Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study.

Few studies have evaluated risk factors for bone loss in elderly women and men. Thus, we examined risk factors for 4-year longitudinal change in bone mineral density (BMD) at the hip, radius, and spine in elders. Eight hundred elderly women and men from the population-based Framingham Osteoporosis Study had BMD assessed in 1988-1989 and again in 1992-1993. BMD was measured at femoral neck, trochanter, Ward's area, radial shaft, ultradistal radius, and lumbar spine using Lunar densitometers. We examined the relation of the following factors at baseline to percent BMD loss: age, weight, change in weight, height, smoking, caffeine, alcohol use, physical activity, serum 25-OH vitamin D, calcium intake, and current estrogen replacement in women. Multivariate regression analyses were conducted with simultaneous adjustment for all variables. Mean age at baseline was 74 years +/-4.5 years (range, 67-90 years). Average 4-year BMD loss for women (range, 3.4-4.8%) was greater than the loss for men (range, 0.2-3.6%) at all sites; however, BMD fell with age in both elderly women and elderly men. For women, lower baseline weight, weight loss in interim, and greater alcohol use were associated with BMD loss. Women who gained weight during the interim gained BMD or had little change in BMD. For women, current estrogen users had less bone loss than nonusers; at the femoral neck, nonusers lost up to 2.7% more BMD. For men, lower baseline weight and weight loss also were associated with BMD loss. Men who smoked cigarettes at baseline lost more BMD at the trochanter site. Surprisingly, bone loss was not affected by caffeine, physical activity, serum 25-OH vitamin D, or calcium intake. Risk factors consistently associated with bone loss in elders include female sex, thinness, and weight loss, while weight gain appears to protect against bone loss for both men and women. This population-based study suggests that current estrogen use may help to maintain bone in women, whereas current smoking was associated with bone loss in men. Even in the elderly years, potentially modifiable risk factors, such as weight, estrogen use, and cigarette smoking are important components of bone health.     

Self-reported number of remaining teeth is associated with bone mineral density of the femoral neck,but not of the spine,in Japanese men and women

Recent studies suggest that a small number of remaining teeth may be associated with low skeletal bone mineral density (BMD) in postmenopausal women. Estrogen deficiency after menopause is considered potential cause relating to tooth loss accompanied by low skeletal BMD in women. Since estrogen plays a dominant role in regulating the male skeleton, it is likely that a small number of remaining teeth also may be associated with low skeletal BMD in men. However, it remains uncertain whether tooth loss is associated with low skeletal BMD in both men and women. We investigated the association between self-reported number of remaining teeth and BMD of the spine and the femoral neck in a cohort of 1914 Japanese subjects aged 48–95 years who were recruited from the Adult Health Study conducted by the Radiation Effects Research Foundation (RERF). BMD of the spine and the femoral neck was measured by dual energy X-ray absorptiometry (DXA). Tooth count was self-reported in response to a simple question to subjects about the number of remaining teeth they had at the time of the survey. Multiple regression analysis adjusted for age, weight, height, smoking, estrogen use, and years since menopause revealed a significant association between number of remaining teeth and BMD of the femoral neck in both men and women; however, no association was found between number of remaining teeth and BMD of the spine in both sexes. Retention of four teeth was significantly associated with a 0.004 g/cm² increase in femoral neck BMD in men (P<0.05), which was similar to that observed in women (P<0.01). Our results suggest the presence of common causes, except age and body weight, relating to tooth loss accompanied by low BMD of the femoral neck in both men and women.     

Assessment of age and risk factors on bone density and bone turnover in healthy premenopausal women

