Association between serum phosphorus levels and pelvic bone mineral density in U.S. adults aged 18–59 years

Abstract

Background

Although the role of serum phosphorus in bone metabolism is well-established, its precise connection to bone density in different anatomical regions remains uncertain. The pelvis, a vital load-bearing structure crucial for movement and stability, has received limited attention because of its relationship with serum phosphorus. This study investigated the potential association between serum phosphorus levels and pelvic bone mineral density (BMD) in adults aged 18 to 59 years.

Methods

Using data from the 2015–2018 National Health and Nutrition Examination Surveys NHANES, we applied multivariable logistic regression models to investigate the association between serum phosphorus levels and pelvic BMD. The analysis was further refined using smoothed curves and generalized additive models.

Results

The analysis included a total of 5,589 adults. After adjusting for confounding variables, a negative association was observed between serum phosphorus levels and pelvic BMD. This inverse association was consistent in the subgroup analyses for females and Whites, however, this correlation was not found in males, Blacks, Mexican Americans, other Hispanics, or other racial groups.

Conclusion

Our findings indicated a notable inverse association between serum phosphorus levels and pelvic bone mineral density in females, while no significant association was observed in males.

Introduction

Musculoskeletal disorders remain main chronic disease worldwide [1–3]. Maintaining bone health is essential to overall well-being, especially as aging populations experience a growing incidence of osteoporosis and related fractures. Osteoporosis involves decreased bone mineral density and structural changes, significantly increasing fracture risk in weight-bearing bones such as the pelvis, spine, and femur [4]. Pelvic fractures, in particular, can be especially severe, as they are often linked to high morbidity and mortality rates, especially among elderly individuals [5]. Identifying factors influencing pelvic bone mineral density is essential for improving clinical care and public health strategies.

Phosphorus is essential for bone metabolism and about 85% of the body’s phosphorus is stored as hydroxyapatite in bones and teeth [6]. In addition to calcium, phosphorus is fundamental for maintaining bone structure and strength. Serum phosphorus levels are tightly controlled by the interaction of dietary intake, renal excretion, and hormonal regulation, primarily involving parathyroid hormone (PTH) and active vitamin D (1,25-dihydroxyvitamin D) [7]. Although the roles of calcium and vitamin D in bone health are well-established, the impact of serum phosphorus on bone mineral density (BMD), particularly in the pelvic area, is less comprehensively studied.

Recent research suggests a potential link between serum phosphorus levels and variations in bone mineral density (BMD) [8]. High phosphorus levels, frequently seen in conditions like chronic kidney disease (CKD), have been linked to increased bone turnover and abnormalities in mineralization, which may lead to bone loss [9]. However, findings on the relationship between phosphorus levels and bone health in the general population are inconsistent. Additionally, the specific influence of serum phosphorus on pelvic BMD has yet to be thoroughly investigated [10].

Fibroblast Growth Factor 23 (FGF23), primarily produced by osteocytes in bone, regulates phosphate balance by reducing phosphate reabsorption in the kidneys, thus promoting phosphate excretion and preventing hyperphosphatemia, which can cause vascular calcification and bone mineralization defects [11]. Osteocytes, particularly trabecular osteocytes in areas of high bone turnover, play a significant role in phosphate metabolism, influenced by mechanical loading and bone matrix dynamics. Additionally, the co-receptor alphaKlotho is essential for FGF23 function, enhancing its binding to receptors in the kidneys to reduce phosphate reabsorption. Disruption of the FGF23-alphaKlotho axis can lead to phosphate imbalances and disorders like chronic kidney disease-mineral bone disorder (CKD-MBD).

Considering the critical role of phosphorus in bone mineralization and the potential effects of disrupted phosphorus metabolism on bone density, it is important to clarify the role of serum phosphorus in regulating pelvic BMD [12]. Understanding this relationship could be key for early detection of individuals at increased risk of osteoporosis and fractures, particularly those with irregular phosphorus metabolism.

This study investigated the association between serum phosphorus levels and pelvic BMD in adult participants. We aimed to evaluate if serum phosphorus levels independently predict pelvic BMD, accounting for confounding factors such as age, sex, BMI, and calcium and vitamin D levels. This study’s findings offer valuable insights into phosphorus’s role in bone health, potentially informing targeted strategies for osteoporosis prevention and management of related complications.

