Novel Developments in the Treatment of Multiple Myeloma-Associated Bone Disease

Simple Summary Multiple myeloma is the second most common hematological malignancy, and the majority of patients have osteolytic lesions by the time of diagnosis. Bone destruction increases the risk of fractures and spinal cord compression, reduces quality of life, and is associated with increased mortality. This paper focuses on current and novel medical and surgical treatment modalities and improvements in prevention and the treatment of therapy-related complications, in particular, medication-related osteonecrosis of the jaw. A special focus reviews new promising targets in the bone marrow microenvironment.Abstract Osteolytic bone disease is present in about 80% of patients with multiple myeloma at the time of diagnosis. Managing bone disease in patients with multiple myeloma is a challenge and requires a multi-faceted treatment approach with medication, surgery, and radiation. The established treatments with intravenous or subcutaneous antiresorptives can cause debilitating adverse events for patients, mainly osteonecrosis of the jaw, which, traditionally, has been difficult to manage. Now, oral surgery is recommended and proven successful in 60-85% of patients. Patients with spinal involvement may benefit from surgery in the form of vertebroplasty and kyphoplasty for pain relief, improved mobility, and reestablished sagittal balance, as well as the restoration of vertebral height. These procedures are considered safe, but the full therapeutic impact needs to be investigated further. Ixazomib, the first oral proteasome inhibitor, increases osteoblast differentiation, and recently published preliminary results in patients treated with Ixazomib maintenance have promisingly shown increased trabecular volume caused by prolonged bone formation activity. Other novel potential treatment strategies are discussed as well.