Jean C. Scott

Risk of mortality following clinical fractures.

Abstract: To examine the risk of mortality following all clinical fractures, we followed 6459 women age 55–81 years participating in the Fracture Intervention Trial for an average of 3.8 years. All fractures and deaths were confirmed by medical record or death certificate. Clinical fractures were fractures that came to medical attention. Fracture status was used as a time-dependent covariate in proportional hazards models. The 907 women who experienced a fracture were older, had lower bone mineral density and were more likely to report a positive fracture history. A total of 122 women died over the course of the study with 23 of these deaths occurring after a clinical fracture. The age-adjusted relative risk (95% confidence intervals) of dying following a clinical fracture was 2.15 (1.36, 3.42). This primarily reflected the higher mortality following a hip fracture, 6.68 (3.08, 14.52); and clinical vertebral fracture, 8.64 (4.45, 16.74). Results were similar after adjusting for treatment assignment, health status and specific common comorbidities. There was no increase in mortality following a forearm or other fracture (non-hip, non-wrist, non-vertebral fracture). In conclusion, clinical vertebral fractures and hip fractures are associated with a substantial increase in mortality among a group of relatively healthy older women.

Factors associated with appendicular bone mass in older women

Fractures are an important cause of disability in elderly women, especially among those with osteopenia. Decreased bone mass increases the risk for most types of fractures [1-4]. In particular, we recently reported [5] that most fractures in elderly women are associated with low bone mass at appendicular sites (the radius and calcaneus). The risk for these fractures, including some fractures not previously linked to osteopenia, such as of the leg and hand, increased 40% to 80% for each standard deviation reduction in appendicular bone mass [5]. We also found that appendicular bone mass predicts the risk for all nonspine fractures as well as for bone mass measured at the hip and spine [6]. Despite the strong relation between appendicular bone mass and risk for fracture, little consensus exists about the many proposed risk factors for decreased bone mass [7, 8], perhaps because most studies have examined a limited number of risk factors in relatively small selected cohorts. To determine what factors might contribute to osteopenia in older women, we examined a wide variety of potential correlates of appendicular bone mass in the Study of Osteoporotic Fractures, a large multicenter, community-based study of elderly women. Methods Patients From September 1986 to October 1988, women who were at least 65 years old were recruited in four areas of the United States: Portland, Oregon; Minneapolis, Minnesota; Baltimore, Maryland; and the Monongahela Valley near Pittsburgh, Pennsylvania. Age-eligible women were identified from membership lists from several sources, as previously reported [1]. We excluded black women because of the reduced incidence of hip fractures in this group [9], and we excluded women who were unable to walk without the assistance of another person or who had bilateral hip replacements. Measurement of Bone Mass Bone mass (in g/cm2) was measured using OsteoAnalyzers (Siemens-Osteon, Wahiawa, Hawaii). We scanned three sites: the distal radius, the midradius, and the calcaneus. The protocol for the bone mass measurements has been described elsewhere [1]. To describe the reproducibility of these measurements, a participant in the study was measured five times on 5 consecutive days at each of the four clinical centers. The average coefficients of variation in these older women (standard deviation/mean for each subject) were 1.5% for the distal radius, 2.0% for the midradius, and 1.3% for the calcaneus. To assess variations between scanners at the four centers, two investigators were measured by all four machines; the mean of their coefficients of variation in these younger subjects was 0.4% for the distal radius, 0.5% for the midradius, and 1.2% for the calcaneus [10]. The correlation coefficients between the measurement sites were distal and midradius, 0.75; calcaneus and distal radius, 0.66; and calcaneus and midradius, 0.63. Predictor Variables Participants completed a self-administered questionnaire and were interviewed and examined at the clinical center. A selected medical history was obtained, including a history of a physician diagnosis of osteoporosis, spine fracture, arthritis, gastric surgery, hyperthyroidism, and stroke. Reproductive history, including age of last menstrual period, genitourinary surgery (hysterectomy, oophorectomy), number of pregnancies, and breast-feeding, was recorded. Previous fractures in subjects and their parents or sisters were noted. We collected detailed records about specific health habits including lifetime smoking history, alcohol use, and caffeine intake. Women who had smoked less than 100 cigarettes in their lifetime were considered nonsmokers. We assumed that a cup of coffee contained 95 mg of caffeine and that tea and cola drinks contained 55 mg and 45 mg, respectively. Participants were asked to bring all prescription and nonprescription medications with them to the interview for verification. The dose and duration of use of sex hormones, diuretics, corticosteroids, thyroid supplements, aluminum-containing antacids, vitamin D, sedative hypnotics, and antiepileptic medications were obtained. The frequency and duration of use of calcium supplements were recorded; use of TUMS (which can be taken as an antacid or calcium supplement) was