Dana G. Seeley

Estrogen Replacement Therapy and Fractures in Older Women

Estrogen replacement therapy is the cornerstone of preventive therapy for osteoporosis and fractures. Current users of estrogen have a statistically significant decreased risk for hip [1-10], wrist [1, 5, 6, 8, 11], and spine fractures [8, 11, 12]. A recent meta-analysis [13] suggested a 25% decrease in the risk for hip fracture in women who reported using estrogen. The International Consensus Development Conference on Osteoporosis [14] concluded that estrogen therapy is the only well-established preventive measure that could significantly decrease the number of osteoporotic fractures. Nevertheless, several important issues remain unresolved. Most research has examined the effect of estrogen on specific fractures associated with osteoporosis (hip, wrist, spine). The effect on all fractures has not been established. The decrease in fracture risk associated with estrogen use is greatest among current or recent users, and the decreased risk tends to diminish with time after stopping estrogen [1, 4, 9]. It is unknown whether previous use, even if initiated around menopause and continued for a substantial length of time, confers any benefit. Most studies [1-9, 12] have examined the relation between unopposed estrogen and fractures. One cohort study [10] with about 30% of participants reporting use of estrogen plus progestin showed similar protective effects on the risk for hip fracture. This study did not, however, compare the relative risks separately for unopposed estrogen and combination therapy (estrogen plus progestin). The effectiveness of estrogen in preventing fractures in elderly women is also uncertain. Estrogen has been shown to be effective in preserving bone mass in elderly women [15, 16], but recent data [17] from Framingham showed little protective effect of an average of 10 years of estrogen therapy on bone density among women 75 years of age and older. In other prospective [9, 10] and casecontrol studies [3], the protective effects of estrogen on fracture were greater in younger women and weaker [3, 9] or nonexistent [10] in older women. In the Study of Osteoporotic Fractures, our prospective study of 9704 women who were 65 years of age or older, we assessed estrogen use and bone mass at baseline and ascertained incident fractures every 4 months to examine the association between estrogen use and fracture in elderly women. Methods Participants From September 1986 through October 1988, women who were at least 65 years of age were recruited for the Study of Osteoporotic Fractures in Portland, Oregon; Minneapolis, Minnesota; Baltimore County, Maryland; and the Monongahela Valley near Pittsburgh, Pennsylvania. Age-eligible women were recruited from population-based lists of women (voter registration, drivers license, and Health Maintenance Organizations membership lists) [18]. The response to these mass mailings varied from 8% in Pittsburgh (voter registration lists) to 19% in Portland (Kaiser Health Plan membership lists). We excluded black women because of their lower incidence of fractures, women who were unable to walk without the assistance of another person, and women who had had bilateral hip replacements. Estrogen Use Detailed information on use of estrogen and progestin was collected at the baseline interview. Information on use of estrogen was missing in 136 women; these women were excluded from all analyses. Participants were asked to bring all medications to the clinic for verification of use, preparation, and dosage. In addition, pictures of tablets were presented to participants to assist them in the recollection of previously prescribed hormone preparations. Information was collected about oral and parenteral estrogens (skin patches, injections, vaginal creams, and suppositories) and oral progestins. Our analyses were confined to oral preparations. Data were also collected on age at initiation of use of hormone preparations and on whether a participant had used such preparations for the entire time period since initiation and, if not, when she had stopped. Initiation of estrogen use with respect to menopause was determined by comparing the age at last menstrual period with the age at initiation of estrogen. To estimate duration of use, women were asked to check all ages, from 40 to 100 years of age, at which they had used estrogen. Duration of use was calculated by adding the total number of years that a woman had used estrogen. Because we were interested in examining the effect of initiation of estrogen and the effect of duration of use with respect to menopause, we excluded from the initiation and duration analyses 889 women for whom age at menopause could not be determined and 231 women who had started estrogen therapy more than 5 years before menopause. Measurement of Bone Mass Bone mineral density (g/cm2) was measured using single-photon absorptiometry (OsteoAnalyzer, Siemens-Osteon, Wahiawa, Hawaii). Details of these methods have been reported elsewhere [18]. We scanned three sites, including the distal