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      Skeletal Fragility in Children with Chronic Disease

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          Abstract

          Skeletal fragility associated with underlying childhood chronic disease is a systemic disorder of poor bone growth and reduction in bone turnover which can lead to abnormal bone mass, geometry and microarchitecture. Due to the growth potential unique to children, remarkable bone recovery following a transient threat to the bone can occur if there is concurrent growth. Addressing bone health in these children should focus on improvement in growth, puberty and removing the primary insult. In conditions where there is a little scope for bone recovery and limited residual growth, bone-targeted therapy may need to be considered, even though there is currently limited evidence. The importance of early detection of signs of bone fragility, by active screening for vertebral fracture using newer imaging techniques such as dual-energy X-ray absorptiometry lateral vertebral morphometry, may now be possible. There is currently, a paucity of evidence to support prophylactic use of anti-resorptive therapy. Where poor growth and low bone turnover are seen, the use of growth-promoting therapies and anabolic bone-protective agents may be more physiological and should be evaluated in well-designed trials. Collaborative studies on long-term fracture outcome and well-designed trials of bone-protective therapies are needed and to be encouraged.

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          Most cited references73

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          Bone Loss Triggered by the Cytokine Network in Inflammatory Autoimmune Diseases

          Bone remodeling is a lifelong process in vertebrates that relies on the correct balance between bone resorption by osteoclasts and bone formation by osteoblasts. Bone loss and fracture risk are implicated in inflammatory autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, and systemic lupus erythematosus. The network of inflammatory cytokines produced during chronic inflammation induces an uncoupling of bone formation and resorption, resulting in significant bone loss in patients with inflammatory autoimmune diseases. Here, we review and discuss the involvement of the inflammatory cytokine network in the pathophysiological aspects and the therapeutic advances in inflammatory autoimmune diseases.
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            High-Resolution Peripheral Quantitative Computed Tomography for the Assessment of Bone Strength and Structure: A Review by the Canadian Bone Strength Working Group

            Bone structure is an integral determinant of bone strength. The availability of high resolution peripheral quantitative computed tomography (HR-pQCT) has made it possible to measure three-dimensional bone microarchitecture and volumetric bone mineral density in vivo, with accuracy previously unachievable and with relatively low-dose radiation. Recent studies using this novel imaging tool have increased our understanding of age-related changes and sex differences in bone microarchitecture, as well as the effect of different pharmacological therapies. One advantage of this novel tool is the use of finite element analysis modelling to non-invasively estimate bone strength and predict fractures using reconstructed three-dimensional images. In this paper, we describe the strengths and limitations of HR-pQCT and review the clinical studies using this tool.
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              Growth and the Growth Hormone-Insulin Like Growth Factor 1 Axis in Children With Chronic Inflammation: Current Evidence, Gaps in Knowledge, and Future Directions.

              Growth failure is frequently encountered in children with chronic inflammatory conditions like juvenile idiopathic arthritis, inflammatory bowel disease, and cystic fibrosis. Delayed puberty and attenuated pubertal growth spurt are often seen during adolescence. The underlying inflammatory state mediated by proinflammatory cytokines, prolonged use of glucocorticoid, and suboptimal nutrition contribute to growth failure and pubertal abnormalities. These factors can impair growth by their effects on the GH-IGF axis and also directly at the level of the growth plate via alterations in chondrogenesis and local growth factor signaling. Recent studies on the impact of cytokines and glucocorticoid on the growth plate further advanced our understanding of growth failure in chronic disease and provided a biological rationale of growth promotion. Targeting cytokines using biological therapy may lead to improvement of growth in some of these children, but approximately one-third continue to grow slowly. There is increasing evidence that the use of relatively high-dose recombinant human GH may lead to partial catch-up growth in chronic inflammatory conditions, although long-term follow-up data are currently limited. In this review, we comprehensively review the growth abnormalities in children with juvenile idiopathic arthritis, inflammatory bowel disease, and cystic fibrosis, systemic abnormalities of the GH-IGF axis, and growth plate perturbations. We also systematically reviewed all the current published studies of recombinant human GH in these conditions and discussed the role of recombinant human IGF-1.
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                Author and article information

                Journal
                HRP
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2016
                October 2016
                19 July 2016
                : 86
                : 2
                : 71-82
                Affiliations
                aDevelopmental Endocrinology Research Group, University of Glasgow, Royal Hospital for Children, and bSchool of Medicine, University of Glasgow, Glasgow, UK
                Author notes
                *Dr. Sze Choong Wong, Developmental Endocrinology Research Group, Royal Hospital for Children, Office Block, Ground Floor, Zone 1 (Paediatrics), South Glasgow, University Hospital, 1345 Govan Road, Glasgow G51 4TF (UK), E-Mail jarod.wong@glasgow.ac.uk
                Article
                447583 Horm Res Paediatr 2016;86:71-82
                10.1159/000447583
                27428665
                33e2e91c-9d96-498a-ba68-df97212a97bb
                © 2016 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 10 February 2016
                : 13 June 2016
                Page count
                Figures: 2, Tables: 4, References: 92, Pages: 12
                Categories
                Mini Review

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Duchenne muscular dystrophy,Glucocorticoid,Inflammatory bowel disease,Inflammation,Fracture,Osteoporosis,Acute lymphoblastic leukaemia,Bone mineral density

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