However, the intervention effect of ZOL on OA has not been fully characterized and remains to be directly demonstrated in animal experiments.
The present study examined the microscopic and macroscopic changes in the anterior cruciate ligament transection ACLT model of OA in rabbits and evaluated the effects of ZOL on cartilage degeneration and subchondral bone loss. The bone mineral density BMD of the knee joint was evaluated by dual-energy X-ray absorptiometry scanning immediately after modeling and at 4 and 8 weeks. At week 8, quantitative measurement of cartilage was performed by a specialized magnetic resonance imaging MRI articular cartilage, including three-dimensional fat-suppressed spoil gradient-recalled sequence and T2 mapping.
The rabbits were sacrificed by air embolism articular cartilage anesthesia and both knee joints were harvested and evaluated by general and histological observation. Toluidine blue and hematoxylin and eosin staining were used to assess histological changes in the articular cartilage.
Quantitative analysis of cartilage histopathology was performed according to the Mankin scoring system. MRI scans demonstrated that in the untreated group, articular cartilages on ACLT knees were thinner than those on normal knees. The high dose of ZOL preserved the cartilage tissue thickness more efficiently than the medium and low doses.
Observation of specimens and pathological slices revealed that the articular cartilage degeneration in the high-dose ZOL group was lightest, while that in the medium- and low-dose ZOL group was moderate, and the untreated group exhibited the most severe defect. The untreated group had the highest Mankin score, whereas the high-dose ZOL group had the lowest score.
In conclusion, ZOL increased the subchondral bone density, improved the microstructure and reduced the degeneration of articular cartilage in OA according to morphological as well as quantitative observation. ZOL exerted significant chondroprotective effects in a dose-dependent manner.
ZOL may represent a novel promising drug to complement the treatment of OA.