radius, the proximal radius, and the calcaneus. The distal radius is composed of about 60% cortical and 40% trabecular bone, the proximal radius is about 99% cortical bone [19], and the calcaneus is about 97% trabecular bone [20]. Other Measurements Reported health status, type of menopause, alcohol consumption, physical activity, and cigarette smoking were assessed by a questionnaire that was reviewed with the participant by a trained interviewer. Women were considered to have had surgical menopause if they reported bilateral oophorectomy at the age they stopped menstruating. The measure of alcohol consumption was drinks per week adjusted for atypical drinking, especially heavy drinking during the previous 30 days. Dietary calcium intake was assessed by a food frequency questionnaire and by interview using standardized food models to estimate portion sizes [21]. Total calcium intake included dietary and supplemental calcium. Women were asked if they walked for exercise and if they had fallen in the previous 12 months. A modified Paffenbarger questionnaire was used to assess sports and recreation for the previous year, expressed in kcal/wk [22]. History of osteoporosis was ascertained by asking women if a physician had ever told them whether or not they had osteoporosis or a spine fracture. Women were also asked whether they had ever taken the following medications: thiazide diuretics, thyroid hormones, sedatives, anxiolytics, and Tums or calcium supplements. Cognitive function was assessed using the Modified Mini-Mental Status examination [23]. During the clinic examination, body weight was measured (after removal of shoes and heavy outer clothing) using a balance beam scale. Height was measured (after removal of shoes) using a Harpenden stadiometer (Holtain Ltd., Dyved, United Kingdom). Height and weight were used to calculate the body mass index (kg/m2). Ascertainment of Incident Fractures Details of our method for identifying new fractures during follow-up have been published [24]. Briefly, we contacted participants every 4 months by postcard or telephone to ask whether they had sustained a fracture or fall. More than 99.5% of these follow-up contacts were completed. We interviewed participants about the way in which the fracture occurred. To confirm fractures, we obtained a copy of the radiographic report, which had to specifically mention the occurrence of an acute fracture. Hip fractures were also confirmed by radiologic review of copies of radiographs. We excluded fractures that occurred because of major trauma such as motor vehicle accidents. Most vertebral fractures do not come to medical attention; these fractures must be discovered by systematically obtaining radiographs from all participants and by comparing them with previous radiographs. Hence, self-reported vertebral fractures were not included. Duration of fracture follow-up was calculated as the time to first occurrence of a fracture. Follow-up for fractures ranged from 0.02 years to 6.5 years. All nonspinal fractures that occurred before 1 April 1993 were included. For women who died during the follow-up period, date of death was used as the end of follow-up when fracture follow-up was not appropriate. The category all nonspinal fractures included hip and wrist fractures. Fractures of the distal radius or ulna were considered wrist fractures. Hip fractures were defined as those of the proximal femur. Statistical Analysis Estrogen use was classified as never, previous, or current. Chi-square tests of homogeneity and analyses of variance and covariance were used to compare baseline characteristics by estrogen use. Proportional hazard regression models were used to assess the relation between estrogen use and fracture. Women who had never used any type of estrogen formed the reference group for all analyses. Separate models were done for current and previous users. To test the hypothesis that the protective effect of estrogen use may be underestimated if a history of osteoporosis is not taken into account, we stratified by history of osteoporosis or spine fracture (or both). We also stratified patients by estrogen regimen (unopposed estrogen compared with estrogen and progestin) and by age ( 75 years or >75 years). Stratification by estrogen regimen was confined to those with wrist and all nonspinal fractures because combination therapy was not used frequently in our cohort and because few participants in this group had hip fractures. The multivariate model included age, body mass index, total calcium intake (supplemental and dietary), physical activity (kcal/wk), surgical menopause (yes or no), history of smoking (yes or no), history of thyroid medication use, current use of thiazide diuretics, history of osteoporosis or spine fracture or both (yes or no), current use of sedatives or anxiolytics, alcohol consumption (drinks/wk), cognitive function (Mini-Mental Status examination 23), and falls in the previous year

BMD at multiple sites and risk of fracture of multiple types: long-term results from the Study of Osteoporotic Fractures.

