Bone, Always Under Construction

The human body is like a large puzzle made of various parts including organs, muscles, and bones. The human skeleton consists of approximately 206 bones that support the body and protect the internal organs. Healthy bones can withstand strong and sudden movements and high pressures. Bone grows as we grow. Older bone is constantly being replaced by new bone to better support the body, repair tiny injuries that occur in everyday situations, and shape the skeleton. For bone replacement to occur, bone is digested by special bone cells called osteoclasts and rebuilt by other bone cells called osteoblasts. This process maintains the right balance within bone tissue, which is called bone homeostasis.

Around the age of 30 years, humans reach their maximum bone mass, when the skeleton is at its strongest [1]. However, bone homeostasis declines with age, resulting in a loss in the quality and amount of bone tissue. Other factors contribute to bone loss, such as a lack of exercise, smoking, and low levels of a hormone called estrogen, which occurs after women go through an age-related change called menopause.

Estrogen, An Important Supervisor At The Construction Site

Menopause is the end of a woman’s menstrual cycles, marking when she can no longer have children naturally, and it generally occurs around the age of 45. After menopause, the ovaries decrease their production of estrogen, a sex hormone important for the sexual and reproductive systems that also plays an important role in maintaining bone homeostasis. Low estrogen levels lead to an imbalance between osteoblasts and osteoclasts, which results in bone loss. Interestingly, a reduction in estrogen also influences the intestine, which can also result in bone loss.

The intestine is one of the largest organs and is essential for all body functions because it is responsible for absorbing nutrients from food. The wall of the intestine is made of cells that are arranged side by side, normally held together very tightly. The decrease in estrogen that happens after menopause reduces how tightly these cells are held together and, consequently, increases intestinal permeability (Figure 1). Intestinal permeability describes how easy it is for things to pass through the cells of the intestinal walls to get into the body. Increased intestinal permeability is like an open door for disease-causing microorganisms and the substances they produce, allowing them to pass through the intestine into the tissues and cause inflammation. Inflammation then stimulates osteoclast activity and bone destruction.

Osteoporosis: When Destruction Overcomes Construction

Healthy bone tissue has a honeycomb-like structure when viewed under a microscope. Osteoporosis is a bone disease that affects this structure and can cause a severe loss of bone mass, making bones fragile and more likely to break. The word “osteoporosis” means “porous bone,” where “porous” describes a material that has lots of small holes. In osteoporosis, there is an increase in the size of the holes and spaces in the normal honeycomb structure of bones (Figure 2).

Many things can increase a person’s risk of developing osteoporosis, including aging, not getting enough calcium or vitamin D, not getting enough exercise, smoking, and importantly, hormonal factors. Osteoporosis can occur in both men and women but, as we noted, it happens more commonly in women after menopause. The dramatic decrease in estrogen levels after menopause is an important factor that increases the risk of osteoporosis in women. In men, the sex hormone testosterone is also important for bone health, but testosterone levels decrease more slowly in men as they age, so they generally have a slower rate of bone loss compared to women.

Medications, hormone replacement therapy, and vitamins are often used to prevent osteoporosis or to treat the disease in postmenopausal women. However, the medications can have unpleasant and even dangerous side effects. Therefore, scientists have been trying to come up with new types of osteoporosis therapy, such as the use of specific bacteria.

What Are Probiotics?

Bacteria can cause many diseases, but they are also an important part of the body’s balance. The gut is home to various helpful microorganisms such as fungi, viruses, and bacteria living together in a community that helps us to digest food and protects us against certain diseases. As researchers learned more about these helpful bacteria, they discovered several types of good bacteria called probiotics, which may help to prevent and treat certain diseases, including osteoporosis. When live probiotic bacteria are eaten in adequate amounts, they can improve our health [2]. They are good guys!

Probiotics are the key to the creation of fermented foods and drinks such as yogurt, sauerkraut, cheese, and kombucha. There are records of fermented beverages from as long ago as 700 B.C.E. However, in addition to being found in fermented foods, probiotic bacteria also make up some of the normal, healthy microbes in the gut, mouth, and breast milk of humans and other animals.

Each type of probiotic bacteria can have unique health effects. For example, bacteria that are helpful for gut diseases may not be as helpful against bone diseases, and vice versa. Probiotics have been extensively studied for the treatment of gut diseases, such as inflammatory bowel disease and diarrhea. Recently, researchers have noticed that some probiotic bacteria can also be good for reducing bone loss due to osteoporosis.

How Can Probiotics Improve Bone Health?

Probiotics can reach the gut by being eaten in food or taken as pills or lozenges. Typically, they are not absorbed into the bloodstream. So, how do they affect bone tissue far from the gut? Scientists do not fully understand how this happens yet; however, there are several hypotheses, many of which are still being studied (Figure 3).

One hypothesis involves the immune system, which has cells and substances that defend the body against dangerous invaders. Sometimes, however, the immune system might be a little too active, and that overactivity can cause problems. Some substances produced by the immune system can increase the number and activity of osteoclasts, so if the immune system is too active for too long, too much bone can be broken down. Probiotics can adjust this kind of unbalanced immune reaction, settling it down to a normal level [3], which can decrease excessive osteoclast activity, protecting the bones.

Another hypothesis has to do with intestinal permeability, which we discussed earlier. Probiotics strengthen the gut barrier and prevent the bacteria and microbial products from getting into the bloodstream. This can help to prevent excessive activation of the immune system which, as we just described, can help to keep osteoclasts in check [4].

Finally, another hypothesis suggests that probiotics produce substances that help the intestine to absorb calcium. You have probably heard that calcium is important for healthy bones, so more calcium being absorbed can lead to stronger bones [3]. In addition, some probiotic bacteria produce vitamins B12 and K, which are also associated with bone health.

Conclusion

As more and more people live to older ages, osteoporosis is becoming a bigger public health issue. Recently, scientists have discovered that probiotics can help to prevent and fight osteoporosis. The exact steps by which probiotics help to improve bone health are still being investigated; however, the results so far are encouraging. Probiotics can reduce intestinal permeability, decrease the overactivation of the immune system that can lead to bone loss, and increase the absorption and production of nutrients—all of which improve bone health! It is important for scientists to continue studying the role of probiotics in osteoporosis so that they can find explanations to many unanswered questions. These little puzzle pieces are slowly coming together to form the big picture of how good bacteria can boost bone health. There is much more to learn. Pay attention to future research to see if helpful microbes can beat bone busters!

Glossary

Osteoclasts: ↑ Bone cells that digest bone tissue.

Osteoblasts: ↑ Bone cells that build bone tissue.

Bone Homeostasis: ↑ Is the process in which bone cells, like osteoblasts and osteoclasts, work together to keep the right balance of breaking down and building up bone tissue.

Menopause: ↑ Is the end of a woman’s menstrual cycles, which means she no longer has periods and can no longer have children naturally.

Intestinal Permeability: ↑ Is like a gate in our intestine walls, controlling how easily things pass through the cells of the intestinal walls and enter the body.

Inflammation: ↑ Is an important component of the body’s defense mechanisms or immune system. However, maintaining a balance is key to good health, as an exaggerated inflammatory response may be harmful.

Osteoporosis: ↑ Is a bone disease that affects the structure of our bones, leading to a significant loss of bone mass, which makes bones fragile and more likely to break.

Probiotics: ↑ Are good live bacteria that may help prevent and treat certain diseases, as well as improve our health.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

This work was supported by the São Paulo Research Foundation FAPESP [2021/097260].