[Markers of bone metabolism in multiple myeloma patients switched from zoledronic acid to denosumab]

Rinsho Ketsueki. 2014 Nov;55(11):2271-6.
[Article in Japanese]

Abstract

To date, intravenous drip infusion of zoledronic acid (ZA) has mainly been used for the treatment and prevention of skeletal-related events (SRE) in patients with multiple myeloma (MM). Recently, denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL), has also become available for the same purpose, but little is known about the impact of switching from ZA to denosumab. Herein, we present a retrospective study on bone metabolic markers in 10 MM patients initially treated with ZA and then switched to denosumab. Consequently, the levels of bone resorption markers, tartrate-resistant acid phosphatase 5b (TRACP-5b) and serum type-I collagen crosslinked N-telopeptide (sNTX), significantly decreased after denosumab treatment, while the levels of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), showed no apparent changes. No patient developed severe hypocalcemia with denosumab treatment. In one patient not given chemotherapy, the M-protein level increased after switching from ZA to denosumab and plateaued when ZA was restarted. Based on this finding, we anticipate that switching from ZA to denosumab would exert a stronger suppressive effect on osteoclasts, but the anti-myeloma activity of ZA must be taken into consideration.

MeSH terms

  • Acid Phosphatase / blood
  • Adult
  • Aged
  • Aged, 80 and over
  • Alkaline Phosphatase / blood
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Biomarkers / blood*
  • Bone Density Conservation Agents / administration & dosage*
  • Bone Diseases, Metabolic / diagnosis*
  • Bone Diseases, Metabolic / drug therapy
  • Bone Diseases, Metabolic / etiology
  • Bone Diseases, Metabolic / prevention & control*
  • Bone Resorption / diagnosis
  • Calcium / blood
  • Cell Differentiation
  • Collagen Type I / blood
  • Denosumab
  • Diphosphonates / administration & dosage*
  • Drug Substitution*
  • Female
  • Humans
  • Imidazoles / administration & dosage*
  • Isoenzymes / blood
  • Male
  • Middle Aged
  • Multiple Myeloma / complications*
  • Myeloma Proteins
  • Osteoblasts / cytology
  • Osteocalcin / blood
  • Osteogenesis
  • Peptides / blood
  • RANK Ligand / immunology*
  • Retrospective Studies
  • Tartrate-Resistant Acid Phosphatase
  • Zoledronic Acid

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Bone Density Conservation Agents
  • Collagen Type I
  • Diphosphonates
  • Imidazoles
  • Isoenzymes
  • Myeloma Proteins
  • Peptides
  • RANK Ligand
  • collagen type I trimeric cross-linked peptide
  • multiple myeloma M-proteins
  • Osteocalcin
  • Denosumab
  • Zoledronic Acid
  • Alkaline Phosphatase
  • ACP5 protein, human
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • Calcium