So, I took Fosamax, an alendronate in the bisphosphenate class, for many years. I have severe osteoporosis, T score at femur at negative 3.7 and a couple of small fragility fractures to seal the deal. But bisphosphenates can cause atypical femur fractures, and some of the stronger bisphosphenates such as zometa can cause osteonecrosis of the jaw. I have eschewed these drugs for decades. Took HRT, and now, raloxifene.
But wait: Nil Barzilai published a paper stack ranking the most powerful longevity drugs. SGLT2’s were at the top along with (can this be?) alendronates!
And what about those SGLT’s? Working my way toward deciding to take for overall protections, not particularly glucose. And then I came across studies that suggest that SGLT’s can cause fractures! Not clearly understood, and canagliflozin seems to be the primary offender. But – given where I am with osteoporosis . . . .?
And then add lithium into the mix. Strong suggestions it is effective for preserving cognition. And SGLT’s tend to remove lithium from the body.
So, SGLT’s are at the top of Barzilai’s and many others’ lists as a good-for-you-with-no issues (except the possibility of UTI’s). And yet – should I take a drug that might cause a fracture when I already have severe osteopososis? And that might flush out the 5 mg of lithium I take every day to prevent/forestall AD?
Should I go back on an alendronate? When I consider the “order of worries,” I have to put osteoporosis at the top – the bone numbers are really bad, whereas at the moment, lipids and glucose are about where they should be. I cannot believe I am considering restarting Fosamax. What to do???
How is your eGFR? If it’s high, no need to add an SGLT2i because your weakest link isn’t your kidneys but your bones so you should put your focus on that.
Whatever your doctor recommends. Make sure your teeth is great before starting them if you do so.
Zoledronic acid by injection is good under doctor or nurse supervision last time I checked. I think you’re supposed to be taking calcium+Vit D before and after. And hydrate well during before and after for kidneys.
Do strength training, exercise, balance training, and avoid going out walking when it’s slippery outside for fall risk etc. Get a hip protector.
Well, you have to look at the evidence objectively. The evidence seems to clearly indicate that bisphosphonates are helpful in osteoporosis in post menopausal women. It really shouldn’t be much of a surprise that drugs that were developed to help with osteoporosis help with osteoporosis. We have decades of clinical experience with bisphosphenates, and the verdict is clear: these are extremely helpful drugs in osteoporosis. The choice of the patient is important. A postmenopausal woman with osteoporosis? That’s the target right there. That’s what the indication is.
Now, are these perfect drugs. No. The question is really of risks and benefits. Yes, there are atypical fractures, bone growth (osteoblasts) and remodeling is inhibited, there are osteonecrosis dangers with the jaw. But you have to ask what is the ultimate risk vs reward. There is one way to judge: ACM. Bisphosphonates not only help with osteoporosis, they reduce all cause mortality. Let me repeat: bisphosponates reduce all cause mortality. What this means is whatever the risks of these drugs, those risks do not increase your chance of dying, instead, they lower your chance of dying regardless of what they do for your bones. Let’s say they harm your bones - but you live longer with them than without them, so clearly those “side effects” don’t cause you to die sooner. And, btw., we actually know that postmenopaual women with severe osteoporosis do better with their bones on these drugs than without these drugs. What more do you want?
Reduced All-Cause Mortality With Bisphosphonates Among Post-Fracture Osteoporosis Patients: A Nationwide Study and Systematic Review
Role of Bisphosphonates in Postmenopausal Women with Osteoporosis to Prevent Future Fractures: A Literature Review
Having said that, choosing the appropriate patient is important. If you are particularly vulnerable to the negative side effects of these drugs, you may be forced to skip them. So, as an example, if you are about to have extensive dental work that involves extractions, implantations and bone surgery, then you should not be on bisphosphonates. Are you someone for whom these drugs would be contraindicated for other reasons, whether because of DDI or any other reason.
This is completely apart from any possible pleiotropic benefits of bisphosphonates in longevity (or speculated CV benefits) per Nir Barzilai. I don’t think this enters into this calculation when you are taking them exclusively for severe osteoporosis.
I’m not sitting here and advising you to take these drugs - I am not a doctor and can offer no medical advice. All I’m doing is reasoning and highlighting information to the best of my ability. Obviously, whatever you do, you should do in strict cooperation with your physician, including any drug you may want to take. When I looked at the literature, it seemed to me risendronate was the best bet (unless you are up for IV), but each situation is individual, which is why you really need to do it under your physician’s supervision.
As to SGLT2i causing bone fractures: the evidence is mixed at best (and more an issue with canagliflozin), and bone health would not be a factor for me in deciding to take say, empagliflozin or dapagliflozin.
Lithium - there’s enough smoke that seems to be some fire there. If you take other drugs, you may have to adjust the dose. Telmisartan spares lithium, SGLT2i excretes it. Ordinarily a 1-5mg/day of lithium orotate seems like a decent dose, but if taking an SGLT2i, you may want to take 10mg like Matt Kaeberlein.
