Impact of smoking status on survival after cytoreductive nephrectomy for metastatic renal cell carcinoma

Objective

To assess the association of smoking status with standard clinicopathological features and overall survival (OS) in a large multi-institutional cohort of patients with metastatic renal cell carcinoma (mRCC) treated with cytoreductive nephrectomy (CNT).

Methods

A total of 613 patients with mRCC treated with CNT in US and Europe institutions between 1990 and 2013 were included. Smoking history comprised smoking status, smoking duration in years, number of cigarettes per day and years since smoking cessation. Cumulative smoking exposure was categorized as light short term, heavy long term and moderate. Association between smoking history and OS was assessed by Cox regression logistic analysis.

Results

One hundred and seventy-one patients (27.9 %) never smoked, 193 (31.5 %) were former smokers and 249 (40.6 %) were current smokers. Smoking status was associated with a higher number of metastases (p < 0.001) and an abnormal preoperative corrected calcium level (p = 0.01). Median follow-up was 16 (IQR 7–24) months. Current smokers had a shorter OS than never and former smokers (log rank, p = 0.004). Smoking status was significantly associated with OS in univariable analysis (HR 1.45; 95 % CI 1.16–1.82; p < 0.001), and in multivariable analysis that adjusted for established prognostic factors (HR 1.46; 95 % CI 1.16–1.84; p = 0.002). Daily consumption of more than 20 cigarettes, more than 20 years of smoking exposure and heavy long exposure were all independent prognosticators of worse OS.

Conclusions

Current smoking and a higher cumulative smoking exposure are associated with a higher risk of death in patients with mRCC treated with CNT. Even at this stage, smoking negatively affects kidney cancer outcomes.

     

The Impact of Smoking on Bone Metabolism,Bone Mineral Density and Vertebral Fractures in Postmenopausal Women

Background: Smoking is recognized among the risk factors for osteoporosis, but only few studies have comprehensively explored its influence on bone metabolism and strength. We aimed to evaluate smoking effects on calcium-phosphate metabolism, bone mineral density (BMD) and fracture risk in postmenopausal women. Methods: Our sample included 1067 postmenopausal women who arrived to our osteoporosis outpatient clinic. Anamnestic data, smoking habits (categorized as never, former, and current; and by smoking intensity and duration), biochemical parameters, lumbar/femoral BMD, and presence of vertebral fractures were recorded. In a subsample of 357 women, the changes in BMD after a 2-yr follow-up period were also assessed. Results: Current smokers had shorter reproductive age, lower body mass index, and higher prevalence of heavy alcohol consumption than former/never smokers. They also had lower PTH values and weaker linear association between serum vitamin D and parathyroid hormone (current β = −0.11[SE = 0.004]; former β = −0.14[SE = 0.01]; never β = −0.20[SE = 0.003]; p < 0.01 for all). Baseline BMD did not reflect differences based on smoking habits, duration or intensity. However, after 2 years, only current smokers significantly worsened in femural BMD. After adjustment for confounders, the chance of having sustained vertebral fractures at the first evaluation increased by 74% (95% confidence interval:1.07–2.83) in current compared with never smokers, especially among heavy smokers. Conclusions: Smoking may negatively affect bone by inhibiting vitamin D-parathyroid hormone axis, reducing estrogen exposure, promoting risky health behaviors, and accelerating bone loss, especially at the femur. No significant differences were observed in these outcomes among former smokers, suggesting that quitting smoking has beneficial effects on bone health.     

Smoking Is Associated with Sex-Specific Effects on Bone Microstructure in Older Men and Women

