Associations of Protein Intake and Protein Source with Bone Mineral Density and Fracture Risk: A Population-Based Cohort Study.

UNLABELLED: High dietary protein has been hypothesized to cause lower bone mineral density (BMD) and greater fracture risk. Previous results are conflicting and few studies have assessed potential differences related to differing protein sources. OBJECTIVE: To determine associations between total protein intake, and protein intake by source (dairy, non-dairy animal, plant) with BMD, BMD change, and incident osteoporotic fracture. DESIGN/SETTING: Prospective cohort study (Canadian Multicentre Osteoporosis Study). Participants/Measures: Protein intake was assessed as percent of total energy intake (TEI) at Year 2 (1997-99) using a food frequency questionnaire (N=6510). Participants were contacted annually to ascertain incident fracture. Total hip and lumbar spine BMD was measured at baseline and Year 5. Analyses were stratified by group (men 25-49 y, men 50+ y, premenopausal women 25-49 y, and postmenopausal women 50+ y) and adjusted for major confounders. Fracture analyses were limited to those 50+ y. RESULTS: Intakes of dairy protein (with adjustment for BMI) were positively associated with total hip BMD among men and women aged 50+ y, and in men aged 25-49. Among adults aged 50+ y, those with protein intakes of <12% TEI (women) and <11% TEI (men) had increased fracture risk compared to those with intakes of 15% TEI. Fracture risk did not significantly change as intake increased above 15% TEI, and was not significantly associated with protein source. CONCLUSIONS: In contrast to hypothesized risk of high protein, we found that for adults 50+ y, low protein intake (below 15% TEI) may lead to increased fracture risk. Source of protein was a determinant of BMD, but not fracture risk.

Antidepressant use and 10-year incident fracture risk: the population-based Canadian Multicentre Osteoporosis Study (CaMoS).

UNLABELLED: We used data from a large, prospective Canadian cohort to assess the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) and fracture. We found an increased risk of fractures in individuals who used SSRI or SNRI, even after controlling for multiple risk factors. INTRODUCTION: Previous studies have suggested an association between SSRIs and increasing risk of fragility fractures. However, the majority of these studies were not long-term analyses or were performed using administrative data and, thus, could not fully control for potential confounders. We sought to determine whether the use of SSRIs and SNRIs is associated with increased risk of fragility fracture, in adults aged 50 + . METHODS: We used data from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective randomly selected population-based community cohort; our analyses focused on subjects aged 50+. Time to event methodology was used to assess the association between SSRI/SNRI use, modeled time-dependently, and fragility fracture. RESULTS: Among 6,645 subjects, 192 (2.9%) were using SSRIs or/and SNRIs at baseline. During the 10-year study period, 978 (14.7%) participants experienced at least one fragility fracture. In our main analysis, SSRI/SNRI use was associated with increased risk of fragility fracture (hazard ratio (HR), 1.88; 95% confidence intervals (CI), 1.48-2.39). After controlling for multiple risk factors, including Charlson score, previous falls, and bone mineral density hip and lumbar bone density, the adjusted HR for current SSRI/SNRI use remained elevated (HR, 1.68; 95% CI, 1.32-2.14). CONCLUSIONS: Our results lend additional support to an association between SSRI/SNRI use and fragility fractures. Given the high prevalence of antidepressants use, and the impact of fractures on health, our findings may have a significant clinical impact.

Longitudinal changes in calcium and vitamin D intakes and relationship to bone mineral density in a prospective population-based study: the Canadian Multicentre Osteoporosis Study (CaMos).

