Multiple myeloma bone disease: from mechanisms to next generation therapy

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