The influence of age and risk factors on bone density and bone turnover was evaluated in 249 healthy premenopausal women. Risk factors were assessed by standardized questionnaires and included reproductive history and lifestyle factors (intake of calcium and vitamin D supplements, consumption of caffeine, smoking habits and physical activity). Bone mineral density (BMD) measurements were obtained in the distal forearm, the lumbar spine and the proximal femur. Bone turnover were assessed by plasma bone Gla proteins (pBGP) and fasting urinary hydroxyproline corrected for creatinine (fUHPr/Cr). Peak bone density seems to be achieved before the age of 30 years, whereafter we found no appreciable bone loss at any skeletal site. Accordingly, the levels of pBGP and fUHPr/Cr were increased before the age of 30, whereafter the values stabilized at a lower level. A dairy calcium intake above 660 mg/day significantly increased BMD in the spine and proximal femur by 3%–5%. Physical activity alone had no influence on BMD, but in combination with calcium intake an additive effect was observed. Women who had an active lifestyle (corresponding to at least 1 h of daily walking) and a dairy calcium intake above 660 mg/day had a 3%–7% increase in BMD compared with more sedentary women with a calcium intake below this limit. Vitamin D supplements, caffeine, smoking and reproductive history did not consistently influence BMD or bone turnover. Only pBGP was selectively reduced by smoking and current use of oral contraceptives, respectively. We conclude that there is no appreciable change in BMD before the menopause once skeletal maturity has been reached. Dietary calcium intake increases peak bone density and this positive effect can be potentiated by an active lifestyle. Other putative risk factors had no influence on premenopausal BMD.     

Effect of dietary protein on bone loss in elderly men and women: the Framingham Osteoporosis Study.

Few studies have evaluated protein intake and bone loss in elders. Excess protein may be associated with negative calcium balance, whereas low protein intake has been associated with fracture. We examined the relation between baseline dietary protein and subsequent 4-year change in bone mineral density (BMD) for 391 women and 224 men from the population-based Framingham Osteoporosis Study. BMD (g/cm2) was assessed in 1988-1989 and in 1992-1993 at the femur, spine, and radius. Usual dietary protein intake was determined using a semiquantitative food frequency questionnaire (FFQ) and expressed as percent of energy from protein intake. BMD loss over 4 years was regressed on percent protein intake, simultaneously adjusting for other baseline factors: age, weight, height, weight change, total energy intake, smoking, alcohol intake, caffeine, physical activity, calcium intake, and, for women, current estrogen use. Effects of animal protein on bone loss also were examined. Mean age at baseline (+/-SD) of 615 participants was 75 years (+/-4.4; range, 68-91 years). Mean protein intake was 68 g/day (+/-24.0; range, 14-175 g/day), and mean percent of energy from protein was 16% (+/-3.4; range, 7-30%). Proportional protein intakes were similar for men and women. Lower protein intake was significantly related to bone loss at femoral and spine sites (p < or = 0.04) with effects similar to 10 lb of weight. Persons in the lowest quartile of protein intake showed the greatest bone loss. Similar to the overall protein effect, lower percent animal protein also was significantly related to bone loss at femoral and spine BMD sites (all p < 0.01) but not the radial shaft (p = 0.23). Even after controlling for known confounders including weight loss, women and men with relatively lower protein intake had increased bone loss, suggesting that protein intake is important in maintaining bone or minimizing bone loss in elderly persons. Further, higher intake of animal protein does not appear to affect the skeleton adversely in this elderly population.     

Radial bone mineral density in pre- and perimenopausal women: a prospective study of rates and risk factors for loss.

Radial bone mineral density (BMD) of 217 white women aged 22-54 years from a single rural community was evaluated in 1984 using single-photon absorptiometry. BMD was measured at a site one-third the distance from the wrist to the elbow, a site that represents predominantly cortical bone tissue. Most of these women (181; 83%) were reexamined 5 years later. The overall average 5 year radial BMD loss was -5.6%. The average rate of loss was -4.5% for women retaining positive estrogen status at follow-up (n = 108) and -7.4% for women who were in negative estrogen status at follow-up (n = 73). Baseline radial BMD measures were highly predictive of the follow-up BMD values (r = 0.80). Women with positive estrogen status and greater baseline BMD also had less BMD change. Greater baseline BMD did not predict the amount of change in women with negative estrogen status. The bone turnover markers osteocalcin and bone-specific alkaline phosphatase were significantly associated with BMD change in women with negative, but not positive estrogen status. There was no conclusive evidence of a "peak age" in the baseline and follow-up BMD measures. Based on rates of BMD change, "peak" bone mineral content appears to occur before age 25 years. Factors significantly associated with lower levels of BMD were menopause without estrogen replacement, nulliparity, smoking, and age at first pregnancy. Factors associated with more bone loss were menopause without estrogen replacement, smoking, shorter duration of oral contraceptive use, and older age. Quetelet index, muscle area, number of lost pregnancies, ever breast-feeding, or calcium intake were not associated with BMD level or its 5 year rate of loss. Physical activity and alcohol intake were not associated with BMD level or change after data were adjusted for age or estrogen status.     

