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Biomedical subjects

D C Bauer

Publications and source records attributed to D C Bauer.

At least 37 records · Page 2Linked to original sources

Bone mineral density and endogenous hormones and risk of breast cancer in postmenopausal women (United States).

OBJECTIVE: This case-cohort study was designed to examine whether total hip bone mineral density (BMD) is independently associated with breast cancer over and above its association with other determinants, including levels of total and bioavailable estradiol and testosterone and sex-hormone binding globulin. METHODS: Our study population was selected from a cohort of 8,203 postmenopausal women who were screened for the Fracture Intervention Trial in 1992, at which time BMD was assessed, and blood samples were obtained. A total of 109 women developed breast cancer during four years of follow-up; 173 other randomly selected women from the larger cohort were also selected. Cox proportional hazards with robust variance adjustment was used for these analyses. RESULTS: Relative to women in the lower fourth of the BMD distribution, the risk associated with being in the upper fourth was 2.6 (95% confidence interval (CI) 1.1-5.8). After adjusting for serum hormone levels, the corresponding relative risk was 2.5 (95% CI 0.9-5.2). With body mass index and number of years since menopause added to the multivariate analysis, the relative risk decreased to 1.4 (95% CI 0.5-4.0). CONCLUSIONS: BMD may not influence breast cancer risk independent of its relationship with endogenous hormones and measured covariates.

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Measuring fitness in healthy older adults: the Health ABC Long Distance Corridor Walk.

OBJECTIVES: The Health ABC Long Distance Corridor Walk (LDCW) was designed to extend the testing range of self-paced walking tests of fitness for older adults by including a warm-up and timing performance over 400 meters. This study compares performance on the LDCW and 6-minute walk to determine whether the LDCW encourages greater participant effort. DESIGN: Subjects were administered the LDCW and 6-minute walk during a single visit. Test order alternated between subjects, and a 15-minute rest was given between tests. SETTING: The Baltimore Veterans Affairs Medical Center. PARTICIPANTS: Twenty volunteers age 70 to 78. MEASUREMENTS: The LDCW, consisting of a 2-minute warm-up walk followed by a 400-meter walk and a 6-minute walk test were administered using a 20-meter long course in an unobstructed hallway. Heart rate (HR) and blood pressure (BP) were recorded at rest and before and after all walks. RESULTS: All 20 subjects walked a faster pace over 400 meters than for 6 minutes, in which the mean distance covered was 402 meters. From paired t-tests, walking speed was faster (mean difference = 0.23 m/sec; P < .001), and ending HR (mean difference = 7.6 bpm; P < .001) and systolic BP (mean difference = 8.3 mmHg; P = .024) were greater for the 400-meter walk than for the 6-minute walk. Results were independent of test order and subject fitness level. CONCLUSIONS: Providing a warm-up walk and using a target distance instead of time encouraged subjects to work closer to their maximum capacity. This low-cost alternative to treadmill testing can be used in research and clinical settings to assess fitness and help identify early functional decline in older adults.

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Airflow limitation is underrecognized in well-functioning older people.

