Can Probiotics Prevent Osteoporosis?

A look at the science and a new study

Olga Zarytska/Images

There is a growing body of evidence that the gut microbiome plays an important role in many aspects of human health, such as hormone health, immune function, metabolism, inflammation, and even bone health. More and more papers have been popping up about the microbiome and bone health, so much so that it feels as if we are at the start of an exponential increase in research looking at how to modulate the gut microbiome to prevent osteoporosis. 

Given this trend and considering that probiotics are already big moneymakers with little to no hard evidence of value for most conditions and menopause has proven to be a gold rush for supplement scammers, I thought it might be interesting to look at some of the data on the gut microbiome and bone health and walk through a new study. There is some really cool science here, but it’s certainly not anywhere near ready for prime time.

Gut Microbiome 101

Our intestines are host to a community of microbes known collectively as the gut microbiome, which includes bacteria, viruses, and fungi. Before we go any further, it’s important to stress that we don’t know what we don’t know about the gut microbiome. We are on the precipice of a brave new world of research, and as technology improves, we will undoubtedly learn more. Here’s a good example using the vaginal microbiome. In the early 1990s, when I was in OB/GYN, we thought it was lactobacillus acidophilus all the way for vaginal health. This was the golden ticket for vaginal health. And then DNA technology became a thing, and all of a sudden, we could identify bacteria we had no idea existed in the vagina because it couldn’t be cultured in a lab. Now, we know a lot more about the vaginal microbiome, and one of those things is that lactobacillus acidophilus isn’t a big deal; it was just easy to grow in the lab, but we couldn’t know that until the technology had advanced far enough to figure that out. Think of our current knowledge of the microbiome as the first few maps of a new world, and we have no idea how complete the maps are or what we may discover as exploration proceeds.

It seems that a healthy gut microbiome is diverse, and while there are communities of bacteria that are associated with a healthier microbiome, people can have quite different microbiomes and still be healthy. The best thing for a diverse microbiome seems to be a fiber-rich diet, and a typical “Western” diet is probably the least healthy as far as the microbiome (and almost every health metric, really) is concerned. The microbiome can change throughout the day and also have seasonal variations, and can also change positively in response to exercise. The microbiome also changes with age. In one study, people whose microbiome changed the most with age had better blood markers of health, were more mobile, and were overall in better health. This suggests that what is good for you microbiome-wise at age 20 or 30 might not be at age 70. But it is also important to remember that a lot of what we know is observational data, and healthier people might move more, make more meals at home, or take fewer antibiotics or other medications, which could result in their microbiome being different. 

While some studies suggest that the gut microbiome may become less diverse with menopause, the data is conflicting. A recent study, albeit a small one, looked at the microbiome of women before and after their ovaries were removed and found there was no change in bacterial diversity. Whether the women took hormone replacement or not also didn’t impact their microbiome. Most microbiome studies on menopause are painfully small, so it’s really important not to jump to conclusions. We need more work here.

There are so many unknowns with the microbiome that it’s important to be highly skeptical of bold claims.  

The Gut Microbiome and Bone Health

The link between the gut microbiome and bone health is often called the “gut-bone axis,” which sounds like a strategic alliance between regions in an alternate timeline of Earth. But really, a strategic alliance is a good way of thinking about how our organs interact. But how can the bacteria in your gut affect your bones? The very idea seems fantastical. 

And that’s the great thing about science: it can explain events that seem fantastical (with enough funding, that is). 

Research on the gut-bone axis kicked into high gear about 10 years ago with studies on germ-free mice, which are mice without a microbiome. It turns out that germ-free mice have better bone density than mice with a regular microbiome, and when germ-free mice receive a fecal transplant from regular mice, their bone mass decreases and becomes like regular mice's.

Fantastical, indeed!

But why? How?

The protective impact of the absence of gut bacteria wasn’t related to estrogen levels. The proxy for this was the weight of the uterus, which was the same for germ-free and regular mice (apparently, it’s challenging to obtain estrogen levels in mice, a tidbit I am tucking away for when I come up with my Menses and Menopause Trivia Game). Interestingly, calcium absorption was also the same in germ-free and regular mice, so that, too, was not the mechanism behind an increase in bone mass. The impact of the gut microbiome on bone health appeared to be via changes in the immune system that ultimately reduced levels of TNF-α (tumor necrosis factor-alpha), a signaling molecule that stimulates osteoclasts, cells that break down bone. If the signal to break down bone is reduced, the result is more bone.

