Associations between low-dose aspirin and bone mineral density in older adults

Associations between low-dose aspirin and bone mineral density in older adults | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Associations between low-dose aspirin and bone mineral density in older adults Hongzhan Liu, Qiaojing Shi, Xianzhe Tang, Yun tian, Xungang Xiao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1483838/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background: The utilization rate of low-dose aspirin in the elderly is increasing, and osteoporosis in the elderly is getting more and more attention. Aspirin has been shown in numerous studies to affect bone metabolism. However, there is no clear link between low-dose aspirin use and bone mineral density (BMD). This study examined differences in bone mineral density between low-dose aspirin users and non-aspirin users in adults aged 50-80 years. Methods: We conducted a cross-sectional study of 4987 participants aged 50–80 years who participated in the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020. We performed multivariable logistic regression models to evaluate the associations between low-dose aspirin use and femoral neck BMD. Results: A total of 1143 adults were included in this study. Higher femoral neck BMD was observed in the low-dose aspirin use group compared with the non-aspirin use group (β=0.023, 95%CI 0.007-0.039). On subgroup analyses stratified by gender, this positive association existed in both gender after adjusting for confounders (males: β=0.020, 95%CI: -0.001-0.042; females: β=0.025, 95%CI: 0.001-0.050 P for interaction = 0.739). On subgroup analyses stratified by age, this positive association existed in three different age groups after adjusting for confounders (50-60 years: β=0.034, 95%CI: 0.004-0.065; 60-70 years: β=0.016, 95%CI: -0.011-0.043; 70-80 years: β=0.026, 95%CI: -0.003-0.055 P for interaction = 0.633). Conclusion: These findings from a human study looking into the correlation between low-dose aspirin use and femoral neck BMD suggest that taking regular low-dose aspirin may be associated with a higher femoral neck BMD. The effect of low-dose aspirin on femoral neck bone mineral density was not significant across age groups and genders. Osteoporosis BMD Aspirin NHANES DXA Figures Figure 1 1. Introduction Osteoporosis (OP) is a systemic bone metabolic disease in which bone loss outnumbers bone formation, leading to reduced bone mass, deterioration of bone microstructure, increased bone fragility, and increased fracture susceptibility[ 1 ]. Bone mineral density measurements at the neck of the femur, a typical site for assessing and treating BMD and a common site for fractures in the elderly, have been used as a marker of BMD in clinical trials for more than 30 years[ 2 ]. Many endogenous and exogenous factors influence bone metabolism. Prostaglandin E2 (PGE2) is a precursor of inflammatory factors synthesized by arachidonic acid in the enzyme Cyclooxygenase (COX), which affects bone metabolism[ 3 ]. It is critical for osteoblast and bone tissue formation and may influence osteoclast formation by altering the RANKL-OPG axis[ 3 – 7 ]. Aspirin belonging to NSAIDs inhibits the synthesis of PGE2 by inhibiting COX, thus affecting bone metabolism[ 8 ]. Aspirin could either result in decreased or increased BMD, depending on the balance of prostaglandins in bone tissue[ 9 ]. Aspirin inhibited osteoclast formation by inhibiting the activation of NF-κB and MAPKS in RANKL-induced RAW264.7 cells, thereby increasing bone mineral density[ 10 ]. However, aspirin, on the other hand, increases physiological nitric oxide (NO) production[ 11 , 12 ], which may result in a decrease in osteoblasts and an increase in osteoclast activity, resulting in a reduction in BMD. Aspirin is a cyclooxygenase inhibitor used mostly by the elderly as a primary prevention of cardiovascular disease and cancer[ 13 ]. Data from the 2010 U.S. National Health Interview Survey found that 19% of 27,157 subjects 18 and older regularly took aspirin[ 5 ]. It is essential in validating the relationship between the use of aspirin and BMD. The purpose of this study was to investigate the association between low-does aspirin use and femoral neck BMD among adults 50–80 years of age using the National Health and Nutrition Examination Survey (NHANES) data. 2. Materials And Methods 2.1. Study population Data for this study came from NHANES conducted between 2017 and March 2020, using a complex, multi-stage, hierarchical, clustered probability sample design to select a representative sample of civilians rather than a simple random sample based on the U.S. population[ 14 ]. The Ethics Review Committee of the National Center for Health Statistics approved all NHANES protocols and obtained written informed consent from all participants. All methods were performed in accordance with the relevant guidelines and regulations. The study population was limited to adults between 50 and 80 years of age (n = 4987). A total of 1,143 people were enrolled in the study, and a total of 3,844 people who were not eligible were excluded for the following reasons: missing data for aspirin use (n = 2794) or femoral neck BMD (n = 520), or a cancer diagnosis (n = 464), or missing data for cancer (n = 1) were excluded. We excluded 65 participants with serum total cholesterol, serum albumin, serum creatinine, serum globulin, serum phosphorus, serum calcium, serum triglycerides, serum uric acid data. Finally, a total of 15,560 participants were analyzed from 2017 to 2020, excluding patients younger than 50 years or older than 80 years, and a total of 4987 participants were analyzed (Fig. 1). The National Center for Health Statistics' Institutional Review Board reviewed and approved the survey protocols, and each participant signed a consent form voluntarily[ 15 ]. 2.2. Evaluation of exposures The exposure variables in this study were based on in-person home interviews with participants who reported aspirin use prophylaxis and followed recommendations for low-dose aspirin use. The questions to prevent aspirin use were asked at home by trained interviewers using a computer-assisted Personal Interview (CAPI) system. This is based on responses to the question, "Have you taken a daily low-dose aspirin as recommended by your doctor and other health care provider to prevent heart disease, stroke, or cancer?". Those who answered "don't know" (n = 3) were classified as deficient, while those who answered "sometimes take aspirin" (n = 59) or "stopped taking medication due to side effects" (n = 42) were excluded from the statistical analysis. 2.3. Outcome The study's outcome was femoral neck BMD, a measurement that has been used in the assessment and treatment of osteoporosis as a result of a clinical trial. All subjects in this study received a dual-energy X-ray absorptiometry (DXA) whole-body scan except for the following categories: First, pregnant women could not undergo dual-energy X-ray bone density determination. Second, within the previous 7 days, the subjects had used a radiographic contrast agent (such as dye or barium). Third, weigh more than 450 pounds (DXA table limit). All scans obtained during March 2017–2020 were analyzed using APEX V4.0 (Hologic) software. Experts checked the scans for accuracy and consistency. 2.4. Covariates The categorical variables listed below were used in this study as covariates: gender, race, smoking behavior, education level, and vigorous work activity. Our analysis included successive covariables: age, a ratio of household income to poverty, serum globulin, serum total cholesterol, serum albumin, serum phosphorus, serum calcium, serum triglycerides, serum uric acid, body mass index, serum creatinine, glycoprotein, and highly sensitive CRP. About the low dose of aspirin use, femoral neck BMD and covariate can be publicly available on http://www.cdc.gov/nchs/nhanes/ for more information. 2.5. Statistical analysis Data analysis in this study was conducted by the analysis guidelines prepared by the U.S. National Bureau of Statistics, using R version 3.4.3 ( http://www.R-project.org ) and filling in statistical software ( http:// www.empowerstats.com ). 0.05 (p value) was defined as a significant level. A multivariate logistic regression model was used to evaluate the relationship between low-dose aspirin use status and femoral neck bone mineral density. Following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement guidelines[ 16 ], subgroup analyses stratified by age and sex were chosen, and interaction tests were run to make the data more useful. All methods were performed in accordance with the relevant guidelines and regulations. Three models were constructed: Model 1: no covariables are adjusted; Model 2: age and race or age and sex are adjusted; Model 3: all covariables are adjusted. 