Background: Smoking is a risk factor for fracture, but the mechanism by which smoking increases fracture risk is unclear. Methods: Musculoskeletal health was compared with dual energy X-ray absorptiometry (DXA), high resolution peripheral quantitative computed tomography (HR-pQCT), trabecular bone score, and vertebral fracture assessment in current and past smokers and nonsmokers from a multiethnic study of adults ≥ age 65. Skeletal indices were adjusted for age and weight. Results: Participants (n = 311) were mean age (±SD) 76.1 ± 6.5 years, mostly female (66.0%) and non-white (32.7% black/39.4% mixed race/26.3% white). Mean pack-years was 34.6 ± 20.4. In men (n = 106), weight and BMI were lower (both p < 0.05) in current vs past smokers. Male smokers consumed half the calcium of never and past smokers. BMD by DXA did not differ by smoking status at any skeletal site in either sex. Current male smokers had 13.5%–15.3% lower trabecular bone score vs never and past smokers (both p < 0.05). By HR-pQCT, trabecular volumetric BMD was 26.6%–30.3% lower and trabeculae were fewer, thinner and more widely spaced in male current vs past and never smokers at the radius (all p < 0.05). Cortical indices did not differ. Tibial results were similar, but stiffness was also 17.5%–22.2% lower in male current vs past and never smokers (both p< 0.05). In women, HR-pQCT trabecular indices did not differ, but cortical porosity was almost twice as high in current vs never smokers at the radius and 50% higher at the tibia (both p < 0.05). Conclusions: In summary, current smoking is associated with trabecular deterioration at the spine and peripheral skeleton in men, while women have cortical deficits. Smoking may have sex-specific skeletal effects. The consistent association with current, but not past smoking, suggests the effects of tobacco use may be reversible with smoking cessation.     

Impact of Cigarette Smoking on Living Kidney Donors

Background

Smoking is known to result in a decline in renal allograft function and survival of recipients; however, the effect of smoking on living kidney donors remains unknown. In this study we evaluated the impact of cigarette smoking on renal function of kidney donors.

Impact of smoking on bone mineral density and bone metabolism in elderly men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study

Summary

Our cross-sectional analysis of 1,576 men aged ??65?years examined smoking effects on bone status. Number of smoking years was associated with decreased bone mineral density (BMD), after adjusting for age, height, weight, and number of cigarettes smoked daily. Smoking did not affect biochemical marker serum values for bone turnover.

Introduction

The impact of smoking on bone status in men has not been conclusively established. We examined how smoking and its cessation influence bone status and metabolism in men.

Methods

We analyzed 1,576 men among a baseline survey of Japanese men aged ??65?years, the Fujiwara-kyo Osteoporosis Risk in Men study, conducted during 2007?C2008.

Results

Lumbar spine (LS) BMD values among never, former, and current smokers were 1.045?±?0.194, 1.030?±?0.189, and 1.001?±?0.182?g/cm² (P?=?0.005), respectively, while total hip (TH) BMD values were 0.888?±?0.120, 0.885?±?0.127, and 0.870?±?0.124 (P?=?0.078), respectively. The significant trend for LS BMD remained after adjusting for the covariates; age, height, weight, physical activity, milk consumption, and drinking habit (P?=?0.036). Among never and ever (current and former) smokers, LS and TH BMD decreased with the number of pack years or the number of smoking years, respectively, adjusted for those covariates. Among ever smokers, LS and TH BMD decreased with the number of smoking years after adjusting for age, height, weight, and number of cigarettes smoked daily. Smoking did not reveal significant effect for serum osteocalcin or tartrate resistant acid phosphatase isoenzyme 5b.

Conclusion

The impact of smoking on bone status is mainly associated with the number of smoking years in elderly men.     

Polymorphisms of Muscle Genes Are Associated with Bone Mass and Incident Osteoporotic Fractures in Caucasians

The interaction between muscle and bone is complex. The aim of this study was to investigate if variations in the muscle genes myostatin (MSTN), its receptor (ACVR2B), myogenin (MYOG), and myoD1 (MYOD1) were associated with fracture risk, bone mineral density (BMD), bone mineral content (BMC), and lean body mass. We analyzed two independent cohorts: the Danish Osteoporosis Prevention Study (DOPS), comprising 2,016 perimenopausal women treated with hormone therapy or not and followed for 10 years, and the Odense Androgen Study (OAS), a cross-sectional, population-based study on 783 men aged 20–29 years. Nine tag SNPs in the four genes were investigated. In the DOPS, individuals homozygous for the variant allele of the MSTN SNP rs7570532 had an increased risk of any osteoporotic fracture, with an HR of 1.82 (95 % CI 1.15–2.90, p = 0.01), and of nonvertebral osteoporotic fracture, with an HR of 2.02 (95 % CI 1.20–3.41, p = 0.01). The same allele was associated with increased bone loss (BMC) at the total hip of 4.1 versus 0.5 % in individuals either heterozygous or homozygous for the common allele (p = 0.006), a reduced 10-year growth in bone area at the total hip of 0.4 versus 2.2 and 2.3 % in individuals heterozygous or homozygous for the common allele, respectively (p = 0.01), and a nonsignificantly increased 10-year loss of total-hip BMD of 4.4 versus 2.7 and 2.9 % in individuals heterozygous or homozygous for the common allele, respectively (p = 0.08). This study is the first to demonstrate an association between a variant in MSTN and fracture risk and bone loss. Further studies are needed to confirm the findings.     