In a large cohort of U.S. women aged 65 and older, we report the relationships of BMD measured at several sites, and subsequent fracture risk at multiple sites over >8 years of follow‐up. Although we found almost all fracture types to be related to low BMD, the overall proportion of fractures attributable to low BMD is modest.

Which Fractures Are Associated with Low Appendicular Bone Mass in Elderly Women

Abstract ▪Objective:To determine which types of fractures have an increased incidence in elderly women with low appendicular bone mass. ▪Design:Prospective cohort study. ▪Setting:Four clinical cent...

Physical Activity and Osteoporotic Fracture Risk in Older Women

An estimated 6 million to 9 million women in the United States have osteoporosis, and approximately 1.3 million women each year have fractures [1-3]. For 16% of women, the most severe outcome is hip fracture, which is often followed by an array of comorbid conditions and is a precursor of death within 6 months in 12% to 40% of cases [3-6]. Prevention of osteoporotic fractures is thought to hinge on the ability to reduce bone loss and risk for falling in older women [6-10]. Physical activity has been associated with enhanced bone mass or reduced bone loss and may reduce the risk for falling in older women by improving muscle strength, balance, mobility, and overall physical function [11-17]. This combination of effects raises the question of whether physical activity prevents osteoporotic fractures. Epidemiologic studies of the relation between physical activity and risk for osteoporotic fracture have been suggestive but inconclusive. Case-control studies have shown that persons with fractures are more likely to report having been inactive recently and earlier in their lives [18-23]. In a prospective study [24], Paganini-Hill and colleagues found that women and men who were active for at least 1 hour daily had a 38% and 49% reduced risk for hip fracture, respectively, compared with their less active peers. Other prospective studies with lower statistical power have suggested that physical activity protects against hip fracture but have not found these relations to be statistically significant in multivariate analyses [25, 26]. In an earlier examination of the risk factors for hip fracture among women in the Study of Osteoporotic Fractures, Cummings and colleagues [10] found that women who reported walking for exercise had a statistically significant 30% reduction in risk for hip fracture compared with women who did not walk for exercise. We expanded our analysis of the Study of Osteoporotic Fractures cohort to examine the relation of several domains of physical activity to the risk for osteoporotic fractures. To determine the association of types, amounts, and intensity of physical activity with risk for fracture in older women, we measured baseline levels of physical activity and inactivity in 9704 women 65 years of age and older who were enrolled in the Study of Osteoporotic Fractures and followed them for incident hip, wrist, and vertebral fractures. Methods Patients The study population consisted of 9704 nonblack women 65 years of age and older who were participating in the Study of Osteoporotic Fractures [9]. Participants were recruited from population-based lists (health maintenance organizations, voter registration, and motor vehicle tapes) in Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela Valley, Pennsylvania, from 1986 to 1988. Women were excluded from the Study of Osteoporotic Fractures if they had had bilateral hip replacement, were unable to walk without the assistance of another person, or were institutionalized. All participants gave written informed consent and attended a clinic visit during which questionnaires were given, interviews were conducted, and measurements were taken. Assessment of Physical Activity and Inactivity Physical activity was assessed by using a modified version of the Harvard Alumni Questionnaire [27, 28]. Participants were asked to report the frequency and duration of their participation in 33 physical activities during the past year. They were also asked to give the number of city blocks or the equivalent walked each day for exercise or as part of daily activities and how many flights of stairs they climbed. A summary estimate of total energy expenditure was calculated according to methods described elsewhere [27, 28]. Leisure-time physical activities were attributed an intensity weighting of 5 kcal/min for low intensity, 7.5 kcal/min for medium intensity, or 10 kcal/min for high intensity; each city block walked was assigned 8 kcal/min, and each stair climbed was assigned 4 kcal/min. The total physical activity index, expressed in kilocalories per week, is the sum of kilocalories expended in sport and recreational activities, blocks walked, and stairs climbed. To estimate physical activity related to household chores, participants were asked, About how many hours per week do you usually spend doing heavy household chores, such as scrubbing floors, vacuuming, sweeping, yard work, gardening, or shoveling snow? To estimate inactivity, women were asked how many hours per day they spend sitting upright. Other Measurements Body weight and height were measured by using a balance-beam scale and a stadiometer. Bone mineral