Management of metastatic bone disease in the elderly with bisphosphonates and receptor activator of NF-kB ligand inhibitors: effectiveness and safety

Abstract

The life expectancy of Western populations has risen in the last few decades, resulting in a steep increase in the number of elderly cancer patients. Metastatic bone disease (MBD) is an important problem in such patients as it is associated with the development of skeletal-related events (SREs), such as fractures and spinal cord compression. These complications do not only deteriorate the quality of life of affected patients, but can also reduce expected survival. Due to the fact that elderly patients have an increased risk of SREs, maintaining bone health and implementing effective treatments for managing MBD is of vital importance. Bisphosphonates have been shown to be effective in reducing the risk of SREs considerably in patients with MBD. Moreover, they have been shown to reduce pain and improve the quality of life of affected patients. Bisphosphonates should be used with caution in elderly patients due to the fact that their use can bring about renal function deterioration. Several preventive measures need to be followed in order to minimise the risk of this complication. Denosumab is a monoclonal antibody inhibiting receptor activator of NF-kB ligand and has shown superiority over zoledronic acid in reducing the risk of SREs. In the three comparative trials between denosumab and zoledronic acid, survival and disease progression were similar between the two groups. Denosumab has been shown not to affect renal function and can therefore be safely used in the elderly. Osteonecrosis of the jaws is a devastating complication that may occur after treatment with either denosumab or zoledronic acid. The incidence rates between the two are comparable and percentage differences not statistically significant. In the three randomised trials, hypocalcaemia occurred more frequently in denosumab-treated patients than in those managed with zoledronic acid, with the corresponding percentages being 5.5-13% versus 3.4-6%. In order to minimise the risk of osteonecrosis of the jaws and hypocalcaemia, all precautionary measures and treatment guidelines should be followed closely. Several studies have investigated the cost-effectiveness of denosumab versus zoledronic acid when used for SRE prevention. These studies reported contradictory results due to the application of different analytical perspectives and model parameters.