The 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‐κB 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.