Osteoprotegerin Lys3Asn polymorphism and the risk of fracture in older women.

CONTEXT: Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator nuclear factor kappa-beta that blocks osteoclastic bone resorption. OBJECTIVE: We investigated the association between a Lys3Asn polymorphism in the OPG gene and bone mineral density (BMD), and the risk of fracture in 6695 women aged 65 yr and older participating in the Study of Osteoporotic Fractures. DESIGN: BMD was measured using either single-photon absorptiometry (Osteon Osteoanalyzer; Dove Medical Group, Los Angeles, CA) or dual-energy x-ray absorptiometry (Hologic QDR 1000; Hologic, Inc., Bedford, MA). Incident fractures were confirmed by physician adjudication of radiology reports. Genotyping was performed using an immobilized probe-based assay. RESULTS: Women who were homozygous for the minor G (Lys) allele had significantly lower BMD at the intertrochanter, distal radius, lumbar spine, and calcaneus than those with the C (Asn) allele. There were 701 incident hip fractures during 13.6-yr follow-up (91,249 person-years), including 362 femoral neck and 333 intertrochanteric hip fractures. Women with the C/C (Asn-Asn) genotype had a 51% higher risk of femoral neck fracture (95% confidence interval, 1.13-2.02) and 26% higher risk of hip fracture (95% confidence interval, 1.02-1.54) than those with the G/G (Lys-Lys) genotype. These associations were independent of BMD. Intertrochanteric fractures were not associated with the Lys3Asn polymorphism. CONCLUSION: These results require confirmation but suggest a role for the OPG Lys3Asn polymorphism in the genetic susceptibility to hip fractures among older white women.

A prospective study of physical activity and cognitive decline in elderly women: women who walk.

BACKGROUND: Several studies have suggested that physical activity is positively associated with cognitive function in elderly persons. Evidence about this association has been limited by the cross-sectional design of most studies and by the frequent lack of adjustment for potential confounding variables. We determined whether physical activity is associated with cognitive decline in a prospective study of older women. METHODS: We studied 5925 predominantly white community-dwelling women (aged > or =65 years) who were recruited at 4 clinical centers and were without baseline cognitive impairment or physical limitations. We measured cognitive performance using a modified Mini-Mental State Examination at baseline and 6 to 8 years later. Physical activity was measured by self-reported blocks (1 block approximately 160 m) walked per week and by total kilocalories (energy) expended per week in recreation, blocks walked, and stairs climbed. Cognitive decline was defined as a 3-point decline or greater on repeated modified Mini-Mental State Examination. RESULTS: Women with a greater physical activity level at baseline were less likely to experience cognitive decline during the 6 to 8 years of follow-up: cognitive decline occurred in 17%, 18%, 22%, and 24% of those in the highest, third, second, and lowest quartile of blocks walked per week (P< .001 for trend). Almost identical results were obtained by quartile of total kilocalories expended per week. After adjustment for age, educational level, comorbid conditions, smoking status, estrogen use, and functional limitation, women in the highest quartile remained less likely than women in the lowest quartile to develop cognitive decline (for blocks walked: odds ratio, 0.66 [95% confidence interval, 0.54-0.82]; for total kilocalories: odds ratio, 0.74 [95% confidence interval, 0.60-0.90]). CONCLUSIONS: Women with higher levels of baseline physical activity were less likely to develop cognitive decline. This association was not explained by differences in baseline function or health status. This finding supports the hypothesis that physical activity prevents cognitive decline in older community-dwelling women.

Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women.

Osteoprotegerin (OPG) and its ligand are cytokines that regulate osteoclastogenesis and that may be involved in the regulation of vascular calcification. We examined whether serum OPG levels were associated with stroke, mortality, and cardiovascular risk factors, including diabetes, as well as with bone mineral density and fractures in a sample of 490 participants in a prospective cohort of white women, at least 65 yr of age. We found that OPG levels, assayed blinded from serum obtained at baseline, were about 30% greater in women with diabetes (mean +/- SD, 0.30 +/- 0.17 ng/mL) than in those without diabetes (0.23 +/- 0.10 ng/mL; P = 0.0001). OPG levels were associated with all-cause mortality [age-adjusted odds ratio, 1.4/SD (0.11 ng/mL) increase in serum OPG level; 95% confidence interval, 1.2--1.8] and cardiovascular mortality (odds ratio, 1.4; 95% confidence interval, 1.1--1.8); these effects were not confounded by diabetes. OPG levels were not associated with baseline bone mineral density or with subsequent strokes or fractures. The association of serum OPG levels with diabetes and with cardiovascular mortality raises the possibility that OPG may be a cause of or a marker for vascular calcification.

