Molecular mechanisms, current management and next generation therapy in myeloma bone disease

Abstract

Multiple myeloma (MM) bone disease is a major cause of morbidity and mortality in MM patients and persists even in patients in remission. This bone disease is caused by an uncoupling of bone remodeling, with increased osteoclast and decreased osteoblast activity and formation, culminating in lytic bone destruction. Bisphosphonates are the current standard of care but new therapies are needed. As the molecular mechanisms controlling MM bone disease are increasingly well understood, new therapeutic targets are extensively explored in the preclinical setting and initial clinical trials with novel compounds now show promising results. In this review, we will provide a comprehensive overview of the biology of MM bone disease, summarize its current clinical management and discuss preclinical and clinical data on next generation therapies.

Keywords:

• Multiple myeloma
• bone disease
• bisphosphonates
• novel therapies
• clinical trials

Acknowledgements

Parts of this article were published in the March 2017 issue of the Belgian Journal of Hematology [151].

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1323272.

Additional information

Funding

This work has been supported by grants from the Belgian Foundation against Cancer, the Fonds National de la Recherche Scientifique (FNRS), Fonds Léon Fredericq and Fonds Spéciaux de la Recherche – University of Liège. Joséphine Muller and Roy Heusschen received a fellowship from Télévie-FNRS and Frédéric Baron is senior research associate of the FNRS Belgium. Eline Menu is supported by the AXA Research Fund and JC is a post-doctorate clinical specialist funded by the Belgian Foundation against Cancer.