The OARSI system was designed to detect histological features prior to the

recognition of overt clinical OA. None of the published validation approaches

included samples with early OA changes [12, 14, 15]. Our data showed a high
agreement level between the two systems in the overall scores and compartment
scores. According to the OARSI system, cartilage matrix swelling is the earliest
histologically detectable change, which in an extreme form would lead to
cartilage hypertrophy. Edema in cartilage may reflect condensation of the
collagen fibers in the superficial and/or upper mid zones or variation in matrix
cationic staining [13]. We question how accurately this parameter can be
recognized and whether it can be differentiated from artifacts due to processing.
The approach towards detecting early changes depends on the type of study and
question being addressed. Changes observed on Toluidine Blue or Safranin O
stained sections are not quantitative indicators of proteoglycan depletion and
may be at least to some extent reversible. On the other hand, macroscopic
structural defects such as fibrillations and partial erosions are relatively late
features that are preceded by molecular changes. In this regard, detection of