Christina Drevinge1,2, Julia M Scheffler1,2, Catalin Koro-Arvidsson3, Daniel Sundh1,4, Hans Carlsten3, Inger Gjertsson5, Catharina Lindholm3, Mattias Lorentzon1,4,6, Anna Rudin5, Anna-Karin Hultgård Ekwall3, Ulrika Islander1,2. 1. Centre for Bone and Arthritis Research, Institute of Medicine, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 2. Krefting Research Center, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 3. Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 4. Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 5. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 6. Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
Abstract
BACKGROUND: Rheumatoid arthritis (RA) is associated with development of generalized osteoporosis. Bone-degrading osteoclasts are derived from circulating precursor cells of monocytic lineage, and the intermediate monocyte population is important as osteoclast precursors in inflammatory conditions. T cells of various subsets are critical in the pathogenesis of both RA and associated osteoporosis, but so far, no studies have examined associations between circulating intermediate monocytes, T cell subsets and bone characteristics in patients with RA. The aim of this study was to investigate the frequency of intermediate monocytes in patients with untreated early rheumatoid arthritis (ueRA) compared to healthy controls (HC), and to explore the correlation between intermediate monocytes and a comprehensive panel of T helper cell subsets, bone density and bone microarchitecture in ueRA patients. METHODS: 78 patients with ueRA fulfilling the ACR/EULAR 2010 criteria were included and compared to 29 age- and sex-matched HC. Peripheral blood samples were obtained before start of treatment and proportions of monocyte subsets and CD4+ helper and regulatory T cell subsets were analyzed by flow cytometry. Bone densitometry was performed on 46 of the ueRA patients at inclusion using DXA and HR-pQCT. RESULTS: Flow cytometric analyses showed that the majority of ueRA patients had frequencies of intermediate monocytes comparable to HC. The intermediate monocyte population correlated positively with CXCR3+ Th17 cells in ueRA patients but not in HC. However, neither the proportions of intermediate monocytes nor CXCR3+ Th17 cells were associated with bone density or bone microarchitecture measurements. CONCLUSIONS: Our findings suggest that in early RA, the intermediate monocytes do not correlate with bone characteristics, despite positive correlation with circulating CXCR3+ Th17 cells. Future longitudinal studies in patients with longer disease duration are required to fully explore the potential of intermediate monocytes to drive bone loss in RA.
BACKGROUND:Rheumatoid arthritis (RA) is associated with development of generalized osteoporosis. Bone-degrading osteoclasts are derived from circulating precursor cells of monocytic lineage, and the intermediate monocyte population is important as osteoclast precursors in inflammatory conditions. T cells of various subsets are critical in the pathogenesis of both RA and associated osteoporosis, but so far, no studies have examined associations between circulating intermediate monocytes, T cell subsets and bone characteristics in patients with RA. The aim of this study was to investigate the frequency of intermediate monocytes in patients with untreated early rheumatoid arthritis (ueRA) compared to healthy controls (HC), and to explore the correlation between intermediate monocytes and a comprehensive panel of T helper cell subsets, bone density and bone microarchitecture in ueRA patients. METHODS: 78 patients with ueRA fulfilling the ACR/EULAR 2010 criteria were included and compared to 29 age- and sex-matched HC. Peripheral blood samples were obtained before start of treatment and proportions of monocyte subsets and CD4+ helper and regulatory T cell subsets were analyzed by flow cytometry. Bone densitometry was performed on 46 of the ueRA patients at inclusion using DXA and HR-pQCT. RESULTS: Flow cytometric analyses showed that the majority of ueRA patients had frequencies of intermediate monocytes comparable to HC. The intermediate monocyte population correlated positively with CXCR3+ Th17 cells in ueRA patients but not in HC. However, neither the proportions of intermediate monocytes nor CXCR3+ Th17 cells were associated with bone density or bone microarchitecture measurements. CONCLUSIONS: Our findings suggest that in early RA, the intermediate monocytes do not correlate with bone characteristics, despite positive correlation with circulating CXCR3+ Th17 cells. Future longitudinal studies in patients with longer disease duration are required to fully explore the potential of intermediate monocytes to drive bone loss in RA.
Authors: S Qin; J B Rottman; P Myers; N Kassam; M Weinblatt; M Loetscher; A E Koch; B Moser; C R Mackay Journal: J Clin Invest Date: 1998-02-15 Impact factor: 14.808
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Authors: M Güler-Yüksel; C F Allaart; Y P M Goekoop-Ruiterman; J K de Vries-Bouwstra; J H L M van Groenendael; C Mallée; M H W de Bois; F C Breedveld; B A C Dijkmans; W F Lems Journal: Ann Rheum Dis Date: 2008-03-28 Impact factor: 19.103