The relationship between pulmonary function and bone mineral density in healthy nonsmoking women: the Korean National Health and Nutrition Examination Survey (KNHANES) 2010

Summary

The aim of this study was to examine the association between pulmonary function and bone mineral density (BMD) in subjects who had never smoked. Pulmonary function was associated with BMD in premenopausal, but not postmenopausal, women.

Introduction

It has been reported that low bone mass is common in patients with pulmonary disorders such as chronic obstructive pulmonary disease. However, in healthy nonsmoking women, the relationship between bone mass and pulmonary function has yet to be clarified. The object of this study was to determine whether pulmonary function is related to BMD in healthy nonsmoking women based on menopausal status.

Methods

This study was a cross-sectional study based on data obtained from the Korean National Health and Nutrition Examination Survey (KNHANES), a nationwide representative survey conducted by the Korean Ministry of Health and Welfare in 2010. This study included 456 subjects who had never smoked and analyzed data concerning pulmonary function and BMD.

Results

Functional vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were correlated with BMD at lumbar spine, femur neck (FN), and total hip in premenopausal women (p = 0.030, p = 0.003, p = 0.019, respectively, for FVC; p = 0.015, p = 0.006, p = 0.059, respectively, for FEV₁). However, FVC and FEV₁ were only correlated with BMD at FN in postmenopausal women (p = 0.003 for FVC; p = 0.006 for FEV₁). Body mass index (BMI), FVC, and FEV₁ were significantly related with BMD at FN, even after adjusting for age and other confounding factors (β = 0.334, p < 0.001; β = 0.145, p = 0.017; and β = 0.129, p = 0.037, respectively) in premenopausal women. However, only age and BMI were correlated with BMD at FN (β = ?0.268, p = 0.001 and β = 0.384, p > 0.001) in postmenopausal women after adjusting for confounding factors.

Conclusions

Pulmonary function, including FVC and FEV₁ are associated with BMD at FN in healthy nonsmoking premenopausal women but not in postmenopausal women.     

Impact of Smoking and Smoking Cessation on Oncologic Outcomes in Primary Non–muscle-invasive Bladder Cancer

Background

Cigarette smoking is the best-established risk factor for urothelial carcinoma (UC) development, but the impact on oncologic outcomes remains poorly understood.

Objective

To analyse the effects of smoking status, cumulative exposure, and time from smoking cessation on the prognosis of patients with primary non–muscle-invasive bladder cancer (NMIBC).

Design, setting, and participants

We collected smoking data from 2043 patients with primary NMIBC. Smoking variables included smoking status, average number of cigarettes smoked per day (CPD), duration in years, and time since smoking cessation. Lifetime cumulative smoking exposure was categorised as light short term (≤19 CPD, ≤19.9 yr), light long term (≤19 CPD, ≥20 yr), heavy short term (≥20 CPD, ≤19.9 yr) and heavy long term (≥20 CPD, ≥20 yr). The median follow-up in this retrospective study was 49 mo.

Interventions

Transurethral resection of the bladder with or without intravesical instillation therapy.

Outcome measurements and statistical analysis

Univariable and multivariable logistic regression and competing risk regression analyses assessed the effects of smoking on outcomes.

Results and limitations

There was no difference in clinicopathologic factors among never (24%), former (47%), and current smokers (29%). Smoking status was associated with the cumulative incidence of disease progression in multivariable analysis (p = 0.003); current smokers had the highest cumulative incidences. Among current and former smokers, cumulative smoking exposure was associated with disease recurrence (p < 0.001), progression (p < 0.001), and overall survival (p < 0.001) in multivariable analyses that adjusted for the effects of standard clinicopathologic factors and smoking status; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation >10 yr reduced the risk of disease recurrence (hazard ratio [HR]: 0.66; 95% confidence interval [CI], 0.52–0.84; p < 0.001) and progression (HR: 0.42; 95% CI, 0.22–0.83; p = 0.036) in multivariable analyses. The study is limited by its retrospective nature.

