Researchers analyzed the critical role osteocytes play in the development of myeloma bone disease (MBD), a major complication in multiple myeloma (MM). Osteocytes contribute to increased osteoclast activity, reduced osteoblast function, and creating an immunosuppressed bone marrow microenvironment. This disruption in bone turnover leads to bone loss and various skeletal complications. MM cells cause osteocyte apoptosis, altering the bone marrow environment and promoting MM growth. Osteoclast activity increases due to dysregulated RANK/RANKL and Notch signaling pathways, while osteoblast activity is suppressed by factors like sclerostin and DKK-1, which inhibit bone formation.

Researchers noted that bisphosphonates, the traditional treatment for MBD, bind to bone areas and inhibit osteoclastogenesis. Denosumab, a monoclonal antibody that binds to RANKL, has shown efficacy in preventing SREs and may be preferable for patients with renal insufficiency. Despite these advancements, ongoing research into the biology of MBD could lead to new therapies that both reduce MM burden and restore bone metabolism.

Reference: Terpos E, Ntanasis-Stathopoulos L, Dimopoulos M. Myeloma bone disease: from biology findings to treatment approaches. Blood. 2019; 133 (14):1534–1539. doi: https://doi.org/10.1182/blood-2018-11-852459.