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Myeloma

Increased osteocyte death in multiple myeloma patients: role in myeloma-induced osteoclast formation

Abstract

The involvement of osteocytes in multiple myeloma (MM)-induced osteoclast (OCL) formation and bone lesions is still unknown. Osteocytes regulate bone remodelling at least partially, as a result of their cell death triggering OCL recruitment. In this study, we found that the number of viable osteocytes was significantly smaller in MM patients than in healthy controls, and negatively correlated with the number of OCLs. Moreover, the MM patients with bone lesions had a significantly smaller number of viable osteocytes than those without, partly because of increased apoptosis. These findings were further confirmed by ultrastructural in vitro analyses of human preosteocyte cells cocultured with MM cells, which showed that MM cells increased preosteocyte death and apoptosis. A micro-array analysis showed that MM cells affect the transcriptional profiles of preosteocytes by upregulating the production of osteoclastogenic cytokines such as interleukin (IL)-11, and increasing their pro-osteoclastogenic properties. Finally, the osteocyte expression of IL-11 was higher in the MM patients with than in those without bone lesions. Our data suggest that MM patients are characterized by a reduced number of viable osteocytes related to the presence of bone lesions, and that this is involved in MM-induced OCL formation.

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Acknowledgements

This study was supported by grants from the International Myeloma Foundation, the Italian Ministry of Health (Progetti Regione Emilia Romagna), and the Associazione Italiana per la Ricerca sul Cancro (AIRC: N.G.: IG2099 No. 8530; A.N.: IG4569 and Special Program Molecular Clinical Oncology 5 per mille No. 9965). We would like to thank Professor David Roodman for critically reviewing the manuscript, and Judy Anderson and Ken Patrene for their technical support.

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Correspondence to N Giuliani.

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Giuliani, N., Ferretti, M., Bolzoni, M. et al. Increased osteocyte death in multiple myeloma patients: role in myeloma-induced osteoclast formation. Leukemia 26, 1391–1401 (2012). https://doi.org/10.1038/leu.2011.381

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