薬理と治療

Abstract

Oxidative responses are well recognized to play essential roles in the development and maintenance of osteoporosis. Although bisphosphonate is well accepted to be effective in the treatment of osteoporosis, the influence of bisphosphonate on oxidative responses is not well understood. Therefore, the present study was designed to examine the influence of bisphosphonate on oxidative responses using risedoronate（RS）, the third generation bisphosphonate, and adjuvant arthritis in vivo. Adjuvant arthritis was induced in male Lewis rats by a single subcutaneous injection of 0.1 mL complete Freund’s adjuvant into the hind paw. Oxidative responses were evaluated by measuring hydroperoxide contents in plasma with a newly developed free radical analysis system, FREE. Daily administration of RS at more than 0.028 mg／kg could suppress the production of hydroperoxide in plasma, which was increased by adjuvant injection. It is also observed that daily administration of RS also suppress the levels of plasma cartilage oligometric matrix protein（COMP）that is the marker of cartilage destruction. The minimum dose of the agent, which causes significant suppression of COMP production, was 0.028 mg／kg, which is a human recommended therapeutic dose. These results may suggest that RS could suppress the production of reactive oxygen species and results in favorable modification of clinical conditions of osteoporosis.（Jpn Pharmacol Ther 2008；36：605−11）KEY WORDS Bisphosphonate, Free radical, Adjuvant arthritis, COMP