The In Vitro Effects of Clodronate Disodium on Normal and Inflamed Equine Joint Tissues. Colbath AC1, Vergara-Hernández F2, Nielsen BD2, Robison C2, Panek C1. 1Michigan State University, Department of Large Animal Clinical Sciences, East Lansing, MI; 2Michigan State University, Department of Animal Sciences, East Lansing, MI.
BP are being used off label for potential anti-inflammatory effects. Clodronate (CLO) reaches detectable concentrations in synovial fluid following intramuscular administration. Our study objective was to evaluate the effects of CLO on normal and inflamed joint tissues in vitro. Monolayer cultures of synoviocytes, chondrocytes and cartilage explants were subjected to six different treatments: Control (Con), CLO 5 ng/mL, CLO 50 ng/mL, interleukin-1β 10 ng/mL (IL), IL + CLO 5 ng/mL and IL1 + CLO 50 ng/mL for 72 h. Media was harvested at 0 h, 24 h, 48 h, and 72 h posttreatment. Explant culture media was analyzed for sulfated glycosaminoglycan (GAG) content and nitric oxide (NO). Prostaglandin-E2 (PGE2) and interleukin-6 (IL-6) was measured in media from monolayer cultures (chondrocytes and synoviocytes). At the conclusion of the study, cartilage was digested for GAG content analysis. The IL treatment group had a higher GAG concentration, PGE2, NO, and IL-6 compared to the Con group (P < 0.05), indicating a catabolic effect of IL-1β on the explants. CLO groups did not result in an increase in GAG, NO, PGE2 or IL-6 compared to Con, indicating no cytotoxic effect. However, the addition of CLO to IL-1β treated explants did not result in a decrease in GAG, NO, PGE2, or IL-6 in the media, suggesting no anti-inflammatory or cytoprotective effects. The currently recommended intramuscular dose of CLO results in concentrations of CLO in the joint which do not appear to have significant negative effects on joint tissues. However, an anti-inflammatory effect was not identified.