Application of computer-based histomorphometry to the quantitative analysis of methylprednisolone-treated adjuvant arthritis in rats.

Analyses of paw edema and histomorphometry were performed on tibio-talar joints to determine arthritic pathological responses in untreated 28-day adjuvant-induced polyarthritis (AIP) rats, and to determine the drug effect on inhibiting these responses in AIP rats treated with methylprednisolone. Histomorphometric measurements were performed on regions including articular joint space, synovial tissue, articular and epiphyseal cartilage, epiphyseal and metaphyseal bone marrow, and endosteal and periosteal cortical bone surfaces. Analysis of paw edema indicated that paw volume was significantly increased in untreated AIP rats. This increase in paw volume was partially prevented in AIP rats treated with 0.3 mg methylprednisolone/kg per day, and completely prevented in AIP rats treated with the two higher dose levels (1 and 3 mg/kg per day). Histomorphometric analysis of untreated AIP tibio-talar joints showed decreased articular joint space whereas synovial tissue area increased and a minor, but significant, articular cartilage erosion area occurred. Epiphyseal growth cartilage area was decreased. Trabecular bone area in distal tibial epiphyseal and metaphyseal regions was markedly decreased whereas bone marrow area increased involving a large number of macrophages and osteoclasts. Eroded endocortical bone area was increased while cortical bone area decreased. Marked osteophyte proliferation occurred on the periosteal surface. These arthritic pathological changes were inhibited by the treatment of methylprednisolone in a dose-dependent fashion. The animals treated with the highest dose of methylprednisolone complete prevented the development of the AIP-induced pathological changes. These data confirmed qualitative histological evaluation of arthritic changes but did not correlate with the anti-edema effects of methylprednisolone (100% inhibition at 1.0 and 3.0 mg/kg, p.o.). It is suggested that quantitative histomorphometry be used to determine more precisely the AIP rat model and the effects of drugs on different histopathological features in this experimental model of arthritis in preference to paw edema which gives a more limited picture of the arthritic response.