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| Citation | Design | Sample Characteristics | Study Purpose | Findings |
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| Ward & Klesges, 2001 [6] | Meta-analysis | (i) N = 40,753 subjects from 1 86 cross-sectional studies
(ii) The average of age was 53.3 years
(iii) The majority were females (74%)
(iv) The average of age (Mean ± SD): 18.9 ± 0.6 | (i) To determine the magnitude and the association between cigarette smoking and bone mass. | (i) Compared with nonsmokers (never and former smokers), smokers had significantly reduced bone mass at all bone sites, averaging a one-tenth standard deviation deficit for combined sites.
(ii) Smoking increases the lifetime risk of developing a vertebral fracture by 13% in women and 32% in men. |
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| Law & Hackshaw, 1997 [7] | Meta-analysis | (i) N= 11,861: 2,156 smokers and 9,705 nonsmokers from 29 cross sectional studies
(ii) N = 3,889 subjects from 19 cohort and case control studies that were recording hip fractures
(iii) The average of age was 54.0 years
(iv) The majority were females | (i) To determine the magnitude and the association between smoking, bone mineral density (BMD), and risk of hip fracture according to age. | (i) In premenopausal women bone density was similar in smokers and nonsmokers.
(ii) In postmenopausal women bone loss was greater in current smokers than nonsmokers, and the bone density diminishing by about an additional 2% for every 10 year increase in age.
(iii) Compared to nonsmokers, current smokers had similar risk of hip fracture at age of 50; however, such risk was increased thereafter by an estimate of 17% at age of 60, 41% at age of 70, 71% at age 0f 80, and 108% at age of 90 years. |
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| Szulc et al, 2002 [22] | Cross-sectional study [sample from MINOS study] | (i) N = 719: 231 never smokers, 405 former smokers, and 83 current smokers
(ii) The range of age was 51-85 years
(iii) All participants were males
(iv) Random sample | (i) To determine the effect of smoking on BMD and bone turnover. | (i) Current and former smokers had similar BMD, except for the forearm.
(ii) Compared with never smokers, former smokers had lower BMD at most skeletal sites.
(iii) The three groups of subjects did not differ in terms of levels of bone formation markers; however, levels of bone resorption markers (urinary C-terminal telopeptide and free and total deoxypyridinoline) were higher in current smokers than in former and never smokers.
(iv) Compared with former and never smokers, current smokers had lower level of 25-hydroxyvitamin D. |
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| Lorentzon et al, 2007 [24] | Cross-sectional study [sample from GOOD study] | (i) N = 1,068: 975 nonsmokers, 93 smokers
(ii) The average of age (Mean ± SD): 18.9 ± 0.6 for nonsmokers and 19.0 ± 0.6 years for smokers
(iii) All participants were young males | (i) To investigate if smoking habit associated with bone size and areal or volumetric BMD (aBMD or vBMD). | (i) Smokers had significantly lower aBMD of the total body, lumbar spine, and trochanter than nonsmokers.
(ii) Smokers had lower cortical thickness of both the radius and tibia than the nonsmokers, whereas no difference was seen for cortical vBMD.
(iii) Smokers had higher levels of testosterone (total and free) and lower 25-OH-D than nonsmokers and the adjustment for such differences did not alter the associations between smoking and bone parameters. |
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| Kargin et al, 2016 [25] | Cross-sectional study | (i) N = 170: 85 nonsmokers and 85 smokers
(ii) The average of age ( Mean ± SD): 43.58 ± 6.58 nonsmokers and 43.52 ± 6.72 smokers
(iii) All participants were males | (i) To compare of the bone turnover markers between smoker and nonsmoker male. | (i) Smoker’s C-terminal telopeptide (CTX) level was significantly lower than that of the nonsmokers (0.30 ± 26.97 ng/ml vs. 65.10 ± 42.41 ng/ml, p = 0.007)
(ii) Smoker’s mean serum Parathyroid Hormone (PTH) level was significantly lower than that of nonsmokers (23.75 ± 9.88 pg/ml vs. 31.35 ± 13.15 pg/ml, p ≤ 0.001), and parallel findings were observed for vitamin D (16.75 ± 8.73 ng/ml vs. 19.50 ± 8.97 ng/ml, p = 0.044). |
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| Kassi et al, 2015 [26] | Cross-sectional study | (i) N = 181: 117 nonsmokers and 64 smokers
(ii) The average of age ( Mean ± SD): 34.69 ± 7.38 with a range of age 20-50 years
(iii) All participants were males
(iv) Random sample | (i) To determine the prevalence of vitamin D (25-OH-D, D-2 and D-3) insufficiency and its association with smoking, BMD, and bone markers. | (i) The prevalence of 25-OH-D < 20ng/ml) was 50.3%.
