation or glucocorticoid exposure within the prior 1 month
  • Lung transplant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cystic Fibrosis

This group will be 36 adolescents, ages 13-20 years old, who have been diagnosed with cystic fibrosis.

All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
Diagnostic test: Magnetic resonance relaxometry
Spin-lattice relaxation (T1) relaxometry acquisition consisting of fast spin echo (FSE) acquisitions through the knee. T1 maps from the T1 relaxometry images will be generated using a two-parameter-fit iterative algorithm developed in-house using IDL software (Harris Geospatial Solutions, Melbourne, FL, USA). Mean T1 values for each region will be recorded. The anatomical locations of these regions will be consistent in size for all subjects and location. The locations chosen for the primary endpoints are ones that are known to be rich in red and yellow marrow, respectively.
Diagnostic test: Magnetic resonance spectroscopy
Magnetic resonance spectroscopy. MRS will be performed within a 1 mL voxel situated in the medial aspect of the distal femoral metaphysis. A single voxel point resolved spectral acquisition (PRESS) technique will be used to acquire non-water suppressed spectra at multiple echo times. Spectral fits using JMRUI MRS processing software (www.jmrui.eu) to the water and methylene/methyl resonances will be used to quantify peak areas and establish T2 corrected fat/(fat + water) ratios.
Diagnostic test: Blood Draw
Blood draw. Blood draws will be used to attain and assess markers of bone formation/resorption and inflammation. Specific markers of bone formation that will be assessed include osteocalcin (OC) and procollagen type 1 N-terminal propeptide (P1NP), and a marker of bone resorption, c-telopeptide (CTX). Additionally, in participants with CF, we will assess inflammation, with a c-reactive protein (CRP), and dysglycemia, with a continuous glucose monitor.
Diagnostic test: DXA
DXA will be utilized to obtain BMD of the total body, lumbar spine, and hip using a Hologic Horizon densitometer (Hologic Inc, Bedford, MA). Body composition will be obtained from total body scans.
Diagnostic test: pQCT
pQCT will be utilized to obtain volumetric BMD (mg/cm3) of the left tibia. Measurements using a Stratec XCT 3000 device (Orthometrix, White Plains, NY) will be obtained at multiple locations, in relation to distal growth plate.
Control

Controls will be matched for age, Tanner staging, BMI percentile, and ancestry.

All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
Diagnostic test: Magnetic resonance relaxometry
Spin-lattice relaxation (T1) relaxometry acquisition consisting of fast spin echo (FSE) acquisitions through the knee. T1 maps from the T1 relaxometry images will be generated using a two-parameter-fit iterative algorithm developed in-house using IDL software (Harris Geospatial Solutions, Melbourne, FL, USA). Mean T1 values for each region will be recorded. The anatomical locations of these regions will be consistent in size for all subjects and location. The locations chosen for the primary endpoints are ones that are known to be rich in red and yellow marrow, respectively.
Diagnostic test: Magnetic resonance spectroscopy
Magnetic resonance spectroscopy. MRS will be performed within a 1 mL voxel situated in the medial aspect of the distal femoral metaphysis. A single voxel point resolved spectral acquisition (PRESS) technique will be used to acquire non-water suppressed spectra at multiple echo times. Spectral fits using JMRUI MRS processing software (www.jmrui.eu) to the water and methylene/methyl resonances will be used to quantify peak areas and establish T2 corrected fat/(fat + water) ratios.
Diagnostic test: Blood Draw
Blood draw. Blood draws will be used to attain and assess markers of bone formation/resorption and inflammation. Specific markers of bone formation that will be assessed include osteocalcin (OC) and procollagen type 1 N-terminal propeptide (P1NP), and a marker of bone resorption, c-telopeptide (CTX). Additionally, in participants with CF, we will assess inflammation, with a c-reactive protein (CRP), and dysglycemia, with a continuous glucose monitor.
Diagnostic test: DXA
DXA will be utilized to obtain BMD of the total body, lumbar spine, and hip using a Hologic Horizon densitometer (Hologic Inc, Bedford, MA). Body composition will be obtained from total body scans.
Diagnostic test: pQCT
pQCT will be utilized to obtain volumetric BMD (mg/cm3) of the left tibia. Measurements using a Stratec XCT 3000 device (Orthometrix, White Plains, NY) will be obtained at multiple locations, in relation to distal growth plate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone marrow adiposity by magnetic resonance relaxometry (MR relaxometry)
Time Frame: Baseline and One Year follow-up
Change in bone marrow adiposity measured by MR relaxometry
Baseline and One Year follow-up
Bone marrow adiposity by magnetic resonance spectroscopy (MRS)
Time Frame: Baseline and One Year follow-up
Change in bone marrow adiposity measured by MRS
Baseline and One Year follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA)
Time Frame: Baseline and One Year follow-up
Change in total body less head BMD Z-score
Baseline and One Year follow-up
Spine BMD Z-score by DXA
Time Frame: Baseline and One Year follow-up
Change in lumbar spine BMD Z-score
Baseline and One Year follow-up
Hip BMD Z-score by DXA
Time Frame: Baseline and One year follow-up
Change in hip BMD Z-score
Baseline and One year follow-up
Volumetric bone mineral density (vBMD)
Time Frame: Baseline and One Year follow-up
Change in quantitative computed tomography (pQCT) scans will be obtained at the left tibia
Baseline and One Year follow-up
polar strength strain index
Time Frame: Baseline and One Year follow-up
Change in pQCT bone strength measure
Baseline and One Year follow-up
osteocalcin
Time Frame: Baseline and One Year follow-up
Change in bone formation assessed by osteocalcin (ng/mL)
Baseline and One Year follow-up
procollagen type 1 N-terminal propeptide
Time Frame: Baseline and One Year follow-up
Change in bone formation assessed by procollagen type 1 N-terminal propeptide (ng/mL)
Baseline and One Year follow-up
c-telopeptide
Time Frame: Baseline and One Year follow-up
Change in bone resorption assessed by c-telopeptide (pg/ml)
Baseline and One Year follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

Cystic Fibrosis Foundation

Investigators

  • Principal Investigator: Rebecca Gordon, MD, Boston Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2024

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

June 30, 2029

Study Registration Dates

First Submitted

January 11, 2024

First Submitted That Met QC Criteria

January 11, 2024

First Posted (Actual)

January 22, 2024

Study Record Updates

Last Update Posted (Estimated)

October 30, 2025

Last Update Submitted That Met QC Criteria

October 28, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-P00047144
  • 005960A123 (Other Grant/Funding Number: Cystic Fibrosis Foundation)

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

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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