For example, Khosla and colleagues[23,24] reported that IGFBP-2 stimulated bone formation in patients with hepatitis C-related osteosclerosis, with this change associated with an increase in IGF-2, while an in vitro study in rats by Palermo et al[25] showed that the addition of equimolar concentrations of IGFBP-2 had a synergistic effect on IGF-2-mediated differentiation in osteoblast cells. Here, IGFBP2 is linked to osteosclerosis.