The effects of bortezomib on bone disease in patients with multiple myeloma

Cancer. 2014 Mar 1;120(5):618-23. doi: 10.1002/cncr.28481. Epub 2013 Nov 18.

Abstract

Bortezomib has demonstrated substantial activity in the treatment of patients with multiple myeloma and is widely incorporated into treatment strategies across the different settings. It is interesting to note that data are accumulating to suggest that the activity of bortezomib extends beyond the tumor cell and microenvironment to encompass effects on bone metabolism. Indeed, data from both the preclinical and clinical settings have suggested that bortezomib directly stimulates osteoblast growth and differentiation, while also inhibiting osteoclast development and activity. Notably, in the clinical setting, the bone anabolic effects of bortezomib could be demonstrated by the healing of lytic lesions as noted in some patients. These results are of importance because bone disease is a hallmark of myeloma and therefore any agent that combines antimyeloma activity with positive effects on bone is of substantial interest. However, further studies are needed to establish how the agent should be used for the treatment of patients with bone disease.

Keywords: bone remodeling; bortezomib; multiple myeloma; osteolysis; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Bone Density / drug effects
  • Bone Diseases / metabolism
  • Bone Diseases / pathology
  • Bone Diseases / prevention & control*
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Boronic Acids / pharmacology*
  • Boronic Acids / therapeutic use
  • Bortezomib
  • Cell Differentiation / drug effects
  • Cell Line, Tumor / drug effects
  • Evidence-Based Medicine
  • Humans
  • Multiple Myeloma / metabolism*
  • Multiple Myeloma / pathology*
  • Osteoblasts / drug effects
  • Osteoclasts / drug effects
  • Osteogenesis / drug effects
  • Pyrazines / pharmacology*
  • Pyrazines / therapeutic use
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Biomarkers
  • Boronic Acids
  • Pyrazines
  • Bortezomib