Our large, multicenter trial showed that the non-stem-cell toxic DRC regimen is an active, well-tolerated treatment for symptomatic patients with WM.

Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-jB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma Bortezomib is a proteasome inhibitor that is currently indicated for patients with multiple myeloma (MM) who have received at least one prior therapy. Although the anti-myeloma effect of bortezomib has been clearly demonstrated, its effect on bone metabolism is still unclear. In addition to increased bone resorption, bone formation is suppressed in patients with myeloma (Silvestris et al, 2004). There are recent reports that bortezomib may increase serum alkaline phosphatase activity, which is consistent with enhanced osteoblast function (Shimazaki et al, 2005;Zangari et al, 2005). However, knowledge of the molecular mechanisms that are involved and the effect bortezomib also has on bone resorption is still lacking. Dickkopf-1 (DKK-1) protein is an inhibitor of Wnt signalling that participates in osteoblast dysfunction in MM (Tian et al, 2003). The receptor activator of nuclear factor-kappa B ligand (RANKL), RANK and osteoprotegerin (OPG) system is considered the final mediator of osteoclastogenesis as well as osteoclast activation in myeloma [Terpos et al, 2003a]. Therefore, this study aimed to evaluate the effect bortezomib has on RANKL and DKK-1 serum levels in MM patients and determine if this correlates to markers of bone metabolism. Patients and methods PatientsThirty-four myeloma patients who had relapsed after previous therapies were evaluated ( SummaryThe effect of bortezomib on bone remodelling was evaluated in 34 relapsed myeloma patients. At baseline, patients had increased serum concentrations of dickkopf-1 (DKK-1), soluble receptor activator of nuclear factor-jB ligand (sRANKL), sRANKL/osteoprotegerin ratio, C-telopeptide of type-I collagen (CTX) and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b); bone-alkaline phosphatase and osteocalcin were reduced. Serum DKK-1 correlated with CTX and severe bone disease. Bortezomib administration significantly reduced serum DKK-1, sRANKL, CTX, and TRACP-5b after four cycles, and dramatically increased bone-alkaline phosphatase and osteocalcin, irrespective of treatment response. This is the first study showing that bortezomib reduces DKK-1 and RANKL serum levels, leading to the normalisation of bone remodelling in relapsed myeloma.

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