density (g/cm2) was measured by using single-photon absorptiometry (OsteoAnalyzer, Siemens-Osteon, Wahiawa, Hawaii) at the distal radius and calcaneus. Hip abduction strength was measured by having the participant lay supine and exert a lateral force against a dynamometer (Sparks Instruments and Academics, Coralville, Iowa) placed 3 cm above the lateral malleolus and held by an observer. Details of these measurements have been reported elsewhere [9, 29]. Additional questions evaluated self-rated health; calcium intake from food; alcohol intake; and use of medications, including hormone replacement therapy, benzodiazepines, and anti-anxiety agents. To assess function, women were asked whether they had difficulty walking two to three blocks on level ground, walking up or down 10 steps, preparing meals, doing heavy housework, or shopping for groceries or clothing. They were also asked about their history of physician-diagnosed medical conditions, including osteoporosis, hypertension, diabetes, arthritis, and stroke. Assessment of Incident Fractures Methods for identifying fractures have been published elsewhere [30]. Participants were contacted every 4 months to ask whether they had had a fracture. Follow-up for fracture ascertainment was more than 99.5% complete. Radiographic reports and films were obtained to confirm hip fractures. Duration of hip and wrist fracture follow-up was calculated as the time to first occurrence of a fracture. Follow-up ranged from 0.2 to 9.6 years (mean, 7.6 years). To measure vertebral fracture incidence, we obtained lateral radiographs of the thoracic and lumbar spine from 7238 women at baseline and an average of 3.7 years later. This sample was reduced because of inadequate technical measurements at baseline (n = 129), failure or refusal to undergo radiography (n = 341), failure to attend the follow-up clinic visit (n = 1528), or death (n = 468). Incident vertebral fracture was defined by morphometry as a reduction in the height of the anterior, middle, or posterior dimension of a vertebral body of 20% and at least 4 mm [31]. Statistical Analysis Women were classified according to quintiles of total physical activity. For heavy chores and sitting, for which there was a limited range of responses and data were skewed, women were grouped into approximate tertiles. To evaluate fracture risk according to intensity of energy expenditure, women were grouped into three exclusive groups: inactivity, low-intensity activity, and moderate to vigorous activity. Inactive women did not participate in any sport or recreational activity and did not walk for exercise. Women who did any sport or recreational activity or walked for exercise were grouped according to the highest intensity activity in which they participated. For example, if a woman reported gardening (light) and aerobic dance (moderate to vigorous), she would be classified in the moderate-to-vigorous intensity group. Additional analyses further stratified women within exercise intensity groups according to whether they did less than or more than 2 hours per week of total sport and recreational activity. Analysis of covariance adjusted for age and chi-square tests of homogeneity were used to evaluate potential confounders across physical activity levels. Proportional hazards regression was done to calculate the relative risk (and 95% CIs) for hip and wrist fracture associated with physical activity level; the least active group for activity variables was the reference group. A multivariate model was also used that included age, weight, smoking status (current or never/past), use of estrogen therapy (current or never/past), self-rated health (five levels ranging from excellent to very poor), dietary calcium intake (mg/d), alcohol intake (drinks/wk), falls in the year before baseline (two or fewer than two), and functional difficulty (yes or no). These variables were selected on the basis of the a priori hypothesis that they could be related to both physical activity and risk for fracture. To determine whether any relations between physical activity and risk for fracture were explained by differences in bone density or muscle strength, calcaneal bone mineral density and hip abductor strength were added to the multivariate models in separate steps. We used logistic regression for vertebral fractures by applying a similar modeling strategy. Additional analyses using different exclusion criteria were done to determine whether any relations among physical activity and fracture risk were explained by differences in health or functional status at baseline. To determine whether the relation between physical activity and hip fracture was explained by poor acute health among inactive women at baseline, analyses excluded 1) women who reported any difficulty walking two to three blocks on level ground, had a severe gait abnormality, or required a walking aid; 2) women with fair or poor self-rated health or history of diabetes, stroke, falls, or hip fracture before baseline measurement; and 3) women who had a fracture or died in the first 3 years after baseline measurement. All analyses were done using Statistical Analysis Software (SAS Institute, Inc., Cary, North Carolina). Results Characteristics of the overall study population, stratified by quintile of total

