Mechanical load on collagen and bone fracture have been reported to generate radicals, and may thus also predispose formation of glycyl radicals, providing an explanation for the observation whereby load-bearing cartilage are first to pigment in AKU. The initial kinetic barrier for glycyl radical formation explains why cartilage at different sites acquire pigmentation at different rates. The elevated HGA levels provide an environment that is especially susceptible to further oxidative stress, ultimately resulting in ochronosis and loss of cartilage function.