Protective Effect Of Alendrnate On Articular Cartilage And Subchondral Bone Of Osteoarthritis Rat Knee Joint

Objective: To access the protective effects of alendrnate on articular cartilage and subchondral bone of osteoarthritic rat model induced by anterior cruciate ligament transaction(ACLT).Methods: Twenty-four 3-month-old female Sprague-Dawley rats were divided randomly into there groups: Sham groups, ACLT+ALN groups, ACLT+NS groups. Rats in ACLT+ALN and ACLT+NS groups received anterior cruciate ligament transaction (ACLT) on the right knee. Rats in Sham group received right knee arthrotomy as pseudo operation controls. Every rat was placed in a cage without any further immobilization. ACLT+ALN group began to receive a subcutaneous injection of alendronate at a dose of 20μg/kg /2d for 12 weeks; In contrast, ACLT+NS group received NS at the same dose. All rats were sacrificed at 12 weeks post surgery respectively. Samples of cartilage were harvested from right femoral condyles. The samples were observed with the macro-pathologic changes and stained with HE and graded by Mankin's scale. The subchondral of right tibial plateau was cut and stain for the measurement of bone histomorphometry. Cartilage sections from right femoral condyle were stained with Masson and immunostained MMP-13 antibodies.Ressults: (1)The Sham group, ACLT+ALN group and ACLT+NS group exhibited OA development in the femoral condyles cartilage. Surfaces of knee joints of the Sham group were all smoothy and glossy, displayed a little light blue, synovial was clear and transparent. Knee joints of ACLT +NS group all swelled, their surfaces were uneven or anabrotic, displayed dim and bloomy, synovial was light yellow and cloudy, their tibial plateaus appeared hypertrophic, osteophyte emerged on the margin. These appearance accorded with OA. In ACLT+ALN group, articular surfaces were uneven and dim, but tibial plateau hypertrophy had not been seen, cartilage degradation were smaller than ACLT +NS group. (2) The static index of Bone histomorphometry trabecular bone volume (BV/TV) trabecular bone number (Tb.N),trabecular thickness (Tb.Th) in Sham group were significantly higher than those of ACLT+NS group; BV/TV,Tb.N in ACLT+ALN group were significantly higher than those of ACLT+NS group;Trabecular separation (Tb.Sp) in Sham group and ACLT+ALN group were significantly lower than those of ACLT+NS group.(3) The Mankin score of the ACLT+NS group were significantly higher than than those of Sham group and ACLT+ALN group. (4) the integral optical density(IOD) of MMP-13 of Sham group and ACLT+ALN group were significantly lower than those of ACLT+ NS group.Conclusions: (1) A subcutaneous injection of ALN at a dose of 20μg/ kg.2d increases subchondral bone bone mass,improves microstructure,and exerts a chondroprotective action in these unstable knee joints models. (2) Alendronate probably protects articular cartilage by decreasing the expression levels of MMP-13.