Urinary incontinence in older women: Who is at risk?

Objective To estimate prevalence of and identify factors associated with urinary incontinence in older women. Methods A cross-sectional study involved 7949 community-dwelling women, with a mean (± standard deviation) age of 76.9 ± 5.0 years, recruited from population-based listings to participate in the Study of osteoporotic Fractures. The prevalence and severity of urinary incontinence during the previous 12 months were assessed by questionnaire. Factors potentially associated with urinary incontinence were assessed by questionnaire, interview, and physical examination. Multivariate logistic regression analysis was sused to determine the independent associations between these factors and the primary outcome of daily incontinence. Results Forty-one percent (3285) of the women reported urinary incontinence, with 14% (1130) reporting daily incontinence. In multivariate analysis, the prevalence of daily urinary incontinence increased significantly with age (odds ratio [OR] 1.3 per 5 years, 95% confidence interval [CI] 1.2–1.5), prior hysterectomy (OR 1.4 95% CI 1.1–1.6), higher body mass index (OR 1.6 per 5 units. 95% CI 1.4–1.7), history of stroke (OR 1.9, 95% CI 1.3–2.7), diabetes (OR 1.7, 95% CI 1.2–2.4), chronic obstructive pulmonary disease (OR 1.4, 95% CI 1.1–1.9), and poor overall health (OR 1.6, 95% CI 1.3–2.0). Faster gait speed (OR 0.8 per 0.2 units, 95% CI 0.6–1.0) was associated with decreased incontinence. Conclusion Urinary incontinence is a common problem in older women, more common than most chronic medical conditions. Of the associated factors that are preventable or modifiable, obesity and hysterectomy may have the greatest impact on the prevalence of daily incontinence.

Correlates of impaired function in older women.

Objective: To determine the factors associated with impaired function in older women.

