Monoclonal antibodies against RANKL and sclerostin for myeloma-related bone disease: can they change the standard of care?

Introduction: Over 80% of the patients with multiple myeloma (MM) develop myeloma bone disease (MBD) during the disease course. The clinical consequences include serious skeletal-related events (SRE) that impact survival and quality of life. Bisphosphonates are the mainstay in the treatment of MBD. Currently, new therapeutic strategies are being introduced and broaden the therapeutic options in MBD. Areas covered: The purpose of this review is to summarize the current clinical management of MBD and present novel data regarding monoclonal antibodies against the receptor activator of NF-kappa B ligand (RANKL) and sclerostin that may change the clinical practice. Expert opinion: Our better understanding of the pathophysiology of MBD has identified several factors as potential therapeutic targets. Recent data have shown that the RANKL inhibitor denosumab constitutes a new promising option. The non-inferiority compared with bisphosphonates in terms of SRE prevention, the potential survival benefit, the convenience of subcutaneous administration, and the favorable toxicity profile makes denosumab a valuable alternative for physicians in the current treatment of MBD. Anti-sclerostin antibodies are currently under clinical development. Further investigations are needed to address open questions in the field including the value of anabolic agents combined with anti-resorptive and anti-MM drugs in MBD.