Denosumab in the treatment of bone metastases

Abstract

Metastatic bone disease has a major impact on both the morbidity and mortality of patients. Antiresorptive bisphosphonates have revolutionized treatment and outcomes for patients with bone metastases, but pain and other skeletal complications still occur, adversely affecting quality of life and survival. Recent understanding of the bone microenvironment has highlighted the importance of RANK, its ligand (RANKL) and the decoy receptor OPG in the vicious cycle of bone resorption and destruction. Exploiting this triad led to the development of denosumab, a fully-human monoclonal antibody to RANKL. The success of this bone-directed agent in early clinical trials and favorable safety and tolerability profile led to the conduct of large multi-center randomized trials in breast, prostate, myeloma and other advanced cancers. In this review, we discuss the development of denosumab, the data that led to its licensing for patients with bone metastases and the future for bone-directed therapies. Keywords: bisphosphonate • bone-directed therapy • bone metastases • denosumab• OPG • RANK • RANKL. Metastatic bone diseaseDenosumab in the treatment of bone metastases

Breast-Cancer Adjuvant Therapy with Zoledronic Acid

“…1 Thus, targeting bone-cell function provides a potential additional approach to preventing bone metastases as a component of standard adjuvant therapy. 2 In many in vivo models, bisphosphonates prevent or delay metastasis. 3 In addition, synergistic interactions between aminobisphosphonates and cytotoxic drugs have been shown in preclinical models.…”

Quantitative assessment of quality of life in New Zealand prostate cancer survivors: the effect of androgen deprivation therapy

“…While considerable research has focused on improving chemoradiation, surgical and pharmacological techniques to reduce side-effects and symptoms and/or maintain physical QOL in prostate cancer survivors on ADT [31,32], cancer patients and survivors may also benefit from research examining complementary therapies focusing on increasing physical activity levels or improving nutritional intake. Physical activity programs, especially those involving resistance training show much promise in improving various domains of QOL as well as body composition and physical function, thereby reducing the risk of osteoporosis, falls related fracture and cardio metabolic syndrome [33].…”

Evaluation and Management of Lower Back Pain in Oncological Patients

“…Preventing such activity may reduce metastatic invasion and spread (Orita, et al, 2011). In addition, by inhibiting bone resorption, a secondary correction of hypercalcaemia and hypercalciuria will be achieved (Woodward & Coleman, 2010).…”