Connection Between Osteoporosis and Gallstones

Osteoporosis and gallstones are both diseases commonly affecting elderly patients worldwide. With osteoporosis, bones get weaker, more fragile, and are more susceptible to fractures. Although both conditions can happen to younger individuals, the risk of developing them increases with aging.

And there are other similar characteristics. Both conditions are more prevalent among females and may emerge during pregnancy and menopause, showing that sex hormones play an important role in their development.  They are both considered “silent diseases”. Gallstones can be asymptomatic for many years and are often just discovered inadvertently or because of a gallbladder attack. Likewise, many people do not know they have osteoporosis until they break a bone.

With all these similarities, it is not surprising to find a few links between the two conditions. This means that patients suffering from osteoporosis are more likely to have gallbladder problems like gallstones. In the same way, gallbladder patients have one more thing to be cautious about.

The Role of Inflammation

One of the most obvious common denominators between the two is the presence of inflammation. Older studies about osteoporosis conclude that the disease is a complicated result of various metabolic, endocrine, and mechanical factors. In recent years, however, evidence suggests that inflammation has a significant influence on bone turnover. Some studies have coined the term “inflammation-induced osteoporosis” since it may develop during chronic inflammation. This systemic inflammation may result in the inhibition of bone formation and the overproduction of pro-inflammatory mediators like prostaglandins, cytokines, and nitric oxide.

Clinical observations reveal that individuals with conditions such as autoimmune diseases, rheumatoid arthritis, HIV infection, inflammatory bowel disease, and other chronic inflammatory diseases have greater risk of developing osteoporosis. In fact, osteoporosis secondary to gastrointestinal disorders such as IBD, celiac disease, and other chronic gastrointestinal disorders has been more and more recognized as a clinically-relevant problem.

As for the gallbladder, inflammation is common within the biliary tree. The excessive and long-term presence of inflammation may cause tissue damage and lead to cholecystitis or cholangitis. The scarring brought about by the constant tissue damage may affect the liver and the bile, influencing enterohepatic circulation, and possibly resulting in gallstones.

Osteopontin and other inflammatory markers

There are numerous factors that may trigger or reduce inflammation. One is the abundance of pro-inflammatory cytokines like osteopontin, interleukin (IL)-1, tumor necrosis factor, and IL-6.

Osteopontin

Osteopontin (OPN) is a pro-inflammatory cytokine with calcium-binding properties present in various tissues involved in different processes like bone mineralization, cell survival, and bone remodeling. It is said to stimulate adhesion, migration, and bone resorption. However, high levels of OPN have been associated with low mineral bone density that may lead to osteoporosis.

Coincidentally, OPN is also a core protein involved in cholesterol and pigment gallstone formation. In an animal study illustrating gallstone formation, it was found out that the level of OPN in the gallbladder wall increased before inflammation started. In another related experiment, stone-laden gallbladders of animal subjects were infiltrated by macrophages with intense OPN expression.

Serum interleukin 6 (IL-6)

Serum interleukin 6 (IL-6), is another cytokine which is considered a major predictor of bone loss. In a study among postmenopausal women, IL-6 was determined to be an effective indicator of bone turnover within the first 10 years after menopause. IL-6 is implicated in the development of different metabolic bone diseases like osteoporosis and Paget’s disease. Similarly, IL-6 may promote gallstone formation, same as TNF-α.

TNF-α and TGF-β

TNF-α  and TGF-β, two other cytokines are also said to affect gallbladder cells to promote gallstone formation and the allele producing them can also be a risk factor of gallstone disease. In the same manner, TNF-α is implicated in tumor-induced bone resorption and osteopenia. Because of these characteristics, anti-TNF drugs have been developed to treat several immunological disorders and for the prevention and reversal of systemic bone loss.

Hormones, Menopause, and Pregnancy

Women have a higher risk of developing both osteoporosis and gallstones as well as other gallbladder diseases.

Estrogen deprivation during menopause contributes to bone loss by increasing the body’s production of osteoclasts, which are cells that reabsorb bone.  This is why this bone condition is highly prevalent among postmenopausal women.

