Osteolytic bone disease is the most common complication of multiple myeloma, 
resulting in skeletal complications that cause significant morbidity and 
mortality. Currently, bisphosphonates (BPs) are the mainstay for the treatment 
of myeloma bone disease. Zoledronic acid which has been found to be superior to 
clodronate, both in terms of reduction of skeletal-related events (SREs) and 
survival, and pamidronate are used for the management of myeloma-related bone 
disease. Patients with active disease (not in CR or VGPR) should receive BPs 
(especially zoledronic acid) even after two years of administration. 
Radiotherapy and surgical interventions can also be used for specific 
conditions, such as pathological fractures, spinal cord compression or 
uncontrolled pain. The better understanding of the biology of myeloma bone 
disease has led to the production of several novel agents, such as denosumab 
(targeting RANKL), sotatercept (activin-A antagonist) and romosozumab (targeting 
sclerostin) that appear very promising and have entered to clinical development.