Skeletal Health and Bone Marrow Composition in Newly Diagnosed Adolescents With Crohn Disease

Summary

The investigators will be evaluating bone marrow composition via magnetic resonance imaging in newly diagnosed adolescents with Crohn disease (CD) 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 and peripheral quantitative computed tomography. This longitudinal project will focus on abnormalities in bone marrow composition, and specifically whether adolescents with newly diagnosed CD exhibit increased bone marrow fat, its association with bone mineral density (BMD) and the underlying pathophysiology, including bone turnover markers and immune cellular/molecular parameters.

Conditions

• Inflammatory Bowel Disease
• Crohn Disease

Interventions

DIAGNOSTIC_TEST

Blood Draw

Blood draw. Blood draws will be used to attain and assess markers of bone formation/resorption and to perform immune studies. 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). We will also evaluate molecular gene signatures from the blood samples that correlate with the previously described bone imaging phenotypes. At that point, the information will be used to develop a CyTOF panel to evaluate differences in immune cellular populations between CD patients with normal versus low BMD, and matched controls.

DIAGNOSTIC_TEST

Coronal T1 weighted spin echo images

Coronal T1 weighted spin echo images will be obtained through the knee with a field of view of 16cm to include distal femoral and proximal tibial metaphyses.

DIAGNOSTIC_TEST

Spin-lattice relaxation (T1)

Spin-lattice relaxation (T1) relaxometry acquisition consisting of seven 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 echo times of 20, 30, 40, and 50 ms using 32 signal averages per echo time with a TR of 2.5 s (total scan time = 5.4 minutes). 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.

Sponsors & Collaborators

• Massachusetts General Hospital

  lead OTHER

Principal Investigators

• Rebecca Gordon, MD · Boston Children's Hospital

Eligibility

Min Age

13 Years

Max Age

20 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-09-10

Primary Completion

2026-12-31

Completion

2026-12-31

Countries

• United States

Study Locations