Interestingly, when germ-free mice have their estrogen removed, either with medication or their ovaries removed, they still don’t lose their bone mass. This doesn’t mean we should be wiping out microbiomes to prevent osteoporosis, but it does suggest the gut microbiome poses a potential avenue for preventing osteoporosis. The fact that germ-free mice with menopause don’t develop poor bone health makes sense when you consider that a major mechanism of menopause bone loss is due to an increase in TNF-α. Estrogen inhibits TNF-α, so in menopause, without the suppressive effect of estrogen on that inflammatory pathway, we see osteoclast activity picking up and accelerated bone loss. Going back to the germ-free mice, reducing estrogen wouldn’t negatively affect bone health because TNF-α was already suppressed given the lack of a microbiome. So fascinating!

This is the kind of basic science research that is needed to move forward in designing therapies. So, the next question is, can a therapy be designed to alter the microbiome so that osteoporosis can be prevented without major risks?

The Most Recent Study

Researchers from Sweden evaluated the impact of two different doses of the probiotic Limosilactobacillus reuteri ATCC PTA 6475 (L reuteri) daily for two years vs. placebo in a randomized controlled trial for bone health. This probiotic was chosen because, in previous studies, it reduced bone loss in a mouse model and also in a study of older postmenopausal women, although the magnitude of the effect was not large. 

As a side note, it is great to see a study for a supplement that lasted for two years. Too often, these studies are short-term, so even when the results are positive, they don’t really mean much. Another good thing about this study is the investigators used bone density, not just blood tests that evaluate bone turnover, which is a proxy for bone health (less turnover is a good sign). While these blood tests are valuable, what we really want to see is changes in bone density (and also, in an ideal world, a reduced risk of fracture). The researchers also examined protein and calcium intake, which could affect bone mass. 

The overall results showed no protective effect of the probiotic on any marker of bone health. However, one finding of note is that those with an increased BMI had an improvement in bone density, with both the high and low-dose probiotics, less so at one year but more significantly by the end of the second year. The magnitude of the effect increased with increasing BMI. This is an interesting finding as gut dysbiosis is more common among those with obesity, and taken together with results from another study showing some benefit for bone health with the same bacteria for women ages 75-80, who statistically are more likely to have gut dysbiosis, one hypothesis that could be generated is the probiotic L. reuteri may not be helpful for those with a diverse microbiome, but could be helpful for bone health when there is dysbiosis (an imbalance or disruption of the microbiome). The researchers appropriately caution that these results are exploratory at best. This is data on which to build more studies, not run out and slap together a supplement to sell (although it wouldn’t surprise me if someone did that). 

What Does This Mean for Me?

First, it does not mean anyone should take a probiotic for bone health! 

Most human data on the microbiome and bone health is observational, so we must be careful before creating new treatment protocols. While we do have some good lab science that shows inflammation that negatively affects bone can originate in the gut, how to use that information to actually protect bone health requires quality randomized trials. First of all, you don’t want to waste money on probiotic supplements that can’t help. But more importantly, probiotic supplements are not risk-free. For example, people who are immune suppressed can develop serious infections from the bacteria in probiotics. When people take probiotics after a course of antibiotics to try to “re-set” their microbiome, what typically happens is the gut gets colonized with the probiotic bacteria, which paradoxically delays the return of the baseline, native bacteria (not considered a good thing). And there is some literature that suggests some probiotics can carry genes for antibiotic resistance, which could theoretically increase antibiotic resistance. 

Instead of spending hundreds of dollars to test your microbiome and/or on probiotics, based on what we know at this time, the best way to cultivate a healthy microbiome for bone health is the eternally unsexy and, hence, less Instagramable advice of sticking to a diet high in fiber (with an emphasis on protein sources from plants and fish) that also includes fermented foods, quit smoking, only take antibiotics when needed, and of course, exercise. 

In the meantime, I will sit back and hopefully (funding and researchers willing) watch this exciting new research unfold.

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