Off-Patent Osteoporosis Drug Also Found to Extend Lifespan

Zoledronate is a biophosphonate, a drug used to strengthen bones and reduce the risk of osteoporosis-related bone fractures. It is well-absorbed into the bones, so it only needs to be administered through infusion once a year.

A 2010 study had found that people who were given zoledronate after experiencing hip fractures showed slightly reduced all-cause mortality compared to a control group. Patients who took the drug were at significantly lower risk for heart arrhythmias and pneumonia.

As this is a drug that is already being given to people, the choice to go back to genetically modified fruit flies, a much simpler model of aging, may seem counterintuitive. The team chose to test these insects for two principal reasons. The first is that Drosophila flies are a common subject of studies on basic aging pathways, which the researchers wished to explore. The second is simpler: Drosophila flies lack bones, making the bone-affecting properties of zoledronate irrelevant to the study.

Giving the drug in moderate doses to middle-aged flies and found that this late administration increased lifespan in both males and females, increasing male lifespan by roughly 5% and female lifespan by 16%, and the team notes that these results are similar to rapamycin. High doses is bad.

Journals of Gerontology – Zoledronate extends healthspan and survival via the mevalonate pathway in a FOXO-dependent manner

Over recent decades, increased longevity has not been paralleled by extended healthspan, resulting in more years spent with multiple diseases in older age. As such, interventions to improve healthspan are urgently required. Zoledronate is a nitrogen containing bisphosphonate, which inhibits the farnesyl pyrophosphate synthase (FPPS) enzyme, central to the mevalonate pathway. It is already used clinically to prevent fractures in osteoporotic patients, who have been reported to derive unexpected and unexplained survival benefits. Using Drosophila as a model we determined the effects of Zoledronate on lifespan, parameters of healthspan (climbing ability and intestinal dysplasia) and the ability to confer resistance to oxidative stress using a combination of genetically manipulated Drosophila strains and Western blotting. Our study shows that Zoledronate extended lifespan, improved climbing activity and reduced intestinal epithelial dysplasia and permeability with age. Mechanistic studies showed that Zoledronate conferred resistance to oxidative stress and reduced accumulation of X-ray-induced DNA damage via inhibition of FPPS. Moreover, Zoledronate was associated with inhibition of pAKT in the mTOR pathway downstream of the mevalonate pathway and required dFOXO for its action, both molecules associated with increased longevity. Taken together, our work indicates that Zoledronate, a drug already widely used to prevent osteoporosis and dosed only once a year, modulates important mechanisms of ageing. Its repurposing holds great promise as a treatment to improve healthspan.

SOURCES- lifespan.io, Journal of Gerontology
Written By Brian Wang, Nextbigfuture.com

30 thoughts on “Off-Patent Osteoporosis Drug Also Found to Extend Lifespan”

  1. With most drugs, it is not found that they zero in on one, narrow, exact, biological effect and do just that with no other results.

    Generally, drugs affect more than one part of the biological system. They may affect a particular molecular receptor, but you probably have that receptor, or one close enough, in multiple types of tissue throughout your body.

    Usually this is called side effects.

    To choose a topical example: Astra Zeneca covid-19 vaccine can also affect the clotting system of your blood. The clotting has nothing to do with the immune system, it's just another reaction from the same complex system.

    Usually, side effect = bad. But not always.

    Aspirin. Original effect = mildly dulls pain. Side effect = reduces blood clotting… hey, this is often more useful than the pain thing.

    Tetracycline antibiotics. Original effect = kills bacteria. Side effect = reduces cytokine storm type over reactions to viral infection.

    That sort of thing.

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  2. Street-light research is a big problem in many areas.

    It is only useful if, metaphorically, you have reason to believe there are actually thousands of keys dropped over the whole carpark. In which case, sure, look in the lighted areas first. Fortunately, this isn't as rare in many areas of research as it is in a literal car park.

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  3. Actually, this article is talking about doing the testing required to put healthspan extension on the label.

    So no it's not talking about doing off-label use.

    Though, of course, there is nothing to stop someone from looking at this research and choosing to do something unsafe such as faking an osteoporosis. Which could result in their bones becoming TOO STRONG or something I guess.

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  4. I've read poetry written by an old ex-viking. (Viking meant you were going to sea, doing the raiding stuff. If you weren't actually doing that you were just a Scandinavian.)
    He was writing poems about sitting in front of the fire, his withered old feet hurting in the cold. Being left behind with the old women when the young men went out. So I'm guessing he was past the physically robust stage.

    But on the other hand, he was in the upper class. Wealthy enough to be literate. Famous enough to have his poems preserved 800 years after his death. And he was famous, he was like the last of the pagan warrior heroes.

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  5. Wait, how does an anti-osteoporosis drug help an arthropod at all? It's not like they suffer even if they have extremely low bone density…

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  6. I'd like them to use pygmy marmosets instead of or after mice. Rhesus monkeys live up to 40 years. They eat a lot of food, and take a lot of space. Pygmy marmosets are small (around 100 grams), eat much less, and live less than half as long.
    They could be genetically modified to be less stressed and happy in smaller cages. Domestication often changes a few critical genes that in turn change a lot of things. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096361/

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  7. Yes, it is likely the troop just abandoned you when you could not keep up in a hunter-gatherer society. If you don't straggle into the camp for the night, or you find the wrong camp…tiger food. Maybe they kept you around, so if anyone did get eaten by creatures out there, it would be you.
    Vikings did not like to die weak. They just paddled off to die at sea. I guess that could be a myth…I don't know. Vikings held slaves. I would think that they thought nothing of making them wipe their fanny.