(ii) There was a strong correlation between 25-OH-D and smoking (P < 0.001); 25-OH-D level was significantly lower in smokers than nonsmokers.
(iii) In total population, regardless of the age group, there was no correlation between 25-OH-D and BMD in the femoral neck and the lumbar spine. Also, 25-OH-D was not correlated with bone turnover markers: serum osteocalcin, P1NP, b-CTXs levels. |
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| Christie et al, 2009 [27] | Cross-sectional study | (i) N = 69 twin
(ii) Average of age (Mean ± SD): 53 ± 8.9 with a range of (40-76) years
(iii) 13 were males, and 56 were females | (i) To examine whether mechanism of bone loss in pair twins could be related to smoking. | (i) Percentage within-pair difference (WPD) that was calculated based on the differences between smokers and nonsmokers were found to be significant for BMD of femoral neck (-5.6%, 95%CI: -9.0 to -2.2, p = 0.002), total hip (- 6.2%, 95%CI: -9.4 to -2.9, p ≤ 0.001), and whole body bone mineral content (BMC) (- 4.1%, 95%CI: -7.2 to -1.1, p = 0.012). However, it was found to be not significant for lumbar spine (-3.5%, 95%CI:-7.0 to 0.0, p = 0.058), and forearm (-0.8%, 95%CI: -2.6 to -1.0, p = 0.290).
(ii) WPD for fat mass was also lower in smoking twins (-12.8%, 95%CI:-20.7 to -4.8, p = 0.005), and lean mass marginally significant (-2.8, 95%CI: -5.9 to 0.3, p = 0.083). |
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| Fujiyoshi et al, 2016 [28] | Cross-sectional study | (i) N = 376: 240 never smokers, 64 former smokers,72 current smokers
(ii) The range of age was 24-36 years
(iii) 205 were males, and 171 were females
(iv) 181 were white, 195 were black | (i) To examine whether smoking was associated with serum parathyroid hormone (PTH) independent of correlates of PTH among young adults and explore potential mechanisms. | (i) Compared to nonsmokers, current smoker had lower PTH and there was no evidence of an interaction by race and sex.
(ii) The lowest level of PTH was detected in current smokers followed by former smokers (intermediate level), while the highest was seen in never smokers (mean of PTH: 23.6, 26.7, 27.4 pg/mL, respectively: p for trend = 0.006, adjusted for calcium intake confounders).
(iii) Current smoker had the lowest biomarkers concentration of serum osteocalcin and 24-hour urinary excretion of calcium. |
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| Krall & Dawson-Hughes, 1999 [31] | Randomized-placebo-controlled study, subjects followed for 3 years | (i) N = 402: 370 nonsmokers, 32 smokers
(ii) The average of age (Mean ± SD): 71 ± 5. nonsmokers, and 70 ± 2 smokers
(iii) 45% were males, and 55% were females | (i) To determine the relationship of smoking to rates of BMD change and to intestinal calcium absorption. | (i) Compared with nonsmokers, smokers had significant higher adjusted annualized rates of BMD loss at the femoral neck, and total body; meanwhile, no significant difference was observed at the spine.
(ii) The adjusted mean of calcium absorption fraction was lower in smokers than nonsmokers. |
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| Rapuri et al, 2000 [32] | Cross-sectional study | (i) N = 444: 390 nonsmokers, 54 smokers (21: heavy smokers, 33: light smokers)
(ii) The range of age was 56-77 years
(iii) All participants were females | (i) To examine the relationship between smoking and BMD, calciotropic hormones, calcium absorption. | (i) The adjusted mean total body bone mineral density was 4% and the total hip density was 6% lower in heavy smokers than that of nonsmokers.
(ii) Compared with nonsmokers, light and heavy smokers had lower level for the adjusted mean calcium absorption.
(iii) Compared with nonsmokers, heavy smokers had significantly lower level of serum 25-OH-D.