Materials and methods

Data source and study population

The National Health and Nutrition Examination Survey (NHANES) assesses the health and dietary status of U.S. adults and children [13]. Every year, NHANES collects data from a representative sample of people from different areas throughout the United States. The interviews address subjects like demographics, socioeconomic background, dietary habits, and health-related factors, while the physical examination aspect involves physiological assessments and laboratory analyses. For this investigation, we utilized NHANES data from 2015 to 2018.Of the 19,225 participants, 10,367 were excluded due to missing pelvic BMD data, 1,863 due to absent serum phosphorus measurements, and 1,406 for being under 18 years old. This left a total of 5,589 participants included in the study (Fig. 1).

Fig. 1.

The selection flowchart of the participants

Ethics statement

The National Center for Health Statistics Research Ethics Review Board approved the NHANES protocol and all participants provided written informed consent. The ethics board at Eastern Hepatobiliary Surgery Hospital also approved the research protocols for this specific study. NHANES data are publicly available after anonymization, allowing researchers to format and analyze them appropriately. This study adheres to data usage restrictions, ensuring that the information is exclusively utilized for statistical analysis and that all procedures comply with applicable standards and regulations.

Study variables

Phosphorus levels in serum were measured through a timed-rate chemical reaction technique. This method involves the reaction of inorganic phosphorus with ammonium molybdate in an acidic solution, resulting in the formation of a colored phosphomolybdate complex. The system subsequently monitors the absorbance change at 365 nm within a set time period, where this change in absorbance is directly linked to the phosphorus concentration in the sample. Pelvic bone mineral density (BMD) was assessed via dual-energy X-ray absorptiometry (DXA) using a Hologic QDR 4500 A scanner with Apex software version 3.2, operated by certified radiologic technologists. To account for potential confounding factors that could obscure the association between serum phosphorus and pelvic BMD, several covariates were included in the multivariate models. The study examined covariates including age, gender, race, education level, BMI, family income-to-poverty ratio, total protein, lifetime smoking history (defined as smoking at least 100 cigarettes), diabetes status, hypertension status, cholesterol, blood urea nitrogen, and total serum calcium. Detailed explanations of these variables and their calculation methods can be found on the NHANES website (http://www.cdc.gov/nchs/nhanes/).

Statistical analysis

Continuous variables are presented as mean ± standard deviation (SD), while categorical variables are shown as counts (percentages). Chi-square tests and t-tests were employed to examine demographic characteristics specific to each gender. Three distinct weighted multiple linear regression models were applied to examine the relationship between serum phosphorus and pelvic BMD. Model I included no adjustments, whereas Model II included adjustments for three common demographic variables: age, gender, and race. Model III was adjusted for all covariates outlined in Table 1. Additional subgroup analyses were performed as well. A weighted generalized additive model with smooth curve fitting was used to address potential nonlinearity. Statistical analyses were performed using R and Empower Stats, with significance determined at P < 0.05.

Table 1.

Weighted characteristics of the study population based on serum phosphorus quartiles

Phosphorus	Q1	Q2	Q3	Q4	P-value
	(0.61–1.23)	(1.23–1.85)	(1.85–2.47)	(2.47–3.1)
Age(years)	39.813 ± 11.356	39.359 ± 11.782	38.714 ± 12.398	36.692 ± 12.595	< 0.00001
Gender, %					< 0.00001
Male	59.741	53.798	48.598	49.810
Female	40.259	46.202	51.402	50.190
Race/Ethnicity, %					0.61404
Mexican American	11.703	11.122	9.926	11.269
Other Hispanic	7.292	9.143	7.642	8.175
None -Hispanic White	58.514	57.620	59.254	58.336
None -Hispanic Black	12.703	11.304	11.363	11.803
Other Race	9.788	10.811	11.816	10.418
Education level, %					0.00096
Less than high school	4.663	4.080	3.915	3.768
High school	32.644	33.818	28.841	29.332
More than high school	62.693	62.101	67.244	66.9
Diabetes, %					0.19776
Yes	5.285	6.304	5.877	5.454
No	94.714	93.696	94.123	94.546
Hypertension, %					0.03491
Yes	22.032	23.586	21.130	19.022
No	77.968	76.414	73.87	80.978
Smoked at least 100 cigarettes in life, %					0.00045
Yes	41.691	44.135	36.784	36.678
No	58.309	55.865	63.216	63.322
Body mass index(kg/m2)	30.184 ± 6.959	30.184 ± 6.959	28.794 ± 6.763	28.558 ± 6.957	< 0.00001
Income to poverty ratio	2.900 ± 1.596	2.902 ± 1.565	2.996 ± 1.626	2.818 ± 1.627	0.02050
Total calcium (mmol/L, mean ± SD)	2.307 ± 0.085	2.326 ± 0.078	2.338 ± 0.081	2.352 ± 0.081	< 0.00001
Blood urea nitrogen (mmol/L, mean ± SD)	4.711 ± 1.413	4.835 ± 1.434	4.877 ± 1.423	4.984 ± 1.749	0.00005
Cholesterol (mmol/L, mean ± SD)	4.912 ± 1.137	4.974 ± 1.059	4.960 ± 1.001	4.958 ± 1.042	0.48077
Total protein (g/dL, mean ± SD)	7.150 ± 0.393	7.172 ± 0.416	7.186 ± 0.413	7.198 ± 0.418	0.01716
Pelvis BMD (g/cm2, mean ± SD)	1.268 ± 0.155	1.244 ± 0.155	1.254 ± 0.166	1.245 ± 0.167	0.00030

