It cut death from all causes by 28% in a landmark trial — and nobody could explain why. Now scientists are discovering it may be one of the most powerful anti-aging drugs ever prescribed.
In 2007, something unexpected happened inside a clinical trial at Duke University.
The study was straightforward. Researchers were testing whether a once-yearly infusion of zoledronic acid—a bisphosphonate, a class of drugs designed to strengthen bones—could prevent repeat fractures in patients who had already broken a hip. It could. The drug reduced new fractures by 35%.
But that wasn’t the surprise.
When the researchers tallied the mortality data, they found that patients who received the drug were 28% less likely to die from any cause during the study. Not just from fractures. From anything.
The finding, published in the New England Journal of Medicine, stunned the osteoporosis community. A bone drug—reducing death from all causes? The numbers were so unexpected that the lead investigators initially suspected a statistical error. It wasn’t.
Nearly two decades later, the evidence has only grown stronger. And the implications extend far beyond bone health.
Bisphosphonates have two rare side effects: atypical femoral fractures and osteonecrosis of the jaw (ONJ). What’s more, the risk increases the longer you take them. If anyone here is currently on bisphosphonates, please share your experience!
Additionally, bisphosphonates should be avoided during dental implant procedures, as they may lead to implant failure.
Not yet. I had ACDF surgery December 2025. I will likely start January 2027, and take it for a year, then take a break. I may repeat that 1 year course a couple more times when I hit my 70’s… but once I do hit my 70’s there may be more research or superior interventions, in which case I will re-evaluate. I’m speculating that these drugs are more useful later in life anyway 70’s-80’s. YMMV.
It hasn’t been tested in healthy people. Also it may have the same mode as Rapa, so I don’t know about taking both. Nobody does. Not really a no brainer.
Zoledronic acid is currently being investigated for its potential to extend lifespan and healthspan, with animal studies in Drosophila and mice showing that the drug can extend median lifespan by 14–18% and improve physical vitality. This geroprotective effect is believed to be mediated by the inhibition of the enzyme farnesyl pyrophosphate synthase (FPPS) , which reduces oxidative stress and senescence-associated inflammatory markers independent of its bone-protective actions.
While retrospective human data suggests that patients treated with zoledronic acid for osteoporosis experience reduced mortality rates and fewer deaths from pneumonia and cardiovascular events, clinical trials specifically using the drug for longevity extension in humans have not yet been completed. Consequently, while the drug is already approved for annual intravenous infusion to treat osteoporosis, its use specifically for life extension remains experimental and is currently the subject of ongoing repurposing research.
Mechanism : Inhibits FPPS in the mevalonate pathway, reducing cellular senescence and DNA damage.
Animal Evidence : Extended lifespan in flies and improved grip strength in aged mice.
Human Observational Data : Associated with lower all-cause mortality in postmenopausal women receiving annual 5 mg infusions for bone health.
Current Status : Approved for osteoporosis; longevity application is under study for futur toe repurposing
As posted countless time…
“If you wait until you are ready, it is almost certainly too late.” Seth Godin
Thanks for sharing this article. Although the longevity claims (“one of the most powerful anti-aging drugs ever prescribed”!) seem to be overstated, the evidence encourages me to follow my physician’s advice for Reclast infusion for osteoporosis. I’ve already stopped Rapamycin on my doctor’s advice, so it’s good to know that zolendrenic acid may also address Alzheimer’s risk through a different mTOR pathway.
I took Bisphosphonates and in a couple of months my jaw ached like nothing I had ever experienced. I was told that the drug has that effect in 1-2% of people. But I don’t believe I that I am 1-2% of anything. I don’t believe my response was rare. I’d be careful.
I dont know how safe as promising as it is. On my Inspire forum for OP there have been some pretty scary experiences of it first hand. In fact because of that, I have decided if ever diagnosed (and I am very petite so higher risk) I rather not take it - I am super sensitive to drugs and vaccines so probably will fall into the adverse event category.
NOTE About the Article: “The evidence discussed is primarily derived from older adults with osteoporosis and from cohorts of patients who have sustained fragility fractures. These groups have higher mortality risk than age-matched controls, and some studies report lower mortality with bisphosphonate treatment, mainly linked to fracture reduction rather than a proven direct survival effect.”- from ChatGPT.
Here is a ChatGPT summary and opinion of the Substack Article:
The Substack article likely extends from “reduced mortality after fractures” to a broader
“possible lifespan extension” narrative. That extrapolation is more speculative than the underlying evidence. Important nuance from the original literature:
● Strong evidence:
○ Bisphosphonates reduce osteoporotic fractures.
○ Hip-fracture prevention itself lowers mortality risk.
○ Post-fracture patients on therapy often survive longer.
● Much weaker evidence:
○ That these drugs directly slow biological aging.
○ That healthy younger people would live longer taking them.
○ That risedronate itself is a “longevity drug.”
Personally, I had a hip fracture a year ago and was prescribed a bisphosphonate. After research I decided it was not a good drug for me because it alters bone metabolism by stopping bone breakdown which can lead to an accumulation of greater bone density, but consisting of weaker bone structure. The increased bone density is bone that the body would normally recycle because it needed to be recycled. The ways to increase bone density naturally are to use HRT to get hormone levels into the normal range, perform high intensity impact exercises, and consume adequate nutrition (protein, calcium foods, vitamin D, etc.).
I also had dental implant surgery after the hip fracture. Had I starting taking a bisphosphonate the dental surgeon would not have accepted me as a patient. In his discussion with me he noted potential problems such as necrosis of the jaw and implant failure even years after having stopped taking a bisphosphonate.
It’s possible there could be some action other than increasing bone density for the drugs mentioned, but I did not get that from the article plus I see disadvantages as being too great for me. As usual, this is just one person’s opinion.
I recently had some dental work and the doc asked if I’d ever taken any of these drugs - I had taken 3 or 4 fosomax 20 years ago and he said there will always be some in the body - that sure surprised me. My old TMJ doc worked with people who got necrosis of the jaw and those pictures were enough for me to stay away. I did have a bad break of femur 6 years ago and never fully recovered - DEXA at that site was -1.9, not super bad but came down really hard. I’ve never understood though why I’m more at risk for a fall now because I’ve had a fall - had I not gone for a walk that day or stepped on that pebble I would still be fall free and lower risk - makes no sense to me, unless that statistic is based on people who haven’t fully recovered and thus their gait is off?