Inner-city older blacks have high levels of functional disability.

OBJECTIVES: To describe the frequency and severity of functional problems in two groups of noninstitutionalized inner-city blacks aged 70 years and older contrasted with results from appropriate groups of white and black older adults and with the goals of the Healthy People 2000 program. DESIGN: Cross-sectional descriptive study. SETTING: Community-based samples. PARTICIPANTS: A population-based sample of 416 older adults living in a 3.5-square mile catchment area in north St. Louis (NSL), Missouri, and a sample of 197 older residents living in public housing in East St. Louis (ESL), Illinois. MEASUREMENTS: Health status, preventive health activities, health services utilization, and risks for progressive frailty were assessed by self report and observation using well validated, standardized instruments. Whenever possible, comparison data were derived from national datasets, original samples used to validate the measures, and other useful comparison groups. RESULTS: The NSL sample had somewhat better health status and risk for progressive disability than the ESL sample. However, compared with national or regional reference groups using age-gender adjustments, both study groups demonstrated increased levels of dependence in intermediate activities of daily living, restricted activity days, inability to walk one-half mile without assistance, reported poor vision, living alone, and limited income compared with both older whites and blacks, and increased levels of worsening health, inability to perform heavy work around the house, never walking a mile or more, and currently unmarried versus whites with variable decrements versus blacks. Contrasted with other comparison groups, the two samples had increased body fat; consistent decrements in gait speed, timed chair stands, timed one-leg balance, and frequency of preventive exercise; and lower levels of dental care; results relative to physician visits and hospital days were mixed. They also had high levels of measured visual and hearing impairments, unmet needs for home delivered meals, and problems with false teeth. Deficiencies compared with the goals of Healthy People 2000 were large. CONCLUSIONS: The special attributes of inner-city blacks, including poverty and access to and acceptance of remedial programs, will have to be considered if the goals of Healthy People 2000 are to be met in this important and growing segment of older Americans. 44:0000-0000, 1996.

Reported and measured physical functioning in older inner-city diabetic African Americans.

BACKGROUND: The impact of diabetes on disability and physical functioning in older African Americans and potential causes of the excessive disability associated with diabetes in other studies have been inadequately investigated. METHODS: A population-based survey was performed comparing 116 self-reported diabetic inner-city African Americans aged 70 years and older to 522 nondiabetic persons from the same population. A subsample (n = 168) received a physical examination focused on body habitus, upper and lower body strength, balance, and timed physical performance tasks. Blood tests were obtained from 173 subjects. RESULTS: Diabetic individuals reported worse general health (p = .01), instrumental activities of daily living (p = .02), and modified versions of the Rosow-Breslau scale (p<.001) and the Stanford Health Assessment Questionnaire (p = .002). Diabetic persons also reported more falls (0.59 per person vs. 0.20, p = .019) and injurious falls (12% vs. 6%, p = .025). There were minimal differences in the strength, balance, and timed performance measures (analyzed separately by gender). In multivariable analyses, impairments in visual function and pain and light touch perception appeared to explain some of the association between diabetic status and poor general health, disability, and falls, with lesser contribution from the number of medical problems, number of medications, and glycemic control. CONCLUSIONS: Older inner-city diabetic blacks demonstrated worse general health, excess disability, and more falls compared to controls, although deficits in strength, balance, and timed performance could not be demonstrated. The cause of decreased functional status in diabetic elders deserves additional investigation, focusing especially on sensory function, glycemic control, and contribution from specific medical problems and medications.

Reduced employment in caregivers of frail elders: impact of ethnicity, patient clinical characteristics, and caregiver characteristics.

