This study investigated associations of depression with osteoporosis in the general U.S. population using a nationally-representative sample. Our results demonstrated that 1.62 times of osteoporosis among depression patients compared with controls. The conclusions were statistically significant in the study population analysis (Table 1), the regression analysis model (Table 2), and the grouping analysis by different participants and study characteristics (Table 3). The consistent results of all these analyses show that our results are robust and consistent. The results of this study suggest that osteoporosis is associated with an increased risk of depression. Given that both depression and osteoporosis are prevalent worldwide, our findings will no doubt have important implications for public health globally.
Our findings of a positive correlation between depression and osteoporosis are consistent with previous studies [15,20]. Despite some studies reporting a positive relationship between depression and osteoporosis, other researchers have found contradictory results. For example, a study by Gharenaz et al. found that depression was not significantly associated with osteoporosis in Iranian women [21]. Similarly, studies by Bistrovic et al. did not find a relationship between osteoporosis and depression, which contradicts the findings of this current study [22]. These contradictory results may be due to differences in the study's design, the characteristics of the study group, and important behavioral factors such as lifestyle, culture, and history of hormone therapy. Genetics may also play a significant role in the relationship between depression and osteoporosis. In our analysis, the relationship between depression and osteoporosis remained significant even after controlling for other risk factors, thus suggesting an independent association. At the same time, we included a large number of samples to reduce the impact of errors on the analysis, further ensuring that the study was accurate and scientific enough to demonstrate a close link between depression and osteoporosis.
Hypercortisolemia is considered a key causative factor of bone deficit in people with depression [23]. Depression causes sustained activation of the stress system, activating the hypothalamic corticotropin-releasing hormone (CRH) neurons through circuits connecting the prefrontal cortex, the amygdala, and the hypothalamus, thereby increasing the amount of cortisol. Corticotropin-releasing hormone hypersecretion and hypercortisolism cause hypogonadism, an established risk factor for bone loss in both sexes [24]. The present study demonstrates that depression could result in an increased incidence of osteoporosis [25]; a possible explanation for the finding is that alterations in the hypothalamo-pituitary-adrenal axis in patients with depression may be involved in the pathogenesis of osteoporosis. The potential mechanisms could be seen in Fig. 1.
In this study, men, with high cholesterol, ages 50 to 64, a high BMI, and depression who take prednisone or cortisone have more problems with osteoporosis (Fig. 2). Studies by Li et al. have shown that with increasing age, bone marrow mesenchymal stem cells (BMSCs) have age-dependent osteogenesis decreases, this conversion reduces the number of osteoblasts, and osteoblast function decreases with age, bone mass loss accelerates, and it is more susceptible to osteoporosis [26]. However, Interestingly, men with depression are more likely to have osteoporosis, but women have more depression, which can be explained by low gender equity or intra-group comparisons. Divorce, widowhood, married but separated or unmarried marital status and low- and middle-income incomes may bring greater stress to life, increasing the risk of depression and other adverse effects, thereby increasing the likelihood of osteoporosis. In addition, analysis of the association between high cholesterol and osteoporosis showed that, consistent with previous studies, high cholesterol increases the risk of osteoporosis by inhibiting bone formation. In an analysis of the association of obesity with osteoporosis, we found that a high BMI increased the risk of osteoporosis in patients with depression, although the association between obesity and osteoporosis has been controversial [27,28]. Taking adrenocortical hormones such as prednisone or cortisone also Increased risk of osteoporosis by 1.92 times on patients with depression because of the use of adrenocorticoids leads to decreased gonadal function [24]. But physical exercise or physical activity can provide an important insight into mitigating risk, revisiting previous literature physical activity can help people reduce bone loss, reduce the risk of osteoporosis, and can also improve osteoporosis problems [29,30]. In addition, healthy sleep patterns are a key to mitigating the risk of osteoporosis, and studies by Wang et al. have shown that proper sleep timing can help delay or prevent osteoporosis in older adults. At the same time, improvements in sleep quality also helped relieve depressive symptoms [31].
There are certain limitations here in our study. First, as a cross-sectional study based on a national database, we can only demonstrate a link between osteoporosis and depression, but cannot describe a causal relationship. However, based on the understanding of other relevant studies and knowledge, we are more inclined to the belief that depression increases the risk of developing osteoporosis. Second, the original report used a self-reporting scale to determine whether participants had depression, which may have been biased by misclassification, thereby underestimating the risk of bone loss and osteoporosis associated with depression. Third, NHANES lacks some basic data, such as whether or not to receive treatment for osteoporosis, detailed smoking habits, detailed demographic information on family history of systemic diseases, and NHANES also lacks more rigorous data on physical activity, which are potential factors for the development of osteoporosis and need to be further studied and refined. Fourth, NHANES lacks information on taking antidepressants and cannot rule out their impact on the study, which needs to be further studied, and the effect of antidepressant use on bone density is controversial, with studies suggesting that antidepressants may cause bone mass loss [32]. Fifth, there is only one assessment method, the 9-item Patient Health Questionnaire (PHQ-9), to assess a patient's depression level. We used a single assessment method, which has some limitations. Therefore, the data may be biased. However, PHQ-9 has higher objectivity and accuracy than other evaluation methods. In summary, our cross-sectional study based on NHANES is a step-by-step confirmation that depression is significantly associated with an increased risk of bone loss and osteoporosis. Due to the high prevalence of depression and osteoporosis worldwide, the link between depression and bone loss and osteoporosis has important implications for global public health, especially as the global population ages. A decrease in bone density increases the risk of fractures, and the prevention and treatment of depression can greatly reduce the risk of osteoporosis and osteoporotic fractures. Further research is needed to investigate the underlying mechanisms by which depression leads to bone loss and increased risk of fractures.