Page 23 - Slipped Capital Femoral Epiphysis Pathogenetic and Clinical aspects

Pathogenesis.
Histological studies of tissue obtained from biopsies during surgery for SCFE
show some characteristic features of the physis of the femoral head. Changes in
longitudinal orientation of the cartilage cells of the physis, which are normally
parallel to the axis of the bone, are seen in tissues taken from biopsies in SCFE. In 2 SCFE, pathologic tangential forces can damage the hypertrophic cartilage. Because
of the longitudinal orientation of these fibers, this zone is least protected from these shearing forces [25]. Obviously as biopsies were taken after the slip occurred, it is not clear whether the observed changes in cell orientation are present before or after the slip occurred.
The resting zones of the physis appeared to be relatively normal in SCFE [3, 40, 49, 80]. The proliferative and hypertrophic zones of the physis in SCFE were wider than in normal physes and showed irregular columnar organization with gradual loss of longitudinal septa and a diminished number of chondrocytes in each column [3, 4, 40, 49, 80]. Interestingly, Adamczyk et al. [2] showed that apoptosis was increased throughout the physis in SCFE, in contrast with controls where apoptosis was limited to the hypertrophic zone. The chondrocytes showed intracellular abnormalities [4, 30, 49]. An increase in nuclear and cytoplasmic density was seen in the proliferative and hypertrophic chondrocytes with SCFE and there was an increase in cytoplasmic glycogen [4, 30]. Other authors, however, could not confirm these findings [3, 80]. The extra cellular matrix (ECM) of the physis had abnormal longitudinal septa with a collagen deficiency [4, 30, 49]. The amount of proteoglycans in the ECM was moderately less in the matrix of the physis in SCFE compared to normal [3, 4, 30]. Also, abnormal proteoglycans were found in the ECM [49]. Matrix vesicles, secreted by hypertrophic chondrocytes, were more abundant than in the controls [4, 30, 49]. Matrix vesicles contained calcium phosphates, hydroxyapatite and matrixmetalloproteinases (MMP). The contents of these vesicles change the structure of the ECM and begin the process of calcification of the matrix [35]. Lacunar spaces in the hypertrophic zones were seen with reactive changes showing callus formation [3, 40, 80].
Scharschmidt et al. performed laser capture microdissection followed by a quantitative reverse transcription-polymerase chain reaction analysis of mRNA on physis tissue of SCFE obtained by biopsies. They observed downregulation of both type 2 collagen and aggrecan in the physis of patients with SCFE [122]. Of interest is a study of Tank et al. [135] where they administered 6-propyl-2-thiouracil (a drug given for hyperthyroidism to decrease the amount of thyroxine) to 11 week old
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