Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis, Bone Marrow, Dual-energy X-ray absorptiometry, Peripheral Quantitative Computed Tomography, Magnetic Resonance Imaging, pediatrics, bone health
Brief summary
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.
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.
Interventions
DIAGNOSTIC_TESTMagnetic 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_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 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_TESTBlood 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_TESTDXA
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_TESTpQCT
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.
Sponsors
Cystic Fibrosis Foundation
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone marrow adiposity by magnetic resonance relaxometry (MR relaxometry) | Baseline and One Year follow-up | Change in bone marrow adiposity measured by MR relaxometry |
| Bone marrow adiposity by magnetic resonance spectroscopy (MRS) | Baseline and One Year follow-up | Change in bone marrow adiposity measured by MRS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hip BMD Z-score by DXA | Baseline and One year follow-up | Change in hip 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 the left tibia |
| polar strength strain index | Baseline and One Year follow-up | Change in pQCT bone strength measure |
| Total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA) | Baseline and One Year follow-up | Change in total body less head BMD Z-score |
| procollagen type 1 N-terminal propeptide | Baseline and One Year follow-up | Change in bone formation assessed by procollagen type 1 N-terminal propeptide (ng/mL) |
| c-telopeptide | Baseline and One Year follow-up | Change in bone resorption assessed by c-telopeptide (pg/ml) |
| osteocalcin | Baseline and One Year follow-up | Change in bone formation assessed by osteocalcin (ng/mL) |
| Spine BMD Z-score by DXA | Baseline and One Year follow-up | Change in lumbar spine BMD Z-score |
Countries
United States
Contacts
Primary ContactRebecca Gordon, MD
Outcome results
None listed