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.
