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      A Cross-Sectional Study of the Association between Autoantibodies and Qualitative Ultrasound Index of Bone in an Elderly Sample without Clinical Autoimmune Disease

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          Abstract

          Bone loss is characteristic of the ageing process and a common complication of many autoimmune diseases. Research has highlighted a potential role of autoantibodies in pathologic bone loss. The confounding effects of immunomodulatory drugs make it difficult to establish the contribution of autoantibodies amongst autoimmune disease sufferers. We attempted to examine the relationship between autoantibodies and bone mass in a population of 2812 elderly participants without clinical autoimmune disease. Serum samples were assayed for a panel of autoantibodies (anti-nuclear, extractable nuclear antigen, anti-neutrophil cytoplasmic, thyroid peroxidase, tissue transglutaminase, anti-cardiolipin, rheumatoid factor, and cyclic citrullinated peptide). Bone mass was measured using quantitative ultrasound (QUS) of the calcaneus. The relationship between each autoantibody and bone mass was determined using linear regression models. Anti-nuclear autoantibodies were the most prevalent, positive in approximately 11%, and borderline in roughly 23% of our sample. They were also the only autoantibody observed to be significantly associated with QUS index in the univariate analysis ( n = 1628; r = −0.20; 95% CI: −0.40–0.00; p = 0.046). However, statistical significance was lost after adjustment for various other potential confounders. None of the other autoantibodies was associated with QUS index in either univariate or multivariate analysis. We are limited by the cross-sectional nature of the study and the low prevalence of autoantibodies in our nonclinical sample.

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          Most cited references119

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          Disorders of bone remodeling.

          The skeleton provides mechanical support for stature and locomotion, protects vital organs, and controls mineral homeostasis. A healthy skeleton must be maintained by constant bone modeling to carry out these crucial functions throughout life. Bone remodeling involves the removal of old or damaged bone by osteoclasts (bone resorption) and the subsequent replacement of new bone formed by osteoblasts (bone formation). Normal bone remodeling requires a tight coupling of bone resorption to bone formation to guarantee no alteration in bone mass or quality after each remodeling cycle. However, this important physiological process can be derailed by a variety of factors, including menopause-associated hormonal changes, age-related factors, changes in physical activity, drugs, and secondary diseases, which lead to the development of various bone disorders in both women and men. We review the major diseases of bone remodeling, emphasizing our current understanding of the underlying pathophysiological mechanisms.
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            Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin.

            Autoimmunity is complicated by bone loss. In human rheumatoid arthritis (RA), the most severe inflammatory joint disease, autoantibodies against citrullinated proteins are among the strongest risk factors for bone destruction. We therefore hypothesized that these autoantibodies directly influence bone metabolism. Here, we found a strong and specific association between autoantibodies against citrullinated proteins and serum markers for osteoclast-mediated bone resorption in RA patients. Moreover, human osteoclasts expressed enzymes eliciting protein citrullination, and specific N-terminal citrullination of vimentin was induced during osteoclast differentiation. Affinity-purified human autoantibodies against mutated citrullinated vimentin (MCV) not only bound to osteoclast surfaces, but also led to robust induction of osteoclastogenesis and bone-resorptive activity. Adoptive transfer of purified human MCV autoantibodies into mice induced osteopenia and increased osteoclastogenesis. This effect was based on the inducible release of TNF-α from osteoclast precursors and the subsequent increase of osteoclast precursor cell numbers with enhanced expression of activation and growth factor receptors. Our data thus suggest that autoantibody formation in response to citrullinated vimentin directly induces bone loss, providing a link between the adaptive immune system and bone.
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              Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies.

              Anticitrullinated protein antibodies (ACPA) are a major risk factor for bone loss in rheumatoid arthritis (RA). We have recently shown that ACPA directly induce bone loss by stimulating osteoclast differentiation. As ACPA precede the clinical onset of RA by years, we hypothesised that ACPA positive healthy individuals may already show skeletal changes.
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                Author and article information

                Contributors
                Journal
                J Immunol Res
                J Immunol Res
                JIR
                Journal of Immunology Research
                Hindawi
                2314-8861
                2314-7156
                2018
                30 April 2018
                : 2018
                : 9407971
                Affiliations
                1Department of Population and Reproductive Health, School of Public Health, Kenyatta University, P.O. Box 43844, Nairobi 00100, Kenya
                2School of Medicine & Public Health, The University of Newcastle, Callaghan, NSW 2308, Australia
                3Hunter Medical Research Institute, Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia
                4Centre for Brain and Mental Health Research, The University of Newcastle, Callaghan, NSW, Australia
                5Brain Behaviour Research Group, School of Science and Technology, University of New England, Armidale, NSW 2351, Australia
                6Laboratory of Affective Neuroscience, The University of Newcastle, Callaghan, NSW, Australia
                7University of Newcastle, Medical Sciences MS413, University Drive, Callaghan, NSW 2308, Australia
                8Department of General Medicine, John Hunter Hospital, New Lambton Heights, NSW, Australia
                Author notes

                Academic Editor: Margarete D. Bagatini

                Author information
                http://orcid.org/0000-0003-2043-5223
                http://orcid.org/0000-0001-9800-1308
                Article
                10.1155/2018/9407971
                5952466
                29854851
                3cf39ae8-455b-4f19-8d38-4d063e01b86d
                Copyright © 2018 Rosebella A. Iseme et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 November 2017
                : 5 March 2018
                : 17 March 2018
                Funding
                Funded by: University of Newcastle Postgraduate Research Scholarship
                Categories
                Research Article

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