(iv) Compared with nonsmokers, heavy smokers had significantly higher levels of serum osteocalcin and urine N-telopeptide/creatinine ratio. |
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| Cetin et al, 2009 [66] | Cross-sectional study | (i) N = 60: 30 nonsmokers, and 30 smokers
(ii) The average of age (Mean ± SD): 51.2 ± 3.4 for nonsmokers, 49.7 ± 3.5 for smokers
(iii) All participants were postmenopausal women
(iv) Participants were randomly selected | (i) To investigate the impact of smoking on the oxidative status in postmenopausal women, and to assess the relationship between BMD and oxidant/antioxidant parameters. | (i) The rates of osteopenia and osteoporosis in smokers and nonsmokers were 75% and 52.5%, respectively.
(ii) The T-scores were significantly lower in smokers than nonsmokers (median: -2.7 vs. -1.4, p < 0.001).
(iii) Activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, paraoxonase) were lower and the levels of oxidative stress products (malondialdehyde, nitric oxide) were higher in smokers than in nonsmokers (p < 0.001).
(iv) In the smoking group, there was a significant correlation between decreased T-score and oxidative stress parameters. |
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| Melhus et al, 1999 [67] | Prospective case-control study | (i) N = 66,651 [44 case developed fracture and 93 age-matched of current smokers]
(ii) The range of age was 40-76 years
(iii) All participants were females | (i) To determine whether the dietary intake of antioxidant vitamins may modify the increased risk for hip fracture among the smoker. | (i) The odds ratio (OR) for hip fracture among current smokers with a low intake of vitamin E was 3.0 (95% CI: 1.6-5.4), and of vitamin C 3.0 (95%CI: 1.6-5.6), and it was increased to 4.9 (95%CI: 2.2-11.0) with a low intake of both vitamins E and C.
(ii) The OR decreased to 1.1 (95%CI: 0.5-2.4) and 1.4 (95%CI: 0.7-3.0) with high intakes of vitamin E and C, respectively. Such effect was not observed for beta-carotene, selenium, calcium, or vitamin B6. |
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| Tang et al, 2009 [75] | Cross-sectional study | (i) N = 149 periodontitis patient: 58 never, 39 former, and 52 current smokers
(ii) The range of age was 26-86 years
(iii) 56 were males, and 93 were females | (i) To compare the levels of the sRANKL, OPG and their relative ratio in gingival crevicular fluid (GCF) among periodontitis patients with varying smoking histories. | (i) There were no significant differences for sRANKL, OPG, and their relative ratio among never smokers, former smokers, and current smokers.
(ii) Compared to never smokers, high pack-years group had significantly reduced OPG and subsequently increased sRANKL/OPG ratio (positively correlated with pack-year even after adjustment for age and status of current smoking). |
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| Lappin et al, 2007 [76] | Cross-sectional study | (i) N = 70: 35 nonsmokers, and 35 smokers
(ii) The average of age (Mean, Range): 43.0 (40.0 -51.5) nonsmokers, 43.0 (41.0 - 50.5) for smokers
(iii) 46 were males, and 24 were females | (i) To compare serum levels RANKL and OPG in age- and sex-matched groups of smokers and nonsmokers with identical levels of periodontal disease. | (i) Compared to nonsmokers, smokers had significantly lower median serum level of OPG (23.76 pM vs. 59.28 pM, p = 0.0006) but not for RANKL (41.47pM vs. 48.23 pM, p = 0.0942).
(ii) Tobacco consumption had statistical significant negative correlation with the concentrations of OPG. |
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| Ozcaka et al, 2010 [77] | Cross-sectional study | (i) N = 86: 44 with CP (31 nonsmokers, 13 smokers), 42 healthy control group (29 nonsmokers, 13 smokers)
(ii) The range of age was 35-65 years for group of CP, and 33-57 for healthy control group
(iii) 43 were males (23 CP, 20 control), and 43 were females (21 CP, 22 control) | (i) To evaluate plasma levels sRANKL and OPG in smoker versus nonsmoker CP patients. | (i) All periodontal measurements were significantly different between the two groups of healthy control and group of CP (p < 0.05). However, these measurements were not differed between smoker and nonsmokers of CP group (p > 0.05).
(ii) Chronic periodontitis smokers exhibited significantly lower plasma OPG concentrations (P = 0.007) and higher sRANKL/OPG ratio (p = 0.01) than healthy control smokers. |
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| Du et al, 2011[78] | Cross-sectional study | (i) N = 703: 281 nonsmokers, 422 smokers (former and current)
(ii) Mean of age was 93.48 years
(iii) 226 were males, and 477 were females | (i) To observe the relationships of osteoporotic fracture with habits of smoking, tea consumption, alcohol consumption, and exercise among very old unrelated Chinese nonagenarians and centenarians. | (i) In older Chinese people, there were significant associations between the increased risk of osteoporotic fracture and current or former alcohol drinking, and the risk for osteoporotic fracture was significantly reduced with habit of former exercise. Smoking and tea consumption were found not to be associated with osteoporotic fracture.
