Bone Erosion

Sergejeva S, Ivanov S, Lotvall J, Linden A Interleukin-17 as a recruitment and survival factor for airway macrophages in allergic airway inflammation. Am J Respir Cell Mol Biol 2005 33 248-253. 96 Bush KA, Farmer KM, Walker JS, Kirkham BW Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgGl Fc fusion protein. Arthritis Rheum 2002 46 802-805. 

The early stages of bone pathology in rheumatoid disease manifest as periarticular osteoporosis and juxta-articular bone erosion. Osteoclast overactivity is the predominant influence in such bone erosion and NO has a direct inhibitory efiect on osteoclastic bone resorption (MacIntyre et al., 1991). Endothelial cells, present in abundance and in close proximity to the osteoclast may therefore play a role in down-regulating osteoclast activity through the production of NO. Since the osteoclast is of macrophage lineage, it is likely to be... 

CX3CL1 (Fractalkine) CIA DBA/1 mice Hamster anti-mouse FKN mAb (ICN Pharmaceuticals) i Reduce infiltration of inflammatory cells in synovium and bone erosion. It did not affect production of serum anti-collagen type II (CII) IgG or IFN-y by CH-stimulated splenic T cells. 215... 

Pyrrolopyrazine 22 has an IC50 of 1.7nM against Syk [88] and significantly decreased ankle swelling in prophylactic and therapeutic rat CIA models, and micro-CT scans of ankle joints showed significant inhibition of bone erosion. While 22 is clearly a potent Syk inhibitor, no selectivity or in vitro functional data has been reported. The pyrrolopyrazine scaffold appears in a series of compounds, exemplified by 23, that are substituted in the pyrrole and pyrazine rings [89-92]. These compounds are claimed to inhibit Syk and JAK, but the limited data disclosed suggests that JAK is the dominant activity. 

Interleukin 1 (IL-1) is produced mainly by activated monocytes-macropha-ges, and its principal action is to stimulate thymocytes. A pleiotropic cytokine, IL-1 induces the expression of a large diversity of cytokines such as IL-6, leukaemia inhibitory factor (LIF), and other proinflammatory molecules (Di-marello 1994). IL-1 and TNF-a carry out as part of their function increasing the expression of NF-/cB and JNK (c-Jun N-terminal kinase). The importance of IL-1 in OCS is demonstrated because the IL-1-receptor-deficient mouse is resistant to ovariectomy (OVX)-induced bone loss (Lorenzo et al. 1998). The importance in pathological bone loss is also illustrated by the fact that treatment with IL-1 receptor antagonist slows down bone erosion for patients affected with rheumatoid arthritis (Kwan et al. 2004). IL-1 increases osteoclast differentiation rather than mature osteoclast activity, and infusion of IL-1 into mice induces hypercalcemia and bone resorption. Finally, IL-1 and TNF-a... 

Two recently introduced biological therapies were designed to interfere with the inflammatory cascade initiate by TNF-a. Etanercept (Enbrel) is indicated for the treatment of moderate to severe rheumatoid arthritis in individuals over age 4. Infliximab in conjunction with methotrexate (Remicade) is approved for use by adults in the treatment of rheumatoid arthritis. It is also indicated for therapy of Crohn s disease. Over the short term, the efficacy of these drugs in the treatment of rheumatoid arthritis appears to be superior to that of methotrexate alone however, their ability to prevent bone erosion for longer than 24 months must be further studied. The cost of both drugs is significantly higher than that of the other DMARDs. 

Corticosteroids have been used in 60-70% of rheumatoid arthritis patients. Their effects are prompt and dramatic, and they are capable of slowing the appearance of new bone erosions. Corticosteroids may be administered for certain serious extra-articular manifestations of... 

Leflunomide (Arava) is a relative newcomer to the antirheumatic drug arsenal. This drug helps decrease pain and inflammation in rheumatoid joint disease, and leflunomide has been shown to slow the formation of bone erosions in arthritic joints.19 Leflunomide is also fairly well tolerated by most patients and may produce beneficial effects fairly soon (1 month) after beginning treatment.57,105 This drug is therefore a po-... 

Methotrexate (Folex, Rheumatrex) is an antimetabolite used frequently in the treatment of cancer (see Chapter 36). There is considerable evidence that this drug is also one of the most effective DMARDs.15 76 Methotrexate has been shown to slow the effects of rheumatoid arthritis as evidenced by decreased synovitis, decreased bone erosion, and less narrowing of the joint space.37 The therapeutic effects of methotrexate have also been reported to be equal to, or better than, other DMARDs such as oral gold or azathioprine, and methotrexate may offer an advantage in terms of a rapid onset.68,90 Hence, methotrexate s popularity as a DMARD has increased during the past few years, and this drug is often the first DMARD used to treat rheumatoid arthritis in both adults and children.76... 

Corticosteroids have been used in 60-70% of rheumatoid arthritis patients. Their effects are prompt and dramatic, and they are capable of slowing the appearance of new bone erosions. Corticosteroids may be administered for certain serious extra-articular manifestations such as pericarditis or eye involvement or during periods of exacerbation. When prednisone is required for long-term therapy, the dosage should not exceed 7.5 mg daily, and gradual reduction of the dose should be encouraged. Alternate-day corticosteroid therapy is usually unsuccessful in rheumatoid arthritis. 

Findings on x-ray films depend on the cause and age of the patient. " Radiographic changes include changes in the growth plate bone areas, bone erosion, osteopenia, and pseudofractures (Looser s zones). 

Radiologic evaluation is an absolute necessity in the diagnosis of OA (see Table 90-3). Bone erosions and unequivocal radiographic osteopenia are uncommon except in erosive or secondary OA. Finally, many patients who do not have clinical OA and do not have pain may nonetheless exhibit radiologic changes typical of OA. ... 

Lubberts E, Koenders MI, Oppers-Walgreen B, van den Bersselaar L, Coenen-de Roo CJ, Joosten LA, van den Berg WB (2004) Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum 50 650-659... 

Women produce less estrogen after menopause. Estrogen inhibits calcium loss and bone erosion. Reduced estrogen levels result in more rapid calcium and bone loss. Osteoporosis can be minimized if adequate calcium intake occurs, especially from adolescence through young adulthood, and if estrogen replacements are taken after menopause. 

First metatarsophalangeal involvement Periarticular osteopenia Bone erosions Heberden s nodes Tests for rheumatoid factor Renal failure(a blood urea of more than 50 mg/lOOml) and/or proteinuria... 

The patients had a much greater frequence of nephrolithiasis, crystalline urate deposits in synovial punch biopsies and were somewhat more tophaceous than expected.The severity of their gout was confirmed by the high incidence of radiographic finding of bone erosions and by the high number of joints involved for each patient. 

Bone erosions Periarticular osteopenia Vascular disease Hypertension Heberden s nodes Renal failure and or proteinuria Rheumatoid factor Tophi... 

In i+T.62 % of the patients stone preceded the development of gouty arthritis by more than a decade in lU.30 percent. The mean duration of gout was higher in patients with subcutaneous tophi (IO.7I t 9 IT years) or with bone erosions (9 19 i 8.U9 years) than in those without tophi (6.9 7 27 years) or without erosions (5 3 i 6.U1 years). 

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