recorded separately. Responses to the questionnaire were checked by a trained interviewer and were verified against the labels of medications that the subject brought to the interview. Recent dietary history (past 12 months), particularly calcium, phosphorus, and protein intake, was assessed by a checklist-interview method developed from the HANES-II survey [11]. Food models were used to estimate portion sizes, and foods that account for 80% of calcium intake in most adults were included. This instrument has a correlation of 0.76 with calcium intake assessed by a 7-day diet diary, but it tends to underestimate calcium intake by approximately 150 mg/day [12]. The frequency of milk consumption as a child and young adult was also assessed by questionnaire. Physical activity was examined with a modified Paffenbarger survey that has been validated in postmenopausal women [13-16]. The type and duration of weight-bearing recreational activities from the previous 12 months were recorded, and these were converted into weekly caloric expenditure. Other current activities, such as stair climbing, walking, and heavy household chores, were included. Intensity-weighted measures were calculated by designating activities as low (for example, walking or gardening), medium (dancing or tennis), or high intensity (jogging or skiing) and multiplying the reported frequency of the activity by 2.5, 5, and 7.5, respectively. Weight (in light indoor clothes with shoes removed) was recorded with a balance beam scale, and height was measured using a standard held-expiration technique with a wall-mounted Harpenden stadiometer [17]. Maximal right knee extension, triceps (arm extension), and hip abduction torque strength were measured with a hand-held isometric dynamometer (Sparks Instruments and Academics, Coralville, Iowa). Grip strength of the right and left hand was assessed as the average of two attempts with the dynamometer. Waist, hip, and abdominal circumferences were measured using standard methods [18]. Statistical Methods The cohort was randomly divided into equal-sized (n = 4852) training and validation groups. In the training group, we analyzed potential associations with bone mass in univariate analyses, adjusted for age. We then adjusted associations (P < 0.05) for other plausible confounding effects. For example, associations between the use of thiazide diuretics and bone mass were also adjusted for body weight, because those who were taking diuretics tended to be heavier. Potentially nonlinear associations between bone mass and continuous variables, such as calcium intake, were examined by plotting bone mass against the median of each decile of the predictor variable. Associations were tested for statistical significance with simple linear regression, Student t-test, or analysis of variance. Variables that were associated with bone mass in univariate analyses (P < 0.05) were examined by multivariate analyses using PROC GLM (SAS Institute, Inc., Cary, North Carolina). Some categories of predictor variables, such as calcium intake and muscle strength, contained several variables associated with bone mass in univariate analyses. After examining these variables for multicollinearity, separate models for strength, family history of fractures, dietary calcium, and physical activity were analyzed to determine the individual variables that explained most of the variance of bone mass within each category. For example, grip strength explained most of the variance for bone mass related to strength; thus, we selected this variable as the measure of strength for subsequent multivariate analyses. Both current dietary calcium and calcium from milk (ingested between ages 18 to 50 years) contributed to bone mass variance; therefore, both were included in the final multivariate models. A history of any maternal fracture after age 50 accounted for most of the bone mass variance from family history, and intensity-weighted lifetime physical activity accounted for most of the variance from physical activity. Selected variables (see Table 2) were then entered into a single multivariate model. We found that results from multivariate models were very similar in both training and validation groups; thus results are reported for the entire (combined) cohort. Results were generally similar for the three bone mass sites, and for those analyses that were concordant at all three sites, only the results for the distal radius are presented. We presented results at the other two sites only when they differed from the distal radius. Results The average age at enrollment was 71.1 years, and the age distributions were similar in the training and validation groups (Table 1). Thirteen percent of patients reported a previous wrist or hip fracture. Table 1. Baseline Characteristics of Patients Demographic and Anthropometric Data Bone mass was strongly and inversely associated with age, decreasing by approximately 5% with every additional 5 years of age after 65 years (Table 2). Northern European ancestry, hair color, and educational level were not associated with bone mass (Table 3). Table 2. Univariate and Multivariate Correlates of Distal Radius Bone Mass Table 3. Variables Not Associated with Distal Radius Bone Mass, Age-Adjusted Univariate Analyses* Several anthropometric measurements were strongly associated with bone mass (see Table 2). Both weight [in kilograms] and obesity (as Quetelet index, in kilograms per square meter) were associated with increased bone mass: after adjusting for age, bone mass increased 5.0% for every 10-kg increase in weight (Figure 1). Although weight and Quetelet were highly correlated (r = 0.91), weight was more strongly associated with bone mass than

