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

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.