Adverse Effects of Smoking on Peak Bone Mass May Be Attenuated by Higher Body Mass Index in Young Female Smokers

Smoking is associated with postmenopausal bone loss and fracture, but the effect of smoking on bone in younger women is unclear. Peak bone mass is an important determinant for fracture risk; therefore, our aim was to evaluate the association between smoking and bone mass in 25-year-old women, specifically the influence of daily cigarette consumption and total exposure, duration, age at starting smoking, and time since smoking cessation on bone density and fracture risk. Smoking and bone mineral density (BMD) data were available for 1,054 women from the PEAK-25 cohort. Analyses comparing current smokers with women who never smoked were performed using number of cigarettes per day, pack-years, smoking duration, age smoking started, and, for former smokers, age at quitting. BMD did not differ between never, former, and current smokers; and the relative fracture risk in smokers was not significant (relative risk [RR] = 1.2, 95 % confidence interval 0.8–1.9). Among current smokers, BMD decreased with a dose response as cigarette consumption increased (femoral neck p = 0.037). BMD was not significantly lower in young women who had smoked for long duration or started smoking early (p = 0.07–0.64); long duration and early start were associated with higher body mass index (BMI; p = 0.038). Lower BMD persisted up to 24 months after smoking cessation (p = 0.027–0.050), becoming comparable to never-smokers after 24 months. Hip BMD was negatively associated with smoking and dose-dependent on cigarette consumption. Smoking duration was not associated with BMD, although young women with a long smoking history had higher BMI, which might attenuate the adverse effects from smoking.     

Interactions of interleukin-6 promoter polymorphisms with dietary and lifestyle factors and their association with bone mass in men and women from the Framingham Osteoporosis Study.

Lifestyle and dietary factors may influence the association of IL-6 polymorphisms with bone mass. In 1574 unrelated men and women from the Framingham Offspring Cohort, we observed significant hip BMD differences between IL-6 -174 genotypes only in older women, those without estrogens, and those with a poor calcium intake. Hence, association of IL-6 polymorphisms with BMD may be limited to discrete population subgroups. INTRODUCTION: Interleukin (IL)-6 plays a central role in the pathogenesis of osteoporosis. Two functional variants in the IL-6 promoter have previously been associated with IL-6 expression, bone resorption levels, and BMD in late postmenopausal women, but results were conflicting in different populations. We hypothesized that the association between IL-6 promoter alleles and BMD may be affected by interactions with lifestyle and dietary factors known to influence bone turnover. MATERIALS AND METHODS: Among the Offspring Cohort of the Framingham Heart Study, 1574 unrelated men and women were genotyped for IL-6 -572 and -174 alleles. Interaction analyses with years since menopause, estrogen status, physical activity, smoking, dietary calcium, vitamin D, and alcohol intake were based on BMD measurements at the hip. RESULTS AND CONCLUSIONS: In models that considered only the main effects of IL-6 polymorphisms, no significant association with BMD was observed in either gender. In contrast, p values (0.003-0.096 by ANOVA) suggestive of an interaction between IL-6 -174 genotypes and years since menopause, estrogen status, dietary calcium, and vitamin D intake were observed in women (n = 819). In turn, BMD was significantly lower with genotype -174 GG compared with CC, and intermediate with GC, in women who were more than 15 years past menopause and in those without estrogens or with calcium intake <940 mg/day. In estrogen-deficient women with poor calcium intake, BMD differences between genotypes CC and GG were 10.2% at femoral neck (p = 0.012), 12.0% at trochanter (p = 0.012), and 16.8% at Ward's area (p = 0.0014). In contrast, no such interactions were observed in men (n = 755). In conclusion, IL-6 genetic variation was prominently associated with hip BMD in late postmenopausal women, those without estrogen replacement therapy, and those with inadequate calcium intake. In contrast, IL-6 polymorphisms are unlikely to be significant determinants of bone mass in other women or men.     

