Trajectories of femoral neck strength in relation to the final menstrual period in a multi-ethnic cohort.

UNLABELLED: The purpose of this study was to describe the evolution of femoral neck strength relative to load across the menopause transition. It declined significantly over the 10 years bracketing the final menstrual period, and the rate of decline was modified by body mass index, race/ethnicity, and smoking status. INTRODUCTION: Composite indices of femoral neck strength, which integrate dual energy X-ray absorptiometry (DXA)-derived bone mineral density and bone size with body size, are inversely associated with hip fracture risk. Our objective was to describe longitudinal trajectories of the strength indices across the menopausal transition. METHODS: Data came from the Study of Women's Health Across the Nation; participants were pre- or early peri-menopausal, ages 42-53 at baseline, and were followed up for 9.1 ± 1.8 years. Composite indices of femoral neck strength in different failure modes (compression, bending, and impact) were created in 921 women who had three or more hip DXA scans and had definable final menstrual period (FMP) dates. We used mixed effects models to fit piecewise linear growth curves to the baseline-normalized strength indices as a function of time to/after the FMP. RESULTS: Compression and impact strength indices did not decline until 1 year prior to the FMP, and declined rapidly thereafter, with some slowing of decline 1 year after the FMP. Bending strength index increased slightly until 2 years prior to the FMP, then plateaued, and began to decline at the FMP. Mean decline in strength indices over 10 years was 6.9 % (compression), 2.5 % (bending), and 6.8 % (impact). Women with higher body mass index had larger declines in two of the three indices. Other major modifiers of rates of decline were race/ethnicity and smoking status. CONCLUSIONS: Femoral neck strength relative to load declines significantly during the menopausal transition, with declines commencing 1 to 2 years prior to the FMP.

A comparison of DXA and CT based methods for estimating the strength of the femoral neck in post-menopausal women.

UNLABELLED: The study goal was to compare simple two-dimensional (2D) analyses of bone strength using dual energy x-ray absorptiometry (DXA) data to more sophisticated three-dimensional (3D) finite element analyses using quantitative computed tomography (QCT) data. DXA- and QCT-derived femoral neck geometry, simple strength indices, and strength estimates were well correlated. INTRODUCTION: Simple 2D analyses of bone strength can be done with DXA data and applied to large data sets. We compared 2D analyses to 3D finite element analyses (FEA) based on QCT data. METHODS: Two hundred thirteen women participating in the Study of Women's Health Across the Nation (SWAN) received hip DXA and QCT scans. DXA BMD and femoral neck diameter and axis length were used to estimate geometry for composite bending (BSI) and compressive strength (CSI) indices. These and comparable indices computed by Hip Structure Analysis (HSA) on the same DXA data were compared to indices using QCT geometry. Simple 2D engineering simulations of a fall impacting on the greater trochanter were generated using HSA and QCT femoral neck geometry; these estimates were benchmarked to a 3D FEA of fall impact. RESULTS: DXA-derived CSI and BSI computed from BMD and by HSA correlated well with each other (R=0.92 and 0.70) and with QCT-derived indices (R=0.83-0.85 and 0.65-0.72). The 2D strength estimate using HSA geometry correlated well with that from QCT (R=0.76) and with the 3D FEA estimate (R=0.56). CONCLUSIONS: Femoral neck geometry computed by HSA from DXA data corresponds well enough to that from QCT for an analysis of load stress in the larger SWAN data set. Geometry derived from BMD data performed nearly as well. Proximal femur breaking strength estimated from 2D DXA data is not as well correlated with that derived by a 3D FEA using QCT data.

Renal function and nonvertebral fracture risk in multiethnic women: the Women's Health Initiative (WHI).

