Comparative effects of benoxaprofen and other anti-inflammatory drugs on bone damage in the adjuvant arthritic rat

Abstract

Benoxaprofen, a new nonsteroidal anti-inflammatory agent recently marketed as an an antirheumatic drug, has been reported to suppress leucocyte migration into inflammatory sites, possibly by its reported inhibition of leukotriene synthesis. Benoxaprofen is also a weak to moderate inhibitor of prostaglandin synthesis. The effect of benoxaprofen was examined on adjuvant-induced arthritis in rats by radiographic assessment of bone damage. The effect of benoxaprofen was compared to other nonsteroidal anti-inflammatory agents, considered to act primarily by the inhibition of synthesis and/or release of prostaglandins. Drugs were administered from the 15th to the 30th day after induction of the adjuvant disease ('established adjuvant'). Radiographs of adjuvant rats showed extensive bone damage that was markedly suppressed by 30-40 mg/kg of benoxaprofen. Benoxaprofen exerted a dose-related inhibition of bone damage. There was less suppression of bone damage by comparable doses of phenylbutazone, oxyphenbutazone, ibuprofen, fenbufen, naproxen, tolectin and sulindac. Indomethacin, piroxicam and flurbiprofen were nearly as effective but only in doses that produced adverse effects or death in rats. Benoxaprofen may modify the progression of the experimental arthritic disease through a suppression of leucocyte migration.

Effect of etodolac on articular and bone pathology associated with adjuvant arthritis in rats: A comparison with aspirin and naproxen

“…However, as reported previously [13,15] naproxen reduced significantly the incidence and severity of the arthritic lesions. Thus naproxen decreased hind paw edema and increased body weight gain but only 3/6 animals had recovered normal hind leg function after 28 days of treatment.…”

Meloxicam: A potent inhibitor of adjuvant arthritis in the Lewis rat

“…The histological changes in the rat indicate a periostitis. The external swelling in the paw conceals destruction of the cartilage and bone which becomes more pronounced with the specific secondary reaction and is visible with histologic [6][7][8][9] or radiologic techniques [10,11].…”

Emerging and future therapies for the treatment of bone loss associated with chronic inflammation

“…Some of the NSAIDs currently used clinically are reported to regulate bone destruction when used for the treatment of periodontal disease and rheumatoid arthritis (Benslay and Nickander, 1982;Pauletto et al, 1997). The relative contributions of inhibition of the cyclo-oxygenases (COX-1, COX-2) that synthesize prostaglandin E 2 , production of nitric oxide, and the leukotrienes, especially LTB 4 , and the peptido-LTs in the development of joint damage or protection are not known.…”

“…The relative contributions of inhibition of the cyclo-oxygenases (COX-1, COX-2) that synthesize prostaglandin E 2 , production of nitric oxide, and the leukotrienes, especially LTB 4 , and the peptido-LTs in the development of joint damage or protection are not known. Several NSAIDs, including clobuzarit (ICI: Clozic) and benoxaprofen (Lilly: Opren) (Benslay and Nickander, 1982), have been found to reduce bone destruction in adjuvant arthritis in rats and in in patients with osteo-or rheumatoid-arthritis.…”