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Focal Erosions (focal + erosion)
Selected AbstractsOsteoblast Function Is Compromised at Sites of Focal Bone Erosion in Inflammatory Arthritis,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2009Nicole C Walsh PhD Abstract In rheumatoid arthritis (RA), synovial inflammation results in focal erosion of articular bone. Despite treatment attenuating inflammation, repair of erosions with adequate formation of new bone is uncommon in RA, suggesting that bone formation may be compromised at these sites. Dynamic bone histomorphometry was used in a murine model of RA to determine the impact of inflammation on osteoblast function within eroded arthritic bone. Bone formation rates at bone surfaces adjacent to inflammation were similar to those observed in nonarthritic bone; therefore, osteoblast activity is unlikely to compensate for the increased bone resorption at these sites. Within arthritic bone, the extent of actively mineralizing surface was reduced at bone surfaces adjacent to inflammation compared with bone surfaces adjacent to normal marrow. Consistent with the reduction in mineralized bone formation, there was a notable paucity of cells expressing the mid- to late stage osteoblast lineage marker alkaline phosphatase, despite a clear presence of cells expressing the early osteoblast lineage marker Runx2. In addition, several members of the Dickkopf and secreted Frizzled-related protein families of Wnt signaling antagonists were upregulated in arthritic synovial tissues, suggesting that inhibition of Wnt signaling could be one mechanism contributing to impaired osteoblast function within arthritic bone. Together, these data indicate that the presence of inflammation within arthritic bone impairs osteoblast capacity to form adequate mineralized bone, thus contributing to the net loss of bone and failure of bone repair at sites of focal bone erosion in RA. [source] Mediation of nonerosive arthritis in a mouse model of lupus by interferon-,,stimulated monocyte differentiation that is nonpermissive of osteoclastogenesisARTHRITIS & RHEUMATISM, Issue 4 2010Kofi A. Mensah Objective In contrast to rheumatoid arthritis (RA), the joint inflammation referred to as Jaccoud's arthritis that occurs in systemic lupus erythematosus (SLE) is nonerosive. Although the mechanism responsible is unknown, the antiosteoclastogenic cytokine interferon-, (IFN,), whose transcriptome is present in SLE monocytes, may be responsible. This study was undertaken to examine the effects of IFN, and lupus on osteoclasts and erosion in the (NZB × NZW)F1 mouse model of SLE with K/BxN serum,induced arthritis. Methods Systemic IFN, levels in (NZB × NZW)F1 mice were elevated by administration of AdIFN,. SLE disease was marked by anti,double-stranded DNA (anti-dsDNA) antibody titer and proteinuria, and Ifi202 and Mx1 expression represented the IFN, transcriptome. Microfocal computed tomography was used to evaluate bone erosions. Flow cytometry for CD11b and CD11c was used to evaluate the frequency of circulating osteoclast precursors (OCPs) and myeloid dendritic cells (DCs) in blood. Results Administration of AdIFN, to (NZB × NZW)F1 mice induced osteopetrosis. (NZB × NZW)F1 mice without autoimmune disease were fully susceptible to focal erosions in the setting of serum-induced arthritis. However, (NZB × NZW)F1 mice with high anti-dsDNA antibody titers and the IFN, transcriptome were protected against bone erosions. AdIFN, pretreatment of NZW mice before K/BxN serum administration also resulted in protection against bone erosion (r2 = 0.4720, P < 0.01), which was associated with a decrease in the frequency of circulating CD11b+CD11c, OCPs and a concomitant increase in the percentage of CD11b+CD11c+ cells (r2 = 0.6330, P < 0.05), which are phenotypic of myeloid DCs. Conclusion These findings suggest that IFN, in SLE shifts monocyte development toward myeloid DCs at the expense of osteoclastogenesis, thereby resulting in decreased bone erosion. [source] The relationship between focal erosions and generalized osteoporosis in postmenopausal women with rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 6 2009Daniel H. Solomon Objective Among rheumatoid arthritis (RA) patients who have had the disease for 10 years, more than half have focal erosions, and the risk of fracture is doubled. However, there is little information about the potential relationship between focal erosions and bone mineral density (BMD). The aim of this study was to determine whether lower BMD is associated with higher erosion scores among patients with RA. Methods We enrolled 163 postmenopausal women with RA, none of whom were taking osteoporosis medications. Patients underwent dual x-ray absorptiometry at the hip and spine and hand radiography, and completed a questionnaire. The hand radiographs were scored using the Sharp method, and the relationship between BMD and erosions was measured using Spearman's correlation coefficients and adjusted linear regression models. Results Patients had an average disease duration of 13.7 years, and almost all were taking a disease-modifying antirheumatic drug. Sixty-three percent were rheumatoid factor (RF) positive. The median modified Health Assessment Questionnaire score was 0.7, and the average Disease Activity Score in 28 joints was 3.8. The erosion score was significantly correlated with total hip BMD (r = ,0.33, P < 0.0001), but not with lumbar spine BMD (r = ,0.09, P = 0.27). Hip BMD was significantly lower in RF-positive patients versus RF-negative patients (P = 0.02). In multivariable models that included age, body mass index, and cumulative oral glucocorticoid dose, neither total hip BMD nor lumbar spine BMD was significantly associated with focal erosions. Conclusion Our results suggest that hip BMD is associated with focal erosions among postmenopausal women with RA, but that this association disappears after multivariable adjustment. While BMD and erosions may be correlated with bone manifestations of RA, their relationship is complex and influenced by other disease-related factors. [source] |