UNLABELLED: To examine the association between renal function and fracture in multiethnic women, we studied postmenopausal women enrolled in the Women's Health Initiative. Postmenopausal White women with mild renal dysfunction were at increased risk of nonvertebral fracture; this association was at least partially explained by effects of renal dysfunction on chronic inflammation. Reduced renal function appeared to increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups. INTRODUCTION: The purpose of this study was to determine whether renal function is associated with fracture risk within racial/ethnic groups. METHODS: A nested case-control study was conducted among 93,673 postmenopausal women; incident nonvertebral fractures were identified in 362 Black, 183 Hispanic, 110 Asian, and 45 American-Indian women. A random sample of 395 White women with incident nonvertebral fracture was chosen. One nonfracture control for each case was selected (matched on age, race/ethnicity, and blood draw date). Cystatin C levels were measured using baseline serum, and estimated glomerular filtration rate calculated (eGFR(cys-c)). RESULTS: Each 1 SD increase in cystatin C was associated with a 1.2-fold increased risk of fracture among White women (adjusted odds ratios [OR], 1.23; 95% confidence intervals [CI], 1.04-1.46). The OR of fracture was 1.16 (95% CI, 0.85-1.58) among women with eGFR(cys-c) 60-90 mL/min/1.73 m(2) and 2.46 (95% CI, 1.16-5.21) among those with eGFR(cys-c) <60 mL/min/1.73 m(2) compared to the reference group (eGFR(cys-c) >90 mL/min/1.73 m(2)) (p trend = 0.05). The association was reduced after adjustment for cytokine TNFα soluble receptors (OR, 1.62; 95% CI, 0.59-4.46 for eGFR(cys-c) <60 mL/min/1.73 m(2)). Among Blacks, there was an association between cystatin C and fracture risk (OR per 1 SD increase, 1.15; 95% CI, 1.00-1.32); after adjustment, this association was only modestly attenuated, but no longer statistically significant. There was no evidence of significant associations among Hispanic, Asian, or American-Indian women. CONCLUSION: Postmenopausal White women with mild renal dysfunction are at increased risk of nonvertebral fracture. Effects of renal function on chronic inflammation may mediate this association. Reduced renal function may increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups.

Ethnic differences in composite indices of femoral neck strength.

UNLABELLED: Bone mineral density does not explain race/ethnicity differences in hip fracture risk. In this study, we demonstrated that race/ethnicity differences in composite hip strength indices were consistent with documented race/ethnicity differences in hip fracture risk, suggesting that unlike bone density, the composite indices may represent ethnicity-independent measures of bone strength. INTRODUCTION: African-American and Asian women have lower risks of hip fracture than Caucasian women, but such racial/ethnic variation in hip fracture risk cannot be explained by bone mineral density (BMD). The composite indices of femoral neck strength integrate femoral neck and body size with BMD and predict hip fracture risk in Caucasian women. We hypothesize that unlike race/ethnic differences in BMD, race/ethnic differences in the composite strength indices would be consistent with race/ethnic differences in hip fracture risk. METHODS: We studied a community-based sample of Caucasian (n = 968), African-American (n = 512), Chinese (n = 221), and Japanese (n = 239) women, premenopausal or in early perimenopause, from the Study of Women's Health Across the Nation. RESULTS: Unadjusted indices were similar in Caucasian and African-American women but higher in Asian women. After adjusting for age, body mass index, and menopause status, all three minority groups had higher composite strength indices than Caucasian women. Foreign-born Japanese women had higher unadjusted and adjusted composite strength indices than US-born Japanese women, but such differences by nativity were not observed in Chinese women. CONCLUSION: We concluded that composite strength indices have the potential to explain racial/ethnic differences in hip fracture risk, suggesting that composite strength indices may represent ethnicity-independent measures of bone strength. This contention needs to be verified by further research on the fracture predictive ability of composite strength indices in multi-ethnic longitudinal cohorts.

Veterans Aging Cohort Study (VACS) meeting summary.

The Veterans Aging Cohort Study (VACS) planning meeting was the first of a series of organizational meetings and VA-sponsored conference calls designed to build the scientific foundation and methodological infrastructure for a multisite, longitudinal study of HIV and chronic disease outcomes among aging veterans. More specifically, it served as a consensus conference to determine scientific priorities, develop hypotheses, and to assemble working groups and committees to outline the specific methodological approaches needed. Scientists, physicians from 20 VA clinical facilities in the United States, community members, and experts in the fields of immunology, cancer, sociology, aging, cognition, psychiatry and mental health, epidemiology, large database analysis, and health services research gathered for an intense, 2-day meeting held in Pittsburgh, PA, November 8-9, 2000.