How Do Reproductive and Lifestyle Factors Influence Bone Density in Distal and Ultradistal Radius of Early Postmenopausal Women? The Nord-Trøndelag Health Survey, Norway

In a population-based health survey, densitometry was performed at the distal and ultradistal radius with single-energy X-ray absorptiometry. Bone mineral density (BMD) data and self-reported reproductive and lifestyle data from 1652 randomly selected peri- and postmenopausal women aged 50–59 years were analyzed. A total of 893 (54.1%) postmenopausal women reported no prior use of hormone replacement therapy (HRT) and constituted the principal group of study. These women were more frequently smokers, consumed less alcohol, more coffee and had made less use of oral contraceptives (OC) than women in the HRT group. The strongest association with both distal and ultradistal radius bone densities was found for age, weight, time since menopause and a history of bilateral oophorectomy. Among reproductive factors, nulliparous women had lower BMD than parous women; however, no linear relationship was found between parity and bone density. A weak, positive relationship was found for OC and BMD in bivariate, but not in multivariate analyses. A history of hysterectomy was positively associated with BMD, stronger at the ultradistal than distal radius. A positive relationship between alcohol consumption and BMD was found at the ultradistal radius. Present or prior smokers had lower BMD than never smokers. In the multivariate model, interaction between pack-years of smoking and daily coffee intake was observed at the distal radius, and both factors had a stronger negative influence on distal than ultradistal radius bone density. In perimenopausal women, most reproductive and lifestyle risk factors found to be associated with BMD of the radius may be explained by different levels of estrogen. Received: 3 April 2000 / Accepted: 12 October 2000     

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.     

Long-term effects of serum cholesterol on bone mineral density in women and men: the Framingham Osteoporosis Study

Laboratory studies have suggested a role for cholesterol in the pathogenesis of both osteoporosis and atherosclerosis. The purpose of this prospective study was to assess whether cholesterol levels, repeatedly measured over three decades in young and middle-aged adult women and men, predicted bone mineral density (BMD) at advanced age. Study participants included 712 women and 450 men enrolled in the Framingham Osteoporosis Study, aged 32-61 years at baseline (1953-55) who underwent bone densitometry 34 years later (1988-1989). BMD was measured at the proximal femur (neck, trochanter, and Ward's triangle) and lumbar spine using dual-photon absorptiometry and at the one-third radial shaft and ultradistal radius using single-photon absorptiometry. Sex-specific multivariable linear regression was used to model each BMD site as a function of total cholesterol level, adjusted for age, cigarette smoking, alcohol consumption, body mass index, systolic blood pressure, diabetes, and estrogen use (women). No significant association between total cholesterol and BMD was found in women for any of the bone sites considered. For example, adjusted mean BMD at the lumbar spine was similar in women from the lowest to highest quartile of total cholesterol, respectively, 1.07, 1.08, 1.06, 1.07 g/cm2; P for trend=0.98. Similarly, the findings in men largely showed no association between cholesterol and BMD, although there was an isolated finding of a statistically significant trend in decreasing mean radial shaft BMD with increasing total cholesterol, 0.73, 0.72, 0.72, 0.70 g/cm2, lowest to highest quartile, P for trend=0.02. Cholesterol levels in women and men from young adulthood to middle age years do not appear to have long-term clinical implications for osteoporosis later in life.     

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.     

Low plasma vitamin B12 is associated with lower BMD: the Framingham Osteoporosis Study.

Vitamin B12 is important to DNA synthesis and may affect bone formation. We examined the association between this vitamin and BMD in 2576 adults. Men with plasma B12 < 148 pM had significantly lower BMD at the hip, and women at the spine, relative to those with higher B12, and trends were similar for both at all sites. Low vitamin B12 may be a risk factor for low BMD. INTRODUCTION: Vitamin B12 is important to DNA synthesis and may affect bone formation. It has been linked to osteoblastic activity in clinical studies and cell culture. MATERIALS AND METHODS: We examined the relationship between plasma vitamin B12 status and BMD in 2576 adult participants in the Framingham Offspring Osteoporosis Study (1996-2001). BMD was measured by DXA at the hip and spine. Plasma vitamin B12 was measured by radioassay. Mean BMD measures were estimated for four categories of vitamin B12 concentration, based on commonly used cut-offs, using analysis of covariance, adjusted for age, BMI, physical activity score for the elderly (PASE), alcohol use, smoking status, total calcium and vitamin D intake, season of bone measurement, and for women, menopause status and current estrogen use. Further adjustment for protein intake and total homocysteine concentration was also performed. RESULTS: Both men and women with vitamin B12 concentrations <148 pM had lower average BMD than those with vitamin B12 above this cut-off. These differences were significant (p < 0.05) for men at most hip sites and for women at the spine. Significance remained after further adjustment for protein intake and plasma homocysteine. CONCLUSIONS: Vitamin B12 deficiency may be an important modifiable risk factor for osteoporosis.     