Inversely, when hormone levels are through the roof during pregnancy, osteoporosis can also develop. The exact cause has not yet been identified but it is common among pregnant women with pre-existing conditions such as Celiac disease, osteogenesis imperfecta, or anorexia nervosa. Gallstone formation is also common during pregnancy.

Hormones, specifically estrogen, can promote the liver’s secretion of biliary cholesterol, increasing cholesterol saturation in the bile and increasing the risk of cholesterol gallstone formation. In “The Risk of Gallbladder Disease After Menopause”, we also mentioned that the sudden drop of estrogen may indirectly result in delayed gallbladder emptying and the prevalence of stone formation.

Stress hormones like cortisol can also be blamed for both osteoporosis and gallstones or other gallbladder diseases. Cortisol indirectly acts on our bones by blocking calcium absorption. Excessive and long-term elevation of cortisol levels is associated with the decrease of mineral bone density and the development of osteoporosis. On the other hand, erratic cortisol levels increase the risk of developing metabolic syndromes and gallbladder disease.

Calcium for Osteoporosis may be Harmful for the Gallbladder?

The mineral calcium is critical for numerous metabolic processes including bone health. Calcium deficiency causes bone loss and osteoporosis. That is why calcium supplementation and inclusion of calcium in the diet is recommended for individuals with low bone density or osteoporosis. Unfortunately, calcium also plays a key role in gallstone formation especially with the presence of too much osteopontin. OPN, present in high levels among osteoporosis patients, binds to calcium and may encourage cholesterol crystallization in the bile. Long-term oral dietary calcium supplementation is also said to promote gallbladder sludge and pigment gallstone formation.

What should we do about it?

Considering the numerous connections between osteoporosis and gallstones or gallbladder diseases, individuals with low bone density should be in the lookout for gallbladder symptoms, and vice versa. There are many factors that are inevitable and out of our control such as ageing, pregnancy, menopause, heredity, and stress. However, there are still ways that may help prevent these two conditions from coinciding.

  1. Manage Inflammation

Since we know that inflammation plays a crucial role in the development of osteoporosis and gallstones as well as other related gallbladder diseases, this is the most important place to start. You can take all kinds of supplements to support your bones and your gallbladder but if you don’t stop the cascade of inflammation, you are fighting a losing battle. You need to do BOTH. Supplements and diet are equally important.

Inflammatory activities

A sedentary lifestyle and over-exercising are almost equal, but not quite; being sedentary is worse. But both cause inflammation.

Poor diet

Trans fats such as fried foods, sugar, and highly-processed flours are inflammatory foods. However, gluten and dairy are just as much so for most people. Any food that you have sensitivity to (and you will need to do an allergy elimination diet to find that out) is just as, or moreso, inflammatory to you. Everyone has different sensitivities and different degrees of reaction, but regardless of how little pain you may feel, if it is causing inflammation on the inside, your bones and your gallbladder and other organs are being affected. You can find an allergy diet and a gallbladder diet on this website which should help you to manage and avoid systemic inflammation from diet.

Insomnia

A bad night of sleep causes inflammation. You need to work on this from several angles – managing stress, right lighting, slowing down at least an hour before bed, not watching stimulating movies before bed, no computer screen in the evenings, balancing blood sugar especially before sleeping by avoiding simple carbs, etc. Taking supplements to help you relax and support sleep are also indicated.

Supplements to reduce inflammation

Foods such as beets, turmeric, black current, fish and others can be included in your diet. Omega 3 oils such as fish oil are known to combat inflammation.

Use anti-inflammatory supplements such as Trans-Resveratrol, Curcumin (use with caution if you have gallstones), Berberine (also great for managing blood sugar) and Ginger.

  1. Make sure you have the right calcium, vitamin D and Vitamin K2

While it is specifically important to be aware of your calcium intake if you are high risk for osteoporosis, that doesn’t mean loading up with too much calcium and especially the wrong kind of calcium. One of the best (and by that I mean most easily absorbed) calcium supplements is sourced from red algae. Marine calcium contains 72 minerals including calcium and magnesium. You can find this in capsule form here, along with added Vitamins D3 and K2.

