Aminobisphosphonate (YM175) Inhibits Bone Destruction in Rat Adjuvant Arthritis

This study was designed to examine the effects of an aminobisphosphonate (YM175, which is also called incadronate) on bone destruction in rat adjuvant arthritis (AA). Thirty-five female Lewis rats were given an intradermal injection of heat-killed Mycobacterium butyricum and randomly allocated to five groups (seven rats/group). In the three YM175-treated (0.01, 0.1 and 1 mg/kg per day) groups, YM175 was injected subcutaneously every day from day 0 to day 42. The effects of YM175 in AA rats were evaluated according to an arthritis score, hind paw volume, and radiological and histological examinations. The results showed that YM175 suppressed the radiological and histopathological changes, as well as the joint swelling, in rat AA in a dose-dependent manner. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells (osteoclasts and preosteoclasts or osteoclast precursors) in bone mar-row spaces and granulation tissue in the YM175-treated groups was also reduced in a dose-dependent manner. This study provides the first evidence that YM175, among aminobisphosphonates, not only inhibits bone destruction in rat AA, probably by reducing osteoclast numbers, but that it also suppresses joint inflammation. These results suggest that YM175 may be a useful drug for the prophylactic treatment of both bone destruction and joint inflammation in patients with rheumatoid arthritis.