Hk. Ronday et al., TRANEXAMIC ACID, AN INHIBITOR OF PLASMINOGEN ACTIVATION, REDUCES URINARY COLLAGEN CROSS-LINK EXCRETION IN BOTH EXPERIMENTAL AND RHEUMATOID-ARTHRITIS, British journal of rheumatology, 37(1), 1998, pp. 34-38
The plasminogen activation system is one of the enzyme systems held re
sponsible 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. F
rom day 7 onward, high-dose TEA (500 mg/kg body weight, once daily) or
placebo was administered orally. Study groups consisted of TEA-treate
d normal rats (C + TEA), placebo-treated normal rats (C + plac). AA ra
ts treated with TEA (AA + TEA) or with placebo (AA + plac). To monitor
joint destruction, urinary collagen cross-link excretion (pyridinolin
e, HP: deoxypyridinoline, LP) was measured by high-performance liquid
chromatography at days 14 and 21. Radiological evaluation of joints wa
s performed at day 21. In the patient study, TEA was administered to n
ine patients with RA as adjuvant medication (similar to 20 mg/kg body
weight, three times daily) for 12 weeks. Urinary HP and LP excretion l
evels were measured before and during TEA treatment, and 4 weeks after
the cessation of TEA treatment. In AA + TEA rats, a significant reduc
tion of HP and a tendency towards a reduction of LP excretion were fou
nd 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 excretio
n. HP/LP ratio and radiological damage score between the TEA- and plac
ebo-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 incr
eased towards baseline levels. No effect on disease activity was obser
ved. The plasmin antagonist TEA reduced the excretion of collagen pyri
dinoline 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 sug
gests a beneficial effect of therapeutic strategies directed against i
nhibition of matrix proteolysis.