Osteoporosis is an important health and societal burden in elderly people, not only in females but also in males. There are numerous osteoporosis-related fracture risk factors, including age, sex, race, lifestyle and concomitant medical conditions16. In men, osteoporosis is underrecognized and undertreated. Only a few men are screened for osteoporosis, even after a fracture17. The treatment rate is much lower in males than in females18. Meanwhile, more men than women die every year due to hip fractures19. Hence, we also included men in the study population to determine the risk factors for osteoporosis.
Some studies about the influence of sex on osteoporosis remain controversial. In our study, there was a significant relationship between H. pylori and osteoporosis in premenopausal females but not in males. The reasons for the difference between males and females are as follows: First, differences in clinical outcomes of osteoporosis in men and women may be rooted in the biologic properties of bone. Barrett-Connor E holds the view that there are sex-specific differences in the number of osteoprogenitor cells and in hormone responses and regulation20, 21. Second, men have a greater bone size, trabecular BMD and bone area at the radius and tibia than women, even after adjusting for weight and height, which may lead to a decrease in osteoporosis and fracture22. Third, men undergo a slow decrease in BMD with increasing age, while women experience a profound period of rapid bone resorption, especially after entering menopause23. Last but not least, some studies support the idea that men are more likely to suffer from secondary disease, for example, rheumatoid arthritis, alcoholism, excessive smoking, gonadal deficiencies and others24, which may lead to sustainable bone loss.
Unfortunately, the relationship between osteoporosis and H. pylori infection is still controversial. Some studies hold the view that there is no difference between men and women in the relationship between H. pylori and osteoporosis25, 26. Some studies hold the view that H. pylori is related to osteoporosis only in women. Shih-Chun Lin conducted a retrospective study including 365 women and showed that H. pylori is related to osteoporosis in females27, while others think that there is no correlation between them in females. Daisuke Chinda conducted a study of 473 healthy women and found that H. pylori is not a significant risk factor for osteopenia28. In our study, we analysed the relationship between H. pylori infection and osteoporosis. We found a significant relationship between H. pylori infection status and bone density in premenopausal females but not in males. We suspect this may be due to the difference in the aetiology of osteoporosis between males and females. However, we did not find any other studies on this, and it requires more systematic research for analysis.
After analysing the differences between males and females, we found that there were significant differences in BMI, WHR, and TG in the study population. This study provides evidence for follow-up research on sex differences in the relationship between H. pylori and osteoporosis.
Most studies hold the view that obesity is related to osteoporosis29. It is generally believed that obesity may be a protective factor against bone loss and osteoporosis30. However, the effect of obesity remains unclear. On the one hand, obesity has traditionally been considered positive for bone because of the beneficial effect of mechanical loading31. On the other hand, people hold the view that BMI may harm BMD. Osteoblasts and adipocytes both stem from marrow mesenchymal stromal cells. Osteoblasts and adipocytes are in a competitive relationship, and an increase in adipocytes will inhibit osteoblasts32. In our study, there was a significant relationship between BMI and osteoporosis. Increased BMD levels in obese people may be associated with increased mechanical loading and strain; this is a complicated problem that cannot be generalized.
In our study, we found that H. pylori infection is associated with a decrease in bone density. The possible reasons are as follows: First, H. pylori infection may cause systemic inflammation and increase the production of tumour necrosis factor-α, interleukin-1, and interleukin-611. These cytokines are directly involved in the reduction of BMD. We found that HCY is related to osteoporosis, which supports this hypothesis. Second, osteoporosis may be related to a decrease in vitamin B12 levels33. Serin et al.'s study examined 145 patients without atrophy, erosions or ulcers, and they found that the histopathological scores for both antral and corpus H. pylori density and inflammation were significantly inversely associated with serum vitamin B12 levels13. In our study, although we did not find a significant relationship between B12 and osteoporosis, we still support the relevant theory. The absence of our results may be due to a lack of sufficient data and the influence of confounding factors. Last but not least, most patients chronically infected with H. pylori manifest pangastritis with reduced acid secretion due to bacterial virulence factors, inflammatory cytokines, and various degrees of gastric atrophy34. Calcium is ionized in acidic conditions and absorbed in the small bowel. Therefore, in either hypochlorhydria or achlorhydric stomachs, calcium absorption is impaired12. Moreover, the long-term use of acid suppressants, for example, proton pump inhibitors, may lead to osteoporosis or a decrease in BMD. Limited experimental evidence indicates that PPI may influence calcium absorption, leading to compensatory physiologic responses, including secondary hyperparathyroidism, which may cause an increase in the rate of osteoclastic bone resorption35. The results showed that calcium had a trend, though it was not statistically significant (P=0.076), with osteoporosis. Our results do not support the theory that there is a correlation between Ca and osteoporosis, but it may be that Helicobacter pylori infection may cause calcium absorption damage and affect BMD. We did not analyse vitamin D levels, which could affect both bone homeostasis and the inflammatory state36. Although H. pylori infection causing a decrease in bone density is supported by most researchers, the effect of early eradication therapy is still insufficient. Replogle ML holds the view that early eradication therapy may eliminate chronic inflammation from H. pylori 37. Some articles have also reported an improvement in B12 levels after complete eradication13, 38, which requires further investigation.
Despite its relevant findings, our study had several limitations. First, because most patients cannot remember the time of HP infection accurately, we were not able to obtain the time of HP infection, so different infection times may have had an impact on the results. Second, we did not collect vitamin D data, the sample size of our data was not large enough, and the study population only included participants from Beijing Shijitan Hospital, meaning that there might have confounding factors because of differences in the distribution of hospital study populations. Further large-scale studies in the general population are needed to validate our results. Third, the study participants were all Chinese, and the findings might not be generalizable to other ethnic populations. In addition, we only found some differences between men and women but failed to further explore them.