Protective Effect Of Alendrnate Onarticular Cartilage And Subchondral Bone In Guinea Pigs With Spontaneous Osteoarthritis

Objective This study aimed to assess whether Alendrnate (ALN) could improve themicro-structure of subchondral bone, and protect against cartilage degradation in ananimal model of naturally occurring osteoarthritis(OA).Methods Thirty-two3-weeks-old Dunkin-Hartley (DH) guinea pigs were divided intofour groups after adaptive feeding a week:16were sacrificed at1and3months of age, asfollow Base line (BL) group and control (Control) group; the other16treated by ALN(20μg/kg/2d) or normal saline from3months of age, and were sacrificed at6months asAlendronate (ALN) group and normal saline (NS) group. Each group was macroscopicgross observed the appearance and synovium of the knee and synovial traits immediately.Histological analysis with hematoxylin-eosin (HE) and Masson’s trichrome stain andMankin scores were used to identify degenerative cartilage, and immunohistochemistryanalysis for matrix metalloproteinase3(MMP-3) and glycosaminoglycan (GAG)expression in cartilage was performed. Bone mineral density (BMD) of the1/4proximaltibial and the subchondral bone of condylus internal or lateral tibial plateaus weremeasured using dual X-ray absorptiometry; Subchondral bone micro-architecture wasassessed by micro-computed tomography (micro-CT).Results Histological and Mankin score analyses revealed Osteoarthritis (OA) occurredat3months of age (Control group) and was more severe with increasing age, and ALNreduced the Mankin scores at6months of age (ALN group). Immunohistochemicalstaining demonstrated that MMP-3expression in cartilage increased with age, Controlgroup significant increased than BL group and NS group markedly increased than inControl group; but no significant difference was found in GAG expression between BLgroup and Control group, after which expression in NS group markedly decreasedcompared with that in control groups; ALN treatment increased GAG expression anddecreased MMP-3expression in the cartilage when compared with the NS groups. Thebone mineral density of the subchondral bone of condylus internal or lateral tibialplateaus increased with the development of OA. Micro-CT analysis indicated that ALNtreatment increased the bone volume ratio, while retarding the subchondral trabecularbone micro-architectural changes from rod-like to plate-like. Conclusions1Age-related articular cartilage degeneration occurred in Dunkin Hartleyguinea pigs beginning at3months of age.2ALN20μg/kg/2d subcutaneous injection for12weeks can inhibit the expression of MMP-3in the cartilage, while reducing thedegradation of GAG to prevent cartilage damage progression; can also retard thedeterioration of subchondral trabecular bone in a model, reducing the articular cartilagedegeneration in a naturally occurring OAof DH guinea pig.