OBJECTIVES: Our objective was to study changes in calcium and vitamin D intakes over time, and their cross-sectional and longitudinal associations with bone mineral density (BMD). METHODS: We followed 9382 women and men aged ≥25 and 899 aged 16-24, for 10 and 2 years respectively. RESULTS: Calcium and vitamin D intakes increased over time in adults, but decreased in women aged 16-18. The increased intakes in adults were largely attributable to the increased use of calcium and/or vitamin D supplements. Both the percentage of supplement users and average dose among users increased over time. There was nevertheless a high prevalence of calcium and vitamin D intake below the estimated average requirement. At baseline, higher calcium and vitamin D intakes were associated with higher total hip and femoral neck BMD in young men, and cumulatively high levels of calcium and vitamin D intakes over time contributed to better BMD maintenance at lumbar spine and hip sites in adult women. CONCLUSIONS: Although total intakes, particularly of vitamin D, frequently fell below the Institute of Medicine recommendations despite an increase over time in supplement use, we found some positive associations between total calcium and vitamin D intake and bone health.

Physical activity, body mass index and bone mineral density-associations in a prospective population-based cohort of women and men: the Canadian Multicentre Osteoporosis Study (CaMos).

BACKGROUND: Physical activity (PA) is an important modifiable risk factor for both bone mineral density (BMD) and body mass index (BMI). However, BMI is itself strongly predictive of BMD. Our aim was to determine the association between PA and BMD, with consideration of BMI as a potential mediating factor. METHODS: The Canadian Multicentre Osteoporosis Study (CaMos) is a population-based prospective cohort study of Canadian women and men. PA was determined from interviewer-administered questionnaires at baseline and Year 5 and summarized as daily energy expenditure in total metabolic equivalents of the task multiplied by minutes/day (MET*m/d). Height, weight, and total hip and lumbar spine BMD were measured at baseline and Year 5. General linear models assessed relationships between PA and BMD, both cross-sectionally (baseline PA with baseline BMD) and longitudinally (average PA and change in PA with change in BMD). BMI was considered as a mediating factor. Potential confounders included age, center, education, caffeine intake, alcohol exposure, smoking history, history of weight-cycling, age at menarche, past use of oral contraceptives, history of >3 months missed menstruation, menopausal status, and antiresorptive use, as relevant. RESULTS: The study included 2855 men and 6442 women. PA was inversely associated with BMI at baseline, and an increase in PA between baseline and Year 5 was associated with a decrease in BMI, with 0.41 (95% CI: 0.22, 0.60) kg/m(2) loss per 1000 MET*m/d increase (in men) and 0.40 (95% CI: 0.23, 0.57) kg/m(2) loss per 1000 MET*m/d increase (in women). BMI was strongly associated with BMD, both cross-sectionally and longitudinally. However, increased PA was associated with a small increase in total hip BMD, 0.004 (95% CI: 0.000-0.008) g/cm(2) per 1000 MET*m/d (in men) and 0.003 (95% CI: 0.000-0.007) g/cm(2) per 1000 MET*m/d (in women). Average PA was associated with an increase in lumbar spine BMD in women, but not in men; it was not associated with change in total hip BMD in either sex. CONCLUSION: Increased PA is associated with an increase in BMD and a concomitant decrease in BMI. These findings suggest that population-level interventions to increase PA would favorably impact bone and other health outcomes.

Fracture prediction and calibration of a Canadian FRAX® tool: a population-based report from CaMos.