Notes: Mean ± SD for continuous variables: the p value was calculated via the weighted linear regression model. (%) For categorical variables: the p value was calculated via the weighted chi-square test

Results

Participants were categorized into quartiles based on serum phosphorus levels: Q1 (0.61–1.23 mmol/L), Q2 (1.23–1.85 mmol/L), Q3 (1.85–2.47 mmol/L), and Q4 (2.47–3.10 mmol/L), as detailed in Table 1. The study comprised 5,589 participants aged 18 to 59. Significant differences were observed in baseline characteristics among the serum phosphorus quartiles. Participants in the highest quartile were predominantly female, had higher education levels, and showed increased levels of total calcium, blood urea nitrogen, and total protein, with reduced pelvic BMD, compared to those in other quartiles.

Table 2 presents the findings from the multivariate regression analysis. The unadjusted model revealed a negative correlation between serum phosphorus and pelvic BMD (β = −0.042, 95% CI − 0.066 to − 0.018, P < 0.05).The significant association persisted after adjusting for covariates in Model 2 (β = −0.038, 95% CI − 0.062, − 0.015, P < 0.05) and Model 3 (β = −0.029, 95% CI − 0.053, − 0.004, P < 0.05).After categorizing serum phosphorus levels into quartiles, individuals in the lowest quartile exhibited a pelvic BMD that was 0.023 g/cm² higher than those in the highest quartile.

Table 2.

Association between serum phosphorus levels and pelvic bone mineral density (g/cm²)

	Model 1β (95% CI) p value	Model 2β (95% CI) p value	Model 3β (95% CI) p value
Phosphorus(mmol/L)	-0.042(-0.066, -0.018) 0.00078	-0.038 (-0.062, -0.015) 0.00157	-0.029 (-0.053, -0.004) 0.02409
Q1	Reference	Reference	Reference
Q2	-0.025 (-0.038, -0.012) 0.00019	-0.020 (-0.033, -0.008) 0.00150	-0.016 (-0.029, -0.004) 0.01097
Q3	-0.015 (-0.026, -0.003) 0.01690	-0.008 (-0.019, 0.004) 0.17825	-0.003 (-0.015, 0.008) 0.58354
Q4	-0.023 (-0.035, -0.011) 0.00015	-0.021 (-0.033, -0.009) 0.00045	-0.016 (-0.028, -0.004) 0.01026
P for trend	0.00178	0.00424	0.04870
Stratified by gender
Men	0.010 (-0.022, 0.042) 0.5259	-0.006 (-0.038, 0.026) 0.7303	-0.010 (-0.043, 0.023) 0.5627
Women	-0.077 (-0.114, -0.041) < 0.0001	-0.069 (-0.105, -0.033) 0.0002	-0.045 (-0.083, -0.008) 0.0187
Stratified by race
Mexican American	-0.054 (-0.127, 0.019) 0.1443	-0.052 (-0.123, 0.020) 0.1555	-0.041 (-0.118, 0.037) 0.3036
Other Hispanic	0.027 (-0.060, 0.115) 0.5396	0.027 (-0.059, 0.113) 0.5450	0.036 (-0.054, 0.127) 0.4304
None-Hispanic White	-0.079 (-0.111, -0.047) < 0.0001	-0.072 (-0.103, -0.040) < 0.0001	-0.060 (-0.093, -0.027) 0.0003
None-Hispanic Black	0.032 (-0.033, 0.097) 0.3339	-0.004 (-0.068, 0.061) 0.9119	0.020 (-0.047, 0.088) 0.5552
Other Race	0.024 (-0.049, 0.098) 0.5184	0.047 (-0.024, 0.119) 0.1959	0.048 (-0.028, 0.125) 0.2156

