Skeletal Health and Bone Marrow Composition in Newly Diagnosed Adolescents With Crohn Disease
- Conditions
- Crohn DiseaseInflammatory Bowel Disease
- Interventions
- Diagnostic Test: Coronal T1 weighted spin echo imagesDiagnostic Test: Spin-lattice relaxation (T1)Diagnostic Test: Magnetic resonance spectroscopyDiagnostic Test: Blood Draw
- Registration Number
- NCT04508088
- Lead Sponsor
- Boston Children's Hospital
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 92
- Crohn's Disease diagnosed within the past 3 months, or a healthy, matched control
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Crohn Disease Coronal T1 weighted spin echo images This group will be 46 adolescents, ages 13-20, who have been recently (within 3 months) diagnosed with Crohn Disease. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed. Crohn Disease Spin-lattice relaxation (T1) This group will be 46 adolescents, ages 13-20, who have been recently (within 3 months) diagnosed with Crohn Disease. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed. Crohn Disease Magnetic resonance spectroscopy This group will be 46 adolescents, ages 13-20, who have been recently (within 3 months) diagnosed with Crohn Disease. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed. Crohn Disease Blood Draw This group will be 46 adolescents, ages 13-20, who have been recently (within 3 months) diagnosed with Crohn Disease. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed. Control Coronal T1 weighted spin echo images Controls will be matched for age, Tanner staging, and BMI percentile. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed. Control Spin-lattice relaxation (T1) Controls will be matched for age, Tanner staging, and BMI percentile. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed. Control Magnetic resonance spectroscopy Controls will be matched for age, Tanner staging, and BMI percentile. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed. Control Blood Draw Controls will be matched for age, Tanner staging, and BMI percentile. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Physical Activity Baseline and One Year follow-up Physical activity will be assessed through a physical activity questionnaire
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
Spine BMD Z-score by DXA Baseline and One Year follow-up Change in Lumbar spine BMD Z-score
Spine apparent density Z-score by DXA Baseline and One Year follow-up Change in Lumbar spine bone mineral apparent density (g/cm3)
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)
Bone Resorption Marker Baseline and One Year follow-up Change in bone resorption assessed by c-telopeptide (pg/ml)
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.
Dietary Calcium Intake Baseline and One Year follow-up Dietary calcium intake will be assessed through a targeted dietary questionnaire
Trial Locations
- Locations (1)
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States