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

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест 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.
• Диагностический тест 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 prima
• Диагностический тест 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
• Диагностический тест 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

Первичные конечные точки

• Bone marrow adiposity by magnetic resonance imaging (MRI) [Срок оценки: Baseline and One Year follow-up]
• Magnetic resonance spectroscopy (MRS) [Срок оценки: Baseline and One Year follow-up]

Вторичные конечные точки (12)

• Total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA) [Срок оценки: Baseline and One Year follow-up]
• Spine BMD Z-score by DXA [Срок оценки: Baseline and One Year follow-up]
• Spine apparent density Z-score by DXA [Срок оценки: Baseline and One Year follow-up]
• Volumetric bone mineral density (vBMD) [Срок оценки: Baseline and One Year follow-up]
• Bone strength by quantitative computed tomography pQCT [Срок оценки: Baseline and One Year follow-up]
• Bone Formation Marker #1 [Срок оценки: Baseline and One Year follow-up]
• Bone Formation Marker #2 [Срок оценки: Baseline and One Year follow-up]
• Bone Resorption Marker [Срок оценки: Baseline and One Year follow-up]
• Immune Studies [Срок оценки: Baseline and One Year follow-up]
• Current Crohn's Disease Activity [Срок оценки: Baseline and One Year follow-up]
• Physical Activity [Срок оценки: Baseline and One Year follow-up]
• Dietary Calcium Intake [Срок оценки: Baseline and One Year follow-up]

Критерии участия

Критерии включения

• Crohn's Disease diagnosed within the past 3 months, or a healthy, matched control

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

США · 1 центр

• Boston Children's Hospital — Boston

Публикации

• Gupta A, Paski S, Issenman R, Webber C. Lumbar spine bone mineral density at diagnosis and during follow-up in children with IBD. J Clin Densitom. 2004 Fall;7(3):290-5. doi: 10.1385/jcd:7:3:290. PMID 15319499
• Sylvester FA, Wyzga N, Hyams JS, Davis PM, Lerer T, Vance K, Hawker G, Griffiths AM. Natural history of bone metabolism and bone mineral density in children with inflammatory bowel disease. Inflamm Bowel Dis. 2007 Jan;13(1):42-50. doi: 10.1002/ibd.20006. PMID 17206638
• Schmidt S, Mellstrom D, Norjavaara E, Sundh SV, Saalman R. Low bone mineral density in children and adolescents with inflammatory bowel disease: a population-based study from Western Sweden. Inflamm Bowel Dis. 2009 Dec;15(12):1844-50. doi: 10.1002/ibd.20962. Epub 2009 Apr 30. PMID 19408319
• Werkstetter KJ, Pozza SB, Filipiak-Pittroff B, Schatz SB, Prell C, Bufler P, Koletzko B, Koletzko S. Long-term development of bone geometry and muscle in pediatric inflammatory bowel disease. Am J Gastroenterol. 2011 May;106(5):988-98. doi: 10.1038/ajg.2010.495. Epub 2011 Jan 11. PMID 21224841
• Bechtold S, Alberer M, Arenz T, Putzker S, Filipiak-Pittroff B, Schwarz HP, Koletzko S. Reduced muscle mass and bone size in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2010 Feb;16(2):216-25. doi: 10.1002/ibd.21021. PMID 19637389
• Dubner SE, Shults J, Baldassano RN, Zemel BS, Thayu M, Burnham JM, Herskovitz RM, Howard KM, Leonard MB. Longitudinal assessment of bone density and structure in an incident cohort of children with Crohn's disease. Gastroenterology. 2009 Jan;136(1):123-30. doi: 10.1053/j.gastro.2008.09.072. Epub 2008 Nov 1. PMID 19026647
• Bonjour JP, Theintz G, Law F, Slosman D, Rizzoli R. Peak bone mass. Osteoporos Int. 1994;4 Suppl 1:7-13. doi: 10.1007/BF01623429. PMID 8081064
• Tuchman S, Thayu M, Shults J, Zemel BS, Burnham JM, Leonard MB. Interpretation of biomarkers of bone metabolism in children: impact of growth velocity and body size in healthy children and chronic disease. J Pediatr. 2008 Oct;153(4):484-90. doi: 10.1016/j.jpeds.2008.04.028. Epub 2008 Jun 16. PMID 18555484

Идентификаторы

NCT: NCT04508088 · IRB-P00034878

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