The global incidence of bullous pemphigoid: a systematic review and meta-analysis.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disorder that mainly affects older people. Although the disease is associated with considerable morbidity and mortality, the burden of disease worldwide is unclear. OBJECTIVES: The study aim is to pool the global incidence of BP and determine whether this varies according to geographic area, age group, setting and study quality. METHODS: Ovid MEDLINE, Ovid Embase and grey literature were systematically searched on 7 April 2020. Two reviewers independently screened, extracted data and appraised each study's quality using the Joanna Briggs Institute critical appraisal tool. Two domains, indicative of selection and survey bias, were used to identify high-quality studies. The cumulative incidence was standardized to 1 year and pooled in a random-effects meta-analysis. Subgroup and sensitivity analyses were conducted. RESULTS: Twenty-seven studies were identified, of which 23 provided cumulative incidence and four provided incidence rates. The cumulative incidence of BP was 8·2 [95% confidence interval (CI) 4·8-13.7] per million people whereas the incidence rate was 34·2 (95% CI 19·2-60·7) per million person-years. Of the continents that contributed more than one study, the cumulative incidence was 10·3 (95% CI 5·8-18·2) and 5·6 (95% CI 3·5-9·0) per million people in Europe and Asia, respectively. The incidence was highest in studies including adults only (n = 2), in population-based studies (n = 9) and in more recent years. The cumulative incidence was higher (13·3 per million people, 95% CI 6·0-29·5) when restricting the analysis to higher-quality studies (n = 11). High heterogeneity (I2 > 82%) was observed across all pooled estimates. CONCLUSIONS: The incidence of BP varies globally, is generally low but appears to be increasing over time. The burden of disease is likely to be underestimated.

Outcome assessment in dermatology clinical trials and cochrane reviews: call for a dermatology-specific outcome taxonomy.

BACKGROUND: Standardized outcome reporting is crucial for trial evidence synthesis and translation of findings into clinical decision-making. The OMERACT 2.0 Filter and COMET outcome domain taxonomy propose frameworks for consistent reporting of outcomes. There is an absence of a uniform dermatology-specific reporting strategy that uses precise and consistent outcome definitions. OBJECTIVES: Our aim was to map efficacy/effectiveness outcomes assessed in dermatological trials to the OMERACT 2.0 Filter as a starting point for developing an outcome taxonomy in dermatology. METHODS: We critically appraised 10 Cochrane Skin Reviews randomly selected from all 69 Cochrane Skin Reviews published until 01/2015 and the 220 trials included covering a broad spectrum of dermatological conditions and interventions. Efficacy/effectiveness outcomes were mapped to core areas and domains according to the OMERACT 2.0 Filter. The extracted trial outcomes were used for critical appraisal of outcome reporting in dermatology trials and for the preliminary development of a dermatology-specific outcome taxonomy. RESULTS: The allocation of 1086 extracted efficacy/effectiveness outcomes to the OMERACT 2.0 Filter resulted in a hierarchically structured dermatology-specific outcome classification. In 506 outcomes (47%), the outcome concept to be measured was insufficiently described, hindering meaningful evidence synthesis. Although the core areas assessed in different dermatology trials of the same condition overlap considerably, quantitative evidence synthesis usually failed due to imprecise outcome definitions, non-comparable outcome measurement instruments, metrics and reporting. CONCLUSIONS: We present an efficacy/effectiveness outcome classification as a starting point for a dermatology-specific taxonomy to provide trialists and reviewers with the opportunity to better synthesize and compare evidence.

Can granulomatosis with polyangiitis be diagnosed earlier in primary care? A case-control study.