Conclusions

Smoking status and a higher cumulative smoking exposure are associated with worse prognosis in patients with NMIBC. Smoking cessation >10 yr abrogates this detrimental effect. These findings underscore the need for integrated smoking cessation and prevention programmes in the management of NMIBC patients.     

Early smoking is associated with peak bone mass and prevalent fractures in young,healthy men

Smoking is associated with lower areal bone mineral density (aBMD) and higher fracture risk, although most evidence has been derived from studies in elderly subjects. This study investigates smoking habits in relation to areal and volumetric bone parameters and fracture prevalence in young, healthy males at peak bone mass. Healthy male siblings (n = 677) at the age of peak bone mass (25 to 45 years) were recruited in a cross‐sectional population‐based study. Trabecular and cortical bone parameters of the radius and cortical bone parameters of the tibia were assessed using peripheral quantitative computed tomography (pQCT). Areal bone mass was determined using dual energy X‐ray absorptiometry (DXA). Sex steroids and bone markers were determined using immunoassays. Prevalent fractures and smoking habits were assessed using questionnaires. Self‐reported fractures were more prevalent in the current and early smokers than in the never smokers (p < .05), with a fracture prevalence odds ratio for early smokers of 1.96 (95% confidence interval 1.18–3.24) after adjustment for age, weight, educational level, and alcohol use and exclusion of childhood fractures. Current smoking was associated with a larger endosteal circumference (β = 0.027 ± 0.009, p = .016) and a decreased cortical thickness (β = ?0.034 ± 0.01, p = .020) at the tibia. In particular, early smokers (≤16 years) had a high fracture risk and lower areal BMD, together with a lower cortical bone area at the tibia and lower trabecular and cortical bone density at the radius. An interaction between free estradiol and current smoking was observed in statistical models predicting cortical area and thickness (β = 0.29 ± 0.11, p = .01). In conclusion, smoking at a young age is associated with unfavorable bone geometry and density and is associated with increased fracture prevalence, providing arguments for a disturbed acquisition of peak bone mass during puberty by smoking, possibly owing to an interaction with sex steroid action. © 2010 American Society for Bone and Mineral Research     

Cigarette Smoking, Alcohol and Caffeine Consumption, and Bone Mineral Density in Postmenopausal Women

The aim of this analysis was to compare the effects of different measures of cigarette, alcohol and caffeine consumption upon bone mineral density (BMD). Five hundred and eighty postmenopausal women aged 45–59 years at recruitment completed a risk factor questionnaire that contained detailed sections on cigarette, alcohol and caffeine consumption. BMD was measured using dual-energy X-ray absorptiometry. Measurements taken at five bone sites were used: anterior-posterior spine, femoral neck, greater trochanter, radius/ulna and whole body. The data were analyzed using multiple linear regression, adjusting for a number of established BMD risk factors. BMD was more strongly related to the number of months spent smoking than to pack-years of smoking at all five sites (p <0.05 at four of the five sites). There were significant reductions in BMD when comparing smokers with non-smokers at ages 20, 30 and 40 years, but not for current smoking. Lifetime alcohol consumption and current alcohol consumption did not have an independent association with BMD. However, the heaviest beer drinkers in the sample had a particularly low bone density. Caffeine consumption at various ages was not associated with BMD. The results of these analyses suggest that for predicting BMD a simple history of smoking duration is as good as trying to obtain more detailed smoking information, but that only 25% of the variation in BMD is explained by personal characteristics, family history and lifestyle factors. Received: 30 June 1997 / Accepted: 23 December 1997     

Smoking and the risk of fracture in older men.

