Effect of Alendronate on the metabolism of cartilaginous and disc cells in vitro

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Bisphosphonates have been widely used for treatment of osteoporosis. Recently, alendronate may have chondroprotective effects that could be of relevance in osteoarthritis. Aggrecan concentration falls markedly during cartilaginous and disc degeneration with unfortunate biomechanical and physiological consequences. However, many questions on the effect of alendronate to disc cells remain unanswered. The goals of this study were to determine the role of extracellular osmolality and oxygen tension in regulating production of GAG by alendronate and its effects on cartilahious and disc matrix turnover.Cells were isolated from the cartilaginous tissue of metatarsal joint and the nucleus pulposus of bovine caudal discs, encapsulated in alginate beads, and cultured in DMEM containing 6% foetal calf serum(FCS) at 400 mOsmol at cell densities of 4 million cells/ml. They were then cultured for 5 days under 21% oxygen with 10^<-1>-10^<-12> mol/l alendronate ; cell cultured without alendronate served as control and the effects of osmolarity and oxygen concentration were compared. Lactate production was measured enzymatically and glycosaminoglycan(GAG) accumulation was examined using a DMB assay. Rate of sulfate GAG synthesis was measured using a standard^<35> S-sulfate radioactive method. In the result, Alendronate at concentrations of 10^<-10>-10^<-8> mol/1 potentiated the GAG production per million cells by cartilaginous and disc cells in 5 days culture. The potentiated effect was maximal at 10^<-8> mol/l. Alendronate(10^<-8> mol/l)-induced increases in GAG production per million cells are prevented by inhibition of cell metabolism under pathologic conditions(270 mOsmol,<1% oxygen) as seen the osteoarthritis and degenerated disc ; but alendronate increased GAG production, cell metabolism(lactate production) and GAG synthesis in healthy conditions(400 mOsmol, 5% oxygen). In conclusion, this data suggest that alendronate may have chondroprotective effects on healthy cells.