Page 69 - Slipped Capital Femoral Epiphysis Pathogenetic and Clinical aspects

found only in the hypertrophic zone [8]. The chondrocytes showed intracellular abnormalities [5, 7, 9]. An increase in the nuclear and cytoplasmic density was seen in the proliferative and hypertrophic chondrocytes with SCFE and an increase in cytoplasmic glycogen [7, 9]. Other investigators, however, could not confirm these findings [3, 6].
The ECM of the physis had abnormal longitudinal septa with deficiency in
collagen [3, 5, 7, 9]. The amount of proteoglycans in the ECM was moderately
decreased in the matrix of the physis in SCFE compared to normal [3, 7, 9]. Also,
abnormal proteoglycans were found [5]. Matrix vesicles, secreted by hypertrophic chondrocytes, were more abundant than in the controls [5, 7, 9]. Matrix vesicles
contain calcium phosphates, hydroxyapatite and matrix metalloproteinases
(MMP). The contents of these vesicles change the structure of the ECM and begin 4 the process of calcification of the matrix [10]. Lacunar spaces in the hypertrophic
zones were seen, with reactive changes showing callus formation [3, 4, 6]. Scharschmidt et al. performed laser capture microdissection followed by quantitative reverse transcription-polymerase chain reaction analysis of mRNA on the physis tissue of SCFE obtained by biopsies. They observed down-regulation of both type 2 collagen and aggrecan in physes of patients with SCFE [11].
In conclusion, the physis in SCFE shows many histological differences compared to the normal physis in columnar organisation, on the cellular level and in the ECM. The fundamental problem is that the role of the described changes is unknown. It is unclear as to whether they are causal or adaptive. Some of these changes can occur also in endocrine or metabolic abnormalities, as will be discussed further in this review (see Figs. 2 and 3).
Endocrinology of growth and puberty
During the pubertal growth spurt, endocrine changes are enormous. Disturbances of the endocrine mechanisms may lead to weakening of the physis of the proximal femur. Before puberty, the major endocrine factors involved in linear growth and skeletal development are the growth hormone–insulin-like growth factor 1 (GH- IGF-1) axis and triiodothyronine (T3).
With the onset of puberty, the gonadal axis is reactivated after years of quiescence. Increasing levels of sex hormones are responsible for an augmentation of the GH- IGF-1 axis activity.
Sex hormones, growth hormone, IGF-1 as well as other endocrine, paracrine and autocrine factors exert a direct and indirect effect on the physis [12-14].
Slipped Capital Femoral Epiphysis
67