3. Results According to the characteristics of the weighted sample shown in Table 1 , the following are the characteristics of non-aspirin and low-dose aspirin users: compared with the non-aspirin group (n = 330), the low-dose aspirin group (n = 813) was older (mean age 65.57 ± 8.49 years and 62.91 ± 8.45 years). In the non-aspirin group, the proportion was 59.52% in females, 40.48% in males, 38.51% in the 50–60 years old group, 40.19% in the 60–70 years old group, and 21.30% in 70–80 years old group. Women accounted for 58.77% of the low-dose aspirin group, while men accounted for 41.23%. A total 28.42% in the 50–60 years old group, 36.68% in the 60–70 years old group, and 34.90% in the 70–80 years old group. Smoking status, education level, serum triglyceride, body mass index, serum glycohemoglobin, serum calcium, serum total cholesterol was also significantly different between the two groups (P < 0.05). Table 1 Weighted Characteristics of Study Sample Non-aspirin users and low-dose aspirin users Low-dose aspirin use P value No(n = 330) Yes(n = 813) Age(years) 62.91 ± 8.45 65.57 ± 8.49 < 0.0001 Age groups < 0.0001 50–60 years 38.51 28.42 60–70 years 40.19 36.68 70–80 years 21.30 34.90 Gender (%) 0.8150 Male 59.52 58.77 Female 40.48 41.23 Race (%) 0.1137 Mexican American 5.66 4.44 Other Hispanic 8.95 5.34 Non-Hispanic White 69.73 71.39 Non-Hispanic Black 9.48 10.32 Other Race-Including Multi-Racial 6.18 8.51 Ratio of family income to poverty 3.16 ± 1.65 3.18 ± 1.49 0.7968 Serum Total Cholesterol (mmol/L) 5.13 ± 1.08 4.66 ± 1.13 < 0.0001 Serum albumin(g/L) 41.00 ± 2.90 40.75 ± 2.98 0.1975 Serum creatinine (mmol/L) 83.15 ± 24.10 83.50 ± 30.84 0.8561 Serum globulin(g/L) 30.21 ± 4.23 29.44 ± 4.14 0.0047 Serum phosphorus(mmol/L) 1.15 ± 0.17 1.14 ± 0.17 0.3782 Serum calcium(mg/dl) 9.31 ± 0.34 9.37 ± 0.37 0.0117 Serum triglycerides(mmol/L) 1.63 ± 1.04 1.80 ± 1.21 0.0297 Serum uric acid (umol/L) 328.01 ± 78.97 328.90 ± 82.34 0.8674 Body mass index (kg/m2) 29.13 ± 5.12 30.06 ± 5.79 0.0104 Serum glycohemoglobin (%) 6.01 ± 1.29 6.25 ± 1.10 0.0021 High-sensitivity CRP (mg/L) 3.65 ± 10.43 3.87 ± 10.67 0.7573 Education level (%) 0.0039 Less than high school 10.38 11.78 High school 26.47 35.60 More than high school 63.15 52.62 Smoking status (%) 0.0004 Every day 15.92 10.29 Some days 4.20 1.24 Not at all 32.95 35.42 Recorded 46.93 53.04 Vigorous work activity(%) 0.4900 Yes 23.58 21.18 No 76.17 78.74 Recorded 0.25 0.07 Femoral neck BMD(gm/cm2) 0.76 ± 0.13 0.78 ± 0.15 0.0532 Mean ± SD for continuous variables: P value was calculated by weighted linear regression model Percent for categorical variables: P value was calculated by weighted chi-square test Table 2 shows the results of multiple regression analysis. In the unadjusted model, low-dose aspirin use was positively associated with femoral neck BMD (β = 0.018, 95%CI: -0.000-0.037). After adjusting for confounders, this positive association persisted in model 2 (adjusted for age, sex, and race) (β = 0.032, 95%CI: 0.017–0.048) and model 3 (adjusted for all covariates) (β = 0.023, 95%CI: 0.007–0.039). On average, low-dose aspirin users had 0.023 g/cm 2 higher bone mineral density than non-aspirin users. Table 2 Associations between low-dose aspirin use and femoral neck bone mineral density Model1, β (95% CI, P) Model2, β (95% CI, P) Model3, β (95% CI, P) Low-dose aspirin use No Reference Reference Reference Yes 0.018 (-0.000, 0.037) 0.05315 0.032 (0.017, 0.048) 0.00006 0.023 (0.007, 0.039) 0.00388 Model 1 no covariates were adjusted; Model 2 age, gender, and race were adjusted; Model 3 age, gender, race, education level, smoking behavior, vigorous work activity, ratio of family income to poverty, total cholesterol, albumin, serum creatinine, globulin, serum phosphorus, serum calcium, serum triglycerides, serum uric acid, body mass index, glycohemoglobin and high-sensitivity CRP were adjusted. Table 3 shows the sex-based stratified analysis and interaction tests. Table 3 shows the sex-based stratified analysis and interaction tests. Low-dose aspirin use was positively correlated with femoral neck BMD in both males (β = 0.020, 95%CI: -0.001-0.042) and females (β = 0.025, 95%CI: 0.001–0.050), P interaction = 0.854, indicating that the effect of low-dose aspirin on femoral neck BMD was not significantly different between genders. Table 3 Subgroup analyses stratified by gender Model1, β (95% CI, P) Model2, β (95% CI, P) Model3, β (95% CI, P) Male Non-aspirin users Reference Reference Reference Low-dose aspirin users 0.017 (-0.005, 0.039) 0.12850 0.028 (0.007, 0.049) 0.00785 0.020 (-0.001, 0.042) 0.06324 Female Non-aspirin users Reference Reference Reference Low-dose aspirin users 0.023 (-0.004, 0.050) 0.09851 0.039 (0.014, 0.063) 0.00230 0.025 (0.001, 0.050) 0.04467 P interaction 0.7391 0.5418 0.8543 Model 1 no covariates were adjusted; Model 2 age and race were adjusted; Model 3 age, race, education level, smoking behavior, vigorous work activity, ratio of family income to poverty, total cholesterol, albumin, serum creatinine, globulin, serum phosphorus, serum calcium, serum triglycerides, serum uric acid, body mass index, glycohemoglobin and high-sensitivity CRP were adjusted. Table 4 shows the stratified analysis and interaction tests by age. Stratified analysis by age showed that the positive association between low-dose aspirin use and femoral neck BMD remained in three different age groups: 50–60 years (β = 0.034, 95%CI: 0.004–0.065), 60–70 years (β = 0.016, 95%CI: -0.001-0.050), 70–80 years (β = 0.026, 95%CI: -0.003-0.055). The interaction P-value for the effect of low-dose aspirin on femoral neck BMD in the age groups of 50–60 years, 60–70 years, and 70–80 years was 0.4181, indicating that there was no significant difference in the effect of low-dose aspirin on femoral neck BMD. Table 4 Subgroup analyses stratified by age Model1, β (95% CI, P) Model2, β (95% CI, P) Model3, β (95% CI, P) 50–60 years Non-aspirin users Reference Reference Reference Low-dose aspirin users 0.055 (0.023, 0.088) 0.00097 0.056 (0.026, 0.086) 0.00034 0.034 (0.004, 0.065) 0.02914 60–70 years Non-aspirin users Reference Reference Reference Low-dose aspirin users 0.028 (0.000, 0.056) 0.04948 0.024 (-0.000, 0.049) 0.05370 0.016 (-0.011, 0.043) 0.24468 70–80 years Non-aspirin users Reference Reference Reference Low-dose aspirin users 0.011 (-0.023, 0.044) 0.52994 0.006 (-0.023, 0.035) 0.70122 0.026 (-0.003, 0.055) 0.08245 P interaction 0.1471 0.0386 0.4181 Model 1 no covariates were adjusted; Model 2 gender and race were adjusted; Model 3 gender, race, education level, smoking behavior, vigorous work activity, ratio of family income to poverty, total cholesterol, albumin, serum creatinine, globulin, serum phosphorus, serum calcium, serum triglycerides, serum uric acid, body mass index, glycohemoglobin and high-sensitivity CRP were adjusted. 4. Discussion This cross-sectional study investigated the relationships of low-dose aspirin use with femoral neck BMD. In summary, our results mainly show a significant increase in femoral neck BMD in low-dose aspirin users compared to non-aspirin users in the general US population. Stratified analysis and interaction test showed that the effect of low-dose aspirin on the bone mineral density of the femoral neck was not significant in different age groups and genders. Low-dose aspirin is a common drug used to prevent cardiovascular diseases, which have a high morbidity and mortality rate[ 17 , 18 ]. In addition to its antiplatelet activity, aspirin may also affect oxidative stress, vascular inflammation, and insulin sensitivity[ 19 – 24 ]. Recent studies have shown that low-dose aspirin can affect bone metabolism[ 13 , 25 – 31 ]. But these research results are contradictory and controversial. Early results suggest that aspirin can improve BMD and bone structure in young rat models of osteoporosis[ 32 – 34 ]. These results come from animal studies, and there is no definitive evidence in humans. Another study observed that, after adjusting for confounders, women who took aspirin five to seven times a week had higher bone mineral density in the hips and spine than women who did not take aspirin[ 29 ]. The findings are difficult to generalize to other populations because the subjects were all white women[ 29 ]. Carbone et al. found significant increases in systemic BMD in subjects using aspirin alone and aspirin plus selective nonsteroidal anti-inflammatory drugs relative to COX2[ 28 ]. Only two ethnic groups were represented in the study: 43.1% African American and 56.9% Caucasian. The average age of the study participants was 73.6 years (19–70 years). One study showed that long-term use of low-dose aspirin was not associated with decreased bone mineral density in the general population[ 35 ]. Individuals over 65 were excluded from the study, even though it was a large population study with multiple confounders adjusted for. However, because the majority of low-dose aspirin users were elderly, the study's sample size was limited to only 47 low-dose aspirin users. So the results are not representative of the general population. Despite a growing number of observational studies, there have been no randomized controlled trials of the effect of aspirin treatment on fracture risk in humans, and the relationship between aspirin use and bone mineral density is contradictory[ 26 , 28 , 29 , 36 ]. This research has several limitations. The fact that cross-sectional studies cannot accurately describe the duration of aspirin use, and thus cannot assess the effect of aspirin duration on bone mineral density, is a major limitation. Second, we were unable to assess the dependence of aspirin dose on BMD because this study lacked information on the exact dose of aspirin. Third, we only used DXA to assess BMD as a proxy for bone quality, rather than other bone quality indicators such as bone conversion biomarkers or quantitative CT measurements[ 37 , 38 ]. On the other hand, to better summarize the U.S. population, this study included a representative multiracial population sample with a large sample size that could be further analyzed by subgroup. In addition, we adjusted for multiple potential confounding factors, including age, sex, race, economic status, employment status, smoking status, and standard biochemical composition. Overall, our research shows that low-dose aspirin improves bone mineral density. There were no significant differences by gender or age, and it was difficult to conduct randomized controlled trials to test aspirin's efficacy because of its side effects. However, because all of these studies were observational, more prospective studies on the effect of low-dose aspirin on bone mineral density are needed. Declarations Ethical Statement The Ethics Review Committee of the National Center for Health Statistics approved all NHANES protocols and obtained written informed consent from all participants. All methods were performed in accordance with the relevant guidelines and regulations. Acknowledgments The authors thank the staff and the participants of the NHANES study for their valuable contributions. Funding The research was not funded. Disclosure The authors report no conflicts of interest in this work. Data availability Statement All data generated or analysed during this study are included in this published article [and its supplementary information files]. References Consensus development conference : diagnosis , prophylaxis , and treatment of osteoporosis . The American journal of medicine 1993, 94 (6):646–650. Hart DJ, Cronin C, Daniels M, Worthy T, Doyle DV, Spector TD: The relationship of bone density and fracture to incident and progressive radiographic osteoarthritis of the knee: the Chingford Study . Arthritis and rheumatism 2002, 46 (1):92–99. Raisz LG: Potential impact of selective cyclooxygenase - 2 inhibitors on bone metabolism in health and disease . The American journal of medicine 2001, 110 Suppl 3A :43s-45s. Zhou Y, Boudreau DM, Freedman AN: Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population . Pharmacoepidemiology and drug safety 2014, 23 (1):43–50. Suda K, Udagawa N, Sato N, Takami M, Itoh K, Woo JT, Takahashi N, Nagai K: Suppression of osteoprotegerin expression by prostaglandin E2 is crucially involved in lipopolysaccharide-induced osteoclast formation . Journal of immunology (Baltimore, Md: 1950) 2004, 172 (4):2504–2510. Liu H, Li W, Liu Y, Zhang X, Zhou Y: Co-administration of aspirin and allogeneic adipose-derived stromal cells attenuates bone loss in ovariectomized rats through the anti-inflammatory and chemotactic abilities of aspirin . Stem cell research & therapy 2015, 6 :200. Agas D, Marchetti L, Capitani M, Sabbieti MG: The dual face of parathyroid hormone and prostaglandins in the osteoimmune system . American journal of physiology Endocrinology and metabolism 2013, 305 (10):E1185-1194. Boutaud O, Sosa IR, Amin T, Oram D, Adler D, Hwang HS, Crews BC, Milne G, Harris BK, Hoeksema M et al : Inhibition of the Biosynthesis of Prostaglandin E2 By Low-Dose Aspirin: Implications for Adenocarcinoma Metastasis . Cancer prevention research (Philadelphia, Pa) 2016, 9 (11):855–865. Blackwell KA, Raisz LG, Pilbeam CC: Prostaglandins in bone: bad cop, good cop? Trends in endocrinology and metabolism: TEM 2010, 21 (5):294–301. Zeng YP, Yang C, Li Y, Fan Y, Yang HJ, Liu B, Sang HX: Aspirin inhibits osteoclastogenesis by suppressing the activation of NF-κB and MAPKs in RANKL-induced RAW264.7 cells . Molecular medicine reports 2016, 14 (3):1957–1962. Grosser N, Schröder H: Aspirin protects endothelial cells from oxidant damage via the nitric oxide-cGMP pathway . Arteriosclerosis, thrombosis, and vascular biology 2003, 23 (8):1345–1351. Taubert D, Berkels R, Grosser N, Schröder H, Gründemann D, Schömig E: Aspirin induces nitric oxide release from vascular endothelium: a novel mechanism of action . British journal of pharmacology 2004, 143 (1):159–165. Chin KY: A Review on the Relationship between Aspirin and Bone Health . Journal of osteoporosis 2017, 2017 :3710959. Dillon CF, Weisman MH: US National Health and Nutrition Examination Survey Arthritis Initiatives, Methodologies and Data . Rheumatic diseases clinics of North America 2018, 44 (2):215–265. Zipf G, Chiappa M, Porter KS, Ostchega Y, Lewis BG, Dostal J: National health and nutrition examination survey: plan and operations, 1999–2010 . Vital and health statistics Ser 1, Programs and collection procedures 2013(56):1–37. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies . PLoS medicine 2007, 4 (10):e296. Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R et al : Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association . Circulation 2018, 137 (12):e67-e492. Patrono C, Bachmann F, Baigent C, Bode C, De Caterina R, Charbonnier B, Fitzgerald D, Hirsh J, Husted S, Kvasnicka J et al : Expert consensus document on the use of antiplatelet agents. The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European society of cardiology . European heart journal 2004, 25 (2):166–181. Hundal RS, Petersen KF, Mayerson AB, Randhawa PS, Inzucchi S, Shoelson SE, Shulman GI: Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes . The Journal of clinical investigation 2002, 109 (10):1321–1326. Costanzo A, Moretti F, Burgio VL, Bravi C, Guido F, Levrero M, Puri PL: Endothelial activation by angiotensin II through NFkappaB and p38 pathways: Involvement of NFkappaB-inducible kinase (NIK), free oxygen radicals, and selective inhibition by aspirin . Journal of cellular physiology 2003, 195 (3):402–410. Ristimäe T, Zilmer M, Zilmer K, Kairane C, Kullisaar T, Teesalu R: Effect of low-dose aspirin on the markers of oxidative stress . Cardiovascular drugs and therapy 1999, 13 (6):485–490. Reilly M, Delanty N, Lawson JA, FitzGerald GA: Modulation of oxidant stress in vivo in chronic cigarette smokers . Circulation 1996, 94 (1):19–25. Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac RL: Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals . The Journal of experimental medicine 2002, 196 (8):1025–1037. Raghavan RP, Laight DW, Cummings MH: Aspirin in type 2 diabetes, a randomised controlled study: effect of different doses on inflammation, oxidative stress, insulin resistance and endothelial function . International journal of clinical practice 2014, 68 (2):271–277. Minn YK, Suk SH, Do SY: Osteoporosis as an independent risk factor for silent brain infarction and white matter changes in men and women : the PRESENT project . Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2014, 25 (10):2465–2469. Bleicher K, Cumming RG, Naganathan V, Seibel MJ, Sambrook PN, Blyth FM, Le Couteur DG, Handelsman DJ, Creasey HM, Waite LM: Lifestyle factors , medications , and disease influence bone mineral density in older men : findings from the CHAMP study . Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2011, 22 (9):2421–2437. Chen CH, Lin CL, Kao CH: Association Between Chronic Hepatitis B Virus Infection and Risk of Osteoporosis: A Nationwide Population-Based Study . Medicine 2015, 94 (50):e2276. Carbone LD, Tylavsky FA, Cauley JA, Harris TB, Lang TF, Bauer DC, Barrow KD, Kritchevsky SB: Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity . Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 2003, 18 (10):1795–1802. Bauer DC, Orwoll ES, Fox KM, Vogt TM, Lane NE, Hochberg MC, Stone K, Nevitt MC: Aspirin and NSAID use in older women: effect on bone mineral density and fracture risk. Study of Osteoporotic Fractures Research Group . Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 1996, 11 (1):29–35. Barker AL, Soh SE, Sanders KM, Pasco J, Khosla S, Ebeling PR, Ward SA, Peeters G, Talevski J, Cumming RG et al : Aspirin and fracture risk: a systematic review and exploratory meta-analysis of observational studies . BMJ open 2020, 10 (2):e026876. Chai SC, Foley EM, Arjmandi BH: Anti-atherogenic properties of vitamin E, aspirin, and their combination . PloS one 2018, 13 (10):e0206315. Yamaza T, Miura Y, Bi Y, Liu Y, Akiyama K, Sonoyama W, Patel V, Gutkind S, Young M, Gronthos S et al : Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents . PloS one 2008, 3 (7):e2615. Wei J, Wang J, Gong Y, Zeng R: Effectiveness of combined salmon calcitonin and aspirin therapy for osteoporosis in ovariectomized rats . Molecular medicine reports 2015, 12 (2):1717–1726. Chen ZW, Wu ZX, Sang HX, Qin GL, Wang LS, Feng J, Wang J, Li XJ, Wang JC, Zhang D: [Effect of aspirin administration for the treatment of osteoporosis in ovariectomized rat model] . Zhonghua yi xue za zhi 2011, 91 (13):925–929. Bonten TN, de Mutsert R, Rosendaal FR, Jukema JW, van der Bom JG, de Jongh RT, den Heijer M: Chronic use of low - dose aspirin is not associated with lower bone mineral density in the general population . International journal of cardiology 2017, 244 :298–302. Hill DD, Cauley JA, Bunker CH, Baker CE, Patrick AL, Beckles GLA, Wheeler VW, Zmuda JM: Correlates of bone mineral density among postmenopausal women of African Caribbean ancestry: Tobago women's health study . Bone 2008, 43 (1):156–161. Hollaender R, Hartl F, Krieg MA, Tyndall A, Geuckel C, Buitrago-Tellez C, Manghani M, Kraenzlin M, Theiler R, Hans D: Prospective evaluation of risk of vertebral fractures using quantitative ultrasound measurements and bone mineral density in a population-based sample of postmenopausal women: results of the Basel Osteoporosis Study . Annals of the rheumatic diseases 2009, 68 (3):391–396. Naylor K, Eastell R: Bone turnover markers: use in osteoporosis . Nature reviews Rheumatology 2012, 8 (7):379–389. Additional Declarations No competing interests reported. Supplementary Files Originaldata.xls Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 24 May, 2022 Reviews received at journal 18 May, 2022 Reviewers agreed at journal 18 May, 2022 Reviewers agreed at journal 09 May, 2022 Reviewers invited by journal 06 May, 2022 Editor assigned by journal 06 May, 2022 Editor invited by journal 01 Apr, 2022 Submission checks completed at journal 01 Apr, 2022 First submitted to journal 24 Mar, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1483838","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":95444719,"identity":"6b91f271-2377-4b1f-947b-a65fa872419c","order_by":0,"name":"Hongzhan Liu","email":"","orcid":"","institution":"University of South China","correspondingAuthor":false,"prefix":"","firstName":"Hongzhan","middleName":"","lastName":"Liu","suffix":""},{"id":95444721,"identity":"b9232500-034f-4c86-b251-88900e44122f","order_by":1,"name":"Qiaojing Shi","email":"","orcid":"","institution":"Affiliated hospital of xiangnan university","correspondingAuthor":false,"prefix":"","firstName":"Qiaojing","middleName":"","lastName":"Shi","suffix":""},{"id":95444722,"identity":"b1bf4ad7-6558-4c82-aa7a-15bd246bb1e8","order_by":2,"name":"Xianzhe Tang","email":"","orcid":"","institution":"Chenzhou First People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xianzhe","middleName":"","lastName":"Tang","suffix":""},{"id":95444723,"identity":"4c91eada-d69e-42b4-b107-2396eff0e9c6","order_by":3,"name":"Yun tian","email":"","orcid":"","institution":"Chenzhou First People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yun","middleName":"","lastName":"tian","suffix":""},{"id":95444724,"identity":"f2d2b0e2-d46a-4054-9bbf-1457a7a939c1","order_by":4,"name":"Xungang Xiao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYHACxgcJFTZybOztB4jWwmzw4UyaMR/PmQSitbBJzmw7nDhPwsGAOPUGN9IvG/OcSUtvk2BIYPhRsY2wFsmeM4WPeSpsctukGw8w9py5TVgLP3tPMsiW3DaZAwnMjG1EaGFj5kmT5m07nM4mkWBAnBZ+9vZjIO8nEK8F6BdwIBu2AQP5IFF+AYbYQ1BUysu3tx988KOCCC0MDDyI6DhAjHogYH9ApMJRMApGwSgYsQAAweo+TeIOFfAAAAAASUVORK5CYII=","orcid":"","institution":"Chenzhou First People's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Xungang","middleName":"","lastName":"Xiao","suffix":""}],"badges":[],"createdAt":"2022-03-24 04:44:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1483838/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1483838/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":19939390,"identity":"338850d1-c607-44bb-9b49-f882c929a10f","added_by":"auto","created_at":"2022-04-04 15:20:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":29301,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of NHANES sample selection from March 2017 to March 2020.\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1483838/v1/ec517be92271ea5c6b4ddb88.png"},{"id":19939391,"identity":"860ec76f-e8da-4d2a-8574-250ae2b42cf4","added_by":"auto","created_at":"2022-04-04 15:20:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1232272,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1483838/v1/7dae4524-fe09-42ce-8e60-821daa4810d5.pdf"},{"id":19939244,"identity":"62e47759-a07f-4900-84a2-1b3a2c277b8f","added_by":"auto","created_at":"2022-04-04 15:15:23","extension":"xls","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1473068,"visible":true,"origin":"","legend":"","description":"","filename":"Originaldata.xls","url":"https://assets-eu.researchsquare.com/files/rs-1483838/v1/50e05fa625e88cff136bc011.xls"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eAssociations between low-dose aspirin and bone mineral density in older adults\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eOsteoporosis (OP) is a systemic bone metabolic disease in which bone loss outnumbers bone formation, leading to reduced bone mass, deterioration of bone microstructure, increased bone fragility, and increased fracture susceptibility[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Bone mineral density measurements at the neck of the femur, a typical site for assessing and treating BMD and a common site for fractures in the elderly, have been used as a marker of BMD in clinical trials for more than 30 years[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Many endogenous and exogenous factors influence bone metabolism. Prostaglandin E2 (PGE2) is a precursor of inflammatory factors synthesized by arachidonic acid in the enzyme Cyclooxygenase (COX), which affects bone metabolism[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. It is critical for osteoblast and bone tissue formation and may influence osteoclast formation by altering the RANKL-OPG axis[\u003cspan additionalcitationids=\"CR4 CR5 CR6\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Aspirin belonging to NSAIDs inhibits the synthesis of PGE2 by inhibiting COX, thus affecting bone metabolism[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Aspirin could either result in decreased or increased BMD, depending on the balance of prostaglandins in bone tissue[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Aspirin inhibited osteoclast formation by inhibiting the activation of NF-κB and MAPKS in RANKL-induced RAW264.7 cells, thereby increasing bone mineral density[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, aspirin, on the other hand, increases physiological nitric oxide (NO) production[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], which may result in a decrease in osteoblasts and an increase in osteoclast activity, resulting in a reduction in BMD.\u003c/p\u003e \u003cp\u003eAspirin is a cyclooxygenase inhibitor used mostly by the elderly as a primary prevention of cardiovascular disease and cancer[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Data from the 2010 U.S. National Health Interview Survey found that 19% of 27,157 subjects 18 and older regularly took aspirin[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. It is essential in validating the relationship between the use of aspirin and BMD. The purpose of this study was to investigate the association between low-does aspirin use and femoral neck BMD among adults 50\u0026ndash;80 years of age using the National Health and Nutrition Examination Survey (NHANES) data.\u003c/p\u003e"},{"header":"2. Materials And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Study population\u003c/h2\u003e \u003cp\u003eData for this study came from NHANES conducted between 2017 and March 2020, using a complex, multi-stage, hierarchical, clustered probability sample design to select a representative sample of civilians rather than a simple random sample based on the U.S. population[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The Ethics Review Committee of the National Center for Health Statistics approved all NHANES protocols and obtained written informed consent from all participants. All methods were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e \u003cp\u003eThe study population was limited to adults between 50 and 80 years of age (n\u0026thinsp;=\u0026thinsp;4987). A total of 1,143 people were enrolled in the study, and a total of 3,844 people who were not eligible were excluded for the following reasons: missing data for aspirin use (n\u0026thinsp;=\u0026thinsp;2794) or femoral neck BMD (n\u0026thinsp;=\u0026thinsp;520), or a cancer diagnosis (n\u0026thinsp;=\u0026thinsp;464), or missing data for cancer (n\u0026thinsp;=\u0026thinsp;1) were excluded. We excluded 65 participants with serum total cholesterol, serum albumin, serum creatinine, serum globulin, serum phosphorus, serum calcium, serum triglycerides, serum uric acid data. Finally, a total of 15,560 participants were analyzed from 2017 to 2020, excluding patients younger than 50 years or older than 80 years, and a total of 4987 participants were analyzed (Fig.\u0026nbsp;1). The National Center for Health Statistics' Institutional Review Board reviewed and approved the survey protocols, and each participant signed a consent form voluntarily[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Evaluation of exposures\u003c/h2\u003e \u003cp\u003eThe exposure variables in this study were based on in-person home interviews with participants who reported aspirin use prophylaxis and followed recommendations for low-dose aspirin use. The questions to prevent aspirin use were asked at home by trained interviewers using a computer-assisted Personal Interview (CAPI) system. This is based on responses to the question, \"Have you taken a daily low-dose aspirin as recommended by your doctor and other health care provider to prevent heart disease, stroke, or cancer?\". Those who answered \"don't know\" (n\u0026thinsp;=\u0026thinsp;3) were classified as deficient, while those who answered \"sometimes take aspirin\" (n\u0026thinsp;=\u0026thinsp;59) or \"stopped taking medication due to side effects\" (n\u0026thinsp;=\u0026thinsp;42) were excluded from the statistical analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Outcome\u003c/h2\u003e \u003cp\u003eThe study's outcome was femoral neck BMD, a measurement that has been used in the assessment and treatment of osteoporosis as a result of a clinical trial. All subjects in this study received a dual-energy X-ray absorptiometry (DXA) whole-body scan except for the following categories: First, pregnant women could not undergo dual-energy X-ray bone density determination. Second, within the previous 7 days, the subjects had used a radiographic contrast agent (such as dye or barium). Third, weigh more than 450 pounds (DXA table limit). All scans obtained during March 2017\u0026ndash;2020 were analyzed using APEX V4.0 (Hologic) software. Experts checked the scans for accuracy and consistency.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Covariates\u003c/h2\u003e \u003cp\u003eThe categorical variables listed below were used in this study as covariates: gender, race, smoking behavior, education level, and vigorous work activity. Our analysis included successive covariables: age, a ratio of household income to poverty, serum globulin, serum total cholesterol, serum albumin, serum phosphorus, serum calcium, serum triglycerides, serum uric acid, body mass index, serum creatinine, glycoprotein, and highly sensitive CRP. About the low dose of aspirin use, femoral neck BMD and covariate can be publicly available on \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.cdc.gov/nchs/nhanes/\u003c/span\u003e\u003cspan address=\"http://www.cdc.gov/nchs/nhanes/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e for more information.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Statistical analysis\u003c/h2\u003e \u003cp\u003eData analysis in this study was conducted by the analysis guidelines prepared by the U.S. National Bureau of Statistics, using R version 3.4.3 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.R-project.org\u003c/span\u003e\u003cspan address=\"http://www.R-project.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) and filling in statistical software (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://\u003c/span\u003e\u003cspan address=\"http://\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003ca href=\"http://www.cdc.gov/nchs/nhanes/\" target=\"_blank\"\u003ewww.empowerstats.com\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.empowerstats.com\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). 0.05 (p value) was defined as a significant level. A multivariate logistic regression model was used to evaluate the relationship between low-dose aspirin use status and femoral neck bone mineral density. Following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement guidelines[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], subgroup analyses stratified by age and sex were chosen, and interaction tests were run to make the data more useful. All methods were performed in accordance with the relevant guidelines and regulations. Three models were constructed: Model 1: no covariables are adjusted; Model 2: age and race or age and sex are adjusted; Model 3: all covariables are adjusted.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eAccording to the characteristics of the weighted sample shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the following are the characteristics of non-aspirin and low-dose aspirin users: compared with the non-aspirin group (n\u0026thinsp;=\u0026thinsp;330), the low-dose aspirin group (n\u0026thinsp;=\u0026thinsp;813) was older (mean age 65.57\u0026thinsp;\u0026plusmn;\u0026thinsp;8.49 years and 62.91\u0026thinsp;\u0026plusmn;\u0026thinsp;8.45 years). In the non-aspirin group, the proportion was 59.52% in females, 40.48% in males, 38.51% in the 50\u0026ndash;60 years old group, 40.19% in the 60\u0026ndash;70 years old group, and 21.30% in 70\u0026ndash;80 years old group. Women accounted for 58.77% of the low-dose aspirin group, while men accounted for 41.23%. A total 28.42% in the 50\u0026ndash;60 years old group, 36.68% in the 60\u0026ndash;70 years old group, and 34.90% in the 70\u0026ndash;80 years old group. Smoking status, education level, serum triglyceride, body mass index, serum glycohemoglobin, serum calcium, serum total cholesterol was also significantly different between the two groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eWeighted Characteristics of Study Sample Non-aspirin users and low-dose aspirin users\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eLow-dose aspirin use\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo(n\u0026thinsp;=\u0026thinsp;330)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eYes(n\u0026thinsp;=\u0026thinsp;813)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.91\u0026thinsp;\u0026plusmn;\u0026thinsp;8.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.57\u0026thinsp;\u0026plusmn;\u0026thinsp;8.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge groups\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50\u0026ndash;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e60\u0026ndash;70 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e70\u0026ndash;80 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.8150\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRace (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1137\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMexican American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic White\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic Black\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther Race-Including Multi-Racial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRatio of family income to poverty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.16\u0026thinsp;\u0026plusmn;\u0026thinsp;1.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7968\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum Total Cholesterol (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.66\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum albumin(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.75\u0026thinsp;\u0026plusmn;\u0026thinsp;2.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1975\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum creatinine (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83.15\u0026thinsp;\u0026plusmn;\u0026thinsp;24.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.50\u0026thinsp;\u0026plusmn;\u0026thinsp;30.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.8561\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum globulin(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.21\u0026thinsp;\u0026plusmn;\u0026thinsp;4.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.44\u0026thinsp;\u0026plusmn;\u0026thinsp;4.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0047\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum phosphorus(mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3782\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum calcium(mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0117\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum triglycerides(mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0297\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum uric acid (umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e328.01\u0026thinsp;\u0026plusmn;\u0026thinsp;78.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e328.90\u0026thinsp;\u0026plusmn;\u0026thinsp;82.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.8674\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index (kg/m2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.13\u0026thinsp;\u0026plusmn;\u0026thinsp;5.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.06\u0026thinsp;\u0026plusmn;\u0026thinsp;5.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0104\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum glycohemoglobin (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh-sensitivity CRP (mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.65\u0026thinsp;\u0026plusmn;\u0026thinsp;10.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.87\u0026thinsp;\u0026plusmn;\u0026thinsp;10.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7573\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEducation level (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLess than high school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore than high school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking status (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEvery day\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSome days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot at all\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecorded\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVigorous work activity(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.4900\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecorded\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemoral neck BMD(gm/cm2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0532\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD for continuous variables: P value was calculated by weighted linear regression model\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003ePercent for categorical variables: P value was calculated by weighted chi-square test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the results of multiple regression analysis. In the unadjusted model, low-dose aspirin use was positively associated with femoral neck BMD (β\u0026thinsp;=\u0026thinsp;0.018, 95%CI: -0.000-0.037). After adjusting for confounders, this positive association persisted in model 2 (adjusted for age, sex, and race) (β\u0026thinsp;=\u0026thinsp;0.032, 95%CI: 0.017\u0026ndash;0.048) and model 3 (adjusted for all covariates) (β\u0026thinsp;=\u0026thinsp;0.023, 95%CI: 0.007\u0026ndash;0.039). On average, low-dose aspirin users had 0.023 g/cm\u003csup\u003e2\u003c/sup\u003e higher bone mineral density than non-aspirin users.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociations between low-dose aspirin use and femoral neck bone mineral density\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel1, β (95% CI, P)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModel2, β (95% CI, P)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModel3, β (95% CI, P)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow-dose aspirin use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.018 (-0.000, 0.037) 0.05315\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.032 (0.017, 0.048) 0.00006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.023 (0.007, 0.039) 0.00388\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eModel 1 no covariates were adjusted;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eModel 2 age, gender, and race were adjusted;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eModel 3 age, gender, race, education level, smoking behavior, vigorous work activity, ratio of family income to poverty, total cholesterol, albumin, serum creatinine, globulin, serum phosphorus, serum calcium, serum triglycerides, serum uric acid, body mass index, glycohemoglobin and high-sensitivity CRP were adjusted.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the sex-based stratified analysis and interaction tests. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the sex-based stratified analysis and interaction tests. Low-dose aspirin use was positively correlated with femoral neck BMD in both males (β\u0026thinsp;=\u0026thinsp;0.020, 95%CI: -0.001-0.042) and females (β\u0026thinsp;=\u0026thinsp;0.025, 95%CI: 0.001\u0026ndash;0.050), P interaction\u0026thinsp;=\u0026thinsp;0.854, indicating that the effect of low-dose aspirin on femoral neck BMD was not significantly different between genders.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSubgroup analyses stratified by gender\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eModel1, β (95% CI, P)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModel2, β (95% CI, P)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eModel3, β (95% CI, P)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNon-aspirin users\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLow-dose aspirin users\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.017 (-0.005, 0.039) 0.12850\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.028 (0.007, 0.049) 0.00785\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.020 (-0.001, 0.042) 0.06324\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNon-aspirin users\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLow-dose aspirin users\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.023 (-0.004, 0.050) 0.09851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.039 (0.014, 0.063) 0.00230\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.025 (0.001, 0.050) 0.04467\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eP interaction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.7391\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5418\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.8543\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eModel 1 no covariates were adjusted;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eModel 2 age and race were adjusted;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eModel 3 age, race, education level, smoking behavior, vigorous work activity, ratio of family income to poverty, total cholesterol, albumin, serum creatinine, globulin, serum phosphorus, serum calcium, serum triglycerides, serum uric acid, body mass index, glycohemoglobin and high-sensitivity CRP were adjusted.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows the stratified analysis and interaction tests by age. Stratified analysis by age showed that the positive association between low-dose aspirin use and femoral neck BMD remained in three different age groups: 50\u0026ndash;60 years (β\u0026thinsp;=\u0026thinsp;0.034, 95%CI: 0.004\u0026ndash;0.065), 60\u0026ndash;70 years (β\u0026thinsp;=\u0026thinsp;0.016, 95%CI: -0.001-0.050), 70\u0026ndash;80 years (β\u0026thinsp;=\u0026thinsp;0.026, 95%CI: -0.003-0.055). The interaction P-value for the effect of low-dose aspirin on femoral neck BMD in the age groups of 50\u0026ndash;60 years, 60\u0026ndash;70 years, and 70\u0026ndash;80 years was 0.4181, indicating that there was no significant difference in the effect of low-dose aspirin on femoral neck BMD.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSubgroup analyses stratified by age\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel1, β (95% CI, P)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModel2, β (95% CI, P)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModel3, β (95% CI, P)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50\u0026ndash;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-aspirin users\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow-dose aspirin users\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.055 (0.023, 0.088) 0.00097\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.056 (0.026, 0.086) 0.00034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.034 (0.004, 0.065) 0.02914\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e60\u0026ndash;70 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-aspirin users\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow-dose aspirin users\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.028 (0.000, 0.056) 0.04948\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.024 (-0.000, 0.049) 0.05370\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.016 (-0.011, 0.043) 0.24468\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e70\u0026ndash;80 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-aspirin users\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow-dose aspirin users\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.011 (-0.023, 0.044) 0.52994\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.006 (-0.023, 0.035) 0.70122\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.026 (-0.003, 0.055) 0.08245\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP interaction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.1471\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0386\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.4181\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eModel 1 no covariates were adjusted;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eModel 2 gender and race were adjusted;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eModel 3 gender, race, education level, smoking behavior, vigorous work activity, ratio of family income to poverty, total cholesterol, albumin, serum creatinine, globulin, serum phosphorus, serum calcium, serum triglycerides, serum uric acid, body mass index, glycohemoglobin and high-sensitivity CRP were adjusted.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis cross-sectional study investigated the relationships of low-dose aspirin use with femoral neck BMD. In summary, our results mainly show a significant increase in femoral neck BMD in low-dose aspirin users compared to non-aspirin users in the general US population. Stratified analysis and interaction test showed that the effect of low-dose aspirin on the bone mineral density of the femoral neck was not significant in different age groups and genders.\u003c/p\u003e \u003cp\u003eLow-dose aspirin is a common drug used to prevent cardiovascular diseases, which have a high morbidity and mortality rate[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In addition to its antiplatelet activity, aspirin may also affect oxidative stress, vascular inflammation, and insulin sensitivity[\u003cspan additionalcitationids=\"CR20 CR21 CR22 CR23\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Recent studies have shown that low-dose aspirin can affect bone metabolism[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26 CR27 CR28 CR29 CR30\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. But these research results are contradictory and controversial.\u003c/p\u003e \u003cp\u003eEarly results suggest that aspirin can improve BMD and bone structure in young rat models of osteoporosis[\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. These results come from animal studies, and there is no definitive evidence in humans. Another study observed that, after adjusting for confounders, women who took aspirin five to seven times a week had higher bone mineral density in the hips and spine than women who did not take aspirin[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The findings are difficult to generalize to other populations because the subjects were all white women[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Carbone et al. found significant increases in systemic BMD in subjects using aspirin alone and aspirin plus selective nonsteroidal anti-inflammatory drugs relative to COX2[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Only two ethnic groups were represented in the study: 43.1% African American and 56.9% Caucasian. The average age of the study participants was 73.6 years (19\u0026ndash;70 years). One study showed that long-term use of low-dose aspirin was not associated with decreased bone mineral density in the general population[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Individuals over 65 were excluded from the study, even though it was a large population study with multiple confounders adjusted for. However, because the majority of low-dose aspirin users were elderly, the study's sample size was limited to only 47 low-dose aspirin users. So the results are not representative of the general population. Despite a growing number of observational studies, there have been no randomized controlled trials of the effect of aspirin treatment on fracture risk in humans, and the relationship between aspirin use and bone mineral density is contradictory[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis research has several limitations. The fact that cross-sectional studies cannot accurately describe the duration of aspirin use, and thus cannot assess the effect of aspirin duration on bone mineral density, is a major limitation. Second, we were unable to assess the dependence of aspirin dose on BMD because this study lacked information on the exact dose of aspirin. Third, we only used DXA to assess BMD as a proxy for bone quality, rather than other bone quality indicators such as bone conversion biomarkers or quantitative CT measurements[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOn the other hand, to better summarize the U.S. population, this study included a representative multiracial population sample with a large sample size that could be further analyzed by subgroup. In addition, we adjusted for multiple potential confounding factors, including age, sex, race, economic status, employment status, smoking status, and standard biochemical composition.\u003c/p\u003e \u003cp\u003eOverall, our research shows that low-dose aspirin improves bone mineral density. There were no significant differences by gender or age, and it was difficult to conduct randomized controlled trials to test aspirin's efficacy because of its side effects. However, because all of these studies were observational, more prospective studies on the effect of low-dose aspirin on bone mineral density are needed.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Ethics Review Committee of the National Center for Health Statistics approved all NHANES protocols and obtained written informed consent from all participants. All methods were performed in accordance with the relevant guidelines and regulations. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the staff and the participants of the NHANES study for their valuable contributions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research was not funded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors report no conflicts of interest in this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eStatement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article [and its supplementary information files].\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003e\u003cstrong\u003eConsensus development conference\u003c/strong\u003e: \u003cstrong\u003ediagnosis\u003c/strong\u003e, \u003cstrong\u003eprophylaxis\u003c/strong\u003e, \u003cstrong\u003eand treatment of osteoporosis\u003c/strong\u003e. \u003cem\u003eThe American journal of medicine\u003c/em\u003e 1993, \u003cstrong\u003e94\u003c/strong\u003e(6):646\u0026ndash;650.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHart DJ, Cronin C, Daniels M, Worthy T, Doyle DV, Spector TD: \u003cstrong\u003eThe relationship of bone density and fracture to incident and progressive radiographic osteoarthritis of the knee: the Chingford Study\u003c/strong\u003e. Arthritis and rheumatism 2002, \u003cstrong\u003e46\u003c/strong\u003e(1):92\u0026ndash;99.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eRaisz LG: \u003cstrong\u003ePotential impact of selective cyclooxygenase\u003c/strong\u003e-\u003cstrong\u003e2 inhibitors on bone metabolism in health and disease\u003c/strong\u003e. \u003cem\u003eThe American journal of medicine\u003c/em\u003e 2001, \u003cstrong\u003e110 Suppl 3A\u003c/strong\u003e:43s-45s.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eZhou Y, Boudreau DM, Freedman AN: \u003cstrong\u003eTrends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population\u003c/strong\u003e. Pharmacoepidemiology and drug safety 2014, \u003cstrong\u003e23\u003c/strong\u003e(1):43\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eSuda K, Udagawa N, Sato N, Takami M, Itoh K, Woo JT, Takahashi N, Nagai K: \u003cstrong\u003eSuppression of osteoprotegerin expression by prostaglandin E2 is crucially involved in lipopolysaccharide-induced osteoclast formation\u003c/strong\u003e. Journal of immunology (Baltimore, Md: 1950) 2004, \u003cstrong\u003e172\u003c/strong\u003e(4):2504\u0026ndash;2510.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLiu H, Li W, Liu Y, Zhang X, Zhou Y: \u003cstrong\u003eCo-administration of aspirin and allogeneic adipose-derived stromal cells attenuates bone loss in ovariectomized rats through the anti-inflammatory and chemotactic abilities of aspirin\u003c/strong\u003e. Stem cell research \u0026amp; therapy 2015, \u003cstrong\u003e6\u003c/strong\u003e:200.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAgas D, Marchetti L, Capitani M, Sabbieti MG: \u003cstrong\u003eThe dual face of parathyroid hormone and prostaglandins in the osteoimmune system\u003c/strong\u003e. American journal of physiology Endocrinology and metabolism 2013, \u003cstrong\u003e305\u003c/strong\u003e(10):E1185-1194.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBoutaud O, Sosa IR, Amin T, Oram D, Adler D, Hwang HS, Crews BC, Milne G, Harris BK, Hoeksema M \u003cem\u003eet al\u003c/em\u003e: \u003cstrong\u003eInhibition of the Biosynthesis of Prostaglandin E2 By Low-Dose Aspirin: Implications for Adenocarcinoma Metastasis\u003c/strong\u003e. Cancer prevention research (Philadelphia, Pa) 2016, \u003cstrong\u003e9\u003c/strong\u003e(11):855\u0026ndash;865.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBlackwell KA, Raisz LG, Pilbeam CC: \u003cstrong\u003eProstaglandins in bone: bad cop, good cop?\u003c/strong\u003e Trends in endocrinology and metabolism: TEM 2010, \u003cstrong\u003e21\u003c/strong\u003e(5):294\u0026ndash;301.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eZeng YP, Yang C, Li Y, Fan Y, Yang HJ, Liu B, Sang HX: \u003cstrong\u003eAspirin inhibits osteoclastogenesis by suppressing the activation of NF-\u0026kappa;B and MAPKs in RANKL-induced RAW264.7 cells\u003c/strong\u003e. Molecular medicine reports 2016, \u003cstrong\u003e14\u003c/strong\u003e(3):1957\u0026ndash;1962.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eGrosser N, Schr\u0026ouml;der H: \u003cstrong\u003eAspirin protects endothelial cells from oxidant damage via the nitric oxide-cGMP pathway\u003c/strong\u003e. Arteriosclerosis, thrombosis, and vascular biology 2003, \u003cstrong\u003e23\u003c/strong\u003e(8):1345\u0026ndash;1351.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eTaubert D, Berkels R, Grosser N, Schr\u0026ouml;der H, Gr\u0026uuml;ndemann D, Sch\u0026ouml;mig E: \u003cstrong\u003eAspirin induces nitric oxide release from vascular endothelium: a novel mechanism of action\u003c/strong\u003e. British journal of pharmacology 2004, \u003cstrong\u003e143\u003c/strong\u003e(1):159\u0026ndash;165.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eChin KY: \u003cstrong\u003eA Review on the Relationship between Aspirin and Bone Health\u003c/strong\u003e. Journal of osteoporosis 2017, \u003cstrong\u003e2017\u003c/strong\u003e:3710959.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eDillon CF, Weisman MH: \u003cstrong\u003eUS National Health and Nutrition Examination Survey Arthritis Initiatives, Methodologies and Data\u003c/strong\u003e. Rheumatic diseases clinics of North America 2018, \u003cstrong\u003e44\u003c/strong\u003e(2):215\u0026ndash;265.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eZipf G, Chiappa M, Porter KS, Ostchega Y, Lewis BG, Dostal J: \u003cstrong\u003eNational health and nutrition examination survey: plan and operations, 1999\u0026ndash;2010\u003c/strong\u003e. Vital and health statistics Ser 1, Programs and collection procedures 2013(56):1\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003evon Elm E, Altman DG, Egger M, Pocock SJ, G\u0026oslash;tzsche PC, Vandenbroucke JP: \u003cstrong\u003eThe Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies\u003c/strong\u003e. PLoS medicine 2007, \u003cstrong\u003e4\u003c/strong\u003e(10):e296.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBenjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R \u003cem\u003eet al\u003c/em\u003e: \u003cstrong\u003eHeart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association\u003c/strong\u003e. Circulation 2018, \u003cstrong\u003e137\u003c/strong\u003e(12):e67-e492.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003ePatrono C, Bachmann F, Baigent C, Bode C, De Caterina R, Charbonnier B, Fitzgerald D, Hirsh J, Husted S, Kvasnicka J \u003cem\u003eet al\u003c/em\u003e: \u003cstrong\u003eExpert consensus document on the use of antiplatelet agents. The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European society of cardiology\u003c/strong\u003e. European heart journal 2004, \u003cstrong\u003e25\u003c/strong\u003e(2):166\u0026ndash;181.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHundal RS, Petersen KF, Mayerson AB, Randhawa PS, Inzucchi S, Shoelson SE, Shulman GI: \u003cstrong\u003eMechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes\u003c/strong\u003e. The Journal of clinical investigation 2002, \u003cstrong\u003e109\u003c/strong\u003e(10):1321\u0026ndash;1326.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCostanzo A, Moretti F, Burgio VL, Bravi C, Guido F, Levrero M, Puri PL: \u003cstrong\u003eEndothelial activation by angiotensin II through NFkappaB and p38 pathways: Involvement of NFkappaB-inducible kinase (NIK), free oxygen radicals, and selective inhibition by aspirin\u003c/strong\u003e. Journal of cellular physiology 2003, \u003cstrong\u003e195\u003c/strong\u003e(3):402\u0026ndash;410.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eRistim\u0026auml;e T, Zilmer M, Zilmer K, Kairane C, Kullisaar T, Teesalu R: \u003cstrong\u003eEffect of low-dose aspirin on the markers of oxidative stress\u003c/strong\u003e. Cardiovascular drugs and therapy 1999, \u003cstrong\u003e13\u003c/strong\u003e(6):485\u0026ndash;490.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eReilly M, Delanty N, Lawson JA, FitzGerald GA: \u003cstrong\u003eModulation of oxidant stress in vivo in chronic cigarette smokers\u003c/strong\u003e. Circulation 1996, \u003cstrong\u003e94\u003c/strong\u003e(1):19\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eSerhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac RL: \u003cstrong\u003eResolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals\u003c/strong\u003e. The Journal of experimental medicine 2002, \u003cstrong\u003e196\u003c/strong\u003e(8):1025\u0026ndash;1037.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eRaghavan RP, Laight DW, Cummings MH: \u003cstrong\u003eAspirin in type 2 diabetes, a randomised controlled study: effect of different doses on inflammation, oxidative stress, insulin resistance and endothelial function\u003c/strong\u003e. International journal of clinical practice 2014, \u003cstrong\u003e68\u003c/strong\u003e(2):271\u0026ndash;277.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMinn YK, Suk SH, Do SY: \u003cstrong\u003eOsteoporosis as an independent risk factor for silent brain infarction and white matter changes in men and women\u003c/strong\u003e: \u003cstrong\u003ethe PRESENT project\u003c/strong\u003e. \u003cem\u003eOsteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA\u003c/em\u003e 2014, \u003cstrong\u003e25\u003c/strong\u003e(10):2465\u0026ndash;2469.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBleicher K, Cumming RG, Naganathan V, Seibel MJ, Sambrook PN, Blyth FM, Le Couteur DG, Handelsman DJ, Creasey HM, Waite LM: \u003cstrong\u003eLifestyle factors\u003c/strong\u003e, \u003cstrong\u003emedications\u003c/strong\u003e, \u003cstrong\u003eand disease influence bone mineral density in older men\u003c/strong\u003e: \u003cstrong\u003efindings from the CHAMP study\u003c/strong\u003e. \u003cem\u003eOsteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA\u003c/em\u003e 2011, \u003cstrong\u003e22\u003c/strong\u003e(9):2421\u0026ndash;2437.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eChen CH, Lin CL, Kao CH: \u003cstrong\u003eAssociation Between Chronic Hepatitis B Virus Infection and Risk of Osteoporosis: A Nationwide Population-Based Study\u003c/strong\u003e. Medicine 2015, \u003cstrong\u003e94\u003c/strong\u003e(50):e2276.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCarbone LD, Tylavsky FA, Cauley JA, Harris TB, Lang TF, Bauer DC, Barrow KD, Kritchevsky SB: \u003cstrong\u003eAssociation between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity\u003c/strong\u003e. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 2003, \u003cstrong\u003e18\u003c/strong\u003e(10):1795\u0026ndash;1802.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBauer DC, Orwoll ES, Fox KM, Vogt TM, Lane NE, Hochberg MC, Stone K, Nevitt MC: \u003cstrong\u003eAspirin and NSAID use in older women: effect on bone mineral density and fracture risk. Study of Osteoporotic Fractures Research Group\u003c/strong\u003e. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 1996, \u003cstrong\u003e11\u003c/strong\u003e(1):29\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBarker AL, Soh SE, Sanders KM, Pasco J, Khosla S, Ebeling PR, Ward SA, Peeters G, Talevski J, Cumming RG \u003cem\u003eet al\u003c/em\u003e: \u003cstrong\u003eAspirin and fracture risk: a systematic review and exploratory meta-analysis of observational studies\u003c/strong\u003e. BMJ open 2020, \u003cstrong\u003e10\u003c/strong\u003e(2):e026876.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eChai SC, Foley EM, Arjmandi BH: \u003cstrong\u003eAnti-atherogenic properties of vitamin E, aspirin, and their combination\u003c/strong\u003e. PloS one 2018, \u003cstrong\u003e13\u003c/strong\u003e(10):e0206315.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eYamaza T, Miura Y, Bi Y, Liu Y, Akiyama K, Sonoyama W, Patel V, Gutkind S, Young M, Gronthos S \u003cem\u003eet al\u003c/em\u003e: \u003cstrong\u003ePharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents\u003c/strong\u003e. PloS one 2008, \u003cstrong\u003e3\u003c/strong\u003e(7):e2615.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eWei J, Wang J, Gong Y, Zeng R: \u003cstrong\u003eEffectiveness of combined salmon calcitonin and aspirin therapy for osteoporosis in ovariectomized rats\u003c/strong\u003e. Molecular medicine reports 2015, \u003cstrong\u003e12\u003c/strong\u003e(2):1717\u0026ndash;1726.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eChen ZW, Wu ZX, Sang HX, Qin GL, Wang LS, Feng J, Wang J, Li XJ, Wang JC, Zhang D: \u003cstrong\u003e[Effect of aspirin administration for the treatment of osteoporosis in ovariectomized rat model]\u003c/strong\u003e. Zhonghua yi xue za zhi 2011, \u003cstrong\u003e91\u003c/strong\u003e(13):925\u0026ndash;929.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBonten TN, de Mutsert R, Rosendaal FR, Jukema JW, van der Bom JG, de Jongh RT, den Heijer M: \u003cstrong\u003eChronic use of low\u003c/strong\u003e-\u003cstrong\u003edose aspirin is not associated with lower bone mineral density in the general population\u003c/strong\u003e. \u003cem\u003eInternational journal of cardiology\u003c/em\u003e 2017, \u003cstrong\u003e244\u003c/strong\u003e:298\u0026ndash;302.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHill DD, Cauley JA, Bunker CH, Baker CE, Patrick AL, Beckles GLA, Wheeler VW, Zmuda JM: \u003cstrong\u003eCorrelates of bone mineral density among postmenopausal women of African Caribbean ancestry: Tobago women\u0026apos;s health study\u003c/strong\u003e. Bone 2008, \u003cstrong\u003e43\u003c/strong\u003e(1):156\u0026ndash;161.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHollaender R, Hartl F, Krieg MA, Tyndall A, Geuckel C, Buitrago-Tellez C, Manghani M, Kraenzlin M, Theiler R, Hans D: \u003cstrong\u003eProspective evaluation of risk of vertebral fractures using quantitative ultrasound measurements and bone mineral density in a population-based sample of postmenopausal women: results of the Basel Osteoporosis Study\u003c/strong\u003e. Annals of the rheumatic diseases 2009, \u003cstrong\u003e68\u003c/strong\u003e(3):391\u0026ndash;396.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eNaylor K, Eastell R: \u003cstrong\u003eBone turnover markers: use in osteoporosis\u003c/strong\u003e. Nature reviews Rheumatology 2012, \u003cstrong\u003e8\u003c/strong\u003e(7):379\u0026ndash;389.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Osteoporosis, BMD, Aspirin, NHANES, DXA","lastPublishedDoi":"10.21203/rs.3.rs-1483838/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1483838/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e The utilization rate of low-dose aspirin in the elderly is increasing, and osteoporosis in the elderly is getting more and more attention. Aspirin has been shown in numerous studies to affect bone metabolism. However, there is no clear link between low-dose aspirin use and bone mineral density (BMD). This study examined differences in bone mineral density between low-dose aspirin users and non-aspirin users in adults aged 50-80 years.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe conducted a cross-sectional study of 4987 participants aged 50–80 years who participated in the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020. We performed multivariable logistic regression models to evaluate the associations between low-dose aspirin use and femoral neck BMD.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e A total of 1143 adults were included in this study. Higher femoral neck BMD was observed in the low-dose aspirin use group compared with the non-aspirin use group (β=0.023, 95%CI 0.007-0.039). On subgroup analyses stratified by gender, this positive association existed in both gender after adjusting for confounders (males: β=0.020, 95%CI: -0.001-0.042; females: β=0.025, 95%CI: 0.001-0.050 P for interaction = 0.739). On subgroup analyses stratified by age, this positive association existed in three different age groups after adjusting for confounders (50-60 years: β=0.034, 95%CI: 0.004-0.065; 60-70 years: β=0.016, 95%CI: -0.011-0.043; 70-80 years: β=0.026, 95%CI: -0.003-0.055 P for interaction = 0.633).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThese findings from a human study looking into the correlation between low-dose aspirin use and femoral neck BMD suggest that taking regular low-dose aspirin may be associated with a higher femoral neck BMD. The effect of low-dose aspirin on femoral neck bone mineral density was not significant across age groups and genders.\u003c/p\u003e","manuscriptTitle":"Associations between low-dose aspirin and bone mineral density in older adults","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-04-04 15:15:21","doi":"10.21203/rs.3.rs-1483838/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-05-24T05:19:20+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-05-19T03:22:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"8c19019e-dab3-42a2-a81b-3314c3011719","date":"2022-05-18T22:56:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"af61e9cf-c4bd-4c8c-8033-9965b8110348","date":"2022-05-09T12:40:54+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-05-06T12:35:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-05-06T12:28:03+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-04-01T17:18:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-04-01T17:03:22+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2022-03-24T04:30:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1dbc80a9-05eb-4d73-8a2a-ab41443805e9","owner":[],"postedDate":"April 4th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-08-26T15:29:16+00:00","versionOfRecord":[],"versionCreatedAt":"2022-04-04 15:15:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1483838","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1483838","identity":"rs-1483838","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}