(ii) The former habit of alcohol consumption was significantly associated with a greater risk of osteoporotic fracture (OR = 2.47, 95%CI: 1.07- 5.53), but the former habit of exercise was associated with a lower risk of osteoporotic fracture. |
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| Eleftheriou et al, 2013 [79] | Retrospective cohort study | (i) N = 723 healthy male military recruits: 329 nonsmokers, 41 Ex-smokers, 35 recent Ex-smokers, and 244 current smokers
(ii) The average of age was 19.92 with a range of 16-18 years.
(iii) All participants were Caucasian males | (i) To investigate the influence of young men lifestyles factors of smoking, alcohol, and physical activity on the peak bone mass as evidenced by the changes on the bone structure and geometry. | (i) Smoking was associated with well-maintained bone geometry, but worse BMD (p = 0.0001) and calcaneal quantitative ultrasound (QUS) (p ≤ 0.0005).
(ii) Alcohol consumption at moderate level was associated with higher BMD (p ≤ 0.015).
(iii) The increment in weight-bearing exercise was associated with improved periostial bone apposition, total hip, and femoral neck BMD (p ≤ 0.0001) at cortical (p < 0.0001) and periostial level (p = 0.016). |
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| Kim et al, 2007 [80] | Cross-sectional study | (i) N = 463: alcohol-only drinking (n = 254), combined alcohol drinking and smoking (n = 125), and control nondrinking/nonsmoking (n = 84)
(ii) Average of age was 23 and the range of age was 20-26 years
(iii) All participants were Korean males | (i) To investigate effects of alcohol and tobacco smoking on BMD and bone metabolism. | (i) There were no significant differences in BMD of the calcaneus among the 3 groups. However, blood total alkaline phosphatase activity (ALP) was significantly lower in the combined drinking and smoking group than in the control group (p < 0.05).
(ii) There were negative relationships between duration of alcohol consumption and ALP N-mid osteocalcin levels (all p < 0.001).
(iii) Daily cigarette use and smoking duration showed a significantly negative correlation with ALP (p < 0.001). |
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| Dorn et al, 2011 [81] | Cross sequential design | (i) N = 262: 171 nonsmokers, 91 smokers
(ii) The average of age (Mean ± SD): 14.9 ± 2.2 years
(iii) All participants were females
(iv) The majority were Caucasian (61.8%) or African American (32.8%) with some mixed race/other (5.4%) | (i) To examine the association between depressive and anxiety symptoms, smoking, and alcohol use on bone health whether the association between depressive and anxiety symptoms varied by smoking or alcohol use individually or by combined use. | (i) The higher state of depressive symptoms was associated with lower BMC and BMD.
(ii) Participants with lowest use of smoking had higher BMD (hip, femoral neck), however; no differences were observed by alcohol use.
(iii) Compared with alcohol (regular, nonusers), the regular users of both cigarettes and alcohol had a stronger negative association between depressive or anxiety symptoms and total body BMC. |
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| Dorn et al, 2013[82] | Cross sequential design | (i) N = 262: 171 nonsmokers, 91 smokers
(ii) The average of age (Mean ± SD) at time 1: 14.35 ± 2.16 years
(iii) All participants were females
(iv) 32% black, and 62% white | (i) To examine the impact of depressive and anxiety symptoms, smoking, and alcohol use on bone accrual in girls 11-19 year with age cohort of 11, 13, 15, and 17 years. | (i) The lower rate of lumbar spine and total hip BMD of ages 13-19 were associated with higher frequency of smoking
(ii) There was an association between high depressive symptoms and lower lumbar spine BMD across 11-19 years of age.