The effect of cyclooxygenase-2 inhibitors on bone mineral density: results from the Canadian Multicentre Osteoporosis Study

Introduction The use of cyclooxygenase-2 (COX-2) inhibitors has been demonstrated to not only impair load-induced bone formation but also prevent menopause-associated bone loss. We hypothesized that COX-2 inhibitor use would be associated with increased bone mineral density (BMD) in postmenopausal women not using estrogen therapy and, conversely, with decreased BMD in men.Methods The Canadian Multicentre Osteoporosis Study is a longitudinal, randomly selected, population-based community cohort. We present data from men (n=2,004) and postmenopausal women age 65 and older (n=2,776) who underwent a BMD measurement and structured interview in the 5th year of the study. The outcome measure was percent difference in BMD (g/cm²).Results Daily COX-2 inhibitor use was reported by 394 subjects. In men, daily use of COX-2 inhibitors was associated with a lower BMD at all hip sites, with a percent difference of −3.1% [95% confidence interval (CI), −6.0, −0.3] between users and nonusers at total hip. In postmenopausal women not using estrogen replacement therapy, daily COX-2 inhibitor use was associated with higher BMD at most sites [percent difference at total hip: +3.0% (95% CI, 0.3, 5.8)]. These effects appeared to be dose-dependent.Conclusion COX-2 inhibitor use was associated with a lower BMD in men and, on the other hand, with a higher BMD in postmenopausal women not using estrogen replacement therapy. Men who have used COX-2 inhibitors may wish to seek BMD measurement to assess their fracture risk. However, COX-2 inhibitors may have utility in postmenopausal women if bone-selective analogs can be developed.     

Genome screen for quantitative trait loci contributing to normal variation in bone mineral density: the Framingham Study.

A genome-wide scan was performed in a randomly ascertained set of 330 extended families from the population-based Framingham Study to identify chromosomal regions possibly linked to bone mineral density (BMD). A set of 401 microsatellite markers was typed at a 10-centimorgan (cM) average density throughout the genome. BMD was measured at the femoral neck, trochanter, Ward's area, and lumbar spine in 1557 participants of both Framingham cohorts. BMDs were adjusted for age, body mass index (BMI), height, alcohol, caffeine, calcium and vitamin D intakes, smoking, physical activity, and estrogen use in women within each sex and cohort. Strong heritabilities (values between 0.543 and 0.633) were found for the adjusted BMD at all sites. Two-point and multipoint quantitative linkage analyses were performed for each BMD site using the maximum likelihood variance components method. By two-point screening, loci of suggestive linkage were identified on chromosomes 6 and 21, with the maximum log10 of the odds ratio (LOD) scores of 2.34 for the trochanter at D21S1446 and 2.93 for the femoral neck at D6S2427. Lumbar spine BMD had maxima at D6S2427 (LOD = 1.88) and at D12S395 (LOD = 2.08). Multipoint linkage analysis revealed suggestive linkage of trochanteric BMD at a broad (approximately 20 cM) interval on chromosome 21q, with the peak linkage close to D21S1446 (LOD = 3.14). LOD scores were 2.13 at 8q24 with Ward's BMD and 1.92 at 14q21.3 with lumbar spine BMD. This largest genome screen to date for genes underlying normal variation in BMD, adjusted for a large number of covariates, will help to identify new positional candidate genes, otherwise unrecognized.     

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.     

Cross sectional investigation of the effects of inhaled corticosteroids on bone density and bone metabolism in patients with asthma

