Cartilage, bone and synovial histomorphometry in animal models of osteoarthritis.

OBJECTIVE: This review focuses on histomorphometry for assessing the pathological changes in various compartments of the joint including cartilage, bone and synovium in animal models of osteoarthritis (OA). METHODS: Different methodological approaches are presented concerning sampling, embedding, sectioning, staining, mounting of stained sections and measurement of histomorphometric parameters using automated and semi-automated methods. Notes are provided describing some methods in greater detail. RESULTS: Histomorphometry allows a significant gain of objectivity, accuracy and reproducibility in the quantification of the main histological parameters which best characterize OA in the affected joint (cartilage thickness (CT), chondrocyte size and density, cartilage fissure, proteoglycan (PG) content, subchondral bone plate thickness (SBPT), thickness of synovial living cell layer) in animal models. CONCLUSION: Use of histomorphometry could contribute to a better quantification of histological differences between control and OA animals. Contributing also to the introduction of normative data, it is a major advantage for therapeutic assessments in experimental OA and particularly for the analytical comparison of the efficacy of disease modifying OA drugs (DMOAD).

Evidence of early subchondral bone changes in the meniscectomized guinea pig. A densitometric study using dual-energy X-ray absorptiometry subregional analysis.

OBJECTIVE: Subchondral bone changes are thought to be an important aetiological element in the pathogenesis of osteoarthritis (OA). To confirm this hypothesis in the meniscectomized (MNX) guinea pig model, bone densitometry was performed in the subchondral bone of the distal femur. METHODS: MNX and sham-operated (SH) guinea pigs were studied 1 and 3 months after partial meniscectomy at the medial side of the left knee. Bone mineral density was measured at the lateral (BMD-L) and medial (BMD-M) sides of the distal femur using dual-energy X-ray absorptiometry (DXA). BMD-M was then compared to the bone volume evaluated by histomorphometry at the medial epiphyseal part of the proximal tibia (BV-M). RESULTS: One month after operation, in MNX animals left femur BMD-M was significantly lower than in the contralateral femur (-9%, P< 0.01) and than in the left femur of SH (-11%, P< 0.01). By contrast, 3 months after meniscectomy BMD-M was higher in the femur than in the contralateral femur (+4%, P< 0.05); BV-M tended to be higher on the left than on the right side (+4%, P< 0.06), and was significantly correlated with BMD-M at the 2 grouped time points: r=0.74 (P< 0.001). CONCLUSIONS: These data emphasize the usefulness of DXA as a simple tool to assess subchondral bone changes at the OA-affected side of the femur and reveal typical variations of bone metabolism in the initiation of OA pathology in the MNX guinea pig: early bone loss at the subchondral level followed by increased bone density.