Effects of Alendronate and Prednisolone on a Model of Rheumatoid Arthritis in Mice

Abstract

The purpose of this study was to investigate the potential effects of the anti-bone resorptive agent alendronate (ALN) and the steroidal anti-inflammatory agent prednisolone (PL) on rheumatoid arthritis (RA) in mice with an anti-type II collagen (CII) antibody-induced model of arthritis. Arthritis was induced in female BALB/c mice with anti-CII antibody and LPS. ALN (1 mg/kg) was subcutaneously and PL (0.3, 3 mg/kg) orally administered once a day for 12 days. Severity of arthritis was evaluated on Days 6, 10 and 12, and paws and femoral bone were collected on Day 12 for histopathological examination and microcomputed tomography (micro-CT) analysis. ALN significantly inhibited bone destruction in the paws, but did not inhibit paw edema, synovial proliferation, or inflammatory cell infiltration. On the other hand, PL inhibited paw edema, synovial proliferation and inflammatory cell infiltration, but had no effect on bone destruction in the paws or bone loss in the femoral bone. ALN inhibited bone destruction in this RA model, with prominent amelioration of bone destruction and osteoclast reduction. PL inhibited inflammation, but not bone destruction in the paws. In addition, PL induced bone loss in the femoral bone as determined by micro-CT analysis. Our findings suggest that not only anti-inflammation effects but also direct inhibition of bone destruction is important for the treatment of arthritis.