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...

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.

Serum vitamin D levels and incident changes of radiographic hip osteoarthritis: A longitudinal study

Objective The purpose of this study was to determine the relationship of serum levels of 25-vitamin D and 1,25-vitamin D to incident changes of radiographic hip osteoarthritis (OA) among elderly white women. Methods Baseline and followup hip radiographs of 237 subjects were obtained an average of 8 years apart. Hips were scored for individual radiographic features (IRF) and assigned a summary grade based on the number and type of IRF present. Serum 25- and 1,25-vitamin D levels from baseline samples were analyzed by radioimmunoassay. Logistic and linear regression were used to examine the association of 25- and 1,25-vitamin D levels with radiographic changes, adjusting for age, health status, physical activity, weight, vitamin D supplement use, and calcaneal bone mineral density. Results The risk of incident hip OA defined as the development of definite joint space narrowing was increased for subjects who were in the middle (odds ratio [OR] 3.21, 95% confidence interval [95% CI] 1.06, 9.68) and lowest (OR 3.34, 95% CI 1.13, 9.86) tertiles for 25-vitamin D compared with subjects in the highest tertile. Vitamin D levels were not associated with incident hip OA defined as the development of definite osteophytes or new disease according to the summary grade. No association between serum 1,25-vitamin D and changes in radiographic hip OA was found. Conclusion Low serum levels of 25-vitamin D may be associated with incident changes of radiographic hip OA characterized by joint space narrowing.

OSTEOARTHRITIS AND RISK OF FALLS, RATES OF BONE LOSS, AND OSTEOPOROTIC FRACTURES

OBJECTIVE To examine the association between osteoarthritis (OA), as defined by radiographic evidence and self report, and osteoporotic fractures, falls, and bone loss in a cohort of elderly white women. METHODS A cohort of 5,552 elderly women from the Study of Osteoporotic Fractures was followed up prospectively for a mean of 7.4 years. Self-reported, physician-diagnosed OA was recorded at interview, and radiologic OA of the hip and hand were defined from pelvis and hand radiographs obtained at baseline by validated techniques. Prevalent and incident vertebral fractures were detected by vertebral morphometry, and data on incident fractures and falls were collected by postcard surveys; fractures were confirmed by radiography. Bone mineral density (BMD) was measured on 2 occasions at the hip, lumbar spine, and calcaneus, and rates of bone loss were calculated. RESULTS Women with radiographic hip OA had a reduced risk of recurrent falls in the first year (relative risk [RR] 0.7, 95% confidence interval [95% CI] 0.5-0.95). However, those with self-reported OA had an increased risk of falls (RR 1.4, 95% CI 1.2-1.5). Radiographic hip OA was associated with reduced bone loss in the femoral neck compared with controls (mean +/- SD -0.29+/-0.09%/year versus -0.51+/-0.03%/year; P = 0.018). However, radiographic hip OA showed nonsignificant trends toward increased bone loss at the calcaneus and lumbar spine. There was no significant association between self-reported OA or radiographic hand OA with bone loss. No definition of OA was associated with incident nonvertebral fracture, hip fracture, or vertebral fracture. CONCLUSION Despite having increased BMD compared with controls, subjects with OA did not have a significantly reduced risk of osteoporotic fracture, although there was a trend toward a reduced risk of femoral neck fractures in subjects with severe radiographic OA. The failure of the observed increase in BMD to translate into a reduced fracture risk may be due, in part, to the number and type of falls sustained by subjects with OA. Patients with OA should not be considered to be at a lower risk of fracture than the general population. Physicians should be aware that a high BMD in patients with OA may be falsely reassuring.

