We analyzed data from a large-scale nationally representative population-based cross-sectional study (NHANES) and determined that higher dietary selenium intake was associated with increased BMD in the femur, femur neck, trochanter, intertrochanter, and lumbar spine, and the effect remained consistent across various age groups and genders. Furthermore, the results from the generalized additive model suggested a nonlinear inverted U-shape association between dietary selenium intake and BMD.
Severe Se deficiency is associated with Keshan disease, an endemic osteoarticular cardiomyopathy that is characterized by the selective necrosis of articular and growth plate chondrocytes [21]. Bone has the second-highest proportion of selenium (16%) in the body, only exceeded by skeletal muscles (27.5%) [22]. Few studies have examined the association between dietary selenium intake and bone health, leading to inconsistent epidemiological results. One study demonstrated that dietary selenium supplementation did not attenuate mammary tumorigenesis–mediated bone loss in a male mouse breast cancer model [23]. A recent randomized double-blinded controlled study by Walsh et al. reported that 200 µg/day selenite supplementation did not affect the musculoskeletal health of postmenopausal women [24]. However, in the present study, a higher dietary selenium intake did result in increased BMD. In line with our findings, a cross-sectional study that included 6267 participants demonstrated that compared with those in the lowest quartile of dietary selenium intake, those belonging to the fourth quartile exhibited a lower odds ratio for osteoporosis (OR: 0.47, 95% CI: 0.31–0.73) [25]. Zhang et al. observed that Se intake was negatively associated with the risk of osteoporotic hip fracture [17].
The biological mechanisms responsible for the effects of Se intake on BMD are uncertain. A previous study demonstrated that changes in the redox state can alter the bone remodeling process, which allows continuous bone regeneration through the coordination of the three major types of bone cells: osteoclasts, osteoblasts, and osteocytes [26]. Changes in reactive oxygen species (ROS) and/or antioxidant systems may be involved in the pathogenesis of bone loss. Osteoblast and osteocyte apoptosis induced by ROS leads to osteoclast formation and inhibits mineralization and osteogenesis. Excessive osteocyte apoptosis is associated with oxidative stress that leads to imbalanced osteoclast formation, which results in increased bone remodeling and bone loss [26–28]. Moreover, Se plays a crucial role in antioxidant, immunological, and anti-inflammatory processes. The physiological function of the essential micronutrient Se is mainly mediated by selenoproteins [29], which have antioxidant activities and are known to maintain the redox cell balance, protect against oxidative stress caused by ROS, and regulate inflammation and osteocyte proliferation and differentiation [30]. Furthermore, it has been reported that interleukin-6 (IL-6) and other cytokines play a crucial role in the pathogenesis of osteoporosis [31]. Therefore, the anti-inflammatory effect of Se may be partly mediated by inhibiting the activity of IL-6 and cytokines [32, 25]. Another potential mechanism linking Se to bone health is the relationship of Se-dependent glutathione peroxidase to thyroid protection [33]. Therefore, Se deficiency may increase the level of thyroid hormone in the blood, leading to accelerated bone loss and osteoporosis [34].
Although limited data confirm the effects of dietary selenium supplementation on bone health, the accumulated evidence indicates a positive association between circulating Se concentrations and bone outcomes. A population-based cohort study conducted in five European cities demonstrated that higher Se levels were associated with increased hip BMD and decreased bone formation at the beginning of the research [15]. Other studies have indicated that Se deficiency can hinder bone growth and alter bone metabolism [35, 36]. In a survey conducted in the United States, increased serum Se concentrations were associated with increased femur BMD, decreased Fracture Risk Assessment Tool (FRAX) scores, and a reduced history of bone fractures [37]. A study, that used plasma Se and selenoprotein P as biomarkers demonstrated that an increase in Se content was associated with an increase in BMD in the lumbar spine and hip in European postmenopausal women [38]. In addition, low hair selenium levels have been reported to be associated with low lumbar and femoral BMD values in Korean adults [39]. The finding of a positive correlation between dietary selenium intake and blood selenium concentration [40, 41] suggests that Se supplementation may positively influence bone health in selenium -deficient patients.
Some observational studies have reported a U-shape relationship between serum Se and the risk of diabetes, coronary heart disease, anemia, and all-cause mortality [40, 42–44]. Data from NHANES Ⅲ indicate an inverse association between serum Se and all-cause mortality at low selenium levels (< 130 ng/mL) and a modest increase in mortality at high Se levels (> 150 ng/mL) [45]. Similar to the findings of these studies, the results of our study indicate a positive relationship between dietary selenium intake and BMD when dietary selenium intake is below a certain threshold and a negative relationship when dietary selenium intake is higher than that threshold. This may be because selenium is an essential element with a narrow safety margin, and higher concentrations often lead to toxicity [42]. Furthermore, the regulation of selenium levels in the body mainly depends on its excretion rather than absorption. When dietary selenium intake is high enough to optimize the levels of selenium protein, any further intake is completely offset by excreta, allowing for only a slight increase in systemic selenium [46].
The present study has several strengths. To our knowledge, this is the first study to assess the nonlinear relationship between dietary selenium intake and BMD in the femur, femur neck, trochanter, intertrochanter, and lumbar spine. Our study was based on a large nationally representative survey, and BMD was measured in a reliable independent lab using established methods. Moreover, we adjusted numerous potentially confounding factors, including socioeconomic, lifestyle, and nutrient intake factors. Our study also has some limitations. First, as a cross-sectional study, inferring a causal association between dietary selenium intake and BMD is challenging. Second, we did not assess the association between dietary selenium intake and the risk of osteoporosis because of the limitations of the original data. Furthermore, bone remodeling is a continuous physiological process that entails bone resorption by osteoclasts and bone formation by osteoblasts. Future high-quality, prospective longitudinal studies are required to confirm the findings of this study.
In summary, our study suggests that higher dietary selenium intake is associated with increased BMD in the femur, femur neck, trochanter, intertrochanter, and lumbar spine. Furthermore, this study identified an inverted U-shape relationship between dietary selenium intake and BMD. Future high-quality, prospective longitudinal studies are required to confirm these findings.