UNLABELLED: A new Canadian WHO fracture risk assessment (FRAX®) tool to predict 10-year fracture probability was compared with observed 10-year fracture outcomes in a large Canadian population-based study (CaMos). The Canadian FRAX tool showed good calibration and discrimination for both hip and major osteoporotic fractures. INTRODUCTION: The purpose of this study was to validate a new Canadian WHO fracture risk assessment (FRAX®) tool in a prospective, population-based cohort, the Canadian Multicentre Osteoporosis Study (CaMos). METHODS: A FRAX tool calibrated to the Canadian population was developed by the WHO Collaborating Centre for Metabolic Bone Diseases using national hip fracture and mortality data. Ten-year FRAX probabilities with and without bone mineral density (BMD) were derived for CaMos women (N = 4,778) and men (N = 1,919) and compared with observed fracture outcomes to 10 years (Kaplan-Meier method). Cox proportional hazard models were used to investigate the contribution of individual FRAX variables. RESULTS: Mean overall 10-year FRAX probability with BMD for major osteoporotic fractures was not significantly different from the observed value in men [predicted 5.4% vs. observed 6.4% (95%CI 5.2-7.5%)] and only slightly lower in women [predicted 10.8% vs. observed 12.0% (95%CI 11.0-12.9%)]. FRAX was well calibrated for hip fracture assessment in women [predicted 2.7% vs. observed 2.7% (95%CI 2.2-3.2%)] but underestimated risk in men [predicted 1.3% vs. observed 2.4% (95%CI 1.7-3.1%)]. FRAX with BMD showed better fracture discrimination than FRAX without BMD or BMD alone. Age, body mass index, prior fragility fracture and femoral neck BMD were significant independent predictors of major osteoporotic fractures; sex, age, prior fragility fracture and femoral neck BMD were significant independent predictors of hip fractures. CONCLUSION: The Canadian FRAX tool provides predictions consistent with observed fracture rates in Canadian women and men, thereby providing a valuable tool for Canadian clinicians assessing patients at risk of fracture.

Construction and validation of a simplified fracture risk assessment tool for Canadian women and men: results from the CaMos and Manitoba cohorts.

UNLABELLED: A procedure for creating a simplified version of fracture risk assessment tool (FRAX®) is described. Calibration, fracture prediction, and concordance were compared with the full FRAX tool using two large, complementary Canadian datasets. INTRODUCTION: The Canadian Association of Radiologists and Osteoporosis Canada (CAROC) system for fracture risk assessment is based upon sex, age, bone mineral density (BMD), prior fragility fracture, and glucocorticoid use. CAROC does not require computer or web access, and categorizes 10-year major osteoporotic fracture risk as low (<10%), moderate (10-20%), or high (>20%). METHODS: Basal CAROC fracture risk tables (by age, sex, and femoral neck BMD) were constructed from Canadian FRAX probabilities for major osteoporotic fractures (adjusted for prevalent clinical risk factors). We assessed categorization and fracture prediction with the updated CAROC system in the CaMos and Manitoba BMD cohorts. RESULTS: The new CAROC system demonstrated high concordance with the Canadian FRAX tool for risk category in both the CaMos and Manitoba cohorts (89% and 88%). Ten-year fracture outcomes in CaMos and Manitoba BMD cohorts showed good discrimination and calibration for both CAROC (6.1-6.5% in low-risk, 13.5-14.6% in moderate-risk, and 22.3-29.1% in high-risk individuals) and FRAX (6.1-6.6% in low-risk, 14.4-16.1% in moderate-risk, and 23.4-31.0% in high-risk individuals). Reclassification from the CAROC risk category to a different risk category under FRAX occurred in <5% for low-risk, 20-24% for moderate-risk, and 27-30% for high-risk individuals. Reclassified individuals had 10-year fracture outcomes that were still within or close to the original nominal-risk range.. CONCLUSION: The new CAROC system is well calibrated to the Canadian population and shows a high degree of concordance with the Canadian FRAX tool. The CAROC system provides s a simple alternative when it is not feasible to use the full Canadian FRAX tool.

The osteoporosis care gap in men with fragility fractures: the Canadian Multicentre Osteoporosis Study.

