No effect of risedronate on articular cartilage damage in the Dunkin Hartley guinea pig model of osteoarthritis.

OBJECTIVES: To investigate whether treatment with a bisphosphonate would influence the subchondral bone plate stiffness and the development of cartilage damage in Dunkin Hartley guinea pigs, which develop osteoarthritis (OA) spontaneously. METHOD: Fifty-six 3-month-old male Dunkin Hartley guinea pigs were randomized into a baseline group and six groups receiving either the bisphosphonate risedronate (30 µg/kg) or vehicle five times a week for 6, 12, or 24 weeks. The medial condyle of the right stifle joint was investigated by histology, using the Osteoarthritis Research Society International (OARSI) score, along with static and dynamic histomorphometry. The subchondral bone plate of the left tibia was tested mechanically with indentation testing. Degradation products of C-terminal telopeptides of type II collagen (CTX-II) were measured in serum. RESULTS: The OARSI score did not differ between risedronate-treated and control animals at any time point. The fraction of bone surfaces covered with osteoclasts (Oc.S/BS) was significantly suppressed in risedronate-treated animals at all time points, as were the fractions of mineralizing surfaces (MS/BS) and osteoid-covered surfaces (OS/BS), and also serum CTX-II. This was accompanied by a significant increase in the epiphyseal content of calcified tissue and in the thickness of the subchondral bone plate. However, this did not result in a stiffer subchondral bone at any time point. DISCUSSION: The risedronate treatment inhibited osteoclastic resorption of calcified cartilage in the primary spongiosa under the epiphyseal growth plate, explaining the risedronate-mediated decrease in CTX-II. Moreover, the serum CTX-II level was not related to the OA-induced articular cartilage degradation seen in this model. CONCLUSIONS: Risedronate did not influence the OARSI score and subchondral plate stiffness, but decreased serum CTX-II in Dunkin Hartley guinea pigs.

Relationship between articular cartilage damage and subchondral bone properties and meniscal ossification in the Dunkin Hartley guinea pig model of osteoarthritis.

OBJECTIVES: To describe the age-related changes of articular cartilage, subchondral bone morphology, and stiffness. Furthermore, to investigate whether subchondral bone histological and mechanical properties and meniscal histological properties are related to articular cartilage damage in the Dunkin Hartley guinea pig model of osteoarthritis (OA). METHODS: Forty male Dunkin Hartley guinea pigs aged 2, 6, 9, and 12 months were studied. The right stifle joints and the left menisci were embedded undecalcified and the tibial articular cartilage and subchondral bone and the menisci were examined using histology. The stiffness of the left tibial subchondral bone was determined with indentation testing. RESULTS: The Osteoarthritis Research Society International (OARSI) grade of the osteoarthritic cartilage lesions of the medial (p < 0.001) and lateral (p < 0.001) condyle and the ossification of the medial (p < 0.001) and lateral (p < 0.001) meniscus increased significantly with age and was significantly more pronounced at the medial condyle than at the lateral condyle. The grade of the osteoarthritic cartilage lesions was significantly correlated (r = 0.78, p < 0.001) with the meniscal ossification, weakly correlated (r = 0.34, p < 0.007) with the subchondral bone plate thickness, and not correlated with the subchondral bone density (r = -0.010, p = 0.94) and the subchondral bone stiffness (r = -0.13, p = 0.30). CONCLUSION: The meniscal ossification observed in Dunkin Hartley guinea pigs may play an important role in the pathogenesis of OA in these animals.