A comparison of clodronate and indomethacin in the treatment of adjuvant arthritis.
OBJECTIVE
The therapeutic effects of an anti-resorptive agent, clodronate, were compared with the effects of an anti-inflammatory agent, indomethacin, in rat adjuvant arthritis after therapy and after a follow-up time of two weeks.


METHODS
Eighty-one male Lewis rats, 6-7 weeks old, were immunized with heat-killed mycobacteria.


METHODS
Fourteen days after immunization the animals were treated either with clodronate (50 mg/kg/day, subcutaneously), indomethacin (3 mg/kg/day, orally) or saline (controls) for two weeks.


METHODS
Clinical signs of arthritis including the severity of paw swelling were assessed, biochemical variables were measured, and histological features of the non-decalcified tarsus with ankle, intertarsal and tarsometatarsal joints were evaluated for inflammatory soft-tissue, articular, and bone changes.


RESULTS
The results indicated that clodronate and indomethacin suppressed significantly the intensity of inflammation, activity of beta-N-acetylglucosaminidase in inflamed hindpaw tissue, serum ICTP (cross-linked carboxyterminal telopeptide of type 1 collagen) level and bone lesions in the tibiotarsal region. The level of serum osteocalcin was also significantly decreased by clodronate. The inhibitory effect of clodronate against arthritic bone changes occurred, however, earlier and was slightly more potent than the effect of indomethacin, while indomethacin was slightly more effective in reducing paw swelling. Both drugs preserved their therapeutic effects during the follow-up time of two weeks.


CONCLUSIONS
Clodronate and indomethacin have fairly similar efficacy in suppressing the intensity of joint swelling and preventing bone lesions in adjuvant arthritic rats.
Osterman
T
T
Biomedical Research Center, Leiras Oy, Turku, Finland.
Kippo
K
K
Laurén
L
L
Pasanen
I
I
Hannuniemi
R
R
Sellman
R
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001862:Bone Resorption / Q000188:drug therapy*; D002250:Carbon Radioisotopes; D004002:Clodronic Acid / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002250:Carbon Radioisotopes; D004002:Clodronic Acid; D007213:Indomethacin