Body Size and Hip Fracture Risk in Older Women: A Prospective Study

Abstract PURPOSE: To determine the relationship between measures of body size and the risk of hip fracture in elderly women. PARTICIPANTS AND METHODS: The association between measures of body size and hip fracture risk was assessed in 8,011 ambulatory, nonblack women 65 years of age or older enrolled in the Study of Osteoporotic Fractures with measurements of total body weight, percent weight change since age 25, hip girth, lean mass, fat mass, percent body fat, body mass index, modified body mass index, and femoral neck bone mineral density (BMD) at the second examination. These 8,011 women were followed prospectively for incident hip fractures occurring after the second examination, which were confirmed by review of x-ray films. RESULTS: During an average of 5.2 years after the second examination, 236 (2.9%) women experienced hip fractures. Similar associations were observed between hip fracture risk and all measures of body size including total body weight, percent weight change since age 25, hip girth, lean mass, fat mass, percent body fat, body mass index, and modified body mass index. Women with smaller body size had a higher risk of subsequent hip fracture compared with those with larger body size, while women with average and larger body sizes shared similarly lower risks of subsequent hip fracture. For example, the incidence rate of hip fracture was 9.35 per 1000 woman-years in women in the lowest quartile of total weight compared with 4.63 per 1000 woman-years in women in the highest quartile of total weight (age-adjusted relative risk 1.93, 95% confidence interval (CI) 1.34 to 2.80), while rates of hip fracture among women in the second and third quartiles of total weight (5.22 and 4.32 per 1000 woman-years, respectively) were not significantly different from the rate among women in the highest quartile ( P > 0.64). The increased risk of hip fracture among women of smaller body size remained after further adjustment for additional potential confounding factors including height at age 25, smoking status, physical activity, health status, estrogen use, and diuretic use. After further adjustment for femoral neck BMD, women with smaller body size were no longer at significantly increased risk of hip fracture compared with those with larger body size. For example, after adjustment for height at age 25, smoking status, physical activity, health status, estrogen use, and diuretic use, thin women had a 2.5-fold increase in the risk of hip fracture (multivariate relative risk 2.51, 95% CI 1.69 to 3.73) compared with the referent group composed of the heaviest women. After further adjustment for femoral neck BMD, the multivariate relative risk of hip fracture among thin women compared to heaviest women was 0.98 (95% CI, 0.64 to 1.50). CONCLUSION: Older women with smaller body size are at increased risk of hip fracture. This effect is because of lower hip BMD in women with smaller body size. Assessment of body size for prediction of hip fracture risk can be accomplished by measuring total body weight.

