Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and microscopic structural deterioration of bone tissue, leading to increased fragility of bones and a higher risk of fractures (1). In older adult individuals, particularly among women, bone pain and fractures are common symptoms of osteoporosis, which can potentially lead to disability or even death. This disease imposes a significant burden on healthcare systems, and with the increasing old population, this burden continues to grow (2). Taking China as an example, there were 411,000 cases of hip fractures in 2015, and it is projected to increase to one million by 2050 (3). Based on an osteoporosis epidemiological study conducted in China, which surveyed 20,416 individuals, the prevalence of osteoporosis among adults aged 40 and above was 5.0% for men and 20.6% for women (4). When combining this data with the sixth Chinese national census (55,191,915 men aged 40 and above and 53,935,201 women aged 40 and above), we estimated that there are 13.87 million osteoporosis patients among the Chinese population aged 40 and above. Therefore, the implementation of comprehensive early prevention and treatment measures for osteoporosis has become extremely urgent and necessary.

Air pollution is recognized a global health challenge (5). As early as 1985, researchers suggested a potential link between air pollution and osteoporosis (6). The Oslo Health Study (7) initially identified a weak but significant negative correlation between a 10-year average of air pollution indicators and whole-body bone density. Recent evidence from the analysis of 9.2 million U.S. health insurance records (8) and data from over 40,000 individuals in South Korea’s health insurance database (9) indicates a close association between increased PM_2.5 concentrations and higher rates of hospitalization due to fractures in the older adults, suggesting a connection between air pollution and osteoporosis. An analysis of data from 341,000 participants in the UK Biobank also suggests that exposure to higher levels of air pollution is associated with lower bone mineral density and an increased risk of osteoporosis (10). However, despite over four decades of research, the existing evidence regarding the relationship between outdoor air pollution exposure and osteoporosis-related outcomes remains scattered and inconclusive (11). Meta-analyses of limited studies indicate heterogeneous results regarding the association between air pollution exposure and osteoporosis (11), and the observed inconsistencies between studies may be attributed to heterogeneity in participant characteristics, study designs, and statistical issues (12). Furthermore, recent studies have adopted diverse lag periods for long-term exposure, while a considerable number have omitted adjustments for meteorological variables, which may constitute significant contributors to the disparate research findings.

Therefore, we conducted a retrospective cohort study in Jiangsu, China, and assessed the 5-year daily exposure of the survey participants to air pollutants and meteorological factors. Our study aimed to assess the impact of various air pollutants and adverse meteorological factors, including three kinds of Particulate Matter with different aerodynamic diameters (PM₁, PM₂.₅, PM₁₀), Nitrogen Dioxide (NO₂), Sulfur Dioxide (SO₂), Carbon Monoxide (CO), and ozone (O₃), as well as high humidity and solar irradiation, on the risk of osteoporosis. This research is crucial in understanding the environmental factors contributing to osteoporosis and informing public health interventions.

This study presents the first evidence of a delayed effect of long-term exposure to air pollution on the occurrence of osteoporosis, with a more stable association observed at 4 to 5 years of exposure lag (lag03, lag04). The emergence of PM₁₀ as a robust indicator for assessing the relationship between particulate matter and osteoporosis is particularly noteworthy. Furthermore, our research identified individuals aged 60 and above, as well as those with a BMI of ≥ 25, as vulnerable populations to air pollutant-related osteoporosis. These significant findings offer valuable insights for further research and intervention strategies, contributing to the enhancement of public health and the formulation of environmental policies.

