Osteoporosis is a skeletal disease characterized by reduced bone mineral density (BMD) and deterioration of the bone tissue microarchitecture, with a consequent increase in the risk of falls, fractures, and reduced mobility (1, 2). In a meta-analysis carried out from studies conducted in the American continent, the average prevalence of osteoporosis was 11.5% in women and 8.5% in men (3). This difference between sexes is due to menopause, which has hypoestrogenism as one of its main characteristics, caused by the ovarian failure characteristic of this phase (4). In addition to its role in bone metabolism, estrogen promotes the secretion of calcitonin, which inhibits bone absorption, increases vitamin D3 levels, promotes intestinal calcium absorption, and regulates the sensitivity of parathyroid hormone (PTH) to calcium in the bloodstream (5).

Consumption and/or supplementation of nutrients such as proteins, calcium, phosphorus, magnesium, and vitamin D have a well-established role in maintaining bone health and preventing osteoporosis (6). In addition to these, selenium (Se) also influences bone metabolism, since its deficiency is related to a decrease in antioxidant capacity and accumulation of reactive oxygen species (ROS), with subsequent activation of osteoclasts and reduction of osteoblastic differentiation (7–9). Different human studies have evaluated the relationship between Se and bone health (10–12). In postmenopausal women, Se status was inversely associated with bone turnover and positively so with BMD (10, 11). A negative association between Se status and bone fractures in adults and the elderly has also been observed (12).

However, these studies evaluated the plasma concentration of Se, while few studies evaluated the intake of this mineral and its relationship with bone outcomes and the results still diverge. Wang et al. (13) evaluated the dietary consumption of Se by elderly men and women. They observed that individuals with lower Se consumption had a higher prevalence of osteoporosis (13). On the other hand, a study carried out with Chinese adults of both sexes found a non-linear association between Se intake and fracture risk, demonstrating that higher Se consumption increased the risk for fractures (14).

Considering the possible contribution of Se, in addition to the nutrients known to be necessary for bone health, investigating the dietary intake of Se in postmenopausal women might help to clarify its relationship with bone mass, given the heterogeneity of available results, populations, forms of assessment, and dietary availability. Thus, in this study we verified the association between dietary Se intake and BMD in postmenopausal women.

The final sample consisted of 124 women (Figure 1). Sixteen women were excluded: one because she was in pre-menopause, three because they were under hormone replacement therapy, and 12 because they did not undergo DXA.

Sociodemographic and lifestyle characteristics of these women are also presented according to the Se quartile. Their mean age was 66.8 ± 6.1 years, with a predominance of women between the ages of 60 and 69.9 years (59.7%), non-white (62.1%), living with a partner (51.6%), with a basic level of schooling (60.5%), and unemployed (83.1%). As for lifestyle habits, half of the sample was classified as insufficiently active (50.0%) and the other half as sufficiently active (50.0%). Regarding alcohol consumption and smoking, most did not consume alcohol (86.3%) and did not smoke (95.2%). There was no significant difference between the quartiles of Se consumption and the variables analyzed (Table 1).

Table 2 shows the distribution of clinical variables and dietary intake according to Se intake quartiles. The women in this study had a mean time since menopause of 19.6 ± 8.8 years and a mean BMI of 27.3 ± 4.7 kg/m². Most of them were classified as having normal weight (42.7%), taking calcium (65.3%) and vitamin D (57.3%) supplements, and not using drugs that affect bone metabolism (53.2%). There was no significant difference between these variables according to the quartiles of Se intake.

When assessing nutrient intake, the mean Se intake was 154.4 ± 88.7 (51.7–564.9) μg/day among the women evaluated. Those with higher consumption of Se (Q4) consumed higher levels of protein (93.5 ± 20.9 g/d; p < 0.001), calcium (835.2 ± 247.7 mg/d; p = 0.001), phosphorus (1,370.0 ± 267.2 mg/d; p < 0.001), and vitamin D (16.7 ± 15.6 μg/d; p = 0.019) compared with women with lower consumption (Q1). The energy intake did not vary between the quartiles (p = 0.749) (Table 2).

