Rheumatoid Bone Erosions

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... 

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. 

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... 

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

Wakefield RJ, Gibbon WW, Conaghan PG et al (2000) The value of sonography in the detection of bone erosions in patients with rheumatoid arthritis a comparison with conventional radiography. Arthritis Rheum 43 2762-2770 Wang CL, Shieh JY, Wang TG et al (1999) Sonographic detection of occult fractures in the foot and ankle. J Clin Ultrasound 27 421-425... 

Fig.l0.70a,b. Bone erosions. a,b Transverse 12-5 MHz US images over the ulnar head in two patients with longstanding rheumatoid arthritis reveal bone erosions (arrows) as small regular defects of the cortical outline. Note the synovial pannus (arrowheads) located inside and around them... 

In rheumatoid arthritis, chronic synovitis leads to hypertrophy and hyperplasia of the synovium (pannus), progressive thinning of the articular cartilage and exposure of the subchondral bone. In early disease, when the cartilage still retains a certain thickness, the pannus typically causes marginal bone erosions, located at the periphery of the joint. 

A 50-year-old female with rheumatoid arthritis has developed erosions in her wrist bones. Which of the following agents should be administered7... 

Iwata Y, Mort JS, Tateishi H et al (1997) Macrophage cathepsin L, a factor in the erosion of subchondral bone in rheumatoid arthritis. Arthritis Rheum 40 499-509... 

The pharmacology of these drugs, which are also used in the treatment of malaria, is presented on p. 351. The mechanism of their anti-inflammatory activity is uncertain. Besides inhibiting nucleic acid synthesis, they are known to stabilize lysosomal membranes and trap free radicals. In treating inflammatory disorders, they are reserved for rheumatoid arthritis that has been unresponsive to the NSAIDs or else they are used in conjunction with an NSAID, which allows a lower dose of chloroquine or hydroxychloroquine to be administered. These drugs have been shown to slow progression of erosive bone lesions and may induce remission. They do cause serious adverse effects (see p. 351). 

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