Abstract
Bone disease, including osteolytic lesions and/or osteoporosis, is a common feature of multiple myeloma (MM). The consequences of skeletal involvement are severe pain, spinal cord compressions, and bone fractures, which have a dramatic impact on patients’ quality of life and, ultimately, survival. During the past few years, several landmark studies significantly enhanced our insight into MM bone disease (MBD) by identifying molecular mechanisms leading to increased bone resorption due to osteoclast activation, and decreased bone formation by osteoblast inhibition. Bisphosphonates were the mainstay to prevent skeletal-related events in MM for almost two decades. Excitingly, the most recent approval of the receptor activator of NF-kappa B ligand (RANKL) inhibitor, denosumab, expanded treatment options for MBD, for patients with compromised renal function, in particular. In addition, several other bone-targeting agents, including bone anabolic drugs, are currently in preclinical and early clinical assessment. This review summarizes our up-to-date knowledge on the pathogenesis of MBD and discusses novel state-of-the-art treatment strategies that are likely to enter clinical practice in the near future.
Highlights
Multiple myeloma (MM) is the second most common hematological malignancy in adults with a median age of diagnosis of approximately 70 years
In addition to bisphosphonates, which represented the standard of care for MM bone disease (MBD) during the last two decades, the receptor activator of NF-kappa B ligand (RANKL) inhibitor, denosumab, was approved in January 2018 for patients with active MM, providing a safe alternative to bisphosphonates in case of compromised renal function
Results of the Medical Research Council (MRC) IX and “468” trials indicate that treatment with bone-modifying agents (BMA) provides a survival advantage for patients with active
Summary
Multiple myeloma (MM) is the second most common hematological malignancy in adults with a median age of diagnosis of approximately 70 years It accounts for 1% of all cancers, with a yearly mortality rate of 4.1/100,000 [1]. In the absence of CRAB features, one or more of the following MM defining events is needed: plasma cell (PC) infiltration of ≥60% of the BM, free light chain ratio ≥100, and ≥1 magnetic resonance imaging (MRI) lesion ≥5 mm in size. These symptoms and signs are absent in premalignant stages of MM, including monoclonal gammopathy of undetermined significance (MGUS) and smouldering myeloma (SMM) [2]. Potential future therapeutic strategies for MBD are discussed
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