The British Journal of Rheumatology, Vol 37, 34-38, Copyright © 1998 by British Society for Rheumatology
HK Ronday, JM Te Koppele, RA Greenwald, SA Moak, JA De Roos, BA Dijkmans, FC Breedveld and JH Verheijen
The plasminogen activation system is one of the enzyme systems held
responsible for bone and cartilage degradation in rheumatoid arthritis
(RA). In this study, we evaluated the effect of tranexamic acid (TEA), an
inhibitor of plasminogen activation, on urinary collagen cross-link
excretion and radiological joint damage in rat adjuvant arthritis (AA) and
on urinary collagen cross-link excretion in patients with RA. In the animal
study, adjuvant arthritis was induced in male Lewis rats. From day 7
onward, high-dose TEA (500 mg/kg body weight, once daily) or placebo was
administered 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, urinary
collagen cross-link excretion (pyridinoline, HP; deoxypyridinoline, LP) was
measured by high-performance liquid chromatography at days 14 and 21.
Radiological evaluation of joints was performed at day 21. In the patient
study, 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 TEA
treatment, and 4 weeks after the cessation of TEA treatment. In AA + TEA
rats, a significant reduction of HP and a tendency towards a reduction of
LP excretion were found compared with AA + plac rats (P < 0.05), at day
14, whereas the HP/LP ratio did not change. No difference was observed in
HP, LP excretion, HP/LP ratio and radiological damage score between the
TEA- and placebo-treated AA rats at day 21. In RA patients, a significant
reduction of HP and LP excretion was found during the TEA treatment period
(P < 0.05). After the cessation of TEA treatment, HP and LP excretion
increased towards baseline levels. No effect on disease activity was
observed. The plasmin antagonist TEA reduced the excretion of collagen
pyridinoline cross-links in both experimental and rheumatoid arthritis. As
such, this study not only supports the involvement of the plasminogen
activation system in the destructive phase of arthritis, but also suggests
a beneficial effect of therapeutic strategies directed against inhibition
of matrix proteolysis.
ORIGINAL PAPERS
Tranexamic acid, an inhibitor of plasminogen activation, reduces urinary collagen cross-link excretion in both experimental and rheumatoid arthritis
Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands.
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