Current Controversies in the Management of Myeloma Bone Disease

Abstract

Recent significant advances in the treatment of multiple myeloma have resulted in an improvement in median overall survival from 4.6 years, for patients diagnosed between 2001 and 2005, to 6.1 years, for those diagnosed between 2006 and 2010 (Kumar et al., 2014). However, myeloma bone lesions persist in the absence of active disease and continue to be frequent and significant causes of patient morbidity and contribute to mortality. While bisphosphonate therapy in combination with anti-myeloma therapy remains the cornerstone of skeletal disease management in myeloma, open questions regarding the optimal management of patients with myeloma bone disease remain. This article will address when to initiate and stop bone-targeted therapy in patients with monoclonal gammopathies, duration of bisphosphonate treatment in the era of more effective anti-myeloma treatment, the role of bone resorption markers in determining the dosing schedule for anti-resorptive therapy, risks and benefits of long term anti-resorptive therapy, and whether anti-resorptive therapies should be stopped to enhance the potential anabolic effects of proteasome antagonists and other anabolic agents. J. Cell. Physiol. 231: 2374-2379, 2016. © 2016 Wiley Periodicals, Inc.

The role of osteoblasts in bone metastasis

“…It therefore seems likely that the close coupling of osteoclasts/osteoblasts will make it impossible to use a single drug or a combination of drugs at the same time point, to both resorb and repair bone. It is also likely that osteoclast targeted therapies designed to prevent progression of osteolytic lesions in bone are also responsible for impaired healing and weakened bones seen in myeloma patients after administration of these treatments [28] . It is therefore proposed that a useful strategy to reverse bone loss would be to turn on osteoblast functions.…”

Epigenetic‐Based Mechanisms of Osteoblast Suppression in Multiple Myeloma Bone Disease

“…New therapies for MM have greatly improved progression‐free survival and overall survival . However, MM remains incurable for most patients, and MM bone lesions persist even after therapeutic remission of active disease . It is becoming increasingly evident that multidirectional interactions between MM cells and the surrounding bone microenvironment are the driving factors orchestrating the evolving transformations and heterogenic nature of myeloma tumors .…”

Emerging Roles of Osteoclasts in the Modulation of Bone Microenvironment and Immune Suppression in Multiple Myeloma

“…These osteolytic lesions were identified by X-rays in 1903 by Weber and whole body skeletal radiography remained the traditional gold standard for identification of lytic bone lesion. However, it does not detect early bone lesions and underestimates the extent of bone involvement ( 29 ) and low-dose computed tomography, magnetic resonance imaging, and positron emission tomography with computed tomography are now recommended for a more sensitive evaluation of myeloma patients ( 30 , 31 ).…”