BACKGROUND: People with granulomatosis with polyangiitis (GPA) commonly described long delays before diagnosis. AIM: To study the natural history of GPA prior to diagnosis using primary care data, and determine whether clinical features could be identified to help earlier diagnosis. DESIGN: Case-control study using the Clinical Practice Research Datalink. METHODS: We compared primary care activity and clinical features between cases and 10 matched controls. RESULTS: We identified 757 cases and matched 7546 controls. Compared to controls, cases had more GP consultations and overall healthcare activity in the 5 years prior to their diagnosis, with a marked increase in the year before diagnosis, and particularly in the last 3 months. However, consultations were mostly for symptoms that were not specifically related to GPA. In the year prior to diagnosis, the most frequent and strongly predictive clinical features of GPA were Ear Nose and Throat (ENT) symptoms [34.5% of cases, odds ratio (OR) 10.5, 95% confidence intervals (CI) 8.6-12.7], and general (constitutional) symptoms (21.5% of cases, OR 9.0, 95% CI 7.1-11.3). In the year before diagnosis a larger number of cases attended secondary care (382, 50.5%) than had records of clinical features of GPA. CONCLUSIONS: After discussing our findings, we conclude that it would be difficult to identify cases of GPA earlier in primary care. Our results support a need for heightened awareness of this condition among secondary care clinicians, especially those assessing emergency admissions, and in the clinics which were most frequently attended by cases 3-12 months prior to diagnosis.

The prevalence of psychological comorbidity in people with vitiligo: a systematic review and meta-analysis.

BACKGROUND: Vitiligo is a chronic disorder causing skin depigmentation with global prevalence varying from 0·2% to 1·8%. U.K. guidelines recommend assessment of psychological state during clinical evaluation of vitiligo. However, the prevalence of psychological comorbidity in people with vitiligo has not been described. OBJECTIVES: To establish the prevalence of psychological symptoms or disorders in people with vitiligo and describe the outcome measures used. METHODS: We performed a comprehensive search of MEDLINE, Embase, CINAHL and PsycINFO to identify observational studies assessing the prevalence of psychological symptoms or disorders (December 2016). DerSimonian and Lard random-effects models were used to estimate the overall pooled prevalence. RESULTS: We identified 29 studies with 2530 people with vitiligo. Most studies included a measure of either depression (n = 25) or anxiety (n = 13). The commonest tools were the Hospital Anxiety and Depression Scale and the Centre for Epidemiology Studies Depression Scale. Ten studies provided information on 13 other psychological outcomes. Pooled prevalence using depression-specific and anxiety-specific questionnaires was 0·29 [95% confidence interval (CI) 0·21-0·38] and 0·33 (95% CI 0·18-0·49), respectively. Prevalence was lower for clinically diagnosed depression (0·21, 95% CI 0·15-0·28) and anxiety (0·15, 95% CI 0·06-0·24). When nonspecific tools were used the prevalence remained similar for depression (0·27, 95% CI 0·08-0·46) but increased for anxiety (0·46, 95% CI 0·39-0·52). High heterogeneity was observed. CONCLUSIONS: A range of psychological outcomes are common in people with vitiligo. The prevalence of anxiety was influenced by type of screening tool, suggesting the need for validation of psychological outcome screening tools in the field of dermatology.

Variation in the risk of venous thromboembolism in people with colorectal cancer: a population-based cohort study from England.

BACKGROUND: Patients with colorectal cancer are at high risk of developing venous thromboembolism(VTE), and recent international guidelines have advised extended prophylaxis for some of these patients following surgery or during chemotherapy. However, our understanding of which patients are at increased risk, and to what extent, is limited. OBJECTIVES: To determine absolute and relative rates of VTE among patients with colorectal cancer according to Dukes stage, surgical intervention,and chemotherapy. METHODS: We analyzed data from four linked databases from 1997 to 2006: the Clinical Practice Research Datalink, linked to Hospital Episode Statistics, Cancer Registry data, and Office for National Statistics cause of death data, all from England. Rates were compared by the use of Cox regression. RESULTS: There were 10 309 patients with colorectal cancer, and 555 developed VTE (5.4%). The incidence varied by Dukes stage, being three-fold higher among Dukes D patients than among Dukes A patients (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.95­4.84), and 40% higher for those receiving chemotherapy than for those not receiving chemotherapy(HR 1.39, 95% CI 1.14­1.69). The risk following surgery varied by stage of disease and chemotherapy, with Dukes A patients having a low incidence of VTE (0.74%; 95% CI 0.28­1.95) at 6 months,with all events occurring within 28 days of surgery, as compared with Dukes B and Dukes C patients, whose risk at 6 months was ~ 2%. CONCLUSION: Twenty-eight days of prophylaxis following surgery for colorectal cancer is appropriate for Dukes A patients. However, Dukes B and Dukes C patients receiving postoperative chemotherapy have a longer duration of risk.