BACKGROUND: Bone mineral density has been reduced in patients with asthma taking inhaled corticosteroids in some cross sectional studies and this could be important if treatment is continued for several decades. The possibility of confounding by age, menopausal status, physical activity and, especially, past oral steroid use has not been excluded in most studies. The present study was designed to assess the magnitude of any reduction in bone mineral density in relation to inhaled steroid use after adjusting for these factors. METHODS: Bone mineral density (BMD), vertebral fractures, and markers of bone metabolism (serum osteocalcin, procollagen peptide I, bone-specific alkaline phosphatase, and urinary deoxypyridinoline cross links) were measured in 81 patients with asthma age 20-40 years; 34 patients (19 men) who had never had inhaled or systemic steroids and 47 (19 men) who had taken inhaled steroids for at least five years with limited exposure to systemic steroids in the past. Data relating to past medication use, physical activity, smoking, and other confounding factors were collected by questionnaire. The relation between inhaled steroid dose and duration and BMD was assessed by linear regression analysis, accounting for potential confounders including weight, exercise, and oral steroid use. RESULTS: The 47 patients taking an inhaled steroid had a mean current dose of 620 micrograms/day (range 100-3000 micrograms), a mean duration of use of 7.8 years, and had had a mean of 0.85 courses of prednisolone in the past. There was no significant difference in mean BMD values between those who were and those who were not on inhaled steroids in men or women. However, on multivariate analysis, cumulative inhaled steroid dose was associated with a reduction in posterior-anterior (P-A) and lateral lumbar spine bone mineral density in women, equivalent to a 0.11 standard deviation reduction in bone density per 1000 micrograms/day inhaled steroid per year after adjustment for potential confounding factors (95% CI for P-A spine 0.01 to 0.22; for lateral spine 0.02 to 0.21). Previous oral steroid use was not an important confounding factor in these patients. Inhaled steroid use was not related to BMD at the wrist or hip in women or at any skeletal site in men. Women taking an inhaled steroid had lower levels of serum osteocalcin than those not taking them, although this was not dose related. Inhaled steroid use was not associated with differences in other markers of bone metabolism in men or women or with the presence of vertebral fractures. CONCLUSIONS: Although an effect of confounding factors cannot be excluded entirely in a cross sectional study, our findings are in keeping with an effect of inhaled steroid therapy in reducing bone density in the spine in women and provide an estimate of the magnitude of this effect.


     

Estrogen receptor beta polymorphisms are associated with bone mass in women and men: the Framingham Study.

ESR2 is expressed in bone cells, yet few studies have tested its variation for association with BMD, an important determinant of osteoporotic fractures. This was investigated in 723 men and 795 women from the Framingham study. Results show association of variation in this gene with BMD in both women and men. INTRODUCTION: Osteoporotic fracture risk is highly dependent on bone density, a quantitative multifactorial trait with a substantial genetic component. In contrast to the growing body of evidence that estrogen receptor alpha (ESR1) plays a role in bone metabolism, few studies have examined the estrogen receptor beta (ESR2) gene for association with BMD. An ESR2 CA repeat polymorphism, D14S1026, was associated with BMD in two small studies, each with <200 women. MATERIALS AND METHODS: The objective of this investigation was to assess whether D14S1026 or four other intronic polymorphisms were associated with BMD in 723 men and 795 women (mean age, 60 years) from the offspring cohort of the population-based Framingham Study. BMD was measured at the femur (neck, trochanter, and Ward's area) and the lumbar spine (L(2)-L(4)). RESULTS: In both women and men, there was significant association of D14S1026 genotype with measures of femoral but not spinal BMD. In addition, genotypes of two common single nucleotide polymorphisms, rs1256031 and rs1256059, in strong linkage disequilibrium with one another but not with D14S1026, were associated with measures of femoral BMD in men. The rs1256031 genotypes had up to a 4.0% difference in mean femoral BMD. An inferred rs1256031-D14S1026-rs1256059 haplotype C-23CA-T was significantly associated with reduced femoral BMD in women (p = 0.03, 0.003, and 0.01 for neck, trochanter, and Ward's area, respectively). Haplotype-based BMD differences ranged from 3.0% to 4.3%. CONCLUSIONS: We have observed significant association of common ESR2 variants with measures of femoral BMD in both men and women.     