Behavioral risk factors for disease and preventive health practices among lesbians.

OBJECTIVES: This study compared the prevalence of health behaviors among lesbians and in the general population of women. METHODS: We used a cross-sectional community-based survey of 1010 self-identified lesbians 18 years or older. RESULTS: Compared with the general population of women, lesbians were more likely to report cigarette use, alcohol use, and heavy alcohol use. A higher percentage of lesbians were categorized as overweight, and lesbians were more likely to participate in vigorous physical activity. They were less likely to report having had a Papanicolaou test within the past 2 years but more likely to report ever having had a mammogram. CONCLUSIONS: While there may be differences in health behaviors between lesbians and the general population of women, how these differences influence the risk of subsequent disease is unknown.

Vitamin D receptor translation initiation codon polymorphism and markers of osteoporotic risk in older African-American women.

A polymorphism at the first of two potential translation initiation codons in the vitamin D receptor (VDR) gene defined by the FokI restriction endonuclease has been associated with reduced bone mineral density (BMD) among Caucasian, Asian, and Mexican-American women. We tested the hypothesis that the FokI polymorphism is related to markers of osteoporotic risk in 104 community-dwelling African-American women aged 65 years and older. Six percent of the African-American women had the ff genotype, 32% were heterozygous, and 63% had the FF genotype. FokI genotype frequencies did not differ from Hardy-Weinberg expectations. Hip and calcaneal BMD, calcaneal ultrasound attenuation and hip geometry from pelvic radiographs did not differ significantly by FokI genotypes or between women with and without the rare FokI allele. There was also no association between the FokI polymorphism and biochemical markers of bone turnover or fractional calcium absorption. We conclude that the VDR start codon polymorphism does not have a major influence on osteoporotic risk in older African-American women.

Familial resemblance of bone mineral density (BMD) and calcaneal ultrasound attenuation: the BMD in mothers and daughters study.

The familial resemblance in bone mineral density (BMD) and calcaneal broadband ultrasound attenuation (BUA) was examined in 207 mother-daughter pairs. Mothers were participants in the Study of Osteoporotic Fractures. Three groups of daughters were recruited based on their maternal history of "fracture," "low BMD" without fracture (< 0.58 g/cm2, t-score < -2.5), and "normal BMD" without fracture (> 0.67 g/cm2, t-score > -1.6). Data on other potentially heritable factors known to influence BMD and BUA were also collected. BMD was measured at the hip, spine, whole body, and calcaneus. Calcaneal BUA was assessed using the Walker-Sonix UBA 575. Total hip and femoral neck BMD were significantly lower (5.0-8.0%, p < 0.017) among daughters, in particular premenopausal daughters, of mothers with established osteoporosis ("fracture" or "low BMD") compared with daughters of mothers at lower risk of osteoporosis ("normal BMD"). BUA did not differ across daughter groups. Lifestyle characteristics (dietary calcium, smoking, physical activity) were not highly correlated in mothers and daughters. Height, weight, and body composition were significantly correlated within mother-daughter pairs and could be a potential mechanism by which BMD is inherited. Among pre- and postmenopausal daughters, heritability estimates ranged from 50-63% and 34-48%, respectively. Heritability for calcaneal BUA (53%) was evident among postmenopausal daughters only. In conclusion, familial association in BMD was strongest among premenopausal daughters. Estimates of heritability suggest that maternal BMD and BUA are important independent predictors of BMD and BUA among daughters, reinforcing the importance of prevention and early intervention among women with a positive family history of osteoporosis.

Vitamin D receptor gene polymorphisms, bone turnover, and rates of bone loss in older African-American women.

