#30

Higher protein diet and lifting weights are the best osteoporosis prevention. Add some vitamin D and K2, omega-3 fatty acids.

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#31

The potent bisphosphonates are possibly associated with increased longevity. This, gives a review of the evidence in humans. Animal evidence also exists (at least for Drosophila). Estrogens could also reasonably be expected to be pro-longevity in many cases. If either of those treatments was indicated for me I wouldn’t hesitate based on longevity concerns.

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#32

Anyone check out Osteostrong? Claim bone density improvements greater than any drug or weight lifting.

#33

A brief on the way bisphosphonates work:

  • they are attaching to the bones surfaces where osteoclasts are usually active in bone destruction

  • they are killing osteoclasts

thus the effect is that less bones are destroyed (and less calcium comes into circulation)

The known side effects:

  • bones at the places where their natural turnover is the highest (jaw parts) will accumulate dead bones forming cells and after some times a quantity will become a quality - necrosis well-described in the literature

  • bones will become more fragile in unusual places - there are described fractures, specific for patients after several years on such drugs

I did not searched for the possible explanation of the idea that these drugs could have some effect for heart desease but a possible ways could be:

  • less calcium in circulation - less calcification in the plaques (this is not the reason but an indicator, perhaps a correlation and not causation)

  • osteoclast-macrophages relativity/ancestry - maybe the drugs are sporadically killing entrapped into tha plaques macrophages when hitting them in the circulation

Or maybe these guesses are too simple, and the possible way is different.

In any case, I would say - these drugs are to be avoided (unless are prescribed and seriously discussed with doctors) as well as working in phosphorus mines where similar things were discovered a century before the drugs were invented.

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#34

Osteoporosis results from the osteoblasts not being formed whilst the osteoclasts are. Ideally that would be fixed.

#35

Not personally, but just saw this on twitter…

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https://twitter.com/daly_prof/status/1629977461558763521?s=20

https://twitter.com/daly_prof

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Can We Turn Old Bones Young Again? Research Suggests Yes
#36

Hi, Alex-

I hope you are well. I got the result of your bone density scan which showed osteoporosis and low bone density. This means you are at increased risk of fragility fractures. I would like you to see one of our endocrine specialists to discuss treatment for this and placed a referral. I also would like you to get some additional testing done (testosterone level, phosphorous, thyroid) before you see one of our endocrinologists.

Ok, so I would like to ask for teriparatide over bisphosphonates, that’s the challenge…

The underlying problem with osteoporosis is excessive bone breakdown. Anti-resorptive medications Will slow bone break down, allowing for increased bone density over time. For bisphosphonates, This is safe and effective for between three and five years. For Prolia- our 10-year freedom extension trial showed that it was safe and effective for much longer durations. Taking a bisphosphonate and slowing bone resorption for too long can allow for an accumulation of micro damage within bone and may increase the risk of exceptionally rare stress fractures. The risk is 1 in 10s of thousands of taken for 5 years or less. Compare that to the risk of hip fractures (1 in 8 women), which carries a 1 in 5 chance of death within 1 year… again, if bisphosphonates are taken appropriately with a drug holiday every 3-5 years, these are reasonably effective meds.

Depends on which indication. Basically our practice is moving away from bisphosphonates completely. For osteoporosis we sometimes use zoledronic acid first-line but will often give denosumab every 6 months as first-line treatment. For osseous involvement in metastatic disease monthly denosumab is first-line all the time.

Bisphosphonates and strontium are both deceptive alignment

#38

This is easier to get insurance to cover

#39

Chances of atypical fracture are way less after 1 to 2 years of discontinuation

holy shit, this basically makes me decide on zoledronate

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#40

Ubiquinone and complex I. I may have to stop metformin if I do this

Minodronate inhibits the synthesis of FPP or GGPP, two mevalonate pathway intermediates, and as a consequence, decreases prenylation of small GTPases such as Ras and Rho[21–25]

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#41

Minodronate inhibits the synthesis of FPP or GGPP, two mevalonate pathway intermediates, and as a consequence, decreases prenylation of small GTPases such as Ras and Rho

Thanks. That likely explains the purported longevity effect.

#42

Hi Alex, could provide some color on the metformin comment?

#43

Zoledronate reduces synthesis of Coenzyme Q which is the endpoint of Complex I transport
Metformin inhibits Complex I (increasing lactate)

I don’t know how much confidence I have in the claim (metformin + statins does not seem to produce adverse effects). I’m seeing more metformin skepticism from some others lately (eg christin gloriso and peter attia). Metformin at high doses does not reduce my appetite.

But Zoledronate would also be another longevity intervention that would reduce my need for metformin. Idk, I’m still banking on metformin + rapamycin synergy

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#44

Thank you for the color!

#45

There is also scientific evidence of high calorie diet, followed by a 10 day fast being effective : The effect of short-term high-caloric feeding and fasting on bone microarchitecture - ScienceDirect

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#46

“Short-term fasting after high-caloric feeding improves vBMD, bone microarchitecture and strength estimates of the distal tibia, while short-term high-caloric feeding does not change vBMD or microarchitecture”

Wonder if it would help to do a certain refeeding approach after the fast?

#47

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https://esmed.org/MRA/mra/article/view/5138/99193547794

Zoledronic acid seems good.

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Cheap drug (Zoledronate) given once a decade slashes risk of bone fractures in older women, ‘astonishing’ Kiwi trial discovers
#48

@DrFraser do you use bisphosphonates in your practice?

#49

They call a 10-day fast “short term fasting”. What would a long fast look like? I’m not participating in any of their concentration camps!

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#50

Right now these agents aren’t on my list of things for longevity. In regard to their indications they are approved for, I’m not impressed on outcomes, as they don’t seem to do much for the life threatening outcomes (hip fractures), have excess osteonecrosis of the mandible … among other outcomes.
With the gerotherapeutics part of this - I’ve not done the deep dive yet and I’ve seen some items come across that look favorable.
I guess the reviews are in isolation, and I think there are a host of drugs/interventions I’d put up first and then is there a benefit to adding these to other agents that I have a preference for? We probably won’t know this for decades, if ever.
Anyway - I must do my research on these, and eventually there will be a blog on these. I may have a favorable or unfavorable disposition on them for aging. For osteoporosis, they get a neutral or thumbs down right now from me.

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