OBJECTIVES: Dyspnea is a common symptom in older people. A reduced forced expiratory volume in 1 second (FEV1) is associated with a higher mortality rate from cardiovascular and respiratory disease, and increased admissions to hospitals. Underrecognized or undertreated airflow limitation may exacerbate the problem. The purpose of this study was to assess the prevalence and treatment of airflow limitation in a cohort of well-functioning older people. DESIGN: Cross-sectional study. SETTING: Baseline of a clinical-epidemiological study of incident functional limitation. PARTICIPANTS: Participants attended the baseline examination of the Health, Aging, and Body Composition study, a prospective cohort study of 3,075 well-functioning subjects age 70 to 79. MEASUREMENTS: Demographic and clinical data were collected by interview. Spirometry was performed unless contraindicated and repeated until three acceptable sets of flow-volume loops were obtained. Patients on bronchodilator medications had spirometry performed posttherapy. Blinded readers assessed the flow-volume loops, and inadequate tests were omitted from analysis. Airflow limitation was defined as a reduced forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) as determined by age-, sex-, and race-normalized values. Severity of airflow limitation was defined by American Thoracic Society criteria. RESULTS: Two thousand four hundred eighty-five subjects (80.8%) had assessable spirometry and data on treatment and diagnosis (1,265 men, 1,220 women). The mean age was 73.6 years. Two hundred sixty-two subjects (10.5%) had airflow limitation; 43 (16.4%) of these never smoked. Only 37.4% of participants with airflow limitation and 55.6% of participants with severe airflow limitation reported a diagnosis of lung disease. Only 20.5% of subjects with at least moderate airflow limitation had used a bronchodilator in the previous 2 weeks. CONCLUSION: Despite their good functional status, airflow limitation was present, and underrecognized, in a considerable proportion of our older population. The low bronchodilator use suggests a significant reservoir of untreated disease. Physicians caring for older people need to be more vigilant for both the presence, and the need for treatment, of airflow limitation.

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Timing of estrogen replacement therapy for optimal osteoporosis prevention.

To determine whether estrogen initiated at age 60 yr or later reduces rates of bone loss and fracture incidence, we performed a prospective cohort study of 6910 nonosteoporotic women, 65 yr of age or older. Estrogen use, medical history, lifestyle, and anthropometric data were obtained by questionnaire, interview and examination. We identified five patterns of estrogen use: never users (67%); past early users (started under age 60 yr with no current use; 23%); past late users (started at age 60 or later with no current use; 2%); current early users (started under age 60 yr with use both at baseline and 6 yr later; 6.7%); and current late users (started at age 60 or later with use at baseline and 6 yr later; 1.5%). Bone mineral density was measured at the total hip twice, an average of 3.5 yr apart, and at the calcaneus, an average of 5.7 yr apart. Incident nonspine fractures were validated by radiographic report. Bone mineral density was significantly higher among current users, compared with never and past users. The annual rate of hip bone loss was significantly lower in current early users (-0.22%/yr) and current late users (-0.35%/yr) in comparison with never users (-0.6%/yr), past early users (-0.6%/yr), and past late users (-0.72%/yr). During an average of 11.0 yr of follow-up, 1953 nonspine fractures were confirmed. The multiple-adjusted relative risk of nonspine fracture was 0.63 (95% confidence interval 0.51-0.78) among current early users and 0.75 (0.50-1.12) among current late users, compared with never users. Early initiation and long-term continuation of estrogen is associated with a reduction in the risk of nonspine fractures, and initiation at or after age 60 yr with long-term continuation may also be associated with a reduced fracture risk.

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Influence of smoking on the antiosteoporotic efficacy of raloxifene.

The efficacy of estrogen therapy may be modified in women who smoke because of increased catabolism of estrogen and the interaction of tobacco products with the estradiol receptor. We examined whether the efficacy of raloxifene differed in smoking vs. nonsmoking women. We compared change in bone mineral density and biochemical markers of bone turnover, and incidence of new vertebral fracture in postmenopausal women of the Multiple Outcomes on Raloxifene Efficacy trial, who were randomized to either raloxifene (60 or 120 mg/d) or placebo. In the 17% of women who were current smokers, we found, compared with nonsmokers, lowered baseline trochanter bone mineral density (0.540 vs. 0.557 g/cm(2); P < 0.001) and serum osteocalcin (24.8 vs. 26.6 ng/liter; P < 0.001). Baseline urinary type I collagen breakdown products was increased among smokers (291.8 vs. 276.9 micromol/liter; P = 0.04). Body mass index was also lower in smokers (24.3 vs. 25.4; P < 0.001). After 6 months of treatment, there was no significant difference in reduction of bone turnover between smokers and nonsmokers. After 4 yr of treatment, the smoking-treatment interaction was not significant between smokers and nonsmokers for the percent increase in femoral neck bone mineral density (P = 0.25), trochanter bone mineral density (P = 0.24), and spine bone mineral density (P = 0.37). The smoking-treatment interaction for reduction in vertebral fracture risk was not significant either [odds ratio for fracture, 0.67 (0.45-0.98) for smokers and 0.56 (0.47-0.68) for nonsmokers; P = 0.44]. These results were not modified after stratification by tertiles of body mass index or when comparing heavy smokers vs. light smokers. We conclude that smoking does not influence the antiosteoporotic effect of raloxifene. This may represent an advantage over estrogen replacement therapy.

