Serum levels of OPG and RANKL and their clinical correlations were analyzed in 66 newly-diagnosed patients with multiple myeloma (MM). RANKL and RANKL /OPG ratio were significantly increased in advanced clinical stages and high grade myeloma bone disease (MBD), while OPG showed a tendency to decrease. Renal failure modified the expression of OPG. RANKL and RANKL/OPG ratios are informative markers for myeloma tumor burden and MBD.