Inflammatory Bowel Disease, Crohn Disease
Conditions
Keywords
Crohn, Bone Marrow, Dual-energy X-ray absorptiometry, Peripheral Quantitative Computed Tomography, Magnetic Resonance Imaging
Brief 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.
Detailed description
Less than optimal bone health has been seen in children that have inflammatory bowel disease (IBD), including Crohn disease (CD). 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 CD 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 CD have more bone marrow fat. The primary hypothesis is that newly diagnosed CD is associated with increased fat levels in bone, which is associated with decreased bone formation and suboptimal bone health. The central objective is to obtain longitudinal data on the differences in bone marrow between healthy adolescents and those with CD. Long term, the investigators want to study how abnormal fat tissue and suboptimal bone health relate to each other. The study involves 46 adolescents recently diagnosed with CD and 46 healthy adolescents. Eligibility criteria include no other chronic diseases that affect bone health and limited use of bone altering medications in the last three months. The CD adolescents will be matched with healthy adolescents based on age, stage of puberty, and BMI percentile. Additional data on CD participants will be collected via a chart review that will enable us to more fully characterize their CD. Imaging will include MRIs of the knee. Measurements will include a visual assessment and quantitative marrow fat analysis, 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 abnormalities, and if there is an incidental finding, it will be reported to the primary care physician. Additionally, blood draws will be used to attain and assess markers of bone formation/resorption and to perform immune studies.
Interventions
DIAGNOSTIC_TESTCoronal 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_TESTSpin-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_TESTMagnetic 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.
DIAGNOSTIC_TESTBlood 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.
Sponsors
Massachusetts General Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
13 Years to 20 Years
Healthy volunteers
Yes
Inclusion criteria
* Crohn's Disease diagnosed within the past 3 months, or a healthy, matched control
Exclusion criteria
* Participants with chronic disease known to affect skeletal metabolism * Participants on certain medications within the prior 3 months that are known to affect skeletal metabolism * Participants who are pregnant * Participants who have a history of: claustrophobia, internal body metal that is not compatible with MRI machine, or a known abnormality on or adjacent to the left knee
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone marrow adiposity by magnetic resonance imaging (MRI) | Baseline and One Year follow-up | Change in Bone marrow adiposity measured by MRI (T1 maps) |
| Magnetic resonance spectroscopy (MRS) | Baseline and One Year follow-up | Change in T2 corrected fat/(fat+ water) ratios |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Spine BMD Z-score by DXA | Baseline and One Year follow-up | Change in Lumbar spine BMD Z-score |
| Volumetric bone mineral density (vBMD) | Baseline and One Year follow-up | Change in Quantitative computed tomography (pQCT) scans will be obtained at sites 3%, 38%, and 66% of tibial length proximal to the distal growth plate |
| Bone strength by quantitative computed tomography pQCT | Baseline and One Year follow-up | Change in PQCT scans will be obtained at sites 3%, 38%, and 66% of tibial length proximal to the distal growth plate |
| Bone Formation Marker #1 | Baseline and One Year follow-up | Change in bone formation assessed by osteocalcin (ng/mL) |
| Bone Formation Marker #2 | Baseline and One Year follow-up | Change in bone formation assessed by procollagen type 1 N-terminal propeptide (ng/mL) |
| Spine apparent density Z-score by DXA | Baseline and One Year follow-up | Change in Lumbar spine bone mineral apparent density (g/cm3) |
| Immune Studies | Baseline and One Year follow-up | Bulk RNA-sequencing on peripheral blood to evaluate molecular gene signatures that correlate with various bone imaging phenotypes; these will then be used to inform development and validation of a Mass Cytometry by Time-of-Flight panel that will be used on matched peripheral blood mononuclear cells samples. |
| Current Crohn's Disease Activity | Baseline and One Year follow-up | Current Crohn's disease activity will be assessed using the pediatric Crohn disease activity index (PCDAI). The assessment will be made based on questionnaires answered. |
| Physical Activity | Baseline and One Year follow-up | Physical activity will be assessed through a physical activity questionnaire |
| Dietary Calcium Intake | Baseline and One Year follow-up | Dietary calcium intake will be assessed through a targeted dietary questionnaire |
| Bone Resorption Marker | Baseline and One Year follow-up | Change in bone resorption assessed by c-telopeptide (pg/ml) |
| Total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA) | Baseline and One Year follow-up | Change in Total body BMD Z-score |
Countries
United States
Contacts
Primary ContactRebecca Gordon, MD
Outcome results
None listed