BACKGROUND: Without family caregivers, many frail elders who live at home would require nursing home care. However, providing care to frail elders requires a large time commitment that may interfere with the caregiver's ability to work. Our goal was to determine the patient and caregiver characteristics associated with the reduction of employment hours in caregivers of frail elders. METHODS: This was a cross-sectional study of 2806 patients (mean age 78, 73% women, 29% African American, 12% Hispanic, 54% with dementia) with at least one potentially working caregiver (defined as one who is either currently employed or who would have been employed if they had not been providing care) and their 4592 potentially working caregivers. Patients were enrollees at 11 sites of the Program of All-Inclusive Care for the Elderly (PACE). Social workers interviewed patients and caregivers at the time of PACE enrollment. Caregivers were asked if they had reduced the hours they worked or had stopped working to care for the patient. Nurses interviewed patients and caregivers to assess independence in activities of daily living (ADLs) and the presence of behavioral disturbances. Comorbid conditions were assessed by physicians during enrollment examinations. RESULTS: A total of 604 (22%) of the 2806 patients had at least one caregiver who either reduced the number of hours they worked or quit working to care for the patient. Patient characteristics independently associated with a caregiver reducing hours or quitting work were ethnicity, 95% confidence interval [CI] 1.14-1.78 for African American;, 95% CI 1.43-2.52 for Hispanic), ADL function below the median (, 95% CI 1.44-2.15), a diagnosis of dementia (, 95% -2.17 if associated with a behavioral disturbance;, 95% CI 1.06-1.63 if not associated with a behavioral disturbance), or a history of stroke (OR = 1.42, 95% CI 1.16-1.73). After controlling for these patient characteristics, caregiver characteristics associated with reducing work hours included being the daughter or daughter-in-law of the patient (OR = 1.69, 95% CI 1.37-2.08) and living with the patient (OR = 4.66, 95% CI 3.65-5.95 if no other caregiver lived at home, OR = 2.53, 95% CI 2.03-3.14 if another caregiver lived at home). CONCLUSIONS: Many caregivers reduce the number of hours they work to care for frail elderly relatives. The burden of reduced employment is more likely to be incurred by the families of ethnic minorities and of patients with specific clinical characteristics. Daughters and caregivers who live with the patient are more likely to reduce work hours than other caregivers. Future research should examine the impact of lost caregiver employment on patients' families and the ways in which the societal responsibility of caring for frail elders can be equitably shared.

Changes in proximal femoral mineral geometry precede the onset of radiographic hip osteoarthritis: The study of osteoporotic fractures.

OBJECTIVE: Radiographic hip osteoarthritis (RHOA) is associated with increased hip areal bone mineral density (aBMD). This study was undertaken to examine whether femoral geometry is associated with RHOA independent of aBMD. METHODS: Participants in the Study of Osteoporotic Fractures in whom pelvic radiographs had been obtained at visits 1 and 5 (mean 8.3 years apart) and hip dual x-ray absorptiometry (DXA) had been performed (2 years after baseline) were included. Prevalent and incident RHOA phenotypes were defined as composite (osteophytes and joint space narrowing [JSN]), atrophic (JSN without osteophytes), or osteophytic (femoral osteophytes without JSN). Analogous definitions of progression were based on minimum joint space and total osteophyte score. Hip DXA scans were assessed using the Hip Structural Analysis program to derive geometric measures, including femoral neck length, width, and centroid position. Relative risks and 95% confidence intervals for prevalent, incident, and progressive RHOA per SD increase in geometric measure were estimated in a hip-based analysis using multinomial logistic regression with adjustment for age, body mass index, knee height, and total hip aBMD. RESULTS: In 5,245 women (mean age 72.6 years), a wider femoral neck with a more medial centroid position was associated with prevalent and incident osteophytic and composite RHOA phenotypes (P < 0.05). Increased neck width and centroid position were associated with osteophyte progression (both P < 0.05). No significant geometric associations with atrophic RHOA were found. CONCLUSION: Differences in proximal femoral bone geometry and spatial distribution of bone mass occur early in hip OA and predict prevalent, incident, and progressive osteophytic and composite phenotypes, but not the atrophic phenotype. These bone differences may reflect responses to loading occurring early in the natural history of RHOA.