Aspirin and other non-steroidal anti-inflammatory drug use and colorectal cancer survival: a cohort study.

BACKGROUND: Aspirin has been widely reported to reduce the incidence of colorectal cancer. Recently, a survival benefit after diagnosis has also been suggested. Data regarding such a benefit are to date contradictory. This study examines the effect of non-steroidal anti-inflammatory drug (NSAID) use on mortality in colorectal cancer in a larger patient cohort than previously to further clarify this effect, especially in terms of exposure timing and dosing. METHODS: A study using the General Practice Research Database assessed whether aspirin or NSAID exposure in the year immediately following diagnosis affected all-cause mortality in a cohort of 13 994 colorectal cancer patients. Cox proportional hazards modelling adjusted for age, gender, smoking, body mass index and comorbidity. RESULTS: Overall mortality was slightly lower in patients treated with aspirin, (hazard ratio (HR)=0.91; 95% confidence interval (CI)=0.82-1.00). This effect was observed only in patients treated with prophylaxis-dose aspirin (HR=0.89, CI=0.80-0.98) and only in patients taking aspirin before diagnosis (HR=0.86, CI=0.76-0.98). Differential effects were observed depending on the time after diagnosis. Up to 5 years, a reduction in mortality was observed for aspirin users (HR=0.83, CI=0.75-0.92), whereas after 10 years there was an increase in mortality (HR=1.94, CI=1.26-2.99). For NSAID use, no significant effect was observed on overall mortality (HR=1.07, CI=0.98-1.15). High-dose NSAID use was associated with a slight increase in mortality (HR=1.41, CI=1.26-1.56). INTERPRETATION: These findings provide further indication that aspirin may be beneficial in reducing mortality in colorectal cancer during the first 5 years. The same cannot be said for other NSAIDs, where a small increase in mortality was observed.

The long-term risk of malignancy following a diagnosis of coeliac disease or dermatitis herpetiformis: a cohort study.

BACKGROUND: People with coeliac disease are known to be at increased risk of malignancy; however, long-term risks of malignancy beyond 10-15 years are largely unstudied. AIM: To estimate how long an increased risk of malignancy among coeliac disease patients persists following diagnosis and treatment, using data from a cohort with an average follow-up of 25 years. METHODS: People with coeliac disease diagnosed in the Lothian region of Scotland, United Kingdom, were followed up from January 1970 or the date of coeliac disease diagnosis (whichever was later) until the first occurrence of death, emigration, cancer diagnosis or the end of 2004. Standardised incidence ratios were calculated to compare the cancer incidence rates among this group with those from the population of Scotland. RESULTS: Overall, the risk of any malignancy in coeliac disease patients compared with the general population was increased 40% [standardised incidence ratio (SIR) = 1.41; 95% CI 1.09-1.78]. An increased risk for cancer overall persisted for up to 15 years, beyond which no overall increase in malignancy risk was observed, although the risk of non-Hodgkin's lymphoma remained raised beyond 15 years (SIR = 5.15; 95% CI 1.40-13.2). In total, there were 14 non-Hodgkin's lymphomas in the cohort, providing an overall incidence of 1.3 per 1000 person-years. CONCLUSIONS: The overall risk of malignancy in coeliac patients declines with time after diagnosis and is not significantly increased after 15 years. Most of the increased risk can be attributed to the development of haematological malignancies, despite their very low absolute rate of occurrence.

The antecedents of biliary cancer: a primary care case-control study in the United Kingdom.

In a case-control study using a large UK primary care database, we found that non-steroidal anti-inflammatory drugs had no protective effect against biliary carcinomas (cholangiocarcinoma and gall bladder cancer). Increased risks were observed for cigarette smoking, diabetes, gallstone disease and obesity.

Severe fibrosis in hepatitis C virus-infected patients is associated with increased activity of the mannan-binding lectin (MBL)/MBL-associated serine protease 1 (MASP-1) complex.