Our study revealed a dose–response relationship between long-term exposure to PM₁, PM₂.₅, and PM₁₀ and the risk of osteoporosis, with the odds ratios (ORs) increasing with prolonged exposure (Figure 2). More specifically, at a 5-year lag (lag04), an average increase of 1 μg/m³ in PM₂.₅ and PM₁₀ was associated with a 9.5 and 5.4% increased risk of osteoporosis, respectively (Figure 4). Notably, the effectiveness of PM₂.₅ was slightly higher than that found in a previous study in Hubei Province, China, which reported a 5% increased risk for every 1 μg/m³ increase in PM₂.₅ using a 2-year average exposure (lag01) without adjusting for temperature and humidity [OR: 1.05 (1.00, 1.11)] (21). However, they did not find a statistically significant association with osteoporosis for 1-year [OR: 1.040 (0.994, 1.088)] and 3-year [OR: 1.037 (0.990, 1.086)] average exposures, highlighting the necessity of correcting for meteorological factors and presenting lag effects comprehensively. Our results corroborated the findings of an analysis from the UK Biobank (10), which found a 9% increased risk of osteoporosis associated with a 1 interquartile range (IQR) increase (1.3 μg/m³) in PM₂.₅ during the follow-up period [HR: 1.09 (1.06, 1.12)]. Another report using UK Biobank data supported our results (22), showing a 94% increased risk of osteoporosis for a 10 μg/m³ increase in PM₁₀ [HR: 1.94 (1.52, 2.48)], with their PM₂.₅ exposure levels ranging from 8.2 to 21.3 μg/m³, averaging 9.9 μg/m³. This highlighted the linear relationship between PM₂.₅ and osteoporosis risk observed in our study (Figure 3), even at lower concentration levels. Regarding PM₁₀, the UK Biobank results demonstrated a 4% increased risk of osteoporosis associated with a 2.4 μg/m³ increase [HR: 1.04 (1.01, 1.07)] (10), consistent with our findings using lag0 (Figure 3). Therefore, our Figure 2 served as a valuable reference for explaining differences in similar studies. Additionally, studies from South Korea (23) and Italy (24) reported associations between PM₁₀ exposure and increased osteoporosis risk, but they employed different categorization methods for PM₁₀ and did not report specific dose–response relationships. Furthermore, the Korean study (23) did not find an association between PM₂.₅ and osteoporosis.

While research on PM₁ was relatively limited (11, 12), our study revealed that after adjusting for EDD (Erythemal Daily Dose), the impact of PM₁ on osteoporosis lacked statistical significance (Figure 4). In contrast, when not adjusting for EDD, PM₁ remained a risk factor (Figure 2), and the effect of PM₁ per unit dose was even more pronounced. Furthermore, it’s worth noting that a study employed a 3-year average PM₁ concentration and found a correlation with a −5.38 unit decrease in quantitative ultrasound index (95% CI: −6.17, −4.60) (21), this harm had already been reflected in PM₂.₅ and PM₁₀. Research on rural populations in Henan, China, also discovered that a 1 μg/m³ increase in the three-year average of PM₁, PM₂.₅, and PM₁₀ resulted in a 14.9, 14.6, and 7.3% higher risk of osteoporosis, respectively (25). It’s important to highlight that the efficacy of these pollutants in their study surpassed our findings, possibly due to their use of quantitative ultrasound bone density measurements to assess osteoporosis (25).

The association between PM and osteoporosis was attributed to their ability to penetrate the lower respiratory tract, exerting both direct and indirect harmful effects on various organs and tissues. These harmful effects stemmed from PM components’ capability to traverse respiratory membranes, gaining access to the bloodstream. The direct effects resulted from PM components’ ability to traverse respiratory membranes and enter the bloodstream, whereas the indirect effects encompassed systemic consequences of localized airway reactions, which involved four potential mechanisms reported in the literature: inflammation, vitamin D, oxidative damage, and some environmental endocrine disruptors (26).

In gaseous pollutants, we observed a relatively stable association between CO and osteoporosis (Figure 4). Previous research has reported a negative correlation between CO exposure and BMD T-scores in a study from Taiwan (27). Furthermore, a prior study based on healthcare data from Taiwan, China, found that an increase in CO exposure was associated with an increase in osteoporosis incidence from 13.58 per 1,000 person-years to 22.25 per 1,000 person-years (28). The binding affinity of CO to hemoglobin is much higher than that of oxygen (O₂) (29), which thus leads to hypoxia by reducing oxygen-carrying capacity and decreasing O₂ release to tissues (30). This hypoxia has been confirmed to reduce the growth of osteoblasts, resulting in bone thinning and osteoporosis (31).

Our study also unveiled a protective effect of O₃ against osteoporosis. This protective effect persisted even after adjusting for EDD (Erythemal Daily Dose), suggesting that O₃ may have independent effects apart from UV radiation (Figure 4). In line with our findings, a study by Lin et al. in 2022 in Taiwan (27) found a positive correlation between annual average O₃ exposure levels and BMD T-scores. Furthermore, literature searches have indicated an increasing clinical use of O₃ therapy for conditions such as disc herniation, jawbone necrosis, and pain management (32, 33). O₃ therapy has been demonstrated to promote complete healing of bisphosphonate-related jawbone necrosis by restoring normal function (32). Additionally, two separate studies involving rats have shown that O₃ has a positive impact on bone formation. One study involved cranial bone defects in rats (34), while another study with 48 rats demonstrated that O₃ therapy increased the number of osteoclasts and osteoblasts and stimulated bone regeneration (35). These combined findings suggest a physiological basis for the protective effect of O₃ against osteoporosis.