The role of smoking on fracture risk in older men was studied within a longitudinal population-based cohort study. Using time-dependent exposure information and analysis, smoking was detected to be a stronger, dose-dependent and a more long lasting risk factor for fracture than has previously been estimated. INTRODUCTION: Although several studies have indicated a negative influence of smoking on fracture risk in women, there are few studies in men. No study in either sex has considered that smoking exposure may vary during follow-up in a cohort study. There is a need for a prospective study with repeated measures to analyze smoking exposure and fracture risk in men. MATERIALS AND METHODS: A total of 2322 men, 49-51 years of age, were enrolled in a longitudinal, population-based cohort study. Smoking status and other lifestyle habits were established at baseline and additionally at 60, 70, and 77 years of age. One or more fractures were documented in 272 men during 30 years of follow-up. Cox proportional hazards regression was used to determine the rate ratio (RR) of fracture according to time-dependent smoking habits and covariates. RESULTS: The overall adjusted fracture risk was increased in current (RR, 2.71; 95% CI, 1.86-3.95) and former smokers (RR, 1.66, 95% CI; 1.18-2.34), and persistent until 30 years after cessation. Among current smokers, the adjusted risk of any fracture increased by 30% (95% CI, 6-58%) for every 5 g of tobacco smoked each day. Smoking duration did not substantially influence fracture risk in either current or former smokers. One-half (52%; 95% CI, 35-65%) of all fractures were attributable to current smoking. CONCLUSIONS: Tobacco smoking seems to be a long-lasting major risk factor for fracture in older men, and the risks depends both on recency of smoking and on the daily amount of tobacco smoked, rather than smoking duration.     

Premenopausal smoking and bone density in 2015 perimenopausal women.

The importance of cigarette smoking in relation to bone mass remains uncertain, especially in younger women. In a recent meta-analysis including 10 studies in premenopausal women no effect was seen in this age group. We used baseline data from a large national cohort study (Danish Osteoporosis Prevention Study [DOPS]) to study the cumulated effect of pre- and perimenopausal smoking on bone mineral density (BMD) measured shortly after the cessation of cyclic bleedings. Baseline observations on 2015 recently menopausal women were available. Eight hundred thirty-two women were current smokers and 285 were exsmokers. Significant negative associations of cigarette smoking coded as current, ex-, or never smoking were seen on bone mass in the lumbar spine (P = 0.012), femoral neck (P<0.001), and total body (P<0.001). Quantitatively, the differences between current smokers and never smokers were limited to 1.6, 2.9, and 1.9%, respectively. A statistical interaction was found between smoking and fat mass, indicating that women in the highest tertile of fat mass were unaffected by cigarette smoking. Serum vitamin D levels and osteocalcin were inversely related to the number of cigarettes smoked per day (r = 0.11 and P<0.001; r = 0.17 and P = 0.04), respectively. Bone alkaline phosphatase (BALP) and urinary hydroxyproline (U-OHP) were unaffected by current smoking. The average cumulated effect of premenopausal smoking on bone is small but biologically significant. Reduced body mass in smokers explains part of the negative effect on the skeleton and a complex interaction between smoking and fat mass on the skeleton is indicated. Serum levels of 25-hydroxyvitamin D (25-OHD) and osteocalcin are lower in smokers, which may effect rate of bone loss.     

Effect of Cigarette Smoking on Bone Mineral Density in Healthy Taiwanese Middle-Aged Men

The effect of cigarette smoking in relation to bone mineral density (BMD) remains inconclusive, especially in middle-aged men. This cross-sectional study was conducted to examine the effect of smoking on BMD in 837 healthy Taiwanese males (532 never-smokers, 258 current smokers, 47 former smokers; aged 46–64 yr), recruited at their routine health examination. Subjects with suspected conditions affecting bone metabolism or receiving any medications affecting bone metabolism were excluded. BMD of the lumbar spine (LSBMD) and femoral neck (FNBMD) was measured with dual-energy X-ray absorptiometry. After adjustment for confounding variables (age, weight, physical activity, alcohol consumption, and caffeine intake), we found that the mean value of LSBMD was significantly (2.9%) lower in current smoker compared with never-smokers (p = 0.024), but no significant difference was observed in FNBMD. No statistically significant association was observed between former smokers and never-smokers in any of the BMD sites, indicating that quitting smoking did have a positive effect on bone density. Compared with never-smokers, current heavy smokers who consumed at least 20 cigarettes/d (n = 94) had 3.8% lower LSBMD (p = 0.04), but no significant difference was observed in FNBMD. In the correlation analysis, the duration of smoking was negatively associated with LSBMD (r = −0.166, p = 0.004), but no association was shown in FNBMD. Our results suggested that both smoking status and duration of smoking were deleterious factors on the bone density of the lumbar spine, and the effect was cumulative with duration and quantity.     