(iii) Alcohol intake and anxiety had no effect on bone outcome, and depressive symptoms had no effect on total body BMC. |
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| Lucas et al, 2012 [83] | Prospective cohort study | (i) N = 731: at age 13 years, one fourth tried smoking, while 59% used alcohol and 20% had both
(ii) The range of age was 13-17
(iii) All participants were females | (i) To quantify the short-and long-term associations between smoking and alcohol drinking initiation and bone mineral density in adolescent girls. | (i) Lower mean BMD was observed at age of 17 years (late adolescence) in girls who had ever smoked by 13, and similar trend was observed for those consumed alcohol at that age. |
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| Holmberg et al, 2011 [84] | Cross-sectional study | (i) N = 15, 038 underwent bone mineral density (BMD) scan: 5, 829 exposed to home passive smoking in their adulthoods
(ii) Mean age of 52.7±13.8 [range: 18-95]
(iii) 40% were males, and 60% were females | (i) To investigate the association between phalangeal BMD and self-reported passive smoking. | (i) Subjects who have been exposed to passive smoking at home as an adult had significantly lower BMD than unexposed subjects (0.343 vs. 0.331 g/cm2; p < 0.01), even when adjusted for age, gender, weight, height, smoking (pack-years; 0.339 vs.0.337 g/cm2; p < 0.05) |
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| Kim et al, 2013 [85] | Cross-sectional study | (i) N = 925 never smokes: 212 with secondhand smoke (SHS), and 713 without SHS
(ii) Mean age of 51.4 ± 9.9 years
(iii) Mean of age (mean ± SD): 64.6 ± 7.1 for subject with SHS, and 66.3 ± 7.8 for subject without SHS | (i) To assess the association between SHS and postmenopausal osteoporosis. | (i) Compared to participants not exposed to SHS, participants who actively exposed to SHS from family members had higher adjusted OR for femoral neck osteoporosis (OR: 3.68; 95%CI: 1.23-10.92).
(ii) Compared with the non-exposed group, the group who lived with cohabitant smokers had increased risk for lumbar and femoral osteoporosis regardless of the number of cigarettes consumed by their cohabitant. |
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| Cornuz et al, 1999 [86] | Prospective cohort study | (i) N = 116,229 [377 case of fracture]
(ii) The range of age was 34-59 years
(iii) All participants were females | (i) To examine effects of cigarette smoking and smoking cessation on the risk of hip fracture in women. | (i) Compared with never smokers, age-adjusted relative risk (RR) of hip fracture among current smokers was 1.3 (95%CI: 1.0 to 1.7).
(ii) There was a linear association between the risk of hip fracture and cigarette consumption (p = 0.09).
(iii) After 10 years, former smokers had a reduced risk of hip fracture (adjusted RR = 0.7, 95%CI: 0.5 to 0.9) compared with current smokers. |
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| Gerdhem & Obrant, 2002[87] | Cross-sectional study [sample from OPRA study] | (i) N = 1,042 [377 case of fracture]
(ii) All participants age was 75 years
(iii) All participants were females
(iv) Participants were randomly selected | (i) To asses effects of cigarette-smoking on bone mass. | (i) Compared to never smokers, current smokers had lower BMD for femoral neck (0.71 vs. 0.76 g/cm2, p < 0.0001) and total body (0.96 vs. 1.02 g/cm2, p < 0.0001); meanwhile, there was no difference in BMD for lumbar spine.
(ii) There was no evident difference between former smokers and never-smokers in any of the skeletal regions assessed by DXA or ultrasound. |
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| Oncken et al, 2002 [88] | Randomized-placebo-controlled study, subjects followed for 6 weeks | (i) N = 66, after 6 weeks of follow up the analysis includes: 20 quitter from smoking cessation group, and 18 from wait-list control group
(ii) All participants were females | (i) To assess effects smoking cessation on hormone profiles and bone turnover markers in postmenopausal women. | (i) After 6 weeks, compared with wait-list control group, smoking cessation group had a significant change in N-terminal collagen cross-links (NTx) (-5% vs. +56%, respectively, p = 0.01) and sex hormone binding globulin (SHBG) (-8% vs. +5%, respectively; p = 0.01).
(ii) There was significant correlation between plasma cotinine and SHBG (r = 0.48; p = 0.004) and NTx (r = 0.36; p = 0.04). |
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| Oncken et al, 2006 [89] | Randomized-placebo-controlled study, subjects followed for 1 year | (i) N = 152 (smoked 10 or more cigarettes/day at baseline), after 1 year of follow-up the analysis includes 42 quitter, and 77 continued smoking
(ii) All participants were females | (i) To examine effects of smoking cessation on BMD, bone turnover markers, and hormone profiles in postmenopausal women. | (i) The BMD of femoral trochanter was significantly increased among quitter than that who continued to smoke (2.9% vs. 0.6%, p = 0.02). Same finding was seen for BMD of total hip (1.52% vs. 0.43%, p = 0.03). However there were no significant changes observed at femoral neck, radius, spine, and total body.
(ii) Smoking cessation was associated with an increase in bone alkaline phosphatase. |
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