Osteosclerosis in idiopathic myelofibrosis is related to the overproduction of osteoprotegerin (OPG)

Abstract

The aim of this study is to investigate the mechanism of osteosclerosis in IMF in relation to OPG derangement. Plasma OPG level was assayed by OPG ELISA in 19 patients with IMF, 15 patients with other myeloproliferative disorders (MPDs), and 12 normal volunteers as controls and correlated with the degree of osteosclerosis. Furthermore, the level of OPG mRNA, in the cultured bone marrow stromal (BMS) cells of patients with IMF and anemia patients used as controls, in the presence or absence of TGF-beta1, was studied by real-time RT-PCR. The present study showed that blood OPG level was significantly elevated in patients with IMF as compared to patients with other MPDs (p < 0.01) or normal volunteer controls (p < 0.05), and there was no significant difference in the level between patients with MPDs and controls. In addition, there was a positive correlation (r=0.67, p=0.04) between plasma OPG levels and the degree of osteosclerosis. There was no difference in the OPG mRNA in patients with IMF as compared with controls even on TGF-beta1 stimulation. These results suggest that osteosclerosis in IMF may be related to overproduction of OPG and enhanced level of OPG is not due to the effect of TGF-beta1 on the BMS cells. It could be due to the effect of TGF-beta1 or other growth factors on cells other than BMS cells such as the osteoblasts.