Osteoporosis drug could have the potential to increase healthspans for all
More than half of people aged over 65 have multimorbidity, the existence of two or more chronic conditions such as osteoporosis, osteoarthritis, cardiovascular disease, COPD, cancer and Alzheimer’s. As highlighted by the Covid-19 pandemic, older people with frailty and multimorbidity have a reduced ability to respond to adverse events such as ill health, and often lose independence following major health-related incidents. Such events have significant consequences for follow up health and social care costs. If geroprotectors can be used to improve resilience in older people, the social and financial benefits would be huge.
Recently, a retrospective analysis of several clinical trials showed that patients treated with Zoledronate, a drug used in the treatment of osteoporosis, had a significant decrease in mortality rates. Among patients admitted to intensive care units, those previously treated with Zoledronate had increased survival rates despite an overall higher level of multimorbidities and older age.
Researchers in the Healthy Lifespan Institute at The University of Sheffield hypothesized that these effects were due to the ability of zoledronate to decelerate biological ageing and improve physical resilience of older organisms so that they were healthier and more able to recover from adverse events. They tested the drug’s lifespan and healthspan extending properties on Drosophila, a type of fruit fly. Fruit flies were used because their genome is 60% homologous to that of humans and they are shown to be excellent models to study how biological ageing processes affect lifespan and healthspan.
The study, published in the Journal of Gerontology shows that Zoledronate extends the median lifespan of female fruit flies by 14-18% when given from middle age. This compares favourably to Rapamycin, one of the most studied geroprotectors. A Rapamycin-like drug has been shown, in phase II clinical trial, to positively impact on the immune system in older patients by boosting their ability to improve flu vaccine responses. It also increases lifespan by 9-14% in female mice when fed late in life and improves several healthspan parameters in mice. A similar level of healthspan extension was shown in other studies testing rapamycin in fruit flies.
Studies in mammalian models are now required to better understand the effects of Zoledronate on specific tissues, and the best approach to elicit the strongest beneficial effects. Zoledronate is off-patent, available at low cost, displays a well understood safety profile with minimal side effects and is given to patients only once a year. Therefore, the researchers predict that studies seeking to widen the use of Zoledronate are likely to identify great potential for the improvement of healthspan and resilience in older people.
These trial results are very exciting. To discover that a safe and readily available drug has geroprotective properties beyond its current use means that we can fast track further testing. Geroprotectors signal a new era of medicine that could boost resilience and help us delay or even prevent the onset of multimorbidity so we can improve healthspans and quality of life, and reduce the costs of care.
Co-Director of The Healthy Lifespan Institute at the University of Sheffield
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