Relationship between serum levels of vascular endothelial growth factor, hepatocyte growth factor and matrix metalloproteinase-9 with biochemical markers of bone disease in multiple myeloma.

Background: Multiple myeloma is characterized by accumulation of plasma cells in the bone marrow, with osteolysis and increased marrow angiogenesis. We studied molecules involved in angiogenesis (MMP-9, HGF, VEGF) in relation to disease stage, extent of bone destruction, and markers of bone turnover (Ntx and PICP).

Methods: MMP-9, HGF, VEGF were measured in the serum of 42 newly diagnosed myeloma patients and 24 controls with commercial ELISA kits. Urinary levels of Ntx were measured by ELISA, and serum PICP with RIA. Extent of radiological bone disease was graded into low and high score. Stage was estimated according to the Durie-Salmon criteria.

Results: HGF, VEGF and Ntx were higher in patients than controls (p<0.001). MMP-9 and PICP did not differ between patients and controls. HGF, VEGF, MMP-9 and Ntx increased significantly with disease stage (I to III, p<0.001) and PICP decreased significantly with advancing stage (p<0.05). There was a positive correlation between HGF and MMP-9 (r: 0.36, p<0.01), VEGF and MMP-9 (r: 0.38, p<0.01), Ntx and MMP-9 (r: 0.39, p<0.01) and an inverse correlation between PICP and MMP-9 (r: -0.66, p<0.0001).

Conclusions: Angiogenesis and bone destruction are closely interrelated in myeloma, and cytokine levels (MMP-9, VEGF and HGF) may be useful in monitoring progression.