Effects of Thiazide Diuretic Therapy on Bone Mass, Fractures, and Falls

Osteoporosis is responsible for about 1.3 million fractures in the United States each year [1]. Further, recent research has shown that the risk for most types of fracture in elderly women is related to low bone mass; thus, the public health impact of osteoporosis may, in fact, be much greater [2] and is projected to increase over the next several decades [3]. Postmenopausal estrogen replacement is the current recommended therapy for the prevention of osteoporosis [4]. However, the use of estrogen is not widespread among elderly women [5]. Clearly, more options for the prevention of osteoporosis and fracture need to be developed and explored. One option is the use of thiazide diuretics. Thiazide diuretics are known to reduce urinary excretion of calcium [6, 7] and may also decrease bone resorption [6] and bone turnover [8]. The use of thiazide diuretics has been associated with a reduced risk for fracture, with risk ratios ranging from 0.3 to 0.8 [9-18]. For example, in a casecontrol study that excluded patients taking other drugs thought to affect bone mass, Ray and colleagues [15] found a 50% reduction in the risk for hip fracture among patients who had used thiazide diuretics for 6 years. In addition, LaCroix and colleagues [16] reported a 30% lower risk for hip fracture in current users compared with nonusers. The Framingham Study also showed a lower risk for hip fracture among users of pure thiazide drugs when compared with those using agents that combined thiazide diuretics with other antihypertensive drugs [17]. However, all of these studies have been observational, which allows the possibility that users of thiazide diuretics have a lower risk for hip fracture because of other confounding factors. In addition, the more recent data of Heidrich and colleagues [19] conflict with these results. These investigators found a crude odds ratio for thiazide use and hip fracture of 1.1, which is not statistically significant. However, when they adjusted for the potentially confounding effects of nursing-home residence; previous hospitalizations; history of stroke, alcoholism or organic brain syndrome; body weight; leg paralysis; and use of phenobarbital, corticosteroids, or other diuretics, a significantly increased risk for hip fracture was found among women who reported current use of thiazide diuretics [19]. No study has prospectively evaluated the relation between thiazide diuretics and other types of fracture. The mechanism by which thiazide diuretics might protect against hip fracture is not known. Thiazide diuretics may decrease fracture risk by preserving bone mass [10, 11, 20-23]. Cross-sectional studies have shown that users of thiazide diuretics have slightly higher cortical and trabecular bone mass than nonusers. Two randomized clinical studies of the effect of thiazide diuretics on bone loss had conflicting results [24, 25]. If thiazide diuretics reduce the risk for hip fracture by slowing bone loss, then these agents should also protect against other types of fracture that are associated with reduced bone mass [2]. On the other hand, thiazide diuretics could increase the risk for fractures by increasing the risk for falls [26]. Thiazide diuretics might do this by causing dizziness or postural hypotension [27], although the association of diuretic use with falling is not consistent [28]. More than 90% of hip fractures are related to falls [29]. No previous study has included a comprehensive analysis of the effects of thiazide diuretics on bone mass, the risk for falls, and the risk for all fractures in a single population. In our prospective study of 9704 women who were 65 years or older (the Study of Osteoporotic Fractures), we assessed thiazide diuretic use and bone mass at baseline and conducted follow-up examinations every 4 months for the occurrence of fractures and falls. Methods Study Sample From September 1986 through October 1988, women who were at least 65 years old were recruited for the Study of Osteoporotic Fractures in four areas of the United States: Portland, Oregon; Minneapolis, Minnesota; Baltimore County, Maryland; and the Monongahela Valley region near Pittsburgh, Pennsylvania. Age-eligible women were recruited through several sources: health maintenance organizations; lists of residents that had been compiled for other epidemiologic studies; jury-selection lists; voter-registration lists; and lists of drivers license holders [30]. We excluded black women because of their lower incidence of fractures, women who were unable to walk without the assistance of another person, and women who had bilateral hip replacements. Measurement of Bone Mass Bone mineral content (g/cm) and density (g/cm2) were measured using single-photon absorptiometry (OsteoAnalyzer, Siemens-Osteon, Wahiawa, Hawaii). Details of these methods have been reported elsewhere [30]. We scanned three sites: the distal radius, the proximal radius, and the calcaneus. The distal radius is composed of about 60% cortical bone and 40% trabecular bone, the proximal radius is about 99% cortical bone [31], and the calcaneus is about 97% trabecular bone [32]. The reproducibility of the bone mass measurements, expressed as coefficients of variation, ranged from 1.3% to 2.0% among individuals and from 0.4% to 1.2% among scanners [30]. Diuretic Use Information on diuretic use was obtained at the baseline clinic interview. Participants were asked to bring all current medications to the clinic for verification. In addition, pictures of tablets were presented to participants to assist them in the recollection of previously prescribed diuretics. Diuretics, including combination drugs, were classified as thiazide diuretics according to the American Medical Association drug evaluations [33]. Separate histories were obtained from participants for use of thiazide and nonthiazide diuretics. Chlorthalidone was classified as a thiazide diuretic because its effects on calcium excretion are similar to those of thiazide diuretics. Analyses in which chlorthalidone was not considered as a thiazide diuretic yielded similar results. Women were asked whether they had ever taken diuretics; at what age they had started taking diuretics; whether they were currently using diuretics and, if not, when they had stopped; whether they took diuretics the entire time or stopped for a few years; and the name of the medication they were currently using. Duration of diuretic use was calculated as the total number of years that they reported using diuretics. No information was collected on dose at the baseline visit, but dose-related data were recorded at the first annual telephone interview. Information on duration of thiazide diuretic use was missing in 15 women. These women were excluded from all analyses. Other Measurements Reported health status, type of menopause, alcohol consumption, and cigarette smoking were assessed using a questionnaire that was reviewed with the participant by a trained interviewer. Women were considered to have had a surgical menopause if they reported having had a bilateral oophorectomy at the age at which they stopped menstruating. Regarding alcohol consumption, participants were asked how much they had consumed during the past 30 days and how many times they had consumed three or more drinks per day and five or more drinks per day during the past 30 days. The measure of alcohol consumption used in our study was drinks per week, which was adjusted for atypical drinking, particularly heavy drinking over the last 30 days. Dietary calcium was assessed by a food frequency questionnaire and an interview using standardized food models to estimate portion sizes [34]. In our study, total calcium intake included dietary and supplemental calcium. Women were also asked if they had ever taken the following medications: thyroid hormones, medicine for seizures, vitamin D or multivitamins containing vitamin D, TUMS, calcium supplements, antacids, prednisone, cortisone, other steroid pills, birth control pills, estrogen pills, estrogen skin patches, estrogen vaginal cream or suppositories, estrogen injections, and progestins. Information was obtained on current use, duration of use, and specific drug and dosage used for the longest period. Functional status was measured by a respondents answers to questions about her ability to perform six instrumental activities of daily living by herself and without using special aids or equipment. These activities were as follows: walking two or three blocks outside on level ground; climbing up 10 steps without stopping; walking down 10 steps; preparing ones own meals; doing heavy housework; and doing ones own shopping for groceries or clothes. The measure used in these analyses is the total number of activities (ranging from 0 to 6) that a woman reported she was unable to do or had difficulty doing. Additionally, women were asked to rate their health status as very good, good, fair, poor, or very poor. During the clinic examination, body weight was measured (after removal of shoes and heavy outer clothing) using a balance beam scale. Height was measured (after removal of shoes) using a Harpenden stadiometer (Holtain, Ltd., Dyved, United Kingdom). Height and weight were used to calculate the body mass index (kg/m2). Ascertainment of Prevalent Vertebral Deformities The prevalence of vertebral deformities as shown by lateral thoracic and lumbar spine films was obtained on 2992 women (31% of the cohort) who were between 65 and 70 years old. The methods used to identify vertebral deformities have been described previously [35]. In summary, six points for each vertebral body, T4 through L4, were marked with a translucent digitizer. We calculated three heights (anterior, posterior, and middle) and three ratios: anterior-to-posterior height (wedge); mid-to-posterior height (endplate); and the posterior height of each vertebra to the posterior height of the adjacent vertebrae (crush). We classified a vertebral body a

