Stimulation of new bone formation by the proteasome inhibitor, bortezomib: Implications for myeloma bone disease

Babatunde O. Oyajobi, I. Ross Garrett, Anjana Gupta, Alda Flores, Javier Esparza, Steve Muñoz, Ming Zhao, Gregory R. Mundy

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Impaired bone formation contributes to the lack of bone healing in multiple myeloma and there is a need for agents with bone anabolic properties to reverse the bone deficit in patients. Bortezomib, a proteasome inhibitor with antitumour efficacy in myeloma patients, enhanced new bone formation in mouse calvarial cultures; this effect was blocked by dickkopf 1(Dkk1), an antagonist of Wnt signalling implicated in myeloma bone disease. Bortezomib inhibited Dkk1 expression in calvariae and bone marrow-derived stromal cells, suggesting a novel mechanism by which bortezomib exerts its effects in bone. Clinical trials in patients with myeloma bone disease are needed to validate these results.

Original languageEnglish (US)
Pages (from-to)434-438
Number of pages5
JournalBritish Journal of Haematology
Volume139
Issue number3
DOIs
StatePublished - Nov 2007

Keywords

  • Bone
  • Bortezomib
  • Dkk1
  • Myeloma
  • Osteoblast

ASJC Scopus subject areas

  • Hematology

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