Interest in additional effects of bisphosphonates beyond fracture reduction was sparked by the Horizon Zoledronic Acid hip fracture study published in 2007, where there was a 28% reduction in mortality, of which only 8% could be attributed to a reduction in subsequent fracture. We subsequently examined the effects of bisphosphonates on mortality in the Dubbo Osteoporosis Epidemiology Study and found a significant survival benefit which remained after adjustment for all confounding factors available. This benefit was also not attributable to a reduction in subsequent fracture. Several other cohort studies have been published with similar findings including some recent large registry studies. However, the problem with cohort studies is that there always remains a potential drug channelling bias where medication may be prescribed to those who are expected to survive.
More recently, there have been other studies suggesting survival benefits following bisphosphonate use in non osteoporosis settings including cancer and critically ill populations. The mechanisms for an apparent survival benefit are not completely understood but there is data to suggest that bisphosphonates may have an effect on non bone parameters such as immune function. Indeed animal studies in cancer models suggest the more potent nitrogen containing bisphosphonates may be taken up in tumour associated macrophages. In addition, their potent suppression of bone turnover may in itself affect release of potential toxic substances or inflammatory factors that have detrimental effects in a compromised individual.
This presentation will discuss some of the clinical studies where bisphosphonates have been found to have an effect on survival in both the osteoporosis setting and in the non osteoporosis setting as well as data surrounding potential mechanisms by which this effect may occur.