Mannan-binding lectin (MBL) binds microorganisms via interactions with glycans on the target surface. Bound MBL subsequently activates MBL-associated serine protease proenzymes (MASPs). A role for MBL in hepatitis C virus (HCV) infection had been indicated by previous studies examining MBL levels and polymorphisms in relation to disease progression and response to treatment. We undertook this study to investigate a possible relationship between disease progression and functional MBL/MASP-1 complex activity. A functional assay for MBL/MASP-1 complex activity was employed to examine serum samples from patients with chronic HCV infection, non-HCV liver disease and healthy controls. Intrapatient consistency of MBL/MASP-1 complex activity levels was assessed in sequential samples from a subgroup of patients. Median values of MBL/MASP-1 complex activity were higher in sera from patients with liver disease compared with healthy controls. MBL/MASP-1 complex activity levels correlate with severity of fibrosis after adjusting for confounding factors (P = 0.003). MBL/MASP-1 complex activity was associated more significantly with fibrosis than was MBL concentration. The potential role of MBL/MASP-1 complex activity in disease progression is worthy of further study to investigate possible mechanistic links.

Human papillomavirus infection in women who develop high-grade cervical intraepithelial neoplasia or cervical cancer: a case-control study in the UK.

Human papillomavirus (HPV) testing might identify older women who could be withdrawn from the cervical screening programme, or require less frequent screening. A case-control study using the United Kingdom cervical screening population was set up to help address this issue. Cases comprised 575 women who developed cervical intraepithelial neoplasia (CIN) grade 2 or worse over a 13-year period following a cytologically normal baseline smear, and were stratified by age group ('under 20', '20-39' and 40 years or over). Controls (n=601) were women who remained disease free over this interval and were the same age on average as cases. DNA was extracted from the baseline smears and tested for HPV by PCR using GP5+/6+ consensus primers. HPV+ samples were tested for HPV types 16 and 18 using specific PCR primers. In all, 27.0% of cases tested positive for HPV at baseline, compared with 15.4% of controls (odds ratio (OR)=2.00; 95% confidence interval (CI), 1.50-2.68). Among women aged 40 years or over, the OR for HPV 16 was 8.95 (95% CI, 2.63-30.4). These results support the need for further cervical screening of HPV- older women, as many of the cases were HPV- at baseline.

Reproductive, menstrual and menopausal factors: which are associated with bone mineral density in early postmenopausal women?

The associations between a number of reproductive and menopausal factors and bone mineral density (BMD) were studied in a sample of early postmenopausal women. The study included 580 women aged 45-61 years who completed a risk factor questionnaire containing sections on obstetric and menstrual history. BMD measurements were taken at the anteroposterior (AP) spine, greater trochanter, femoral neck, total radius and whole body, along with whole body bone mineral content (BMC). In analyses adjusting for key confounders, number of pregnancies was more strongly associated with increased BMD than number of live births at all sites (p<0.05 at femoral neck and total radius), and menstrual years was more strongly associated with increased BMD than years since menopause (p<0.05 at all sites). Hysterectomized women had a significantly higher adjusted mean BMD than non-hysterectomized women at all sites (AP spine: 0.999 g/cm2 vs 0.941 g/cm2, p<0.001), although there were no significant differences in BMD between hysterectomized women who had a bilateral oophorectomy and those whose ovaries were preserved. Negative associations between the duration of hot flushes and BMD were statistically significant (p<0.05) at the three non-hip sites. In multiple regression analyses containing all reproductive terms, duration of hormone replacement therapy (HRT) use, menstrual years and hysterectomy status were significantly associated with BMD at all five sites, whilst oral contraceptive use before the age of 23 years was significantly associated with increased BMD at all sites except the total radius. Breastfeeding duration, the duration of oral contraceptive use and premenopausal amenorrhea were found to have no association with BMD. Results for whole body BMC were consistent with those for the five BMD sites, across all the variables considered here. These findings confirm the importance of HRT use and duration of menses as predictors of BMD, whilst the results for hysterectomy status and early oral contraceptive use require further consideration.

Risks, costs, and compliance limit colorectal adenoma surveillance: lessons from a randomised trial.

