Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kappaB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma

Br J Haematol. 2006 Dec;135(5):688-92. doi: 10.1111/j.1365-2141.2006.06356.x.

Abstract

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-kappaB 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.

MeSH terms

  • Acid Phosphatase / blood
  • Adult
  • Aged
  • Aged, 80 and over
  • Alkaline Phosphatase / blood
  • Biomarkers / blood
  • Bone Remodeling / drug effects*
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Case-Control Studies
  • Collagen Type I / blood
  • Diphosphonates / therapeutic use
  • Female
  • Humans
  • Imidazoles / therapeutic use
  • Intercellular Signaling Peptides and Proteins / blood*
  • Isoenzymes / blood
  • Male
  • Middle Aged
  • Multiple Myeloma / blood
  • Multiple Myeloma / drug therapy*
  • Osteocalcin / blood
  • Osteoprotegerin / blood
  • Peptides / blood
  • Protease Inhibitors / therapeutic use*
  • Pyrazines / therapeutic use*
  • RANK Ligand / blood*
  • Recurrence
  • Statistics, Nonparametric
  • Tartrate-Resistant Acid Phosphatase
  • Zoledronic Acid

Substances

  • Biomarkers
  • Boronic Acids
  • Collagen Type I
  • DKK1 protein, human
  • Diphosphonates
  • Imidazoles
  • Intercellular Signaling Peptides and Proteins
  • Isoenzymes
  • Osteoprotegerin
  • Peptides
  • Protease Inhibitors
  • Pyrazines
  • RANK Ligand
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Bortezomib
  • Zoledronic Acid
  • Alkaline Phosphatase
  • ACP5 protein, human
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase