Effect of Secondhand Smoking, Determined by Urinary Cotinine Level on Bone Health.

BACKGROUND: We evaluated the relationship between secondhand smoke (SHS) inhalation, as verified by urinary cotinine levels, and bone health.
METHODS: We analyzed the nationwide, population-based, cross-sectional health survey. We included 1936 men aged 50 years or older who checked bone mineral density (BMD) from the Korean National Health and Nutrition Examination Survey (2008-2010). Current smokers assessed by urinary cotinine levels higher than 500 ng/mL were excluded (n = 616). Exposure to SHS was determined using a 50 ng/mL urinary cotinine threshold.
RESULTS: The estimated prevalence of SHS exposure in our cohort was 13.9%. After adjusting for age and body mass index (BMI), T-scores at total femur (P < 0.001), femoral neck (P < 0.001), and lumbar spine (P = 0.004) were lower in SHS exposure versus nonexposure groups. Impaired bone health (osteopenia or osteoporosis) at femoral neck or lumbar spine was evident in 61.7% and 48.6% of SHS exposure and nonexposure cases, respectively (P = 0.004). Moreover, after adjusting for age, BMI, and health habits, the odds ratio for impaired bone health in the SHS exposure group was 1.89 (95% confidence interval: 1.31-2.74).
CONCLUSIONS: Our findings suggest that SHS exposure, determined by urinary cotinine levels, is negatively associated with BMD and is a leading cause of impaired bone health in Korean men.

Introduction

The incidence of osteopenia and osteoporosis in men has increased. According to a recent report, the prevalence of osteopenia is 46.5% and that of osteoporosis is 7.3% in Korean men aged 50 years and older.[1] The lifetime fracture risk associated with osteoporosis in men of this age group is 13%–30%.[2] Furthermore, once a hip fracture has occurred, men have a 2–3 times higher mortality rate than women.[3] Thus, osteoporosis in men is not as well-known as it is in women; nevertheless, it is a major public health concern.[4]

Inhalation of secondhand smoke (SHS) consists of 15% mainstream smoke and 85% sidestream smoke. Sidestream smoke that originates from the ends of burning cigarettes is considered more toxic than mainstream (inhaled) smoke.[5] SHS exposure is known to be associated with several health problems, including asthma,[6] diabetes,[7] cardiovascular disease,[8] and reduces the quality of life.[9] Firsthand tobacco smoke is an important risk factor for impaired bone health (osteopenia and osteoporosis).[1011] However, the effect of SHS exposure on bone mineral density (BMD) is not well understood, especially in Asian men.

The status of tobacco smoke exposure can be estimated by determining concentrations of urinary cotinine, a major metabolite of nicotine. Cotinine has a relatively long half-life (16–20 h) and is present in higher concentrations in body fluids than other biological markers of tobacco.[12] Furthermore, urinary cotinine is easy to collect. The aim of this study was to evaluate the significance of SHS exposure, as verified by urinary cotinine levels, on bone health in Korean men, aged 50 years and older.

Methods

Study design and participants

We analyzed the nationwide, population-based, cross-sectional health survey. The participants were 1320 male participants of the Korean National Health and Nutrition Examination Survey (2008–2010), conducted since 1998, by the Korea Centers for Disease Control and Prevention. It is a nationwide survey representing the health status of the entire Korean population. In our study, we selected men aged 50 years and older who had undergone dual-energy X-ray absorptiometry (DXA) and measurements of urinary cotinine concentration. We excluded individuals with chronic liver or kidney disease, thyroid disease, rheumatic arthritis, asthma, osteoporosis, or any form of malignancy. Obvious current smokers (urinary cotinine levels higher than 500 ng/mL) were also excluded.

Measurements

Spot urine samples collected for the measurement of urinary cotinine levels were assayed by gas chromatography and mass spectrometry, using a PerkinElmer Clarus 600T Mass Spectrometer (PerkinElmer Inc., Turku, Finland). All data were reviewed internally by our quality control center. Cutoff values for distinguishing SHS exposure from nonexposure and current smokers from SHS exposure are varied. No validated cutoff values for urinary cotinine levels have been published in the Korean population. According to previous studies, urinary cotinine levels below 50 ng/mL have defined nonexposure to tobacco smoke,[13] whereas a cutoff threshold of above 500 ng/mL is most commonly set for classifying an obvious current smoker.[14] In our study, individuals with urinary cotinine levels above the 500 ng/mL threshold were classified as current smokers and removed from further analyses. Individuals with urinary cotinine levels >50 ng/mL but ≤500 ng/mL were defined as having been exposed to SHS.

BMD at total femur, femoral neck, and lumbar spine (L1–L4) were measured using the DXA scanner (Hologic Inc., Bedford, MA, USA). T-scores were calculated by the Asian equation: (BMD minus reference BMD) divided by (reference standard deviation). Owing to the lack of Korean diagnostic criteria, maximum BMD values for Japanese patients were substituted as reference measurements instead. In our study, osteopenia and osteoporosis were defined as impaired bone health. In our study, impaired bone health (osteopenia and osteoporosis) was defined by T-scores of <−1.

Statistical analyses

All quantitative variables have been reported as mean ± standard error (SE), and qualitative variables as estimated proportion (SE). To reflect the sampling method and to represent the health status of the entire Korean population, we used a weighted population sample in our study. A Complex Samples General Linear Model was used to estimate means and SEs for BMD, and T-scores at total femur, femoral neck, and lumbar spine. A Complex Samples Logistic Regression Analysis was applied to estimate proportions and SEs for impaired bone health (osteopenia and osteoporosis). Multivariable logistic regression analyses were also carried out to assess the relationship between urinary cotinine levels and impaired bone health. All analyses were performed using Statistical Package of the Social Sciences for Windows version 20.0 (IBM, New York, NY, USA). P < 0.05 were considered statistically significant.

Results

General characteristics of the study participants are summarized in Table 1. Among the total number of study participants, 13.9% were classified as having been exposed to SHS. The average level of urine cotinine in the nonexposed group was 7.89 ng/mL, in comparison to 260.08 ng/mL in the exposed group (P < 0.001). Differences in mean age and body mass index (BMI) between the two groups were not statistically significant (P = 0.656 and P = 0.433, respectively). The frequency of alcohol consumption and exercise did not differ meaningfully between the two groups.

Table 1

General characteristics of the study participants according to secondhand smoke exposure

Table 2 presents the relationship between urinary cotinine levels and bone health. The SHS-exposed group demonstrated lower BMD at total femur and femoral neck compared to the nonexposed group, which was statistically significant (P = 0.004 and P = 0.003, respectively). At lumbar spine, however, although the SHS-exposed group demonstrated lower BMD than the nonexposed group, the result was not statistically significant (P = 0.486). After adjustments were made for age and BMI, T-scores at total femur and femoral neck were significantly lower in the SHS-exposed group compared to the nonexposed group (all P < 0.001). Furthermore, the average T-score at lumbar spine of the non-exposed group was −0.57 ± 0.04 compared to −0.68 ± 0.10 in the SHS-exposed group (P = 0.004) [Figure 1].

Table 2

Association between secondhand smoke exposure and bone health parameters

Figure 1

Comparison of SHS exposure age, BMI-adjusted T-scores at total femur, femoral neck, and lumbar spine, calculated using a complex sample general linear model. SHS=Secondhand smoke, BMI=Body mass index

To reveal the independent relationship between SHS exposure, as verified by urinary cotinine levels, and impaired bone health, we conducted multivariate logistic regression. The prevalence of impaired bone health was higher in the SHS-exposed group than the nonexposed group, regardless of the location measured. The prevalence of impaired bone health at femoral neck or lumbar spine, for example, was 48.6% and 61.7% in the nonexposed and SHS-exposed groups, respectively (P = 0.004). After adjusting for age, BMI, and health habits, participants identified in the SHS-exposed group, as verified by urinary cotinine levels, were found to be associated with an increased risk of impaired bone health at femoral neck or lumbar spine with an odds ratio of 1.89 (95% confidence interval: 1.31–2.74) [Table 3].