Notes: Model 1:no covariates were adjusted. Model 2: age, gender, and race were adjusted. Model 3: age, gender, race, educational level, BMI, family income-to-poverty ratio, smoking at least 100 cigarettes over the life period to the point of data collection, diabetes status, hypertension status, total calcium, blood urea nitrogen, total protein, and cholesterol were adjusted. In the subgroup analysis stratified by gender and race, the model is not adjusted for sex and race, respectively

In the gender-stratified subgroup analysis, the negative association between serum phosphorus and pelvic BMD remained significant among women (β = −0.045, 95% CI: −0.083, − 0.008, P = 0.00187) but was not significant in men (β = −0.01, 95% CI: −0.043, 0.023, P = 0.5627).Similarly, in the race-stratified analysis, the negative correlation remained significant among Whites (β = −0.06, 95% CI: −0.093, − 0.027, P = 0.0003), but was not observed in Blacks (β = 0.020, 95% CI: −0.047, 0.088, P = 0.5552), Mexican Americans (β = −0.041, 95% CI: −0.118, 0.037, P = 0.3036), other Hispanics (β = 0.036, 95% CI: −0.054, 0.127, P = 0.4304), or other racial groups (β = 0.048, 95% CI: −0.028, 0.125, P = 0.2156). Figures 2, 3 and 4 show the smooth curve fitting and generalized additive models describing the nonlinear relationship between serum phosphorus and pelvic BMD.

Fig. 2.

Association between serum phosphorus levels and pelvic bone mineral density. (A) Each black point represents a sample. (B) The solid red line represents the smooth curve fit between variables. The blue bands represent the 95% confidence intervals from the fit. Age, gender, race, educational level, BMI, family income-to-poverty ratio, smoking at least 100 cigarettes over the life period to the point of data collection, diabetes status, hypertension status, total calcium, blood urea nitrogen, total protein, and cholesterol were adjusted

Fig. 3.

Association between serum phosphorus levels and pelvic bone mineral density stratified by gender. Age, race, educational level, BMI, family income-to-poverty ratio, smoking at least 100 cigarettes over the life period to the point of data collection, diabetes status, hypertension status, total calcium, blood urea nitrogen, total protein, and cholesterol were adjusted

Fig. 4.

The association between serum phosphorus levels and pelvic bone mineral density stratified by race. Age, gender, educational level, BMI, family income-to-poverty ratio, smoking at least 100 cigarettes over the life period to the point of data collection, diabetes status, hypertension status, total calcium, blood urea nitrogen, total protein, and cholesterol were adjusted

Discussion

Main interpretation

Multivariate logistic regression analysis showed an association between elevated serum phosphorus levels and reduced pelvic BMD.A 1 mmol/L rise in serum phosphorus corresponds to a 0.029 g/cm² reduction in pelvic BMD. These findings suggest that elevated serum phosphorus significantly increases the risk of fracture. Subgroup analysis showed an inverted U-shaped correlation between serum phosphorus levels and pelvic BMD in Whites, a pattern absent in Blacks, Mexican Americans, and other racial groups. Furthermore, a negative association was identified in men, while this relationship was not significant in women.

This study not only reveals an association between serum phosphorus levels and pelvic BMD but also offers potential therapeutic insights for clinicians. This negative correlation suggests that individuals with lower serum phosphorus levels may have higher pelvic BMD. Subgroup analyses were performed to gain a more detailed understanding of the dataset. Our results indicate that in women and Whites, lower serum phosphorus is linked to higher pelvic BMD. Additionally, an inverted U-shaped relationship was found between serum phosphorus levels and pelvic BMD. Further prospective studies with larger populations are needed to clarify the relationship between serum phosphorus and pelvic BMD across various genders and racial groups.

