Why do myeloma patients have bone disease? A historical perspective

Blood Rev. 2020 May:41:100646. doi: 10.1016/j.blre.2019.100646. Epub 2019 Nov 29.


The question of how myeloma cells cause destruction of skeletal tissue has interested scientists for many years, and knowledge in this field has developed in parallel with the understanding of physiological bone remodeling. The identification of bioactive proteins of the cytokine class during the last decades of the previous century and mapping of their role in the regulation of anabolic and catabolic processes in bone, led to a sequence of hypotheses about how the same peptides also could be involved in myeloma-driven bone destruction. Although bone remodeling is now understood in detail, there is still no clear unified theory of how myeloma cells degrade bone. The reason for this could be that there is no single mechanism that is active in every patient. The common trait is possibly that myeloma cells benefit from bone destruction per se, and the strategy they use to accomplish this vary between patients.

Keywords: Activin A; BDNF; Bone disease; CCL3; Cancer; DKK1; FRZB; GDF-15; HGF; IL-1β; IL-6; MIP-1α; MIP-3α; Multiple myeloma; OPG; RANKL; SFRP-3; SOST; Sclerostin; c-Met.

Publication types

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

MeSH terms

  • Animals
  • Bone Diseases / etiology*
  • Bone Diseases / metabolism
  • Bone Diseases / pathology
  • Cytokines / analysis
  • Cytokines / metabolism
  • Humans
  • Multiple Myeloma / complications*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteoclasts / metabolism
  • Osteoclasts / pathology


  • Cytokines