Regarding BMD classification, 41.9% of women were classified as having osteopenia and 36.3% osteoporosis. According to the BMD classification, 51.9% of women with normal BMD had a higher dietary intake of Se (Q4). On the other hand, 57.7% of the women with osteopenia and 60% of those with osteoporosis were among the quartiles with the lowest consumption of Se (Q1 and Q2) (p = 0.003). Nutritional status, calcium and vitamin D supplementation, and use of drugs that affect bone metabolism did not vary between the quartiles (p > 0.05) (Table 2).

Table 3 presents the association between dietary Se intake quartiles and BMD classification from multivariate logistic regression. In the crude model, the OR for osteopenia were 0.11 (95%CI: 0.01–0.99; p = 0.048) and 0.04 (95%CI: 0.01–0.38; p = 0.005) and for osteoporosis 0.08 (95%CI: 0.01–0.77; p = 0.029) for the third and fourth quartiles, respectively, when compared with the first quartile. After adjusting for possible confounding variables, the association between selenium intake and BMD remained negative only for osteoporosis. The OR for osteoporosis in postmenopausal women in the fourth quartile was 0.02 (95%CI: 0.001–0.41; p = 0.012), compared with women in the first quartile.

The present study revealed an inverse association between Se consumption and the presence of osteoporosis. Women who were in the highest Se consumption quartile were less likely to have osteoporosis compared with those in the lowest quartile of Se consumption.

Few studies have evaluated dietary Se consumption and its outcomes in relation to BMD and osteoporosis. In line with our results, Wang et al. (13), when evaluating 6,267 Chinese adults aged in average 52.2 years, of which 2,640 were women, found a negative association between Se intake assessed from an FFQ and the prevalence of osteoporosis in women [0.53 (95%CI: 0.32–0.89), p = 0.018], even after adjusting for age, BMI, energy intake, smoking, alcohol consumption, physical activity level, fiber intake, calcium, dietary supplements, diabetes, and hypertension (13). However, BMD was evaluated in the medial phalanges of the non-dominant hand by compact radiographic absorptiometry, a method that is not considered the gold standard (19).

Wolf et al. (33) evaluated 11,068 women between 50 and 79 years old and did not find an association between Se consumption and BMD; however, most women had normal BMD, which may have caused the loss of association (33). De França et al. (34), when evaluating antioxidant intake and BMD in Brazilian postmenopausal women, also found no association between Se intake and BMD at various bone sites (femoral neck, total femur, lumbar spine, and whole-body) (34). Pedrera-Zamorano et al. (35) found that high Se consumption negatively affected BMD in postmenopausal women aged over 51 years only if calcium intake was below 800 mg/d. When calcium consumption exceeded 800 mg/d, Se intake appeared to no longer affect BMD (35). These results contradict those obtained in this study, which showed the high consumption of Se as a protective factor for the development of osteoporosis.

The average consumption of Se by the women evaluated in the present study was 154.4 ± 88.7 μg/d, which is above the 55 μg/d recommended for women over 50 years of age by the Dietary Reference Intakes (DRI) (36) and the averages reported in similar studies (85.9, 43.5 and 95.5 μg/d) (13, 33, 35), although it was similar to that of a study with Brazilian postmenopausal women (108 μg/d) (34). One of the hypotheses for the high intake of Se in our study may be related to the eating habits of the study population. The women evaluated reported consuming food sources such as meat, eggs, and nuts both frequently and in high amounts. Se can be obtained from food sources such as seafood, meat, eggs, and cereals. Brazil nuts have approximately 95.5 μg of Se in just one unit (5 g) (37), which may explain our results. When evaluating the consumption of antioxidants in 2,344 Brazilian adults, Pinheiro et al. (38) found that women consumed an average of 84.8 ± 40.1 μg/d of Se, and only 11.5% of women had low consumption of this mineral (38), demonstrating that the consumption of Se by the Brazilian population is higher than the nutritional recommendations (36). Still, women had higher dietary intake of protein, calcium, phosphorus, and vitamin D. This finding can be explained by the consumption of foods that are sources of these nutrients, since meat, chicken, fish, and eggs are foods rich in proteins and contain high levels of selenium, and milk and dairy products also contribute a considerable fraction of dietary intake of Se (39).

