To characterize cartilage degradation, Mankin et al  developed a histologic grading scale that ranges from 0 (normal cartilage) to 14 (severe degradation). Scoring reflects the loss of structural organization (0-6), cellular characteristics (0-3), loss of safranin-O staining (0-4) and tidemark integrity (0-1). More recently, a new histopathologic grading system has been proposed by Osteoarthritis Research Society International (OARSI) . With normal cartilage as grade 0, OA severity is divided into six grades. Grades 1 to 4 involve changes in articular cartilage, and grades 5 to 6 involve the subchondral bone as well. It is important to note that both grading systems are histologic, assessed at a particular location. A patient may have severely degraded cartilage in the weight-bearing regions (Mankin score, Ms >10; OARSI grade >4), yet still have near-normal cartilage in non-weight-bearing regions (Ms <5; OARSI grade 1-2), however severe the patient's OA.
The stages in cartilage degradation can readily be seen in histologic sections, graded according to the Mankin score (53). In control cartilage (Ms = 1, OARSI = 0) obtained from the femoral heads of patients who had fractured the neck of the femur, aggrecan is evenly distributed throughout the cartilage, as indicated by safranin-O (Fig. 1.6A) and Alcian blue (Fig. 1.6E) staining. Loss of aggrecan in the superficial zone, as shown by loss of safranin-O staining (Fig. 1.6B), is the first indication of OA (Ms = 3-4, OARSI = 1). At this stage, the collagen network remains intact, on the basis of positive sirius-red staining (Fig. 1.6F). Aggrecan loss leads to reduced resistance to mechanical loading and to damage to the collagen network. The stage that follows is erosion of
Mankin score = 1
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