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      Peripheral quantitative computed tomography detects differences at the radius in prepubertal children with cystic fibrosis compared to healthy controls

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          Abstract

          Introduction

          In 2015, 11.9% of people with cystic fibrosis (CF) in the United States had osteopenia, 5.1% osteoporosis, and 0.3% experienced a fracture. Screening for CF-related bone disease starts in childhood, and dual energy x-ray absorptiometry (DXA) is the recommended method. It is unknown whether peripheral quantitative computed tomography (pQCT) can detect deficits earlier than DXA. This study compared pQCT and DXA scans in a group of pre-pubertal children with CF and healthy controls.

          Methods

          This was a cross-sectional study of children at Tanner stage 1. A pQCT scan of the radius at proximal and distal sites was performed plus a total body DXA scan. Serum C-reactive protein, interleukin-6 and tumor necrosis factor-alpha were also measured.

          Results

          A total of 34 subjects completed the study; 14 with CF and 20 controls. At the distal radius, pQCT showed a lower total bone mineral density (BMD) Z-score for the CF group (P = 0.01 and P = 0.03 for 2 different reference databases) compared to controls. At the proximal site, the polar strength-strain index was lower in the CF group (P = 0.017). Finally, the total body BMD Z-score by DXA was lower in the CF group, although it did not meet the definition of reduced bone density (P = 0.004). Biomarkers of inflammation were not different.

          Conclusions

          In this group of pre-pubertal children with CF, measures of bone strength and density by both pQCT and DXA were reduced compared to healthy controls.

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          Most cited references20

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          Bone density, body composition, and inflammatory status in cystic fibrosis.

          Low body weight and loss of bone mass are major problems in adults with cystic fibrosis (CF) and chronic pulmonary infection. Although these complications probably have a multifactorial origin, we hypothesized that the continuous acute-phase inflammatory and catabolic state may contribute. We determined body composition, bone turnover, physical activity, and circulating interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and their soluble receptors in 22 adults with CF and 22 age- and sex-matched healthy subjects. Comparisons were also made within patients before and after treatment of an exacerbation of respiratory symptoms. The patients had a lower mean (95% confidence interval [CI]) fat-free mass (FFM) 39.9 (36.3, 43.6) kg than healthy subjects, 49.4 (45.1, 53.7) kg, p < 0.05. The patients were in negative nitrogen balance and 20 had bone mineral density (BMD) Z scores
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            Peripheral quantitative computed tomography in children and adolescents: the 2007 ISCD Pediatric Official Positions.

            Peripheral quantitative computed tomography (pQCT) has mainly been used as a research tool in children. To evaluate the clinical utility of pQCT and formulate recommendations for its use in children, the International Society of Clinical Densitometry (ISCD) convened a task force to review the literature and propose areas of consensus and future research. The types of pQCT technology available, the clinical application of pQCT for bone health assessment in children, the important elements to be included in a pQCT report, and quality control monitoring techniques were evaluated. The review revealed a lack of standardization of pQCT techniques, and a paucity of data regarding differences between pQCT manufacturers, models and software versions and their impact in pediatric assessment. Measurement sites varied across studies. Adequate reference data, a critical element for interpretation of pQCT results, were entirely lacking, although some comparative data on healthy children were available. The elements of the pQCT clinical report and quality control procedures are similar to those recommended for dual-energy X-ray absorptiometry. Future research is needed to establish evidence-based criteria for the selection of the measurement site, scan acquisition and analysis parameters, and outcome measures. Reference data that sufficiently characterize the normal range of variability in the population also need to be established.
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              Peripheral quantitative computed tomography of the distal radius in young subjects - new reference data and interpretation of results.

              Application of bone densitometry to clinical use requires the availability of accessible reference data and is helped by an interpretative framework that is based on bone physiology. The aim of this contribution is to provide both reference data and help in the interpretation of results for peripheral quantitative computed tomography (Stratec XCT2000 performed at the distal radius of young subjects. Data from a previous reference data study on 478 subjects between 6 and 40 years were re-analyzed and smooth curves were fitted. The corresponding equations allow for calculation of age- and sex-specific z-scores of bone mineral content, volumetric bone mineral density (vBMD) of the trabecular compartment, vBMD of the entire radial cross-section, total cross-sectional area and cortical thickness. These data should facilitate the clinical use of peripheral quantitative computed tomography in young subjects.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                11 January 2018
                2018
                : 13
                : 1
                : e0191013
                Affiliations
                [1 ] Department of Pharmacy Practice, University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, Arkansas, United States of America
                [2 ] Department of Pediatrics, University of Southern California, Keck School of Medicine, Los Angeles, California, United States of America
                [3 ] Barnstable Brown Obesity and Diabetes Center University of Kentucky, Lexington, Kentucky, United States of America
                [4 ] Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America
                [5 ] Arkansas Children’s Hospital, Little Rock, Arkansas, United States of America
                Universidad Europea de Madrid, SPAIN
                Author notes

                Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: The spouse of Catherine O'Brien owns stock in Radius Health. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-6826-3785
                Article
                PONE-D-17-28097
                10.1371/journal.pone.0191013
                5764746
                29324908
                eabba1c6-980b-4768-ab50-8f7364b033fe
                © 2018 O’Brien et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 July 2017
                : 27 December 2017
                Page count
                Figures: 0, Tables: 3, Pages: 8
                Funding
                Funded by: Children's University Medical Group, Arkansas Children's Hospital Research Institute
                Award Recipient :
                This work was supported by the Children's University Medical Group, Arkansas Children's Hospital Research Institute intramural grant, http://www.archildrens.org/research/resources-for-researchers/intramural-grant-overview. Principal Investigator: CO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Bone
                Bone Density
                Medicine and Health Sciences
                Anatomy
                Bone
                Bone Density
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Connective Tissue
                Bone
                Bone Density
                Medicine and Health Sciences
                Anatomy
                Biological Tissue
                Connective Tissue
                Bone
                Bone Density
                Medicine and Health Sciences
                Clinical Genetics
                Genetic Diseases
                Autosomal Recessive Diseases
                Cystic Fibrosis
                Biology and Life Sciences
                Developmental Biology
                Fibrosis
                Cystic Fibrosis
                Medicine and Health Sciences
                Pulmonology
                Cystic Fibrosis
                Medicine and Health Sciences
                Critical Care and Emergency Medicine
                Trauma Medicine
                Traumatic Injury
                Bone Fracture
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Bone Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Bone Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Bone Imaging
                Medicine and Health Sciences
                Inflammatory Diseases
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Medicine and Health Sciences
                Pulmonology
                Pulmonary Function
                Medicine and Health Sciences
                Pediatrics
                Child Health
                Medicine and Health Sciences
                Public and Occupational Health
                Child Health
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