Biomarkers↗

Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: the Health, Aging, and Body Composition Study.

Two factors generally reported to influence bone density are body composition and muscle strength. However, it is unclear if these relationships are consistent across race and sex, especially in older persons. If differences do exist by race and/or sex, then strategies to maintain bone mass or minimize bone loss in older adults may need to be modified accordingly. Therefore, we examined the independent effects of bone mineral-free lean mass (LM), fat mass (FM), and muscle strength on regional and whole body bone mineral density (BMD) in a cohort of 2,619 well-functioning older adults participating in the Health, Aging, and Body Composition (Health ABC) Study with complete measures. Participants included 738 white women, 599 black women, 827 white men, and 455 black men aged 70-79 years. BMD (g/cm2) of the femoral neck, whole body, upper and lower limb, and whole body and upper limb bone mineral-free LM and FM was assessed by dual-energy X-ray absorptiometry (DXA). Handgrip strength and knee extensor torque were determined by dynamometry. In analyses stratified by race and sex and adjusted for a number of confounders, LM was a significant (p < 0.001) determinant of BMD, except in white women for the lower limb and whole body. In women, FM also was an independent contributor to BMD at the femoral neck, and both FM and muscle strength contributed to limb BMD. The following were the respective beta-weights (regression coefficients for standardized data, Std beta) and percent difference in BMD per unit (7.5 kg) LM: femoral neck, 0.202-0.386 and 4.7-5.9%; lower limb, 0.209-0.357 and 2.9-3.5%; whole body, 0.239-0.484 and 3.0-4.7%; and upper limb (unit = 0.5 kg), 0.231-0.407 and 3.1-3.4%. Adjusting for bone size (bone mineral apparent density [BMAD]) or body size BMD/height) diminished the importance of LM, and the contributory effect of FM became more pronounced. These results indicate that LM and FM were associated with bone mineral depending on the bone site and bone index used. Where differences did occur, they were primarily by sex not race. To preserve BMD, maintaining or increasing LM in the elderly would appear to be an appropriate strategy, regardless of race or sex.

Absorptiometry, Photon↗

Type 2 diabetes in older well-functioning people: who is undiagnosed? Data from the Health, Aging, and Body Composition study.

OBJECTIVE: To assess, in an older population, the prevalence of diagnosed and undiagnosed diabetes, the number needed to screen (NNTS) to identify one individual with undiagnosed diabetes, and factors associated with undiagnosed diabetes. RESEARCH DESIGN AND METHODS: Socioeconomic and health-related factors were assessed at the baseline examination of the Health, Aging, and Body Composition (Health ABC) Study, a cohort of 3,075 well-functioning people aged 70-79 years living in Memphis, Tennessee and Pittsburgh, Pennsylvania (42% blacks and 48% men). Diabetes was defined according to the 1985 World Health Organization criteria (fasting glucose > or =7.8 mmol/l or 2-h glucose > or =11.1 mmol/l) and the 1997 American Diabetes Association criteria (fasting glucose > or =7.0 mmol/l). RESULTS: The prevalence of diagnosed and undiagnosed diabetes was 15.6 and 8.0%, respectively, among all participants (NNTS 10.6), 13.9 and 9.1% among white men (NNTS 9.5), 7.8 and 7.4% among white women (NNTS 12.4), 22.7 and 9.1% among black men (NNTS 8.5), and 21.6 and 6.2% among black women (NNTS 12.6). In multivariate analyses, compared with individuals without diabetes, individuals with undiagnosed diabetes were more likely to be men and were more likely to have a history of hypertension, higher BMI, and larger waist circumference. NNTS was lowest in men (9.1), individuals with hypertension (8.7), individuals in the highest BMI quartile (6.9), and individuals in the largest waist circumference quartile (6.8). CONCLUSIONS: In approximately one-third of all older people with diabetes, the condition remains undiagnosed. Screening for diabetes may be more efficient among men and individuals with hypertension, high BMI, and large waist circumference.

