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IOF World Congress Abstracts Contributory role of TNF-alpha in secondary osteoporosis linked to rheumatoid arthritis, compound also has role in potential new treatment strategy Patients with rheumatoid arthritis may be more likely to develop osteoporosis, especially as a secondary condition from medications used to treat rheumatoid arthritis and a variety of contributing factors. Prolonged treatment with bone-eroding corticosteroids, less physical activity, extended duration and severity of rheumatic disease have all been identified as factors contributing to later generalized osteoporosis. Researchers from the University of Graz, Austria, have now added another contributory factor to this list: the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). They have also identified a potential new treatment strategy. The protein TNF-alpha is abnormally active, or upregulated, in chronic inflammatory diseases such as rheumatoid arthritis. Over time this upregulation, according to lead investigator Dr. T. Mueller and colleagues, contributes to osteoporosis in several ways: driving the production of other proinflammatory cytokines, promoting the differentiation of osteoclast progenitors into mature bone-eroding osteoclasts, and activating mature osteoclasts so that they begin the process of bone erosion. Infliximab, one of the newer anti-rheumatic drugs on the market (marketed in the U.S. since 1999) is effective in many rheumatoid arthritis patients in reducing the signs and symptoms of active inflammation. As a TNF-alpha inhibitor, Mueller and colleagues hypothesized that this agent may also prevent bone loss in rheumatoid arthritis patients. They conducted a small study in which 12 methotrexate-nonresponding patients with rheumatoid arthritis received a single infusion of infliximab (10 mg/kg i.v.). Blood samples were obtained two and one days prior to drug administration and one day and 14 days post-treatment, and were analyzed for the markers c-reactive protein (CRP), serum beta-CrossLaps and osteocalcin. Beta-CrossLaps decreased by 41% at 24 hours after infliximab infusion and remained low, although not significantly so, 14 days postinfusion. Disease activity score (DAS) and CRP were also lower 24 hours and 14 days after infliximab administration. Based on the results obtained in this single-dose study, the investigators concluded that infliximab therapy may prevent bone resorption while having no adverse effects on bone formation, and that its long-term use may prevent secondary osteoporosis in patients with rheumatoid arthritis.
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