UNLABELLED: We examined osteoporosis diagnosis/treatment in 2,187 community dwelling men age 50+. After five years in the study, 90% of men with fragility fractures remained undiagnosed and untreated for osteoporosis. The need to treat fragility fractures is well established in guidelines, and these numbers represent an important care gap. INTRODUCTION: Whether physicians in the community are recognizing and appropriately treating osteoporosis and fragility fractures in men remains unknown. We examined the rate of diagnosis and treatment in community dwelling men participating in the Canadian Multicentre Osteoporosis Study (CaMos). METHODS: Between February 1996 and September 2002, 2,187 participants were recruited from nine sites across Canada and prospectively followed. Information on osteoporosis diagnosis, fractures, medications were collected annually by a detailed questionnaire. DXA examination of lumbar spine (L1-4) and hip were conducted at baseline and year five. RESULTS: Diagnosis and treatment in men with clinical fragility fractures was low: at baseline and year five only 2.3% and 10.3% of men with a clinical fracture reported an osteoporosis diagnosis, respectively. At year five, 90% of men with a clinical fragility fracture were untreated. Hip fractures were the most commonly treated (37.5% by year five). A diagnosis of osteoporosis resulted in greater treatment: 67% of participants with diagnosed osteoporosis were treated with a bisphosphonate and 87% were taking calcium and/or vitamin D (year five). CONCLUSIONS: In this population-based study, both a diagnostic and therapeutic gap existed between knowledge and practice related to fragility fractures and osteoporosis in men aged >or=50 years.

Periodontal disease and perinatal outcomes: a case-control study.

AIM: Our aim was to measure the association of maternal periodontitis with low birth weight (LBW), pre-term LBW, and intra-uterine growth restriction. MATERIAL AND METHODS: An inclusive case-control design including subjects examined for periodontitis through attachment loss, information on perinatal outcomes and general health. Data were analysed through conditional logistic regression. RESULTS: Cases (n=304) and controls (n=611) had similar prevalence and severity of periodontitis, defined as at least three sites, in different teeth, with loss of three or more millimetres of clinical attachment level. Several factors were associated with the outcome, but the crude odds ratio for periodontitis was not significant. Odds ratio were 0.93 [95% confidence interval (CI): 0.63-1.41] for LBW and 0.92 (95% CI:0.54-1.57) for pre-term LBW in the presence of periodontitis, after adjustment for maternal age, previous pregnancies, pre-natal care, smoking, previous low birth or premature birth and other medical conditions, on a hierarchical model. CONCLUSIONS: Results do not support the hypothesis of association observed in previous studies after appropriate controlling for confounding variables. Negative peri-natal outcomes are better explained by determinants other than periodontal health. This study adds to the growing body of literature on the relationship between periodontal diseases and systemic health.

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/cm(2)). 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.

Oral contraceptive use and bone mineral density in premenopausal women: cross-sectional, population-based data from the Canadian Multicentre Osteoporosis Study.

BACKGROUND: Positive and negative effects on bone mineral density (BMD) have been described as a result of the premenopausal use of oral contraceptives (OCs); increased fracture rates have also been reported. This study assessed the relation between OC use and BMD in a population-based, 9-centre, national sample of women aged 25-45 years. METHODS: Premenopausal women who had been enrolled in the Canadian Multicentre Osteoporosis Study were classified as having ever been OC users (> or = 3 months) or as having never been OC users (0 to < 3 months). Data were obtained through extensive questionnaires and measuring of participants' weight, height and the BMD of lumbar vertebrae and the proximal femur. RESULTS: Of the sample of 524 women, whose mean age was 36.3 (standard deviation [SD] 5.9) years, 454 had used OCs; their mean age when they started using OCs was 19.8 (SD 3.5) years and the mean duration of use was 6.8 (SD 4.8) years. Women who had ever and those who had never used OCs showed no differences in age, age at menarche, parity, current calcium intake, exercise, body mass index (BMI), education, past irregular cycles or amenorrhea. OC users reported more alcohol and cigarette use and more use of medications to create regular cycles. Mean BMD values (adjusted for age, BMI and height) were 0.02-0.04 g/cm2 (that is, 2.3%-3.7%) lower in OC users, and were significantly lower in the spine and trochanter. The BMD of the spine in OC users was 1.03 (SD 0.12) g/cm2 versus 1.07 (SD 0.12) g/cm2 (95% confidence interval [CI] of difference -0.07 to -0.001) in those who had never used OCs. BMD was neither related to the duration of OC use nor to gynecological age at first use. Current and past users had similar BMD values. INTERPRETATION: National, population-based data show lower BMD values for the trochanter and spine in premenopausal women who have used OCs compared with those who have never used OCs.

