Bisphosphonates Trigger Anti-Ageing Effects Across Multiple Cell Types and Protect Against Senescence

#1

Are biphosphonates a viable intervention stragy?

BPs are associated with reduced incidence of cardiovascular diseases, cancers, diabetes and neurodegeneration.

Zoledronate altered 352 plasma proteins associated with apoptosis, autophagy, inflammation, telomere regulation, and lysosomal function in human patients after 18–36 months of treatment.
These changes included downregulation of inflammatory SASP markers such as IL-6 and NFκB, indicating suppression of cellular senescence.

In aged mice, Zoledronate shifted gene expression in heart, liver, spleen, intestine, and lung tissues to resemble that of younger animals

Pre-treatment with low-dose BPs protected cells against DNA damage-induced senescence. This was confirmed via:
Increased LaminB1 and decreased γ-H2AX and p16 expression.
Reduced SA-β-Gal staining (a senescence marker).
Improved cell cycle progression and viability.

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Rapamycin and Acarbose effect on bone health
#2

Stat pearls

Zoledronate

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#3

Many women and some men have been using medications from this group for the treatment of osteoporosis for years. Is there any data regarding anti-ageing effect of Bisphosphonates in this population?

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#4

That study mentions a 28% reduction in all cause mortality in bisphosphonate users, but it’s only observational data. I’m still not convinced it’s a good idea to take it prophylactically like rapamycin or SGLT2 inhibitors.

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#5

When seeing papers like this it makes one wonder, which method is the right one to slow or reverse aging? (As though there can only be one right way.) But then I remember how there are drugs that can work completely differently from one another to achieve a similar outcome. For example, ACE inhibitors and beta-blockers both reduce blood pressure, but in very different ways.

There may be no one right, best way to slow or reverse aging…

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#6

Thanks for initiating this topic.

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#7

I was interested in this chart that I saw earlier here and the high ranking for biphosponates by this respected longevity researcher.
It seems the discussion I’ve seen here around this drug class has been controversial.
I am considering Fosamax for my diagnosis of osteopenia (67 yo male). If there are other benefits beyond bone density so much the better.

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#8

One thing worth pointing out regarding bisphosphonates: in humans, to treat osteoporosis, say, they accumulate and bind to bone and remain in that state for years, so have a long-lasting effect on health, long after people stop taking them. It would be interesting if their anti-aging effects were similar, so that after someone takes them for a period of several months, then stops taking them, the anti-aging effects lasts for years or even decades.

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#9

I am considering taking a bisphosphonate ever since I detected osteopenia in my femur. Which one is the best? Are there any downsides?

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#10

I’m no expert but the risks I’m aware of are the small chances of osteonecrosis of the jaw and femur fractures.

My doc feels the juice is not worth the squeeze unless you are desperate and have exhausted all other avenues.

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#11

I have been considering bisphosphonates for two reasons. First, and most salient, I intend to go on low dose (7.5mg/day) pioglitazone, and pio can cause fractures because it inhibits osteoblasts without inhibiting osteoclasts. Second, well, it appears there may be some pleiotropic benefit vs health/longevity (highly speculative and context dependent).

At the same time, bisphosphonates are very tricky drugs with great downside potential. Even in my pio scenario, all they do is inhibit osteoclasts without activating osteoblasts. This means you might get better bone density, but not bone strength/health.

Researching the topic, I have reached a few conclusions. Of the readily available (non-IV) bisphosphonates, risedronate (Actonel) appears the best of the bunch.

Best to take it once a week 35mg at a time. Careful how you take it. Empty stomach. Enough time to pass through (90 minutes) - sitting up or standing, i.e. don’t lie down or it’ll burn your esophagus.

Best to take for a limited period of time, unless there are strong reasons to persist. If you are a younger person (under 70), I would consider 3-6 months or up to 1 year, not more. During that time, do NOT plan on any dental surgeries, implants or extractions. Give it at least a 6 month margin on both sides, so if you take Actonel for 1 year, effectively, 6 months before, 1 year during and 6 months after, do not plan on such dental procedures, i.e. 2 years.

Once you’ve built up bone density with Actonel, give it a break and only revisit if you get osteopenic again, at which point, you may repeat the 3-6 mo - 1 year course of Actonel.

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#12

Thank you @CronosTempi That is exactly the information I was looking for.

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#13

DeStrider,

I suggest you talk to your dentist before taking a bisphosphonate. If implant surgery is in your your future (very possible) it may be a definite problem. My specialist said he will not treat patients who’ve taken bisphosphonates. There is the very real problem of osteonecrosis that could occur with implants for patients who’ve taken bisphosphonates. There are several topics related to bone density and ways to improve it without a prescription on this site. Some of the topics have great information.

My researched opinion is that bisphosphonates inhibit osteoclasts from breaking down weak bone that needs to be broken down. Of course, the bone density will then look better, but the bone will be of poorer quality (in my opinion).

If you like video presentations I suggest “The Dr Doug Show” on YouTube. He has some excellent researched data on how to improve bone density. He does, like other YouTubers, try to sell products. But, I like his information so I don’t mind.

Just one person’s opinion,
Jay

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#14

Why do the drugs reduce fracture rates in randomized trials then by up to 50%?

#15

The majority of the post dental procedure complications are in patients with metastatic cancer and not in patients with ordinary osteoporosis/penia. Hip fractures in the elderly have a very high mortality rate the following year. It’s a question of risks and benefits, and yes these medications reduce fracture rates. In my opinion the benefits are worth the risk. Get all your dental work done first and be impeccable with your dental hygiene.