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Upper gastrointestinal tract safety profile of alendronate: the fracture intervention trial.

OBJECTIVES: To determine whether alendronate sodium treatment is associated with upper gastrointestinal (GI) tract adverse experiences (AEs)-particularly those of the stomach, duodenum, or esophagus-in the Fracture Intervention Trial, and to assess the relationship between alendronate use and upper GI tract events among women at increased risk for these outcomes. DESIGN: Randomized, double-blind, placebo-controlled trial with a mean follow-up of 3.8 years. Women were initially randomized to receive alendronate sodium, 5 mg/d, or placebo. After 2 years, the alendronate sodium dose was increased to 10 mg/d. PARTICIPANTS: A total of 6459 women aged 54 to 81 years recruited from 11 US clinical centers. All participants had low hip bone mineral density. Women with major upper GI tract disease (recent ulcers, upper GI tract bleeding, or use of daily medication for dyspepsia) were excluded. Regular nonsteroidal anti-inflammatory drug users were not excluded. MEASUREMENTS: Self-reported upper GI tract AEs were ascertained by interview every 3 months. Serious upper GI tract AEs were confirmed and classified by review of hospital records and endoscopy reports, if available. Upper GI tract AEs were further analyzed in 2 specified groups-gastroduodenal and esophageal-to examine events that might be related to upper GI tract mucosal irritation. Gastric and duodenal perforations, ulcers, and bleeding events were combined for analysis of these clinically important outcomes. RESULTS: The overall incidence of upper GI tract events was similar in the alendronate and placebo groups (47.5% vs. 46.2%; relative risk [RR], 1.02; 95% confidence interval [CI], 0.95-1.10). The incidence of gastroduodenal perforations, ulcers, and bleeding events was 1.6% in the alendronate group and 1.9% in the placebo group (RR, 0.86; 95% CI, 0.59-1.24). The incidence of nonspecific upper GI tract conditions, such as abdominal pain, dyspepsia, nausea, and vomiting, was also similar in the 2 groups. Esophageal events occurred in 10.0% and 9.4% of patients in the alendronate and placebo groups, respectively (RR, 1.06; 95% CI, 0.91-1.24). Esophagitis not reported as reflux was more common in the alendronate group (0.7%) than in the placebo group (0.4%), but not significantly so (RR, 1.71; 95% CI, 0.90-3.39). Alendronate use was not associated with a significant increase in upper GI tract events among women at increased risk for these events (those aged > or =75 years with previous upper GI tract disease or using nonsteroidal anti-inflammatory drugs). CONCLUSION: In these older women, upper GI tract complaints, particularly dyspepsia and abdominal pain, were common, but alendronate treatment was not associated with an increased incidence of upper GI tract events, even in high-risk subgroups.

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Clinical use of biochemical markers of bone remodeling: current status and future directions.

Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of bone mineral density (BMD). This review evaluates the use of commercially available bone turnover markers as aids in diagnosis and monitoring response to treatment in patients with osteoporosis. High within-person variability complicates but does not preclude their use. Elevated bone resorption markers appear to be associated with increased fracture risk in elderly women, but there is less evidence of a relationship between bone formation markers and fracture risk. The critical question of predicting fracture efficacy with treatment has not been answered. Changes in bone markers as currently determined do not predict BMD response to either bisphosphonates or hormone replacement therapy. Single measurements of markers do not predict BMD cross-sectionally (except possibly in the very elderly), or change in BMD in individual patients, either treated or untreated. On the other hand, research applications of bone turnover markers are of value in investigating the pathogenesis and treatment of bone diseases. Markers have potential in the clinical management of osteoporosis, but their use in this regard is not established. Additional studies with fracture endpoints and information on negative and positive predictive value are needed to evaluate fully the utility of bone turnover markers in individual patients.

Biomarkers↗

Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group.

We examined the effect of alendronate treatment for 3-4 yr on risk of new fracture among 3658 women with osteoporosis enrolled in the Fracture Intervention Trial. This cohort included women with existing vertebral fracture and those with osteoporosis as defined by T score of less than -2.5 at the femoral neck but without vertebral fracture. All analyses were prespecified in the data analysis plan. The magnitudes of reduction of fracture incidence with alendronate were similar in both groups. The two groups were, therefore, pooled to obtain a more precise estimate of the effect of alendronate on relative risk of fracture (relative risk, 95% confidence interval): hip (0.47, 0.26-0.79), radiographic vertebral (0.52, 0.42-0.66), clinical vertebral (0.55, 0.36-0.82), and all clinical fractures (0.70, 0.59-0.82). Reductions in risk of clinical fracture were statistically significant by 12 months into the trial. We conclude that reductions in fracture risk during treatment with alendronate are consistent in women with existing vertebral fractures and those without such fractures but with bone mineral density in the osteoporotic range. Furthermore, reduction in risk is evident early in the course of treatment. This pooled analysis provides a more precise estimate of the antifracture efficacy of alendronate in women with osteoporosis than that in prior reports.

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Biochemical markers of bone turnover and prediction of hip bone loss in older women: the study of osteoporotic fractures.

To examine the ability of commercially available biochemical markers of bone formation and resorption to predict hip bone loss, we prospectively obtained serum and timed 2-h urine specimens from 295 women age 67 years or older who were not receiving estrogen replacement therapy. Serum was assayed for two markers of bone formation: osteocalcin (OC) and bone-specific alkaline phosphatase (BALP). Urine specimens were assayed for four markers of bone resorption: N-telopeptides (NTX), free pyridinolines (Pyr), free deoxypyridinoline (Dpyr), and C-telopeptides (CTX). Measurements of hip bone mineral density were made at the time the samples were collected and then repeated an average of 3.8 years later. Higher levels of all four resorption markers were, on average, significantly associated with faster rates of bone loss at the total hip, but not at the femoral neck. Women with OC levels above the median had a significantly faster rate of bone loss than women with levels below the median, but there was no significant association between levels of BALP and hip bone loss. The sensitivity and specificity of higher marker levels for predicting rapid hip bone loss was limited, and there was considerable overlap in bone loss rates between women with high and low marker levels. We conclude that higher levels of urine NTX, CTX, Pyr, Dpyr, and serum OC are associated with faster bone loss at the hip in this population of elderly women not receiving estrogen replacement therapy, but these biochemical markers have limited value for predicting rapid hip bone loss in individuals.

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Physical activity and osteoporotic fracture risk in older women. Study of Osteoporotic Fractures Research Group.