Smoking predicts incident fractures in elderly men: Mr OS Sweden

The aim of this study was to investigate the association between smoking and bone mineral density (BMD) and radiographically verified prevalent vertebral fractures and incident fractures in elderly men. At baseline 3003 men aged 69 to 80 years of age from the Swedish Mr Os Study completed a standard questionnaire concerning smoking habits and had BMD of the hip and spine measured using dual‐energy X‐ray absorptiometry (DXA); 1412 men had an X‐ray of the thoracic‐ and lumbar spine. Radiologic registers were used to confirm reported new fractures after the baseline visit. At baseline, 8.4% were current smokers. Current smokers had a 6.2% lower BMD at the total hip and a 5.4% lower BMD at the lumbar spine (p < .001). Current smoking remained independently inversely associated with BMD at the hip and lumbar spine after adjusting for age, height, weight, calcium intake, physical activity, and centers as covariates. Prevalent vertebral fractures among current smokers were increased in unadjusted analyses [odds ratio (OR) = 1.90, 95% confidence interval (CI) 1.26–2.87] and after adjustment for lumbar BMD (OR = 1.67, 95% CI 1.09–2.55). Smokers had a high risk for two or more prevalent vertebral fractures (OR = 3.18, 95% CI 1.88–5.36). During the average follow‐up of 3.3 years, 209 men sustained an X‐ray‐verified fracture. Incident fracture risk among smokers was calculated with Cox proportional hazard models. Current smokers had an increased risk of all new fractures [hazard ratio (HR) = 1.76, 95% CI 1.19–2.61]; nonvertebral osteoporotic fractures, defined as humerus, radius, pelvis, and hip fractures (HR = 2.14, 95% CI 1.18–3.88); clinical and X‐ray‐verified vertebral fractures (HR = 2.53, 95% CI 1.37–4.65); and hip fractures (HR = 3.16, 95% CI 1.44–6.95). After adjustment for BMD, including other covariates, no significant association between smoking and incident fractures was found. Current tobacco smoking in elderly men is associated with low BMD, prevalent vertebral fractures, and incident fractures, especially vertebral and hip fractures. © 2010 American Society for Bone and Mineral Research     

Short-term preoperative smoking cessation and postoperative complications: a systematic review and meta-analysis

Purpose

The literature was reviewed to determine the risks or benefits of short-term (less than four weeks) smoking cessation on postoperative complications and to derive the minimum duration of preoperative abstinence from smoking required to reduce such complications in adult surgical patients.

Source

We searched MEDLINE, EMBASE, Cochrane, and other relevant databases for cohort studies and randomized controlled trials that reported postoperative complications (i.e., respiratory, cardiovascular, wound-healing) and mortality in patients who quit smoking within six months of surgery. Using a random effects model, meta-analyses were conducted to compare the relative risks of complications in ex-smokers with varying intervals of smoking cessation vs the risks in current smokers.

Principal findings

We included 25 studies. Compared with current smokers, the risk of respiratory complications was similar in smokers who quit less than two or two to four weeks before surgery (risk ratio [RR] 1.20; 95% confidence interval [CI] 0.96 to 1.50 vs RR 1.14; CI 0.90 to 1.45, respectively). Smokers who quit more than four and more than eight weeks before surgery had lower risks of respiratory complications than current smokers (RR 0.77; 95% CI 0.61 to 0.96 and RR 0.53; 95% CI 0.37 to 0.76, respectively). For wound-healing complications, the risk was less in smokers who quit more than three to four weeks before surgery than in current smokers (RR 0.69; 95% CI 0.56 to 0.84). Few studies reported cardiovascular complications and there were few deaths.

Conclusion

At least four weeks of abstinence from smoking reduces respiratory complications, and abstinence of at least three to four weeks reduces wound-healing complications. Short-term (less than four weeks) smoking cessation does not appear to increase or reduce the risk of postoperative respiratory complications.     

Smoking and bone loss among postmenopausal women.

We examined the effect of smoking on bone mineral density (BMD), rates of bone loss, and fractional whole-body retention of 47Ca in healthy postmenopausal women enrolled in a 2-year calcium supplementation trial. Bone density was measured by single- and dual-photon absorptiometry. BMD of the radius at the study baseline was inversely related to pack-years of exposure when controlled for body mass index and years since menopause (partial r = -0.18, p = 0.05, n = 125). The adjusted mean (+/- SD) annualized rate of bone change from the radius was greater among smokers than nonsmokers (-0.914 +/- 2.624%/year, n = 34, versus 0.004 +/- 2.568%/year, n = 278, respectively; p = 0.05). Similar trends were observed at the femoral neck, os calcis, and spine. Rates were were adjusted for caffeine intake, alcohol use, supplement type, and, at the spine only, menopausal status. At entry into the trial higher serum levels of alkaline phosphatase and lower levels of total and ionized calcium were found in smokers compared to nonsmokers. These differences did not persist with supplementation. In 44 women studied fractional 47Ca retention was lower in the 8 smokers than the 36 nonsmokers (16.6 versus 19.1%, respectively; p = 0.03). These results demonstrate an increased rate of bone loss at the radius after menopause and suggest that smoking is associated with decreased calcium absorption.