Bone mineral density (BMD) is under genetic control. Some studies in Caucasian and Asian women suggest that polymorphisms in the vitamin D receptor (VDR) gene are associated with BMD and the rate of postmenopausal bone loss. We determined if similar associations exist in 101 African-American women aged 65 years and older (71 +/- 5 years, mean +/- SD). We also examined the relation between VDR genotype and fractional 45Ca absorption and markers of bone formation (osteocalcin) and resorption (N-telopeptides) in these women. BMD was measured at the proximal femur and whole body at baseline and after 1.9 +/- 0.4 years (femur only) on a Hologic QDR-2000 densitometer using dual-energy X-ray absorptiometry. Calcaneal BMD was measured with single x-ray absorptiometry. VDR gene polymorphisms were defined by the endonucleases BsmI, ApaI, and TaqI. These polymorphisms were not associated with BMD at any skeletal site or with markers of bone turnover. There was a significant interaction between age and VDR genotype where the oldest women (> 70 years) with the TT genotype experienced greater hip bone loss than women with the TT genotype (-2.1%/year vs. -0.4%/year, respectively), whereas heterozygous women experienced an intermediate rate of bone loss (-1.3%/year). Women homozygous for the B allele had 14% lower fractional 45Ca absorption compared with women homozygous for the b allele, although this difference was not statistically significant (p = 0.08). We conclude that VDR gene polymorphisms are not associated with BMD or indices of bone turnover in this population of older African-American women. However, DNA sequence variation in the VDR gene or a nearby locus may influence intestinal calcium transport and the rate of postmenopausal bone loss in African-American women.

Calcaneal ultrasound attenuation in older African-American and Caucasian-American women.

The lower fracture rates among African-American women relative to Caucasian women may reflect their higher bone mass. However, bone mass is not the only determinant of bone strength: the quality and microarchitecture of the bone are also important. Quantitative ultrasound is believed to measure properties of bone strength that are independent of bone mass. To test the hypothesis that there are racial differences in quantitative ultrasound measures of bone, we recruited 154 African-American women age > or = 65 years. A random sample of 300 Caucasian women participating in the Study of Osteoporotic Fractures in Pittsburgh, Pennsylvania, was chosen for comparison. The Walker Sonix UBA 575+ was used to measure calcaneal broadband ultrasonic attenuation (BUA). Duplicate BUA measurements were obtained with a reproducibility of 5%. We measured bone mineral density (BMD) of the hip and calcaneus using single (calcaneus) or dual (hip) energy X-ray absorptiometry. The correlation between BUA and calcaneal BMD was similar in Caucasians (r = 0.66, p < 0.001) and African-Americans (r = 0.58, p < 0.001). Age-adjusted BUA (dB/MHz) was higher among the African-American women than Caucasian women (69.1 and 66.2, respectively), but these differences were not statistically significant, (p = 0.12). Adjustment for calcaneal BMD completely attenuated the racial differences in BUA. BMD at the femoral neck and calcaneus was higher among the African-American women, even after adjusting for age, height and weight. In conclusion, our results suggest that racial differences in rates of fracture cannot be explained by differences in bone quality as assessed by ultrasound attenuation.

Physical activity and its association with plasma lipids and lipoproteins in elderly women.

The association of physical activity to plasma lipid and lipoprotein levels was examined cross-sectionally in 634 elderly, postmenopausal women whose mean age was 70.7 years. Leisure-time physical activity in kilocalories per week was assessed by the Paffenbarger Questionnaire, a composite index of sports/recreation, stair climbing, and walking. Subjects were categorized by tertile of kilocalories per week from total physical activity, number of flights of stairs climbed, and number of blocks walked. After adjustment for age, body mass index, education, and oral estrogen use, no significant differences were noted in total cholesterol, high-density-lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, low-density-lipoprotein cholesterol (LDL-C), or triglycerides across tertile of total activity or number blocks walked. Total cholesterol was significantly different across tertile of number of flights of stairs climbed (P < 0.05), and only a borderline association was noted with LDL-C (P < 0.08). The study suggests that leisure-time physical activity, as measured by the Paffenbarger Questionnaire, is not associated with a favorable lipid profile in elderly, postmenopausal women. Failure to find an association may reflect the relatively small number of women who engaged in moderate- or high-intensity activity.