Tranexamic acid, an inhibitor of plasminogen activation, reduces urinary collagen cross-link excretion in both experimental and rheumatoid arthritis

The plasminogen activation system is one of the enzyme systems heldresponsible for bone and cartilage degradation in rheumatoid arthritis(RA). In this study, we evaluated the effect of tranexamic acid (TEA), aninhibitor of plasminogen activation, on urinary collagen cross-linkexcretion and radiological joint damage in rat adjuvant arthritis (AA) andon urinary collagen cross-link excretion in patients with RA. In the animalstudy, adjuvant arthritis was induced in male Lewis rats. From day 7onward, high-dose TEA (500 mg/kg body weight, once daily) or placebo wasadministered orally. Study groups consisted of TEA-treated normal rats (C +TEA), placebo-treated normal rats (C + plac), AA rats treated with TEA (AA+ TEA) or with placebo (AA + plac). To monitor joint destruction, urinarycollagen cross-link excretion (pyridinoline, HP; deoxypyridinoline, LP) wasmeasured by high-performance liquid chromatography at days 14 and 21.Radiological evaluation of joints was performed at day 21. In the patientstudy, TEA was administered to nine patients with RA as adjuvant medication(approximately 20 mg/kg body weight, three times daily) for 12 weeks.Urinary HP and LP excretion levels were measured before and during TEAtreatment, and 4 weeks after the cessation of TEA treatment. In AA + TEArats, a significant reduction of HP and a tendency towards a reduction ofLP excretion were found compared with AA + plac rats (P < 0.05), at day14, whereas the HP/LP ratio did not change. No difference was observed inHP, LP excretion, HP/LP ratio and radiological damage score between theTEA- and placebo-treated AA rats at day 21. In RA patients, a significantreduction of HP and LP excretion was found during the TEA treatment period(P < 0.05). After the cessation of TEA treatment, HP and LP excretionincreased towards baseline levels. No effect on disease activity wasobserved. The plasmin antagonist TEA reduced the excretion of collagenpyridinoline cross-links in both experimental and rheumatoid arthritis. Assuch, this study not only supports the involvement of the plasminogenactivation system in the destructive phase of arthritis, but also suggestsa beneficial effect of therapeutic strategies directed against inhibitionof matrix proteolysis.