Nonsteroidal anti-inflammatory drug use and breast cancer risk.

Findings from previous epidemiological studies are inconclusive, though they suggest nonsteroidal anti-inflammatory drug (NSAID) use is associated with a reduction in breast cancer risk. In addition, animal studies report that NSAIDs inhibit mammary tumor development. The association between NSAID use and breast cancer risk was evaluated using a case-control study design. Cases were a random sample of women diagnosed with a first primary cancer of the breast, aged 25-74 years, identified through the Ontario Cancer Registry, and diagnosed between July 1996 and September 1998. Controls were an age-matched random sample of the female population of Ontario. Cases (n = 3133) and controls (n = 3062) completed a mailed questionnaire with information on their past use of NSAID and other medications, as well as many risk factors thought to be associated with breast cancer. Multivariate logistic regression analysis was used to obtain adjusted odds ratio (OR) estimates. Use of any NSAID medication (daily use for > or =2 months) was found to be associated with a significant 24% reduction in breast cancer risk (OR = 0.76; 95% confidence interval: 0.66, 0.88). The reduced risk was strongest for use lasting > 8 years, compared with nonusers (OR = 0.68; 95% confidence interval: 0.54, 0.86). No marked trends were observed for time since first use or last use or age at first use. Our results suggest a reduction in breast cancer risk associated with any regular NSAID use. NSAID use is a modifiable factor, and any protective effect attributed to its use could be of great public health importance.

Hormonal factors and pancreatic cancer in women.

PURPOSE: The aim of the study was to evaluate hormonal risk factors for carcinoma of the exocrine pancreas among postmenopausal women. METHODS: Mailed questionnaire data from 52 cases and 233 population-based controls in Ontario were used to assess parity, age at first birth, and other hormonal factors on pancreatic cancer risk. RESULTS: Reduced risk was seen with three or more pregnancies [adjusted odds ratio (OR) = 0.22, 95% confidence interval (CI) = 0.07-0.65] and use of oral contraceptives (adjusted OR = 0.36, 95% CI = 0.13-0.96), whereas no significant associations were found for age at menarche or menopause, or estrogen replacement therapy. Among parous women, later age at first full-term pregnancy significantly increased the risk of this cancer (adjusted OR = 4.05, 95% CI = 1.50-10.92 for ages 25-29 years, adjusted OR = 3.78, 95% CI = 1.02-14.06 for ages 30+ years). CONCLUSIONS: Our data support the hypothesis that pancreatic cancer is, at least in part, an estrogen-dependent disease; there is growing epidemiological evidence that aspects of reproductive history and hormonal exposure are associated with risk of this disease.

Misclassification of exposure: coffee as a surrogate for caffeine intake.

This study was conducted to assess the effect of exposure misclassification when coffee is used as a surrogate measure of caffeine exposure. Subjects were randomly selected from the telephone directories of four regional municipalities in southern Ontario, CANADA: Data on daily caffeine intake from foods, beverages, and medications were collected from June to November 1995 through self-administered, mailed questionnaires from 481 men and women aged 30-75 years. Although coffee was the main source of caffeine, cross-tabulations of exposure to coffee by total caffeine intake showed that assessment of coffee alone severely underestimated caffeine intake by at least one exposure level. A hypothetical 10-fold increase in risk was completely obscured when only coffee was used to estimate total caffeine intake. The results of this study suggest that measuring coffee instead of caffeine intake may contribute to a lack of positive findings in studies of coffee as a risk factor for disease occurrence, if in fact caffeine is the exposure of interest. On the other hand, measurement of coffee, tea, and cola soft drink intake in the present study appeared to approximate caffeine intake sufficiently and not affect risk estimates adversely.

A qualitative study of subject recruitment for familial cancer research.