A Pediatric Bone Mass Scan Has Poor Ability to Predict Adult Bone Mass: A 28-Year Prospective Study in 214 Children

As the correlation of bone mass from childhood to adulthood is unclear, we conducted a long-term prospective observational study to determine if a pediatric bone mass scan could predict adult bone mass. We measured cortical bone mineral content (BMC [g]), bone mineral density (BMD [g/cm²]), and bone width (cm) in the distal forearm by single photon absorptiometry in 120 boys and 94 girls with a mean age of 10 years (range 3–17) and mean 28 years (range 25–29) later. We calculated individual and age-specific bone mass Z scores, using the control cohort included at baseline as reference, and evaluated correlations between the two measurements with Pearson’s correlation coefficient. Individual Z scores were also stratified in quartiles to register movements between quartiles from growth to adulthood. BMD Z scores in childhood and adulthood correlated in both boys (r = 0.35, p < 0.0001) and girls (r = 0.50, p < 0.0001) and in both children ≥10 years at baseline (boys r = 0.43 and girls r = 0.58, both p < 0.0001) and children <10 years at baseline (boys r = 0.26 and girls r = 0.40, both p < 0.05). Of the children in the lowest quartile of BMD, 58 % had left the lowest quartile in adulthood. A pediatric bone scan with a value in the lowest quartile had a sensitivity of 48 % (95 % confidence interval [CI] 27–69 %) and a specificity of 76 % (95 % CI 66–84 %) to identify individuals who would remain in the lowest quartile also in adulthood. Childhood forearm BMD explained 12 % of the variance in adult BMD in men and 25 % in women. A pediatric distal forearm BMD scan has poor ability to predict adult bone mass.     

Plasma Level of Homocysteine Associated with Severe Vertebral Fracture in Postmenopausal Women

The aim of this cross-sectional cohort study was to clarify risk factors for severe vertebral fractures in postmenopausal Japanese women. Subjects were ambulatory volunteers age over 50 years who were recruited from a population of outpatients at a primary care institute. At registration, age, body mass index (BMI), bone mineral density (BMD), and present illness were investigated. Biochemical parameters including urinary levels of type I collagen cross-linked N-telopeptides (NTXs), and pentosidine and plasma levels of homocysteine were measured. Values were compared with different fracture grades (grade 0–3). A total of 1,475 postmenopausal women (66.6 ± 9.0 years) were included in the present study. Distributions of vertebral fracture grades were grade 1, 137 cases (9.3 %); grade 2, 124 cases (8.4 %); and grade 3, 162 cases (11.0 %). Age, BMI, BMD, NTX, pentosidine, and homocysteine were significantly associated with vertebral fracture in unadjusted analysis. In addition, a higher prevalence of hypertension was observed in patients with severe fracture. When comparing vertebral fracture grade 0 versus grade 2–3 by multiple regression analysis, pentosidine and homocysteine levels were a significant risk for moderate/severe vertebral fracture (odds ratio [OR] = 1.17, 95 % confidence interval [CI] 1.00–1.38, p = 0.049; OR = 1.22, 95 % CI 1.03–1.46, p = 0.013). Homocysteine levels were also a significant risk when comparing vertebral fracture grade 0 versus grade 3 (OR = 1.27, 95 % CI 1.04–1.58, p = 0.021). Plasma level of homocysteine was an independent risk for severe vertebral fractures.     

Impact of Smoking and Smoking Cessation on Outcomes in Bladder Cancer Patients Treated with Radical Cystectomy

Background

Cigarette smoking is the best-established risk factor for urothelial carcinoma development.

Objective

To elucidate the association of pretreatment smoking status, cumulative exposure, and time since smoking cessation on outcomes of patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC).

Design, setting, and participants

We retrospectively collected clinicopathologic and smoking variables, including smoking status, number of cigarettes per day (CPD), duration in years, and time since smoking cessation, for 1506 patients treated with RC for UCB. Lifetime cumulative smoking exposure was categorized as light short-term (≤20 CPD for ≤20 yr), light long-term (≤20 CPD for >20 yr), heavy short-term (>20 CPD for ≤20 yr), and heavy long-term (>20 CPD for >20 yr).

Intervention

RC and bilateral lymph node (LN) dissection without neoadjuvant chemotherapy.

