IOF World Congress on Osteoporosis

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MAY 12, 2002

Lisboa Congress Center, Portugal

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.

The International Osteoporosis Foundation (IOF) is a worldwide organization dedicated to the fight against osteoporosis around the world. It brings together scientists, physicians, patient societies and corporate partners. Working hand in hand with its 139 member societies in 71 countries and other healthcare-related organizations around the world, IOF encourages awareness and prevention, early detection and improved treatment of osteoporosis.

The IOF World Congress on Osteoporosis is being held May 10-14, 2002 in Lisbon, Portugal. Some 5,000 participants are expected for the congress, expected to be the largest gathering ever of osteoporosis specialists from around the world. Abstracts from the congress are published in a supplementary volume of the journal Osteoporosis International. For more information visit the congress website:

IOF World Congress on Osteoporosis abstracts can be accessed on:

IOF website:

For more information contact Siofra Sharpe:

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