In the end, again - you need to look at the literature and consider your own individual situation.
I haven’t heard him say that specifically, only that he takes 10mg/day, but that’s my speculation. He started with an SGLT2i recently, and if on average that causes a 50% lithium loss - then if you want to end up with 5mg/day, taking 10mg makes sense. At least that’s my reasoning for myself (I’m considering 10mg myself for that reason), so I thought it likely for MK too.
I keep changing my mind on my own lithium dose as I take 10mg Empagliflozin too. Currently, I am on 2mg but thinking of going back up to 5mg. The Alzheimer’s mouse study used a human equivalent of slightly less than 1mg but of course they weren’t taking an SGLT2
Yeah, I wouldn’t get too attached to the “human equivalent” in that study. I’ve seen these “equivalents” distort like crazy depending on the drug - f.ex. there really is no human equivalent for rapamycin from the mouse studies - no dose has been validated as “equivalent”. I’d rather look at whether a given molecule crosses the BBB, what action it might have, any human dose effects observed in other contexts and based on all that do a WAG as to what the dose to roll the dice on. Based on all that, I think MK is right - somewhere around 5mg. Now, 10mg is not suddenly going to abolish those effects, I think it’s pretty safe up to about 15mg or so (complete WAG!). I’d rather err slightly on the “more” than the lowest possible effective dose, because we really don’t know what that dose might be - 0.3mg, 1mg, 5mg, 10mg. I figure 10mg will still give me that effect (if it does at all in humans) and likely so will 5mg. Below that, who knows. Why gamble. So, my bottom line is to spring for 10mg if I’m aiming at 5mg given that I take 25mg empagliflozin. Eh, it’s all speculation and I have no better grounds for it than the next fella, so YMMV.
Yes, I’m on dapagliflozin and it’s for that reason I take 6mg of lithium.
I just wanted to add one thing that I’ve heard here… while an SGLT2 will lower your dose, if you are on telmisartan, it will raise your dose. I don’t believe I’ve heard how much of a multiplying effect it has.
My brother is on telmisartan, so without wanting to recommend anything risky for him, I only recommended he take 1mg.
Also, and while I don’t understand it, I’ll point out John Hemming has mentioned too much lithium might interfere with citrate transporters (I am probably not saying this correctly!)
Yes, I mentioned the telmisartan effect - though it’s not very large. And at these low doses any citrate effects are negligible, certainly insofar as renal impact.
If you only read key findings, you’d think it was worse for those without diabetes. (Someone sent this to me yesterday and said glp1s cause bone loss!)
KEY FINDINGS:
Among adults without diabetes, osteoporosis risk was slightly higher for patients prescribed a GLP-1 than for patients prescribed other weight loss medications, compared to a baseline of stable-weight patients who were prescribed weight loss medications other than a GLP-1.
Later it says:
Among groups that lost more weight, osteoporosis risk rose for those with and without GLP-1s, but the increase in risk was consistently smaller among GLP-1 users. Weight gain was associated with increased osteoporosis risk among those not on a GLP-1, while weight gain was not associated with statistically significant change in osteoporosis risk for those on a GLP-1.
I would strongly consider eating natto, Japanese fermented soybean.Natto is loaded with vitamin k2, and “nattokinase” (which is a protein but not a kinase). These things are adept at “activating matrix GLA protein” -in short, natto helps keep calcium out of arteries and in bones. It is also a potent fibrinolytic: it helps prevent the kind of clotting in the heart attack process. DO NOT EAT NATTO WHILE ON Bisphosphonates, or WARFARIN-like drugs. I actually buy and eat natto from the Japanese grocery, but I also buy nattokinase and K2 in the form of ("mk7 or Menaquinone-7), for ex. Doctors’Best brand, which also includes vit. D. And do squats. Good luck.
It depends on which study you are reading from LOL
In a large analysis of more than 146,000 adults with obesity and type 2 diabetes, GLP-1 users were found to have a 29% higher relative risk of osteoporosis over five years compared to nonusers, according to reports.
Bisphosphonates affect your jaw that it becomes incredibly difficult/impossible to do dental work. So here’s hoping your teeth are well taken care of! This is why I won’t touch this drug class
What are you talking about? Isn’t that a rare side effect? That you should reduce risk for but not assume you’ll get?
If you learned about all the rare side effects from all of the supplements you were taking (they are not elucidated because they never were studied), you wouldn’t take either of those either.
The risk appears to be 0.2%. That should be weighed against fracture risk. Risk vs. reward, total mortality and net expected quality of life, as always.
Tooth extraction while on bisphosphonates (e.g., Fosamax, Zometa) carries a risk of Medication-Related Osteonecrosis of the Jaw (MRONJ), a rare condition causing poor healing and bone necrosis. While risk is low for oral, short-term users, it increases significantly with long-term or IV use.
I’m assuming that people here will be in that significant increased risk of long term usage where the chance goes up to 0.5-1.7%. Still low, but horrible if it happens.