Outcome measurements and statistical analysis

Logistic regression and competing risk analyses assessed the association of smoking with disease recurrence, cancer-specific mortality, and overall mortality.

Results and limitations

There was no difference in clinicopathologic factors between patients who had never smoked (20%), former smokers (46%), and current smokers (34%). Smoking status was associated with the cumulative incidence of disease recurrence (p = 0.004) and cancer-specific mortality (p = 0.016) in univariable analyses and with disease recurrence in multivariable analysis (p = 0.02); current smokers had the highest cumulative incidences. Among ever smokers, cumulative smoking exposure was associated with advanced tumor stages (p < 0.001), LN metastasis (p = 0.002), disease recurrence (p < 0.001), cancer-specific mortality (p = 0.001), and overall mortality (p = 0.037) in multivariable analyses that adjusted for standard characteristics; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation ≥10 yr mitigated the risk of disease recurrence (hazard ratio [HR]: 0.44; p < 0.001), cancer-specific mortality (HR: 0.42; p < 0.001), and overall mortality (HR: 0.69; p = 0.012) in multivariable analyses. The study is limited by its retrospective nature.

Conclusions

Smoking is associated with worse prognosis after RC for UCB. This association seems to be dose-dependent, and its effects are mitigated by >10 yr smoking cessation. Health care practitioners should counsel smokers regarding the detrimental effects of smoking and the benefits of smoking cessation on UCB etiology and prognosis.     

A meta-analysis of the effects of cigarette smoking on bone mineral density

To determine the magnitude and mediators of the association between cigarette smoking and bone mass in the epidemiologic literature we reviewed articles, published abstracts and conference proceedings, identified through MEDLINE, psychological abstracts, conference proceedings, and article bibliographies. We studied cross-sectional and prospective human studies that provided a quantitative measure of bone mass (X-ray, absorptiometry, or computed tomography) as a function of cigarette smoking exposure. Effects were expressed as pooled standardized mean differences for categorical comparisons (e.g. bone mass in current versus nonsmokers), and as pooled correlation coefficients for continuous comparisons (e.g., correlation of bone mass and pack-years of smoking). Effects were derived for combined bone sites (all bone sites pooled within each study) and four specific sites (hip, lumbar spine, forearm, and os calcis), and were examined overall and as a function of subject and methodologic characteristics (gender, age, body weight, menopausal status, health status). Data were pooled across 86 studies, enrolling 40, 753 subjects. Smokers had significantly reduced bone mass compared with nonsmokers (never and former smokers) at all bone sites, averaging a one-tenth standard deviation (SD) deficit for combined sites. Deficits were especially pronounced at the hip, where the bone mass of current smokers was one-third of a SD less than that of never smokers. Overall, effects were greatest in men and in the elderly, and were dosedependent. In prospective studies, smokers had greater rates of bone loss over time compared with nonsmokers. Bone mass differences remained significant after controlling for age and body weight differences between the two groups. Absolute effect sizes at most bone sites were greatest for current smokers compared with never smokers, intermediate for current smokers compared with former smokers, and lowest for former smokers compared with never smokers, suggesting that smoking cessation may have a positive influence on bone mass. Based on these data, it is estimated that smoking increases the lifetime risk of developing a vertebral fracture by 13% in women and 32% in men. At the hip, smoking is estimated to increase lifetime fracture risk by 31% in women and 40% in men. It appears that smoking has an independent, dose-dependent effect on bone loss, which increases fracture risk, and may be partially reversed by smoking cessation. Given the public health implications of smoking on bone health, it is important that this information be incorporated into smoking prevention and cessation efforts     

The association between breastfeeding, maternal smoking in utero, and birth weight with bone mass and fractures in adolescents: a 16-year longitudinal study

Summary

The aim of this birth cohort study was to determine whether early life factors (birth weight, breastfeeding, and maternal smoking) were associated with bone mass and fractures in 16-year-old adolescents. The results suggest that breastfeeding is associated with higher bone mass and lower fracture risk at age 16 but not in utero smoking or birth weight.

Introduction

There are limited data on early life influences on bone mass in adolescence but we have previously reported in utero smoking, breastfeeding, and birth weight were associated with bone mass at age 8.