BACKGROUND AND AIMS: In the USA and many other countries, endoscopic surveillance of colorectal adenoma patients is now widely practised. However, the optimal frequency and mode of such surveillance are not yet established. The aim of this trial was to compare surveillance at one, two, or five year intervals using either flexible sigmoidoscopy or colonoscopy. METHODS: Analysis of a randomised trial of flexible sigmoidoscopy and colonoscopy over one, two, or five years after stratification for "high" or "low" risk of recurrent adenomas. The trial started in 1984. RESULTS: A total of 776 patients were stratified into "high" (n=307) and "low" (n=469) recurrence risk groups and randomised to flexible sigmoidoscopy or colonoscopy at varying intervals. Only 81 recurrent adenomas (30/81 were >1 cm in diameter) were detected in the 2307 person years of follow up within the surveillance study. Adenoma recurrence was significantly higher in the high risk group (relative rate 1.82; 95% confidence interval 1.2-2.9) but recurrence rates per 1000 person years were low and not significantly different in those surveyed by colonoscopy or flexible sigmoidoscopy. Loss to follow up was greatest in those having an annual examination compared with two or five yearly surveillance examinations. Despite surveillance, invasive cancer developed in four patients compared with an expected value of 9.12 for the general population in England (p=0.10); of these four patients who developed cancers, only one was detected by surveillance examination. CONCLUSIONS: Adenoma recurrence rates were much lower than expected in both high and low risk groups. This suggests that endoscopic surveillance should be targeted at high risk groups. A surveillance interval of five years was as effective as shorter intervals in terms of cancer prevention, and was associated with similar compliance to two yearly examinations.

Social support, personality and depressive symptoms over 7 years: the Health and Lifestyle cohort.

BACKGROUND: We tested the hypothesis that a negative relationship between social support and depression is stronger in extroverts. METHODS: Data on social support and personality were obtained from an existing cohort of 9003 adults (the Health and Lifestyle Survey, UK), of whom 3594 respondents who were followed-up 7 years later contributed to the present analysis. Six depression items from the 30-item General Health Questionnaire, summed, were divided into five levels and a proportional odds analysis was performed. Information on social support was also obtained at follow-up. RESULTS: For females, there was a highly significant interaction between Time of Residence in Area and extroversion (P<0.001). For males, interactions involving Adults in Household and Living as Married reached borderline significance (0.050.10). CONCLUSION: It is unlikely that a lack of social support is more or less harmful for introverts, although the hypothesis should be re-tested in a study with a much shorter period of follow-up and higher response rate.

Occupational activity and bone mineral density in postmenopausal women in England.

Few studies have assessed the relationship between occupational activity and bone mineral density (BMD), although two case-control studies have reported a protective effect of occupational activity on hip fracture. In the present study 580 postmenopausal women aged 45-61 years completed a risk factor questionnaire including a detailed occupational history. For each job, hours spent sitting, standing, walking, lifting and carrying were recorded; these measures, evaluated at ages 20, 30, 40 years, in the current job and over the working lifetime, were used in the analysis. BMD was measured with dual-energy X-ray absorptiometry, and measurements at five sites were used in a multiple regression analysis adjusting for potential confounding variables. There was a significant negative association between sitting at age 20 years and BMD at the radius (p = 0.037), with negative relationships of borderline significance at the anteroposterior spine (p = 0.091) and whole body (p = 0.078). There were significant positive associations between standing at age 30 years and BMD at all five sites (p < 0.05), but no significant linear associations for standing at ages 20 and 40 years. No significant associations were found for lifetime or current occupational measures of sitting, standing, walking and lifting or carrying. The lack of consistency of these significant findings suggests that they may have occurred by chance, and that occupational activity has little if any effect on BMD in postmenopausal women.

Cross-sectional analysis of renal transplantation osteoporosis.