It is important to maintain the right vitamin D3 and K2 levels so the calcium you take in will be used and absorbed properly by the body. Be sure you get a blood test to monitor your D3 levels. If your Vitamin D is low, you will need more supplementation than what is found in the AlgaeCal Plus. 100 mcg – 300 mcg is recommended for Vitamin K2. MK-7 or menaquinone-7 is the best form for Vitamin K2.

AlgaeCal Plus – Natural Calcium, Magnesium, Vitamin K2 + D3 Supplement – Increase Bone Strength – All Natural Ingredients – Plant-Based – Dietary Supplement – One Bottle – 120 veggie capsules

If you prefer to take your Vit D3 and K2 separately, you can find the same red algae in powdered form under the name of AquaMin (F). It is a smooth powder that blends easily in drinks with no taste.

  1. Healthy lifestyle

We may sound like a broken record here but regular physical exercise, getting enough sleep, giving up smoking, and reducing alcohol consumption can do a lot of good things to your body. Not only does it help prevent osteoporosis and gallstones or gallbladder diseases, but it supports good health and energy levels overall.

In conclusion, while it does not appear that either disease actually causes the other, there seems to be enough evidence to support the connection between osteoporosis and gallstones through similar causative factors. And therefore, taking some serious preventative measures for one may just ward off the other condition as well.

References:

  1. Armour, K. J., & Armour, K. E. (2003). Inflammation-Induced Osteoporosis. In Bone Research Protocols (pp. 353-360). Humana Press.
  2. Ebadi, P., Daneshmandi, S., Ghasemi, A., & Karimi, M. H. (2013). Cytokine single nucleotide polymorphisms in patients’ with gallstone: dose TGF-β gene variants affect gallstone formation?. Molecular biology reports, 40(11), 6255-6260.
  3. Ginaldi, L., Di Benedetto, M. C., & De Martinis, M. (2005). Osteoporosis, inflammation and ageing. Immunity & Ageing, 2(1), 14.
  4. Ichikawa, H., Imano, M., Takeyama, Y., Shiozaki, H., & Ohyanagi, H. (2009). Involvement of osteopontin as a core protein in cholesterol gallstone formation. Journal of hepato-biliary-pancreatic surgery, 16(2), 197.
  5. Imano, M., Satou, T., Itoh, T., Takeyama, Y., Yasuda, A., Peng, Y. F., … & Yasuda, T. (2010). An immunohistochemical study of osteopontin in pigment gallstone formation. The American Surgeon, 76(1), 91-95.
  6. Kahles, F., Findeisen, H. M., & Bruemmer, D. (2014). Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes. Molecular metabolism, 3(4), 384-393.
  7. Klahan, S., Kuo, C. N., Chien, S. C., Lin, Y. W., Lin, C. Y., Lin, C. H., … & Chang, W. P. (2014). Osteoporosis increases subsequent risk of gallstone: a nationwide population-based cohort study in Taiwan. BMC gastroenterology, 14(1), 192.
  8. Magnuson, T. H., Lillemoe, K. D., Peoples, G. E., & Pitt, H. A. (1989). Oral calcium promotes pigment gallstone formation. Journal of Surgical Research, 46(4), 286-291.
  9. Mandal, C. C. (2015). High cholesterol deteriorates bone health: new insights into molecular mechanisms. Frontiers in endocrinology, 6, 165.
  10. Scheidt-Nave, C., Bismar, H., Leidig-Bruckner, G., Woitge, H., Seibel, M. J., Ziegler, R., & Pfeilschifter, J. (2001). Serum interleukin 6 is a major predictor of bone loss in women specific to the first decade past menopause. The Journal of Clinical Endocrinology & Metabolism, 86(5), 2032-2042.
  11. Yang, L., Chen, J. H., Cai, D., Wang, L. Y., & Zha, X. L. (2012). Osteopontin and integrin are involved in cholesterol gallstone formation. Medical science monitor: international medical journal of experimental and clinical research, 18(1), BR16.
  12. Zhang, Q., Chen, B., Yan, F., Guo, J., Zhu, X., Ma, S., & Yang, W. (2014). Interleukin-10 inhibits bone resorption: a potential therapeutic strategy in periodontitis and other bone loss diseases. BioMed research international, 2014.