Methods

Birth weight, breastfeeding intention and habit, and maternal smoking during pregnancy were assessed at phase one in 1988–1999 and by recall during phase two in 1996–1997. Bone mineral density (BMD) was measured by dual-energy X-ray densitometry. Fractures were assessed by questionnaire. Subjects included 415 male and female adolescents from Southern Tasmania representing 29 % of those who originally took part in a birth cohort study in 1988 and 1989.

Results

Breastfeeding (assessed in a number of ways) was associated with a 2–3 % increase in BMD at all sites apart from the radius and around a one third reduction in fracture risk which persisted after adjustment for confounders. In univariate analysis, birth weight was associated with BMD at the hip, radius, and total body but this did not persist in multivariate analysis and there was no association with fracture. Smoking in utero had no association with BMD at any site or fracture.

Conclusions

Breastfeeding is associated with a beneficial increase in bone mass at age 16 and a reduction in fracture risk during adolescence. The association previously observed at 8 years of age is no longer present for birth weight or smoking in utero.     

Lower vitamin E serum levels are associated with osteoporosis in early postmenopausal women: a cross-sectional study

The aim of this study was to evaluate the relationship between vitamin E status and osteoporosis in early postmenopausal women. Anthropometric data, osteoporosis risk factors, vitamin E serum levels, bone mineral density (BMD) and other serum parameters which may influence bone mineral density in postmenopausal women were analyzed in a cross-sectional study. The association between osteoporosis and age, age of menopause, body mass index, osteocalcin, calcium, vitamin D, vitamin E (measured as 25 hydroxyvitamin D and as α-tocopherol:lipids ratio, respectively), bone alkaline phosphatase, smoking status, leisure physical activity and alcohol intake were modeled by a multivariate logistic regression and multi-linear regression analysis in 232 early postmenopausal women. A lower vitamin E:lipid ratio was associated with osteoporosis in multivariate logistic regression. In a multivariate linear model with BMD of the lumbar spine as a dependent variable, the vitamin E:lipid ratio was clearly related with BMD of the lumbar spine (F ratio = 6.30, p = 0.002). BMD of the lumbar spine was significantly higher in the highest tertile of the vitamin E:lipid ratio than in the lowest tertile. The mean vitamin E:lipid ratio was significantly lower in osteoporotic postmenopausal women (T score ≤?2.5) (3.0 ± 0.6 μmol/mmol) than normal (neither osteoporotic nor osteopenic) postmenopausal women (T score >?1) (3.5 ± 0.7 μmol/mmol) using multivariable-adjusted BMD. These findings highlight that vitamin E may increase BMD in healthy postmenopausal women.     

The Effect of High-Dose Vitamin D Supplementation on Calciotropic Hormones and Bone Mineral Density in Obese Subjects with Low Levels of Circulating 25-Hydroxyvitamin D: Results from a Randomized Controlled Study

Low levels of 25-hydroxyvitamin D (25OHD) are associated with increased bone turnover and risk of fractures. Plasma 25OHD is inversely related to body mass index, and vitamin D deficiency is common in obesity. We aimed to determine whether vitamin D supplementation affects bone turnover and bone mineral density (BMD) in obese subjects. Fifty-two healthy obese men and women aged 18–50 years with plasma 25OHD levels below 50 nmol/L were randomized to 7,000 IU of cholecalciferol daily or placebo for 26 weeks. We measured plasma levels of 25OHD, parathyroid hormone (PTH), and markers of bone turnover, as well as BMD at the hip, spine, forearm, and whole body. Compared with placebo, treatment with cholecalciferol increased mean plasma 25OHD from 35 to 110 nmol/L (p < 0.00001) and significantly decreased PTH (p < 0.05). BMD increased significantly at the forearm by 1.6 ± 0.7 % (p = 0.03). The bone resorption marker C-terminal telopetide of type 1 collagen (CTX) decreased borderline significantly in the cholecalciferol group compared with the placebo group (p = 0.07). Changes in plasma 25OHD correlated inversely with changes in plasma levels of bone-specific alkaline phosphatase (r = ?0.38, p = 0.01) and CTX (r = ?0.33, p = 0.03). Changes in CTX correlated inversely with changes in spine BMD (r = ?0.45, p = 0.04). Increasing circulating 25OHD levels by cholecalciferol treatment is of importance to bone health in young obese subjects as increased levels of 25OHD are associated with a decrease in both PTH and bone turnover and with an increase in BMD at the forearm.