The connection between serum phosphorus and pelvic BMD may be explained by phosphorus’s essential role in bone mineralization. Along with calcium, phosphorus forms hydroxyapatite crystals, which are essential for maintaining bone strength and density [14, 15]. Elevated phosphorus levels may stimulate osteoblast activity and promote bone mineralization, resulting in higher BMD [16]. However, excessive phosphorus can disrupt calcium absorption and trigger increased parathyroid hormone (PTH) secretion, which may lead to bone resorption and a decrease in BMD [17]. Phosphorus also regulates the production of active vitamin D, which is crucial for calcium and bone metabolism [18]. This delicate balance highlights the importance of maintaining optimal serum phosphorus levels for preserving bone density, particularly in weight-bearing bones such as the pelvis. High phosphorus levels can cause bone resorption through secondary hyperparathyroidism and increased fibroblast growth factor-23 (FGF-23) activity, disrupting calcium-phosphorus balance and impairing bone mineralization [19–21]. These findings align with prior research showing that hyperphosphatemia negatively affects skeletal health, especially in chronic kidney disease (CKD) patients, where impaired renal function leads to increased serum phosphorus levels [22, 23].

Bone mineral density (BMD) is a key indicator of bone health, influenced by complex interactions between parathyroid hormone (PTH), vitamin D, and the calcium-phosphorus (Ca-P) balance [24]. PTH, released in response to low calcium levels, increases calcium release from bones and decreases calcium excretion by the kidneys, while also promoting phosphate excretion, thus maintaining an inverse relationship between calcium and phosphorus [25]. Vitamin D enhances calcium and phosphorus absorption in the intestines, supporting bone mineralization [26]. Disruptions in this regulatory system, such as vitamin D deficiency, hyperphosphatemia, or hyperparathyroidism, can lead to reduced BMD and an increased risk of fractures, contributing to bone disorders like osteoporosis.

Our findings align with those of several previous studies, including Salamat MR et al. (2023) identified a positive correlation between serum phosphorus levels and hip BMD [27]. However, our results differ from those of Zhu Z J et al. (2023) identified a negative correlation between serum phosphorus levels and bone mineral density (BMD) [28]. These discrepancies could be attributed to differences in sample characteristics, such as age, dietary habits, and the methods used to measure both phosphorus and BMD. Moreover, Salamat MR et al. The study investigated different skeletal regions, such as the spine and femoral neck, which may respond variably to alterations in serum phosphorus levels.

In our study, we found a negative association between phosphate levels and bone mineral density (BMD) in women, which contrasts with the findings from the Rotterdam cohorts and MrOS study, where this relationship was observed in men but not in women [29]. Interestingly, the study “Linear and Non-linear Correlations Between Serum Phosphate Level and Bone Mineral Density in Type 2 Diabetes” also reported that in men with type 2 diabetes (T2D), serum phosphate levels were not associated with BMD. However, in women with T2D, a non-linear correlation was found between serum phosphate levels and femur neck or total hip BMD [30]. These differences between studies may arise from variations in study design, sample populations, or measurement methods. Gender differences in bone metabolism, such as the influence of estrogen and menopause on bone density, could contribute to these discrepancies. Additionally, our study did not account for factors like hormonal status or age-related changes that may affect phosphate metabolism and BMD. Future research should explore these variables and investigate the biological mechanisms that could explain why phosphate might have a stronger impact on BMD in women than in men.

Dietary phosphorus intake may significantly impact serum phosphorus levels, subsequently affecting BMD [31]. Phosphorus is plentiful in protein-rich foods like dairy products, meat, and processed items. Excessive consumption, particularly of processed foods, is linked to increased bone loss risk due to an imbalanced calcium-phosphorus ratio [32]. However, one limitation of our study is that we did not account for dietary phosphorus intake. Future studies should include dietary assessments to clarify the effect of dietary phosphorus on serum phosphorus levels and BMD.

Although our research concentrated on the link between serum phosphorus and pelvic BMD, bone metabolism is influenced by multiple factors, including calcium, vitamin D, PTH, and kidney function. Previous research has demonstrated that impaired kidney function can cause phosphorus retention, which may lead to hyperphosphatemia and disruptions in bone metabolism [33]. Moreover, PTH and vitamin D are key regulators in the feedback mechanisms controlling serum phosphorus and calcium levels, impacting bone turnover [34]. Interpreting the relationship between phosphorus and bone density requires considering these interconnected factors. Future studies should include a wider range of biochemical markers to improve insights into bone health.

