Incadronate Disodium Inhibits Joint Destruction and Periarticular Bone Loss Only in the Early Phase of Rat Adjuvant-induced Arthritis

Destruction of articular cartilage and subchondral bone loss in the affected joints of rat adjuvant arthritis have never been quantified histologically. This study aimed to evaluate the effect of incadronate disodium on joint destruction and periarticular bone loss, using histomorphometric measurements. Seven-week-old female Lewis rats were injected with 0.1 mg of heat-killed Mycobacterium butyricum into the tail base. Immediately after sensitization, vehicle, or incadronate at 10 or 100 microg/kg per day, was administered subcutaneously, three times per week. Hind-paw volume was measured weekly and the animals were killed at 2, 4, 6, and 10 weeks after sensitization. After taking X-rays, decalcified sagittal sections of the ankle joint were prepared and stained with toluidine blue and tartarate-resistant acid phosphatase. Articular cartilage destruction and subchondral bone loss were evaluated histomorphometrically. At 2 weeks after sensitization, no radiographic or histologic changes were observed. However, at 4 weeks, severe articular cartilage destruction and subchondral bone loss were found in the arthritic control group, while these changes were inhibited dose-dependently by incadronate treatment. At 6 and 10 weeks, both the destructive changes and the bone loss had further progressed, and they were not inhibited by incadronate treatment. Incadronate dose-dependently inhibited articular cartilage destruction and subchondral bone loss at 4 weeks after sensitization in this adjuvant arthritis model. However, the suppressive effects of incadronate did not continue until 6 and 10 weeks.