PURPOSE: Familial epidemiological studies of cancer raise familiar ethical issues relating to informed consent and recruitment of participants. When the family is the unit of study, however, additional complexity arises. Educating and recruiting participants must be tailored to the relatives', as well as the proband's needs. An understanding of the prospective participants' concerns will aid the development of strategies for recruitment and will facilitate informed and voluntary consent. In the present study, qualitative methods were used to investigate these issues. METHODS: Focus groups with cancer patients, relatives of cancer patients, and individuals from the general population were separately conducted to identify issues that concern people who are asked to participate in family studies. RESULTS: Many of the issues which arose in the course of the focus group discussions were similar to those in any study. Yet, some of the themes emerging from the discussions were specific to familial research. In particular, participants expressed that the study should be endorsed by a trusted and familiar source; group discussions might facilitate the consent process; the benefit of the research should be clear and personal, as well as benefit the participants' family members; risks of participation should be explicit (e.g., insurance discrimination); and education about the disease and its familial nature would maintain commitment to the study. Finally, participants expressed concerns about being approached by programs to facilitate the identification and recruitment of other family members for research on family health issues. CONCLUSIONS: Findings from this study will aid future familial studies in developing a protocol that both adequately informs potential participants of the nature of familial research and maximize participation.

Cancer prevention in the community: a survey of community residents.

Lifestyle exposures account for the greatest proportion of risk factors for cancer, yet these exposures have proven most difficult to alter. Despite intensive intervention efforts, many behaviour change programs are ill suited to the community. This research was undertaken to increase our understanding of prevention activities of interest to a sample of residents in two Ontario communities. 248 (62.3%) adult residents responded to a semi-structured self-administered questionnaire including open-ended questions on health issues, exposures and prevention activities of interest. While some of the beliefs expressed by respondents might have been anticipated (e.g., cigarette smoking and family history increase risk of cancer), others were not (e.g., only between 40 and 75% of respondents thought a high fat diet increased risk). Furthermore, many of those with personal health concerns expressed an interest in prevention. This process is proposed as a first step in launching more appropriate and sustainable community-based health promotion programs for cancer prevention.

Cigarette smoking and the risk of thyroid cancer.

Thyroid cancer, whose aetiology is largely uncertain, has been negatively associated with cigarette smoking in a number of studies, possibly consistent with the greater occurrence of the disease in women than in men. This association was explored in the context of a Canadian case-control study of thyroid cancer. Newly diagnosed cases were identified primarily through provincial cancer registries in Canada and controls were identified from the general population. Data were collected through mailed questionnaires, yielding 1224 cases and 2659 controls. Reduced risk was observed for ever/never cigarette smoking (risk ratio estimate (RR) of 0.71 (95% confidence interval (CI)=0.60-0.83) for females and 0.77 (95% CI=0.58-1.02)) for males. Dose-response effects were observed with duration, quantity smoked and pack-years of exposure, although there was no decreasing protective effect with the age started smoking or years since stopped smoking. There is evidence of reduced risk for all histological subgroups. The protective effect of smoking may be due to a number of different mechanisms, including an effect on thyroid stimulating hormone and on oestrogen metabolism.

Pre-natal and peri-natal exposures and risk of testicular germ-cell cancer.

The present case-control study was undertaken to investigate the association between exposure to maternal hormones and risk of testicular germ-cell cancer by histologic subgroups. Cases were males, aged 16 to 59 years, diagnosed with testicular germ-cell cancer in Ontario between 1987 and 1989. Histologic review was performed on all eligible cases for the purpose of categorizing cases as seminoma or non-seminoma (the latter classified 2 ways, with and without tumors containing seminoma). Risk factor data were collected on 502 cases, 346 case mothers, 975 age-matched controls, and 522 control mothers. Exogenous hormone exposure was associated with elevated risk (OR = 4.9, 95% CI 1.7-13.9). Several additional risk factors were associated with risk of testicular cancer: bleeding and threatened miscarriage (OR = 0.6, 95% CI 0.3-1.0), maternal cigarette smoking (12+ cigarettes/day OR = 0.6, 95% CI 0. 4-1.0). pre-term birth (OR = 1.6, 95% CI 1.0-2.5), and treatment for undescended testicle (OR = 8.0, 95% CI 3.2-20.0). First births were associated with elevated risk (OR = 1.7, 95% CI 1.0-2.8) among mothers below the age of 24 years at conception. There was little evidence that risk factors differed by histologic subgroup. We found evidence that exposure to maternal hormones, particularly estrogens, is associated with testicular germ-cell cancer risk. Not only does exposure to elevated levels (exogenous hormone use, pre-term birth, and first births among young mothers) increase risk but also exposure to relatively lower levels (heavy cigarette consumption and, perhaps, bleeding and threatened miscarriage) may decrease cancer risk.