BACKGROUND: Physical activity has been related to enhanced bone mass and improved physical functioning and thus may reduce the risk for osteoporotic fracture. OBJECTIVE: To determine whether higher levels of physical activity are related to lower incidence of hip, wrist, and vertebral fractures. DESIGN: Prospective cohort study. SETTING: Four clinical centers in Baltimore, Maryland; Portland, Oregon; Minneapolis, Minnesota; and the Monongahela Valley, Pennsylvania. PARTICIPANTS: 9704 nonblack women 65 years of age or older. MEASUREMENTS: Physical activity was assessed by questionnaire at baseline. Hip and wrist fractures were followed for an average of 7.6 years. The incidence of vertebral fracture was determined morphometrically by using radiography at baseline and an average of 3.7 years later. RESULTS: Higher levels of leisure time, sport activity, and household chores and fewer hours of sitting daily were associated with a significantly reduced relative risk for hip fracture after adjustment for age, dietary factors, falls at baseline, and functional and health status. Very active women (fourth and fifth quintiles) had a statistically significant 36% reduction in hip fractures (relative risk, 0.64 [95% CI, 0.45 to 0.891) compared with the least active women (lowest quintile). The intensity of physical activity was also related to fracture risk: Moderately to vigorously active women had statistically significant reductions of 42% and 33% in risk for hip and vertebral fractures, respectively, compared with inactive women. Total physical activity, hours of household chores per day, and hours of sitting per day were not significantly associated with wrist or vertebral fractures. CONCLUSIONS: Among older community-dwelling women, physical activity is associated with a reduced risk for hip fracture but not wrist or vertebral fracture.

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Warfarin use and risk for osteoporosis in elderly women. Study of Osteoporotic Fractures Research Group.

BACKGROUND: Vitamin K deficiency may be associated with osteoporosis. OBJECTIVE: To assess the effects of warfarin on bone. DESIGN: Prospective observational study. SETTING: Four centers in the United States. PARTICIPANTS: 6201 elderly, postmenopausal women. MEASUREMENTS: Self-reported warfarin use, bone mineral density at the hip and the heel, hip bone loss over 2 years, and fractures during 3.5 years of follow-up. Analyses were adjusted for baseline differences, age, weight, and estrogen use. RESULTS: Compared with warfarin nonusers (n = 6052), warfarin users (n = 149) more frequently had poor health, involuntary weight loss, nonthiazide diuretic use, and frailty but had similar bone mineral density at the hip (difference, 1.6% [95% CI, -0.7% to 4.1%]) and heel (difference, 2.1% [CI, -1.6% to 5.6%]). Users and nonusers had similar rates of bone loss (1.1% and 0.8%; P = 0.18) and fractures (relative hazard, 1.0 [CI, 0.60 to 1.71). CONCLUSION: In this population, warfarin use did not decrease bone mineral density or increase fracture rates.

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Genetic variation in alpha 2HS-glycoprotein is related to calcaneal broadband ultrasound attenuation in older women.

Calcaneal broadband ultrasound attenuation (BUA) is an independent predictor of hip and vertebral fractures. BUA is under genetic control, but the specific genes contributing to BUA are not well defined. We examined the relationship between genetic variation in alpha2HS-glycoprotein (AHSG), an abundant noncollagenous protein of bone matrix, and calcaneal BUA. Genetic polymorphism in AHSG was determined in 222 Caucasian women (age 66-92) enrolled in the Pittsburgh Study of Osteoporotic Fractures clinical center by isoelectric focusing of serum samples. Calcaneal BUA and bone mineral density (BMD) were measured on the same foot with a Walker Sonix UBA 575(+) and single X-ray absorptiometry. Hip and spine BMD were determined with a Hologic QDR-1000 densitometer using dual-energy X-ray absorptiometry. AHSG polymorphism was not significantly related to hip, lumbar spine, or calcaneal BMD. Compared with the homozygous AHSG*2 women, calcaneal BUA was 13% lower in heterozygous (P < 0.05) and 16% lower in homozygous AHSG*1 women (P < 0.05). This relationship persisted after controlling for age, weight, height, walks for exercise, and calcaneal BMD. Current and self-reported height were also lowest in homozygous AHSG*1 women, intermediate in heterozygous women, and highest among homozygous AHSG*2 subjects. These results suggest that the AHSG polymorphism may contribute to the genetic influence on calcaneal BUA and stature.

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