Neuropsychiatric Function and Dehydroepiandrosterone Sulfate in Elderly Women: A Prospective Study

BACKGROUND Though among the most abundant human steroid hormones, the physiologic role of dehydroepiandrosterone and its sulfate (DHEAS) is not known. Our goal was to determine if DHEAS is associated with cognition and mood in older women, and if baseline DHEAS levels are predictive of cognitive decline. METHODS In a prospective cohort, we studied 394 randomly selected community-dwelling women, aged 65 years or older, currently enrolled in the Study of Osteoporotic Fractures. Subjects were administered a modified Mini-Mental State Exam, Trials B, Digit Symbol, and the Geriatric Depression Scale-Shortened (GDSS), at study onset and 4-6 years later. Serum was obtained at study initiation for DHEAS analysis. RESULTS DHEAS levels declined with age, as expected. There was no consistent association of DHEAS quartile or log DHEAS with any of the four outcomes, even after multivariate adjustment. Change in cognitive performance overtime was not associated with DHEAS levels. Analysis of the 32 women without any detectable DHEAS compared to those with detectable levels revealed higher measures on the GDSS (mean score 3.4 +/- 3.6 compared with 1.6 +/- 2.3, p = .028) and a higher percentage with depression (21.7% compared with 4.6%, p = .001). CONCLUSIONS Serum DHEAS is not a sensitive predictor of cognitive performance or decline on a selected neuropsychological battery in elderly community women; however, nondetectable levels may be associated with depression.

Modifiable risk factors predict functional decline among older women : A prospectively validated clinical prediction tool

OBJECTIVE: To identify modifiable predictors of functional decline among community‐residing older women and to derive and validate a clinical prediction tool for functional decline based only on modifiable predictors.