Table 3

Multivariate logistics regression analysis of association between secondhand smoke exposure and the risk of osteopenia or osteoporosis at total femur, femoral neck, and lumbar spine

Discussion

The results of our study indicate that exposure to SHS, as verified by urinary cotinine levels, is negatively associated with bone health in Korean men. Only a few studies have investigated the relationship between urinary cotinine levels and impaired bone health in Asian men. In a Korean study of adults, aged 30 years or older, participants with urinary cotinine levels above 10 mcg/mL were associated with lower femoral neck T-scores than participants with urinary cotinine levels of 10 mcg/mL or less.[15] Moreover, urinary cotinine levels and T-scores at femoral neck and lumbar spine exhibited a negative association that was statistically significant. However, the group with urinary cotinine levels above 10 mcg/mL contained active smokers and nonsmokers with exposure to SHS. Because the previous study did not distinguish between the group with SHS exposure and the group of current smokers, the effects of SHS exposure on bone health could not be evaluated.

The mechanisms of SHS exposure on impaired bone health are not fully understood. In general, smokers tend to have lower body fat percentage and BMI than nonsmokers.[16] Furthermore, tobacco smoke may lead to increased bone turnover[17] and a decrease in calcium absorption.[18] In one animal study, smoked-exposed rats had fewer bone marrow cells and black carbon dust-like substance in a region found in their bones.[19] In an in vitro study, nicotine acted to increase osteoclastogenesis while inhibiting osteoblastogenesis; however, the effects of low-dose nicotine administration on bone health are still not fully understood.[20] Furthermore, in epidemiologic studies with or without a history of tobacco exposure, the levels of 25-hydroxy vitamin D3, parathyroid hormone, and alkaline phosphatase were found to be comparable.[21]

Our study has a number of strengths. Assessment of smoking status (i.e., active smoker, passive smoker, or nonsmoker) by means of a self-reported questionnaire can have important biases that may result in the prevalence of smoking and SHS exposure to be underreported.[22] Estimating exposure to tobacco smoke by measuring urinary cotinine levels can more accurately determine a participant's smoking status than by assessment through self-reported questionnaires. Previously, some studies in women have reported exposure to SHS and osteoporosis to exhibit a positive association, with a dose-response relationship between BMD and urinary cotinine levels.[2324] However, little information is available regarding exposure to SHS, as verified by urinary cotinine levels, and bone health in men. We classified nonsmoking men as having exposure or nonexposure to SHS, based on urinary cotinine levels, which has not been investigated in previous studies. We also used national data that were representative of the general Korean population of men, aged 50 years and older.

Despite these strengths, however, the current study does have several limitations. First, this was a cross-sectional study, which meant we were unable to establish a causal relationship between SHS exposure and bone health. Second, we used urinary cotinine cutoff points of 50 ng/mL and 500 ng/mL, respectively, to distinguish between nonexposure/exposure to SHS and active smokers. However, urinary cotinine cutoff points have not previously been established for distinguishing passive smokers from active smokers, and in particular, there has been no published guide for the Korean population. Third, through measurements of urinary cotinine levels, we could only estimate the previous 2–3 days of exposure and were not able to assess the full extent of SHS exposure or the age at which SHS exposure began. Finally, not only smoking habits but also the status of calcium intake can play an important role in the development of osteoporosis. Unfortunately, however, we were unable to evaluate nutrition as part of this study. Additional studies are required, therefore, to assess longitudinal duration of exposure and dietary intake for evaluating the cause-effect relationship between SHS exposure and impaired bone health.

Conclusions

This study suggests that SHS exposure, determined by urinary cotinine levels, is negatively associated with BMD and is a major risk factor for impaired bone health in Korean men.

Financial support and sponsorship

This research was supported by the 2017 scientific promotion program funded by Jeju National University.

Conflicts of interest

There are no conflicts of interest.