Clinical performance of osteoporosis risk assessment tools in women aged 67 years and older.

UNLABELLED: Clinical performance of osteoporosis risk assessment tools was studied in women aged 67 years and older. Weight was as accurate as two of the tools to detect low bone density. Discriminatory ability was slightly better for the OST risk tool, which is based only on age and weight. INTRODUCTION: Screening performance of osteoporosis risk assessment tools has not been tested in a large, population-based US cohort. METHODS: We conducted a diagnostic accuracy analysis of the Osteoporosis Self-assessment Tool (OST), Osteoporosis Risk Assessment Instrument (ORAI), Simple Calculated Osteoporosis Risk Estimation (SCORE), and individual risk factors (age, weight or prior fracture) to identify low central (hip and lumbar spine) bone mineral density (BMD) in 7779 US women aged 67 years and older participating in the Study of Osteoporotic Fractures. RESULTS: The OST had the greatest area under the receiver operating characteristic curve (AUC 0.76, 95% CI 0.74, 0.77). Weight had an AUC of 0.73 (95% CI 0.72, 0.75), which was >or=AUC values for the ORAI, SCORE, age or prior fracture. Using cut points from the development papers, the risk tools had sensitivities >or=85% and specificities

Association between aortic calcification and total and cardiovascular mortality in older women.

OBJECTIVES: To determine whether older women with abdominal aortic calcification had a greater cardiovascular and all-cause mortality, as such data are limited in older adults. DESIGN: Prospective cohort study with a mean follow-up of 13 years. SETTING: Community-based sample with four US clinical centres. SUBJECTS: A total of 2056 women aged > or =65 years with abdominal aortic calcification assessed on baseline radiographs. MAIN OUTCOME MEASURE: Mortality rate (all, cardiovascular, cancer or other cause) adjudicated from death certificates and hospital records. RESULTS: The prevalence of abdominal aortic calcification increased with age, ranging from 60% at age 65-69 years to 96% at 85 years and older. Participants with aortic calcification were more likely to die during follow-up of any cause (47% vs. 27%) or a cardiovascular-specific cause (18% vs. 11%, both P < 0.001) than those without aortic calcification. In age-adjusted analyses, aortic calcification was associated with a greater rate of all-cause and cause-specific mortality (cardiovascular, cancer, and other, all P < or = 0.01). In analyses adjusted for age and cardiovascular risk factors, aortic calcification was associated with an increased rate of all-cause mortality (HR: 1.37, 95% CI: 1.15-1.64), and noncardiovascular noncancer mortality (HR: 1.57, 95% CI: 1.17-2.11). The associations between aortic calcification and cancer mortality (HR: 1.44, 95% CI: 1.00-2.08) or cardiovascular mortality (HR: 1.18, 95% CI: 0.88-1.57) showed a similar pattern without reaching statistical significance, but was slightly stronger for mortality from coronary heart disease (HR: 1.53, 95% CI: 0.91-2.56). CONCLUSIONS: Abdominal aortic calcification in older women is associated with increased mortality. Future research should examine potential mechanisms for this association.

Cognitive decline in women in relation to non-protein-bound oestradiol concentrations.

BACKGROUND: Previous studies have found no association between serum concentrations of total oestradiol and cognitive function, but these measurements may not reflect concentrations of hormone available to the brain. We tested the hypothesis that concentrations of non-protein-bound (free) and loosely bound (bioavailable) sex hormones are associated with cognitive function in older women. METHODS: We measured cognitive performance with a modified mini mental status examination (mMMSE) at baseline (1986-88) and 6 years later in 425 women (65 years or older). Concentrations of non-protein-bound and bioavailable oestradiol and total and non-protein-bound testosterone were measured by RIA in serum samples taken at baseline. FINDINGS: Initial cognitive scores did not differ by tertile of non-protein-bound oestradiol, bioavailable oestradiol, or testosterone. Cognitive impairment (a decrease of 3 points or more in mMMSE score) occurred in five (5%) of 94 women in the high tertile for non-protein-bound oestradiol and in 17 (16%) of 106 in the low tertile (odds ratio 0.3 [95% CI 0.1-0.8]). After adjustment for age, years of education, body-mass index, current oestrogen use, history of surgical menopause, and baseline mMMSE score, the odds ratio was 0.3 (0.1-0.9). The results were similar for bioavailable oestradiol (five [5%] vs 15 [15%]; adjusted odds ratio 0.3 [0.1-1.0]). There was no association between risk of cognitive impairment and serum testosterone. INTERPRETATION: Women with high serum concentrations of non-protein-bound and bioavailable oestradiol, but not testosterone, were less likely to develop cognitive impairment than women with low concentrations. This finding supports the hypothesis that higher concentrations of endogenous oestrogens prevent cognitive decline.