Evidence indicates that Se is involved in bone remodeling and metabolism, and consequent decreased BMD (10–13). It is known that bone metabolism is controlled by RANKL, an NF-κB ligand, present on the surface of osteoblasts. RANKL binds to its receptor, RANK, expressed on the surface of osteoclasts, and stimulates osteoclast activity and bone resorption. An exacerbated resorption will cause bone loss that cannot be overcome by bone formation (9). Se modulates this process through several mechanisms: the anti-inflammatory property presented by this mineral reduces the expression of NF-κB and inhibits the activity of interleukin-6 (IL-6) and other inflammatory cytokines (40), thus regulating bone turnover, since these cytokines mediate the maturation of osteoclasts and the increase in bone resorption (41, 42). Additionally, Se can stimulate mitochondrial biogenesis, playing a protective role in mitochondrial function and preventing metabolic bone damage, as it induces apoptosis in mature osteoclasts through mitochondrial pathways (43). Furthermore, Se has an important antioxidant role through its selenoproteins, suppressing the generation of ROS and inhibiting osteoclast differentiation by supressing RANKL (9, 44, 45). Finally, the selenoenzymes iodothyronine deiodinases protect the thyroid hormones from oxidative stress and regulate blood circulation. A Se deficiency can lead to an excess of these hormones in the blood, consequently increasing bone turnover and accelerating bone loss, which results in osteoporosis (46, 47). Therefore, inadequate Se intake can alter bone metabolism by decreasing the redox capacity, thus increasing ROS formation and inducing oxidative stress and inflammation in an unregulated way. This exacerbation increases bone resorption and compromises bone microarchitecture (9, 45).

This study has several strengths. First, BMD was obtained from DXA of the lumbar spine (L2–L4) and femoral neck, the gold standard method for the diagnosis of osteoporosis (19). Second, women on hormone replacement therapy were excluded. Third, by adjusting the multivariate model for several potential confounders, the reliability of the results was strengthened. However, some limitations are present. Because of the cross-sectional design of this study, it is not possible to state a causal relationship between Se consumption and the development of osteoporosis, suggesting that longitudinal studies, especially in this population, should be performed. The quantification of Se from the FFQ can be impaired, as the Se content in foods can vary depending on the region (48) and due to inherent flaws in the evaluation method (49), although the FFQ used was validated for the Brazilian population (21). The use of glucocorticoids was not evaluated and women who used drugs that affect bone metabolism such as bisphosphonates were not excluded from the analyses, although that was used as an adjustment in the multivariate model. Also, data on sun exposure and outdoor activities, which are important for vitamin D synthesis and bone health, were not collected.

In conclusion, Se consumption was associated with BMD in postmenopausal women, and those with higher Se consumption were less likely to have osteoporosis. Based on this premise, our results expand the knowledge about the relationship between Se and the maintenance of bone health, although longitudinal investigations are necessary to clarify the role of Se in BMD and its consequences, since the results are still conflicting (10–14, 33–35).

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Research Ethics Committee of the Federal University of Espírito Santo. The patients/participants provided their written informed consent to participate in this study.

PG, GC, BA, JM-R, TP, and VG contributed to conception and design of the study. PG, CV, and GC conducted research. PG, TP, and VG performed the statistical analysis, wrote the paper, and had primary responsibility for final content. All authors contributed to manuscript revision, read and approved the submitted version.

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.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.