Smoking, alcohol, and neuromuscular and physical function of older women. Study of Osteoporotic Fractures Research Group.

OBJECTIVE To determine the associations of current and lifetime smoking and alcohol use with physical function in an older population. DESIGN Survey. SETTING Four clinic centers in the United States. PARTICIPANTS A total of 9704 community-dwelling, ambulatory white women 65 years or older recruited from four areas of the United States. MAIN OUTCOME MEASURES Twelve performance tests of muscle strength, agility and coordination, gait and balance, and self-reported functional status. RESULTS Compared with women who never smoked, current smokers had significantly poorer function on all of the performance measures except grip strength after adjusting for age, history of stroke, body mass index, clinic site, physical activity, and alcohol use (P < .05). This decrease in function was 50% to 100% as great as that associated with a 5-year increase in age, and most measures worsened with increasing numbers of pack-years. Compared with current moderate drinkers, nondrinkers had significantly poorer function on all of the performance measures except tandem walk (P < .05). Evaluation of a dose effect with alcohol was limited by the small number of heavy drinkers in the study. CONCLUSIONS In this population, women who currently smoke are weaker and have poorer balance and poorer performance on measures of integrated physical function than nonsmokers. Smoking is associated with a decline in physical function. Current moderate drinkers have better physical function compared with nondrinkers, but associations of function with heavy drinkers could not be assessed.

Effects of Blood Lead Levels on Cognitive Function of Older Women

Elevated blood lead concentrations are known to have detrimental effects on neuropsychological function in both children and occupational cohorts of men and women. Although it is generally accepted that lead exposure at low levels is more dangerous for infants and children than for adults, the issue of the lowest level of exposure at which lead causes deleterious health effects in adults is yet to be solved. There is no available data on the role of lead exposure in cognitive dysfunction in nonoccupational cohorts of older persons. In the current study, we examined the cross-sectional relationship between blood lead levels and a variety of measures of neuropsychological function in a large cohort of elderly women recruited at both urban and rural sites. This study of elderly women demonstrates that blood lead levels as low as 8 micrograms/dl were significantly associated with poorer cognitive function as measured by certain neuropsychological tests. Even a slight decrement in cognition would have a large public health impact due to the large number of elderly at risk.

Alendronate Reduces the Risk of Multiple Symptomatic Fractures: Results from the Fracture Intervention Trial

To evaluate the effect of alendronate on the occurrence rate of multiple symptomatic fractures and on the risk of multiple symptomatic fractures (likelihood of having more than one fracture diagnosed because of the symptoms the fractures caused over the study period) among women with osteoporosis.

A survey of blood pressure in the state of Maryland.

To provide baseline data for a state program to coordinate hypertension resources, a blood pressure (BP) survey was undertaken in Maryland in 1978. A statewide probability sample of households was chosen; each adult member was eligible for interview and measurement of BP. A total of 6,425 adults were interviewed for an overall response rate of 79.5%. Using a definition of diastolic blood pressure (DBP) of 95 mm Hg or higher or use of antihypertensive medication, 15.1% of state residents were estimated to be hypertensive. Of these, 85.8% were estimated to be aware of their condition, 77.6% of them were treated, and 67.6% had their BP controlled to a normal level by medication. Data are also presented using DBP 90 mm Hg or higher. A comparison of data from the Hypertension Detection and Follow-up Program (HDFP) home screen in 1973-1974 and comparable information from this survey showed lower rates of awareness, treatment, and BP control in hypertensives at HDFP home screen. Results of this survey will be compared with those of a second statewide survey conducted four years later to assess changes in rates of hypertension awareness, treatment, and control.