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  8. "Transferring" typically means, IIRC, that you can get to and from various resting points, (Beds, wheel chairs, toilets, shower seats, car seats.) without somebody having to lift you. As long as you're capable of that, you can be wheel chair bound, and still live on your own. Once you lose that, you need living care.

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  9. It's not NO difference. If it were, there'd obviously only be one line.

    It's more of a curve squaring effect: They all die by the same date, but 1uM suppresses early mortality, while 10uM is really, really bad.

    And, while all three tests showed beneficial effects for the male fruitflies at 1um, only one of them showed any good effects for the females.

    Honestly, these are not impressive results. Much, much better results have been found for other interventions that proved to do very little for longer lived species.

    This barely suggests anything for humans, honestly. Fruit flies are terrible experimental subjects for mammalian drug trials, the best you can say is that they're cheap and convenient. They're the medical researcher's equivalent of looking under the street light for your dropped keys, because the light's better there.

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  10. Ok, let's use your phrase and say I picked the wrong phraseology, that hardly changes my point.

    This article is talking about using off-patent drugs for off-label purposes, and we just had over a years worth of people trying to claim using off-patent drug for off-label purposes was some how unsafe and unethical all because a certain politician advocated for more expirementation of said drug.

    The hypocrisy of certain cohorts knows no bounds.

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  11. If we use reductio sad absurdum living in a primitive hunter gatherer society required good physical fitness. Or more recently, Vikings had to be close to their peak performance shapes

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  12. Some of this "independent living" is contingent on technology. Someone independent today might not be 200 years ago even though they are in the same health. It was not easy to wash clothing, get water and dozens of other things we never give a second thought to. Similarly, in the future the elderly will be further empowered to extend the time that they can be independent. Robots may prepare and drones deliver prepared food for only marginally more than the cost of the ingredients in the store…perhaps less. You can't make clothing as cheaply as you can buy it today. That was not true 50 years ago.
    In Idiocracy, clothing was throwaway. That could certainly happen.
    Finances could be streamlined in the future. Some payments are already automatic. Maybe in 20 years, most people young or old, will trust AI to deal with the bills, hiring home/yard maintenance and such.

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  13. You can have a lousy quality of life and no health issues.
    Healthspan is a mostly useful concept. It is the length of life that one is healthy. 
    It certainty has issues. It is somewhat arbitrary and difficult to measure and without standardization it is difficult to compare study to study.
    Then there is poor health that has nothing to do with aging.
    And you can often recover from bad health. That means it does not necessarily "span" at all.

    One definition I found is this: "the length of adult life during which a person can perform all activities of daily living (dressing, bathing, eating, toileting, transferring) and instrumental activities of daily living (finances, shopping, transportation, food preparation, managing medications, using the telephone)." "Transferring" sounds rather vague. I am guessing this means getting around in your house? Kinda redundant.

    Does not seem to incorporate suffering, pain, itchiness, nausea, dizziness, depression, anxiety, loneliness, ear ringing (or other sensory phantoms), degradation in ability to sense and inability to do the things you love. 

    And there is the issues of enduring all the side effects of medications. How do you even categorize that? The conditions are not from your health they are from these medications. 

    And there is the mater of how much time you have to devote to maintaining health. If you are an older person and must go to 5 medical treatment visits a week for a couple hours each, that sucks…probably.

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  14. Off-patent means far more than that, cupcake… https://pubmed.ncbi.nlm.nih.gov/32877182/

    Just as with these drugs talked about in this NBF article, I'm talking about using long known and well understood drugs for purposes not originally intended.

    We have a politicized media and ruling class, as well as all those people they influenced, who went apoplectic over the idea of using off-patent drugs as it applied to… COVID. It was literally claimed that these drugs were unsafe and untested, even though the medical community had long used these drugs, and knew what dosages were safe for the human body.

    When studies and anecdotal accounts from doctors either supported the use of a drug or seemed to discount the use, this same politicized cohort would reflexively discount studies or accounts that demonstrated the effectiveness of said drugs as the ramblings of conspiracy theorist or worse, or they discounted the critics of studies that supported their narrative in the same manner.

    So, imagine my surprise when one of the purveyors of the 'unsafe and untested' lines of argumentation publishes a piece which positively talks about using old drugs never intended for the purpose for which they were now being used.

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  15. Are you seeing same graphs I am? NO difference b/w control (PBS) & low dose drug & high dose worse than control.

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  16. When and from whom did it mean that? These concepts are extremely different and should not be conflated.

    'Off-patent' just means that a drug has been around for long enough that the patent wore off. Generally that suggests it has more research and safety testing behind it.

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  17. Healthspan versus life span is just a fancy way of saying 'quality of life'. Who wants to live forever if it means lying in bed drooling on yourself, and having someone change your diaper? Not me.

    Now, if they could extend life while also tripling my sex drive and give me a young, muscular body? Now we're talking…

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