Association between serum fructosamine and mortality in elderly women: the study of osteoporotic fractures.

Serum fructosamine levels can be used to estimate long-term serum glucose values and can be measured in frozen serum. The authors examined whether fructosamine levels were associated with mortality in a cohort of 9,704 white women (> or = 65 years of age) recruited from September 1986 to October 1988 at four clinical centers in the United States. A random sample of women who had died during a mean of 6 years of follow-up (n = 55) was compared with randomly selected controls (n = 276, 54 of whom had died). Fructosamine assays were performed blinded to vital status. Hazard ratios with 95% confidence intervals were adjusted for age, clinical center, smoking, hypertension, and serum albumin and cholesterol levels. Each standard deviation (46 micromol) increase in fructosamine level was associated with a 1.3-fold (95% confidence interval (CI) 1.0-1.6, p = 0.04) increased rate of all-cause mortality, including a 1.5-fold (95% CI 1.0-2.1, p = 0.03) increase in cardiovascular disease mortality. Elevated fructosamine levels (>285 micromol/liter) were associated with a 4.3-fold (95% CI 1.6-12, p = 0.004) increased rate of cardiovascular mortality; in women without a history of diabetes, the hazard ratio was 4.6 (95% CI 1.3-16, p = 0.02). Fructosamine level, or another indicator of glycemia, should be included when the risk of cardiovascular disease among older patients is evaluated.

Comparison of the prevalence of knee osteoarthritis between the elderly Chinese population in Beijing and whites in the United States: The Beijing Osteoarthritis Study.

OBJECTIVE: To estimate the prevalence of radiographic and symptomatic knee osteoarthritis (OA) in a population-based sample of elderly subjects in Beijing, China and compare it with that reported in the Framingham (Massachusetts) OA Study. METHODS: We recruited a sample of persons age > or = 60, using door-to-door enumeration in randomly selected neighborhoods in Beijing. Subjects completed a home interview including questions on knee symptoms and a hospital examination including knee radiographs obtained during weight bearing. The protocol was identical to that used in the Framingham OA Study. A reader read intermingled Beijing and Framingham Study films to ensure high reliability. We defined a subject as having radiographic knee OA when the Kellgren/Lawrence grade was > or = 2 in at least 1 knee. Symptomatic knee OA was recorded as present when knee pain was reported and the symptomatic knee had radiographic OA. We estimated the prevalence of these entities in elderly subjects in Beijing and compared it with OA prevalence in Framingham, using an age-standardized prevalence ratio. RESULTS: Of 2,180 age-eligible Beijing subjects contacted, knee radiographs were obtained in 1,787 (82.0%). The prevalence of radiographic knee OA was 42.8% in women and 21.5% in men. Symptomatic knee OA occurred in 15.0% of women and 5.6% of men. Compared with women of the same age in Framingham, women in Beijing had a higher prevalence of radiographic knee OA (prevalence ratio 1.45, 95% confidence interval 1.31-1.60) and of symptomatic knee OA (prevalence ratio 1.43, 95% confidence interval 1.16-1.75). The prevalence of knee OA in Chinese men was similar to that in their white US counterparts (for radiographic OA, prevalence ratio 0.90; for symptomatic OA, prevalence ratio 1.02). CONCLUSION: Using identical methods and definitions to evaluate the prevalence of OA across populations, we found, surprisingly, that older Chinese women have a higher prevalence of knee OA than women in Framingham, Massachusetts. The prevalence in men was comparable. Possible explanations for these differences range from genetic differences to heavy physical activity among Chinese.