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A compromised blood supply to the epiphysis of the femoral head seems to be the underlying pathomechanism of LCPD, but the cause of the disturbed blood flow is still unknown. Earlier studies report thromboembolic events due to coagulation abnormalities. Factor V Leiden mutations and decreased levels of protein C and S have been reported for patients with LCPD , but the findings are inconsistent . Perry et al. found a reduced diameter and reduced blood flow of the brachial artery in patients with LCPD compared to an age- and gender-matched control group. Maternal and passive smoking during pregnancy has been implicated in the pathogenesis of atherosclerosis, hypertension among children , and LCPD. The nicotine could provoke oxidative stress in the offspring, which could affect not only vascular formation but also growth, and could also have neurotoxic effects by disrupting neurodevelopment. Patients with LCPD were found to have had lower birth weights or were shorter at birth and had decreased skeletal maturation at time of diagnosis . Catterall developed the concept of the “susceptible child” for LCPD. He defined this as “primarily boys between ages five and nine years who are smaller than their friends and first-degree relatives and have delayed bone age. In all other aspects healthy, and very active children; many of them are hyperactive”. Hyperactivity in children is hard to quantify, though in children with ADHD a hyperactive behavior pattern is well described . More recent publications confirm an association between LCPD and both ADHD and high levels of physical activity. An interesting issue is the pathway of insulin-like growth factor in the discussion of LCPD. Neidel et all and Matsumoto et all found lower levels of circulating IGF-1 in patients at the onset of LCPD which normalized within 2 years during the course of the disease. IGF-1 plays an important role in the growth of many tissues during childhood and could explain the delayed skeletal maturation, hyperactive behavior, and possibly also vascular abnormalities seen in patients with LCPD. That said, other pathways could also have a similar impact on both angiogenesis and neurodevelopment in patients with LCPD. In summary, it seems that on the basis of a possible systemic vascular fragility, hyperactivity might trigger or catalyze LCPD in the epiphysis of the femoral head.