Page 77 - Slipped Capital Femoral Epiphysis Pathogenetic and Clinical aspects

in the kidneys to calcitriol (1,25-dihydroxycholecalciferol), the biologically active form of vitamin D. Calcitriol circulates as a hormone in the blood, regulating the concentration of calcium and phosphate in the bloodstream and promoting growth, mineralization and remodeling of bone.
Calcitriol has a direct action on epiphyseal chondrocytes. They stimulate cell
growth in a dose-dependent, biphasic manner: proliferation is stimulated at low concentrations and inhibited by high concentrations. Also, it has synergetic effects
with PTH on chondrocyte proliferation. A possible link between IGF and calcitriol
has been described by showing an increased expression of IGF-1 receptor and/or
local IGF-1 synthesis [21, 41]. Accelerated growth after the treatment of nutritional
vitamin D, in vitamin-D-deficient patients, is mediated through activation of the
GH-IGF1 system and suggests an important role of vitamin D as a link between the 4 proliferating cartilage cells of the growth plate and GH-IGF1 secretion [41].
In the literature, an association has been described between seasonal variation and SCFE. This might be related to a decrease of vitamin D [42].
Chronic disease
Growth failure is a distinctive feature in children with chronic diseases. Some children with chronic diseases can suffer from inflammation, malnutrition and metabolic acidosis, which may result in abnormal GH-IGF-1 axis activity [43]. Chronic disease caused by inflammatory processes may, in some patients, lead to elevated titers of proinflammatory cytokines in serum. For effects on growth, the duration of exposure to these proinflammatory cytokines is important. The inflammatory cytokines interleukin 1β (Il1β), interleukin 6 (Il6) and tumor necrosis factor α (TNFα) may inhibit growth either directly at the physis or indirectly by reducing IGF-1 [43].
In addition, malnutrition in children with chronic diseases also plays an important role in growth impairment and, typically, circulating IGF-1 and GHBP levels are decreased [43, 44].
Metabolic acidosis in children with chronic renal failure (CRF) down-regulates cartilage matrix proteoglycans, collagen type 2 syntheses and expression of IGF-1 and IGF-1R in the physis, thereby, inducing GH resistance. Acidosis also changes the pulse amplitude of GH secretion, sup-presses serum IGF-1 and decreases the expression of hepatic IGF-1 mRNA, hepatic growth hormone receptor (GHR) mRNA and epiphyseal IGF-1 mRNA [44-46].
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