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      Natural History of Growth and Body Composition in Juvenile Idiopathic Arthritis

      review-article
      a , b
      Hormone Research in Paediatrics
      S. Karger AG
      Body composition, Juvenile idiopathic arthritis

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          Abstract

          Background: In patients with juvenile idiopathic arthritis (JIA), growth impairment and altered body composition, including disturbed skeletal development, are well-known long-term complications. Data on longitudinal growth in patients with systemic and polyarticular JIA reveal growth impairment in the active phases of the disease. With reduction in disease activity and lower glucocorticoid (GC) doses, some patients experience ‘catch-up’ growth; however, many have only a slight improvement in height standard deviation during puberty or after cessation of GC treatment. The consequence is a final height below the 3rd percentile and below the genetic height potential. Although few studies have specifically addressed body composition in children with JIA, studies on the development of bone mass have described notable deficits in both GC-treated and GC-naïve children. In recent years, the deficits in bone mass have been related, in part, to the deficits in muscle mass, which are prevalent in these patients. Conclusions: The major goal for physicians caring for patients with JIA is optimal disease control while maintaining normal growth. Early recognition of patients who develop prolonged growth disturbances and altered body composition is important as these abnormalities contribute to long-term morbidity and need to be addressed both diagnostically and therapeutically when treating children with JIA.

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          Most cited references24

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          Rheumatoid cachexia: metabolic abnormalities, mechanisms and interventions.

          We have previously identified the phrase 'rheumatoid cachexia' to describe the loss of body cell mass (BCM) that may occur among patients with rheumatoid arthritis (RA). Specifically, rheumatoid cachexia is characterized by altered energy and protein metabolism (reduced total energy expenditure, increased resting energy expenditure and increased whole-body protein catabolism) and increased inflammatory cytokine production (interleukin-1beta and tumour necrosis factor-alpha). Patients with rheumatoid cachexia consistently have a diet that appears adequate in protein and calories (based on US Dietary Reference Intakes), but with reduced physical activity. These phenomena are similar to some of the metabolic abnormalities that occur with normal ageing, but the aetiology appears to be different in RA. This review will focus on describing the metabolic abnormalities observed in rheumatoid cachexia, identifying potential mechanisms for loss of BCM and discussing strategies for intervention.
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            A two-year prospective controlled study of bone mass and bone turnover in children with early juvenile idiopathic arthritis.

            To explore early changes and predictors of bone mass in children with juvenile idiopathic arthritis (JIA) in order to identify patients who will develop bone mass reductions. We conducted a prospective cohort study of 108 children with early JIA (ages 6-18 years; mean disease duration 19.3 months) who were individually matched with 108 healthy children for age, sex, race, and county of residence. Bone mass and changes in total body, spine, femur, and forearm bone mineral density and bone mineral content (BMC), body composition, growth, and biochemical parameters of bone turnover were examined at baseline and at followup a mean of 24 months later. Low bone mass was defined as a Z score >1 SD below the reference population. Of the 200 children evaluated at followup, the 100 healthy children had greater gains in total body BMC (P = 0.035), distal radius BMC (P < 0.001), and total body lean mass (P < 0.001) than did the 100 JIA patients. Low or very low total body BMC was observed in 24% of the patients and 12% of the healthy children. Bone formation, bone resorption, and weight-bearing activities were reduced in the patients compared with the healthy children. Multiple regression analysis showed that in patients with JIA, serum bone-specific alkaline phosphatase, serum C-telopeptide of type I collagen, and weight-bearing activities were independent predictors of changes in total body BMC. Total body BMC was lower in patients with polyarticular onset than in those with oligoarticular disease onset. Patients with JIA have moderate reductions in bone mass gains, bone turnover, and total body lean mass early in the disease course.
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              The role of muscles in joint adaptation and degeneration.

              Muscles are the primary contributors to joint loading. Loading is typically associated with the onset and progression of joint degeneration, and in turn, joint degeneration is known to affect negatively the control of muscle forces and co-ordination patterns. Nevertheless, the role of muscles in joint adaptation and degeneration has been largely ignored. Here, we review some of our research on the in vivo changes in muscular forces and joint loading in animal models of osteoarthritis and in patients with joint injury and disease. We attempt to emphasize the close dependence of muscle forces, joint loading and degeneration and, vice versa, try to point out how joint degeneration affects muscle forces and joint loading. We measured the forces and electromyographic signals in normal and anterior cruciate ligament transected feline knees and measured (1) a consistent decrease in the knee extensor and ankle extensor muscle forces for weeks following intervention; (2) a corresponding decrease in the static and dynamic external ground reaction forces; and (3) a change in the electromyographic signals (in terms of the firing patterns of individual muscles and of the co-ordination of extensors and flexors during locomotion). We introduced results on the biosynthetic response of articular cartilage to controlled, in vivo, loading and discuss preliminary results from an experimental animal model of muscle weakness. In contrast to much of the published literature, loading, in our case, is introduced by controlled nerve stimulation and the corresponding muscular forces that load the joint in its in vivo configuration. We found that short-term loading (30-60 min) in the cat knee produces distinct up-regulation of mRNA of specific metalloproteinases (MMPs) and some of the MMP inhibitors. In our newly developed muscle-weakness model, we confirmed that controlled Botox injections in the rabbit knee extensor muscles cause a 60-80% decrease in muscle force, and that these changes in muscle force are associated with changes in the external ground reaction forces, and most importantly, that muscle weakness seems to be associated with degeneration of the knee in the absence of joint instability or any other intervention. From the results of our research, we conclude that muscle health and muscle rehabilitation are key components for the successful prevention of, and recovery from, joint injury and disease.
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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                978-3-8055-9292-5
                978-3-8055-9293-2
                1663-2818
                1663-2826
                2009
                November 2009
                27 November 2009
                : 72
                : Suppl 1
                : 13-19
                Affiliations
                aDivision of Pediatric Endocrinology, University Children’s Hospital, Munich, Germany; bDivision of Pediatric Rheumatology, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ont., Canada
                Article
                229758 Horm Res 2009;72(suppl 1):13–19
                10.1159/000229758
                19940490
                789cd2c0-01f3-48cc-a088-d8962e5c644f
                © 2009 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
                Page count
                Figures: 3, References: 30, Pages: 7
                Categories
                Section I: Clinical Aspects

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Juvenile idiopathic arthritis,Body composition

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