Non-fasting conditions are known to attenuate the associations between serum phosphate and health outcomes, such as mortality and fracture risk, and fasting serum phosphate is crucial for accurately assessing its relationship with bone mineral density (BMD) and fracture risk [35]. However, the data used in our study from the 2015–2018 NHANES cycles did not include fasting serum phosphate measurements, which means our analysis incorporated both fasting and non-fasting phosphate levels. This may have introduced variability in our findings. While we could not repeat the analyses with only fasting serum phosphate data, we acknowledge this limitation and plan to address it in future research. Studies using data from cycles with fasting serum phosphate measurements or designed to assess the impact of fasting status on phosphate metabolism would provide a clearer understanding of the true associations between phosphate and bone health outcomes.

This study suggests that serum phosphorus could be an effective biomarker for assessing bone health, particularly concerning pelvic BMD. This result has significant clinical implications, particularly for high-risk groups like postmenopausal women and individuals with chronic kidney disease, who frequently experience disruptions in phosphorus metabolism. Routine monitoring of serum phosphorus levels could help identify individuals at risk for bone density loss, allowing for timely interventions like dietary modifications or phosphate-lowering therapies. Additional studies are needed to determine precise serum phosphorus levels that can effectively predict changes in BMD and fracture risk.

In conclusion, this study suggests that serum phosphorus may serve as a valid biomarker for assessing bone health in the pelvic region, particularly in high-risk populations. Monitoring phosphorus levels, alongside calcium and vitamin D levels, could be an effective strategy for preventing bone loss and fractures in vulnerable groups. Future studies should investigate how phosphorus affects pelvic bone metabolism and develop therapeutic approaches to regulate phosphorus levels in individuals with impaired bone health.

Limitations

It is important to recognize that this study has some limitations. The cross-sectional design of this study limits the ability to determine a causal relationship between serum phosphorus levels and BMD. Longitudinal studies are necessary to confirm the direction of this association. Second, although the sample size was sufficient to detect significant correlations, it may limit the generalizability of our findings to populations with different demographic or health characteristics. Finally, we did not consider dietary phosphorus intake, which can influence serum phosphorus levels and bone health. Future research should incorporate dietary assessments and explore potential interactions between phosphorus intake and bone density outcomes.

While the study explores racial differences, the representation of certain racial and ethnic groups (such as Mexican Americans, Blacks, and other Hispanics) in the analyses may not be large enough to draw strong conclusions. The findings of no significant association in some groups could be influenced by sample size limitations or other demographic factors. The observed lack of significant associations in some subgroups could be attributed to these sample size constraints, as well as potential unmeasured demographic and socioeconomic factors.

While the study adjusts for a wide range of confounding variables (e.g., BMI, calcium levels, smoking history), there may be other unmeasured confounders (e.g., physical activity, medication use, or other comorbidities) that could influence the relationship between serum phosphorus and BMD. Future research should consider these variables to more accurately assess this relationship.

Conclusion

The study identified a negative relationship between serum phosphorus levels and pelvic BMD in females, with no corresponding relationship observed in males. Further studies are necessary to clarify the mechanisms linking serum phosphorus levels to pelvic bone mineral density.

Abbreviations

BMD

bone mineral density

NHANES

National Health and Nutrition Examination Survey

BMI

body mass index

PTH

parathyroid hormone

CKD

chronic kidney disease

FGF-23

fibroblast growth factor-23

Author contributions

Tao Jiang and Yin-quan Zhang conceived and designed the study. Yubo Pan, Jianing Xu, Jun yong Ge undertook the statistical analyses. Tao Jiang and Tian Li wrote the first draft of the manuscript. Shiliang Ji: Manuscript conception, Writing-Reviewing and Editing, Statistical supervision. All authors provided important comments to the manuscript and approved the final version of the manuscript.

Funding

No.

Data availability

The survey data are publicly accessible on www.cdc.gov/nchs/nhanes and https://www.jianguoyun.com/p/DUhyi70QuaiFChi7ut4FIAA

Declarations

Ethic approval and consent to participate

The NHANES protocols were approved by the Ethics Review Board of Third Affiliated Hospital of Naval Medical University, and written informed consent was obtained. Additionally, the study, in accordance with the Declaration of Helsinki, protocols received approval from the Third Affiliated Hospital of Naval Medical University’s research ethics committee at the Naval Medical University in Shanghai, China.

Consent for publication

N/A.

Competing interests

The authors declare no competing interests.

Clinical trial number

Not applicable.