Page 74 - Slipped Capital Femoral Epiphysis Pathogenetic and Clinical aspects

Chapter 4
pre-existence of obesity. This delay can, thus, be involved in the slip of the epiphysis in SCFE and most children with this condition are, indeed, obese [1, 31].
Leptin and SCFE Leptin is a protein hormone that plays a key role in regulating energy intake and energy expenditure. It is secreted mostly in the adipocytes of white adipose tissue. The level of circulating leptin is proportional to the total amount of fat in the body [13, 32]. In obese children, leptin levels are in direct proportion to the increase in body mass index (BMI) [13].
Leptin plays a permissive role in the onset of puberty and in pubertal growth. Leptin has a direct effect on the physis through leptin receptors and induces an increase in the width of the proliferative zone in a dose-dependent manner. This leads to the enhancement of proliferation and differentiation of the chondrocytes in the physis [12, 32]. Interestingly, in many patients with SCFE, an increase in the width of the proliferative and hypertrophic zones has been found [3-7]. Leptin has synergistic effects with the GH-IGF axis [12, 13] as a skeletal growth factor that, independent of the presence of GH, stimulates IGF-1 and IGF-1 receptor gene expression, indicating that a relation exists between mechanisms regulating weight and mechanisms regulating linear growth. Most likely, there are many links between leptin, adipocytes, GH, thyroxine, IGF-1 and chondrocytes, but the precise nature of these interactions is incompletely understood [32].
In obese children, serum GH levels are usually low. Indirect growth effects in obese children may not be induced by leptin but mediated by insulin. Obesity leads to insulin resistance and, thereby, to an increase of insulin blood levels. Insulin, an anabolic hormone, can, to a certain extent, promote growth as a result of the resemblance of the insulin and IGF-1 receptors. Insulin in high levels may bind to and activate the IGF-1 receptor. Furthermore, insulin may also stimulate accelerated growth by decreasing IGFBP-1, which leads to an increase of free IGF-1 and, consequently, in its biological activity [13].
In conclusion, SCFE is found more often in overweight children [31]. In obese children, leptin levels are increased. Leptin can cause an increase in the width of the proliferative zone, as has been found in SCFE.
Thyroid hormones and SCFE
Triiodothyronine (T3) and thyroxin (T4) are tyrosine-based hormones, produced by the thyroid gland, that are primarily responsible for regulation of the metabolism. Thyroid hormones are regulated by thyroid-stimulating hormone (TSH) by the
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