We report a cross-sectional study of 54 adult female renal transplant recipients. We measured bone mineral density (BMD) of the lumbar spine, femoral neck, total hip, and mid- and total radius, and 38 patients underwent transiliac crest bone biopsy. Osteopenia was widespread with 31/54 (57%) of patients osteoporotic at one or more sites. Seventeen out of 54 (32%) of the patients had a prevalent low-trauma fracture. There was a clear trend in BMD reduction across spine, hip and midradius, with the predominantly cortical midradial site showing the greatest loss. We found no relationship between BMD and body mass index, parathyroid hormone (PTH), dose of immunosuppressant, years since transplantation, age at menopause, or years since menopause. Histologically, abnormal biopsies could be classified into three categories: hyperparathyroid (n = 20), adynamic (n = 14), and osteomalacic (n = 2). Mean PTH was lower (p = NS) and mean cumulative prednisolone dose was higher (p = 0.04) in the adynamic group compared with the hyperparathyroid group, but because of overlap between groups neither was an effective discriminator of histology. We suggest that bone biopsy is indicated in these patients to direct appropriate treatment. At the cellular level, there were significant negative correlations between osteoclast function (eroded surface, r = 0.47, p = 0.003) and osteoblast numbers (osteoblast surface, r = -0.40, p = 0.01) and cumulative exposure to prednisolone. We postulate that suppression of osteoblast function by prednisolone with unopposed bone resorption may result in relative hypercalcaemia and low PTH. This progressive reduction in bone turnover may promote or prolong the adynamic state.

Association between a family history of fractures and bone mineral density in early postmenopausal women.

The aim of this analysis was to measure the strength of the association between a family history of fractures and bone mineral density (BMD), and to determine what definition of family fracture history best predicts BMD. Five hundred and eighty postmenopausal women aged 45-59 at recruitment completed a risk factor questionnaire. Women were asked to recall details of fractures sustained by any female relative. BMD measurements taken at five sites were used. The data were analysed using linear regression, adjusting for age. Two hundred and ninety-seven (52.8%) women reported a family history of fractures, and they had a significantly lower BMD at two of the sites measured (p < 0.05). The associations with BMD were most significant when only counting fractures that occurred in the subject's mother or a sister as a result of low trauma, with no restrictions made on age at the time of fracture and site of fracture (p < 0.01 at three sites; 0.01 < p < 0.05 at two sites). Women with a family history according to this definition had a 4.6% reduction in BMD at the femoral neck. When T scores were used to categorize women as either osteopenic/osteoporotic (T < -1) or normal at the femoral neck, the sensitivity of using this definition was 39% and the specificity was 74%. The small group of women that reported a low-trauma hip fracture in a mother or sister (n = 23) had a mean femoral neck BMD which was 8.9% lower than that of the remainder of the sample, although this difference was less statistically significant than when low trauma fractures at any site were counted. Of these 23 women, 70% were osteopenic or osteoporotic, compared with 57% of those reporting a low-trauma fracture at any site and 47% of the sample as a whole. The sensitivity of this definition, however, was low (6%). From these analyses it can be concluded that the definition of family fracture history that best predicts BMD in postmenopausal women is a fracture at any age in a mother or sister resulting from low trauma, although the sensitivity and specificity of using a family history of fractures by itself to screen for low BMD were poor.

Habitual physical activity and bone mineral density in postmenopausal women in England.

BACKGROUND: Reduced levels of physical activity have been found to be associated with an increased risk of osteoporotic fracture in a number of epidemiological studies, and intervention studies have shown beneficial effects of exercise regimes on bone mineral density. It is not yet established, however, which specific forms of customary physical activity are most strongly associated with bone mineral density in postmenopausal women. METHODS: A cross-sectional study was conducted in 580 postmenopausal women, aged 45-61 years, resident in Nottingham, England. The participants completed a detailed interviewer-administered activity questionnaire. Physical activity was assessed as total hours of participation per week in activities including housework, walking, gardening and sports. Stair-climbing and self-reported walking pace were also reported. Bone mineral density measurements were made using dual energy x-ray absorptiometry, measurements at five sites were used in analysis. RESULTS: The strongest associations between the activity measures and bone mineral density were for stair-climbing and walking pace, which both gave statistically significant positive associations at the trochanter hip site and the whole body. In women reporting a fairly brisk or fast walking pace, bone mineral density at the proximal femur was also significantly and positively associated with the frequency of walking at least a mile. There were no significant associations with aggregate measures of total customary physical activity. CONCLUSIONS: This study has identified two forms of physical activity, namely stair-climbing and brisk walking which are associated with increased bone mineral density at the hip and whole body in postmenopausal women. Both are feasible forms of activity for promoting to middle-aged women.

Cigarette smoking, alcohol and caffeine consumption, and bone mineral density in postmenopausal women. The Nottingham EPIC Study Group.

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.