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No Bones About It

When examining bones and joints, toxicologic pathologists and those working on experimental models have the advantage of being able to examine sections from an equal number of agematched control animals that are sectioned in the same plane as treated animals. Diagnostic pathologists have the advantage of input from clinicians who may have radiographs and, in some cases, other types of imaging data. Despite these advantages, bones and joints are often not favorite tissues, largely because of the tremendous heterogeneity in the appearance of normal features that can make lesions hard to distinguish. This heterogeneity is influenced by many variables, including but not limited to plane of section, differences in appearance of the various bones of the body and their associated structures (ligaments, tendons, menisci), age of the individual, and the fact that abnormal structures (eg, periarticular osteophytes) can assume a normal appearance through remodeling over time, thus requiring the pathologist to have expertise in the normal morphology (particularly the shape) of the affected site to appreciate changes due to chronic disease. Depending on the age of the animal, there may be the presence or absence of growth plates, remodeling in the cutback zone and endosteum, irregularities around ligament insertions and nutrient vessels, and a variable amount of new bone in the periosteum of the metaphysis. Whenever possible, plane of section should be standardized for comparison between affected and control tissues, particularly when histomorphometry measurements are taken. This is nicely exemplified in the article on animal models of osteoarthritis by McCoy 10 in this issue, in which an ideal, mid-coronal section of a murine stifle joint is included for orientation. Age of the individual can dramatically affect the healing potential of joint tissues, as evidenced by studies of osteochondrosis, a disease that develops only in immature individuals. Due to the remarkable healing properties of epiphyseal cartilage (discussed by Olstad et al 14,15 in the studies on osteochondrosis), most lesions occurring in animals with this disease are subclinical and known to heal spontaneously. Largely because it is not possible to biopsy these sites and confirm their features in the human disease, subclinical lesions of osteochondrosis in humans often are misinterpreted by MD radiologists as ‘‘ossification variants’’ rather than evidence of disease. Conversely, lesions of osteoarthritis occurring in older individuals, in whom the articular cartilage undergoes chronic degenerative changes, remain static at best and usually progress (Figs. 1, 2). Preparing bones for histopathology can be problematic if careful handling is not followed throughout the process. This includes allotting sufficient time for fixation, collecting a sample of an appropriate thickness, rinsing to remove ‘‘bone dust,’’ and using an appropriate decalcifying agent in which the end point can be monitored to prevent over-decalcification. The processing schedule should allow good penetration of the solutions and impregnation of paraffin. At microtomy, using positively charged or coated slides ensures good adherence of the tissue. Finally, it is important to optimize the staining procedure to achieve crisp nuclear and cytoplasmic details. Most sections are routinely stained with hematoxylin and eosin, but broad horizons of color (with diagnostic significance) are available in bone and joint sections stained with safranin O (see Olstad et al, 14 Fig. 18) or toluidine blue, cationic dyes that stain proteoglycans and glycosaminoglycans in cartilage (Figs. 3–5). For those who keep their polarizing lens handy, examining the birefringence of collagen in bone is another scintillating reward and allows one to easily distinguish mature, lamellar bone from newly formed, woven bone (Figs. 6, 7).