In our study, both SO₂ and NO₂ did not independently affect osteoporosis, which is consistent with research conducted in Hubei, China (21). Furthermore, we discovered a U-shaped relationship between NO₂ and osteoporosis, indicating a non-linear association that might have limited our ability to identify a clear link between them. Furthermore, a meta-analysis indicated that SO₂ exposure was associated with a non-significant increase in bone mineral density (BMD) (11).

Subgroup analysis indicated that individuals aged 60 and above were the most susceptible to air pollution-induced osteoporosis, potentially due to age-related immunosuppression, rendering them more vulnerable to environmental pollution. We also observed that males were more sensitive to the effects of PM₂.₅ and PM₁, which was consistent with previous reports that found that the non-standardized coefficient β (95% CI) between BMD T-score and each 1 μg/m³ increase in PM₂.₅ was higher in males than females [−0.005 (−0.011, 0.000) for males vs. −0.001 (−0.007, 0.005) for females] (27). Notably, individuals with a BMI ≥25 were more susceptible to the impact of air pollution, despite the protective effect of higher BMI against osteoporosis (Table 1). This susceptibility among lower-risk individuals could be explained by the fact that air pollution can trigger systemic inflammation and oxidative stress. Overweight or obese individuals often exhibited a chronic inflammatory state due to the presence of inflammatory cells and mediators in adipose tissue (36). This chronic inflammation may have heightened their sensitivity to the detrimental effects of air pollutants, as inflammation can increase cellular susceptibility to the harmful effects of gasses and particulate matter.

This study is the first to correct for the influences of both humidity and solar radiation in quantitatively assessing the correlation between air pollutants and osteoporosis. Our study also has several strengths. Firstly, we employed DXA, the gold standard for diagnosing osteoporosis, to assess bone density at six sites. This was executed meticulously through a rigorous process of stratified random sampling and the use of standardized equipment. Furthermore, we diligently standardized the equipment across all hospitals involved in the project, a crucial step that ensured the uniformity and reliability of our test results. Secondly, we also considered temperature, humidity, and ultraviolet radiation in our comprehensive analysis of air pollution and osteoporosis. Finally, for the first time, we showed how osteoporosis risk varies with different pollutants and lag times. Our study strongly indicates that as exposure duration to pollutants increases, the osteoporosis risk per unit dose of pollutants fluctuates.

Our study still has some limitations, primarily the relatively small sample size. Conducting active monitoring using DXA measurement, while ensuring result reliability, constrained our sample size. The present research cohort size has already enabled us to identify a statistically significant correlation between exposure to air pollutants and osteoporosis. While a larger sample size may bolster the observed correlation between short-term exposure and osteoporosis, it is unlikely to alter our established conclusion that the association is notably stronger with long-term exposure. However, extending the conclusion to a broader scope might necessitate a wider range of exposure to pollutants, thereby gaining further insights into the health effects at higher or lower concentrations. In the future, we plan to obtain national data from all participants in our project for further analysis. Second, due to limited air pollution data availability, we could only access data from 2013 onwards, limiting our analysis of longer exposure lags on osteoporosis. Finally, despite our best efforts to adjust for confounding factors, we cannot eliminate residual confounding, especially since factors influencing osteoporosis and bone mineral density are not yet fully understood.

Conclusively, this study reveals a potential link between air pollutants and osteoporosis, particularly emphasized with prolonged exposure. The susceptibility to air pollution-induced osteoporosis seems heightened in individuals aged 60 and above, those with a BMI exceeding 25, and among males. These findings identify specific demographics requiring targeted public health interventions to mitigate the adverse effects of air pollution on their bone health.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding authors.

HS: Conceptualization, Formal analysis, Funding acquisition, Supervision, Writing – original draft, Writing – review & editing. YW: Conceptualization, Data curation, Methodology, Writing – original draft, Writing – review & editing. XP: Investigation, Writing – review & editing, Supervision. WY: Investigation, Writing – review & editing. JS: Investigation, Resources, Writing – review & editing. JL: Investigation, Writing – review & editing. GZ: Investigation, Writing – review & editing. XL: Investigation, Writing – review & editing. XX: Investigation, Resources, Writing – review & editing. YZ: Conceptualization, Data curation, Investigation, Resources, Writing – original draft, Writing – review & editing.