Antidepressant medication use and breast cancer risk.

Experimental and epidemiologic studies suggest that antidepressant medication use may be associated with breast cancer risk. This hypothesis was investigated using a population-based case-control study; cases diagnosed in 1995-1996 were identified using the Ontario Cancer Registry, and controls were randomly sampled from an Ontario Ministry of Finance database. Data were collected using a self-administered questionnaire, and multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals. Adjusted odds ratio estimates ranged from 0.7 to 0.8 and were not statistically significant for "ever" use of antidepressants, tricyclics, and selective serotonin reuptake inhibitors. Compared with no antidepressant use, use of tricyclic antidepressants for greater than 2 years' duration was associated with an elevated risk of breast cancer (odds ratio (OR) = 2.1, 95% confidence interval (CI): 0.9, 5.0). Of the six most commonly reported antidepressant medications, only paroxetine use was associated with an increase in breast cancer risk (OR = 7.2, 95% CI: 0.9, 58.3). Results from this study do not support the hypothesis that "ever" use of any antidepressant medications is associated with breast cancer risk. Use of tricyclic medications for greater than 2 years, however, may be associated with a twofold elevation, and use of paroxetine may be associated with a substantial increase in breast cancer risk.

Development and validation of the Osteoporosis Risk Assessment Instrument to facilitate selection of women for bone densitometry.

BACKGROUND: Although mass screening for osteoporosis is not recommended among postmenopausal women, there is no consensus on which women should undergo testing for low bone mineral density. The objective of this study was to develop and validate a clinical tool to help clinicians identify which women are at increased risk for osteoporosis and should therefore undergo further testing with bone densitometry. METHODS: Using Ontario baseline data from the Canadian Multicentre Osteoporosis Study, we identified all cognitively normal women aged 45 years or more who had undergone testing with dual-energy x-ray absorptiometry (DXA) at both the femoral neck and the lumbar spine (L1-L4). Participants who had a previous diagnosis of osteoporosis or were taking bone active medication other than ovarian hormones were excluded. The main outcome measure was low bone mineral density (T score of 2 or more standard deviations below the mean for young Canadian women) at either the femoral neck or the lumbar spine. Logistic regression analysis and receiver operating characteristic (ROC) analysis were used to identify the simplest algorithm that would identify women at increased risk for low bone mineral density. RESULTS: The study population comprised 1376 women, of whom 926 were allocated to the development of the tool and 450 to its validation. A simple algorithm based on age, weight and current estrogen use (yes or no) was developed. Validation of this 3-item Osteoporosis Risk Assessment Instrument (ORAI) showed that the tool had a sensitivity of 93.3% (95% confidence interval [CI] 86.3%-97.0%) and a specificity of 46.4% (95% CI 41.0%-51.8%) for selecting women with low bone mineral density. The sensitivity of the instrument for selecting women with osteoporosis was 94.4% (95% CI 83.7%-98.6%). Use of the ORAI represented a 38.7% reduction in DXA testing compared with screening all women in our study. INTERPRETATION: The ORAI accurately identifies the vast majority of women likely to have low bone mineral density and is effective in substantially decreasing the need for all women to undergo DXA testing.