Bisphosphonates and an Unusual Longevity
Recent analysis of a bisphosphonate treatment for osteoporosis, or age-related loss of bone mass and strength, has turned up an intriguing finding - the treatment considerably improves life expectancy in the recipients. It's not often that an effect of this magnitude turns up out of the blue in humans in this day and age:
Australian clinical researchers have noted an extraordinary and unexpected benefit of osteoporosis treatment - that people taking bisphosphonates are not only surviving well, better than people without osteoporosis, they appear to be gaining an extra five years of life. ... Out of a total cohort of around 2,000, a sub-group of 121 people were treated with bisphosphonates for an average of 3 years. When compared with other sub-groups taking other forms of treatment, such as Vitamin D (with or without calcium) or hormone therapy, the longer life associated with bisphosphonate treatment was marked and clear.
While the results seemed surprisingly good, they are borne out by the data - within the limitations of any study - and appear to apply to men as well as women. When we first looked at the figures, we thought that there had to be a fallacy, that we were missing something. One of the most obvious things might be that these are people who seek medical attention, so may be healthier and live longer. So we compared the bisphosphonate group with people taking Vitamin D and calcium or women on hormone therapy. The comparison against these other groups of similarly health-aware people simply confirmed that our results were not skewed by that factor.
In a group of women with osteoporotic fractures over the age of 75, you would expect 50% to die over a period of five years. Among women in that age group who took bisphosphonates, the death rate dropped to 10%. Similarly, in a group of younger women, where you would expect 20-25% to die over 5 years, there were no deaths.
The mechanism by which this extension of healthy life occurs is unknown. The authors of the study offer a guess relating to heavy metal deposition in bone tissue - but it is only a guess and frankly doesn't seem all that plausible, given all of the other potential candidate systems that might be influenced by bisphosphonate therapy. Whatever the mechanism, I can see this discovery being a tremendous encouragement for the industries of people who believe that great good can be achieved for human longevity through the old style development of injections, pills, and other forms of traditional medicine.
I think they're all wrong, and that the future of longevity lies in other directions - but this sort of discovery does tend to undermine that position. It's all a utilitarian and economic argument: if someone today discovers a cheap way to boost life expectancy by five years for most of the population, then obviously that is worth developing out into a product. But is it worth spending billions hunting for the possibility of a nebulous old-style medical therapy that can boost life expectancy by five years versus spending that same amount on the development of rejuvenation biotechnology? No, of course not.
Given the present systems of regulation in place in much of the world, it seems unlikely that anyone in the mainstream research community will run the obvious follow-up study on healthy older folk - despite, I'm sure, there being no shortage of volunteers should such a study take place. There is a considerable institutional and regulatory bias against the investigation and development of any form of therapy not targeted against designated diseases, and aging is not a designated disease.
It is a good thing that bisphosphonates such as risedronate are already approved drugs with a strong track record of extending life via reduction or prevention of bone fractures from Osteoporosis. These investments have already been made, approvals already secured, and the records of usage outcomes have been followed in multiple locations for more than a decade. ISTM that we have here a wonderful unintended longevity drug trial which is worthy of much closer examination.
In other studies, bisphosphonates such as Risedronate impart an anti-cancer effect by causing cell death of cancer cells. eg: Oncol Rep (2007) 18: 1291-8. "Isoprenoid-independent pathway is involved in apoptosis induced by Risedronate"
Additionally, this study:
Journal of Atherosclerosis and Thrombosis Vol. 15 (2008) , No. 3 130-137
states in part (and tantalizingly): "7-ketocholesterol significantly enhanced the calcium deposition, phenotypic change of VSMCs, and apoptosis in the presence of Pi. Treatment with RISEDRONATE, a bisphosphonate,..., completely or partially prevented the effects induced by 7kc in the presence of Pi, respectively."
This study you referenced may be pointing to an important way to increase quality and length of life in the middle/late-elderly perhaps by preventing undiagnosed cancers and/or protecting the circulatory system (heart attack, stroke etc), especially intriguing since the study showed that bisphosphonates gave a mortality advantage when compared to the general age matched population.
Despite some positive studies in regards to certain types of cancer, bisphosphonate drugs have been linked to increased bone fractures when used over a prolonged period, to jaw necrosis, and to esophageal cancer. Moreover, bisphosphonates inhibit a pathway (phosphatidylinositol 3/AKT kinase) that provides protection against Alzheimer's disease. Since bisphosphonate drugs began to be prescribed in the mid-1990s, the number of people diagnosed with Alzheimer's disease has increased by around one million people. This may be just a coincidence, but once you understand the pathways that lead to Alzheimer's disease it appears to be a cause.
it's been 5 years since that study of bisphosphonates extending lifespan. Any followup studies with larger number of subjects??
@Nestor London: Not that I'm aware of. I think the only thing happening, and even that without much energy or interest, is an investigation of possible mechanisms. See for example: