Controversies in the use of new bone‐modifying therapies in multiple myeloma

Abstract Bone‐modifying therapies are essential in the treatment of patients with multiple myeloma. Zoledronic acid is preferred over other bisphosphonates due to its superiority in reducing the incidence of skeletal‐related events and improving survival. The anti‐receptor activator of nuclear factor‐κΒ ligand (RANKL)‐targeted agent denosumab has shown its non‐inferiority compared to bisphosphonates in preventing skeletal‐related events among newly diagnosed patients with myeloma bone disease. Denosumab may confer a survival benefit in patients eligible for autologous transplantation. Denosumab may present a safer profile for patients with renal impairment. Discontinuation of bone‐directed therapies can be considered for patients with deep responses and after an adequate time period on treatment; however, a rebound effect may become evident especially in the case of denosumab. Three‐monthly infusions of zoledronic acid or at‐home denosumab administration should be considered during the coronavirus disease 2019 (COVID‐19) pandemic. Measures to prevent hypocalcaemia, renal toxicity and osteonecrosis of the jaw are important for all bone‐modifying agents.