A bone resorption marker as predictor of rate of change in femoral neck size and strength during the menopause transition.

We assessed whether a bone resorption marker, measured early in the menopause transition (MT), is associated with change in femoral neck size and strength during the MT. Higher levels of bone resorption were associated with slower increases in femoral neck size and faster decreases in femoral neck strength. PURPOSE: Composite indices of the femoral neck's ability to withstand compressive (compression strength index, CSI) and impact (impact strength index, ISI) forces integrate DXA-derived femoral neck width (FNW), bone mineral density (BMD), and body size. During the menopause transition (MT), FNW increases, and CSI and ISI decrease. This proof-of-concept study assessed whether a bone resorption marker, measured early in the MT, is associated with rates of change in FNW, CSI and ISI during the MT. METHODS: We used previously collected bone resorption marker (urine collagen type I N-telopeptide [U-NTX]) and femoral neck strength data from 696 participants from the Study of Women's Health Across the Nation (SWAN), a longitudinal study of the MT in a multi-ethnic cohort of community-dwelling women. RESULTS: Adjusted for MT stage (pre- vs. early perimenopause), age, body mass index (BMI), bone resorption marker collection time, and study site in multivariable linear regression, bone resorption in pre- and early perimenopause was not associated with transmenopausal decline rate in femoral neck BMD. However, each standard deviation (SD) increase in bone resorption level was associated with 0.2% per year slower increase in FNW (p = 0.03), and 0.3% per year faster declines in CSI (p = 0.02) and ISI (p = 0.01). When restricted to women in early perimenopause, the associations of bone resorption with change in FNW, CSI, and ISI were similar to those in the full sample. CONCLUSIONS: Measuring a bone resorption marker in pre- and early perimenopause may identify women who will experience the greatest loss in bone strength during the MT.

Bone mineral density changes among women initiating blood pressure lowering drugs: a SWAN cohort study.

SUMMARY: We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women's Health Across the Nation. Thiazide users had a slower decline in BMD compared to nonusers, while decline among ACE inhibitor and beta blocker users were similar to rates in nonusers. INTRODUCTION: Several blood pressure lowering drugs may affect bone mineral density (BMD), leading to altered fracture risk. We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women's Health Across the Nation. METHODS: We conducted a propensity score matched cohort study. Women were initiators of ACE inhibitors (ACEi), beta-blockers (BB), or thiazide diuretics (THZD). Their annualized BMD changes during the 14 years of observation were compared with nonusers. RESULTS: Among the 2312 eligible women, we found 69 ACEi, 71 BB, and 74 THZD users who were matched by a propensity score with the same number of nonusers. THZD users had a slower annual percent decline in BMD compared to nonusers at the femoral neck (FN) (-0.28% vs -0.88%; p = 0.008) and the spine (-0.74% vs -1.0%; p = 0.34), albeit not statistically significant. Annual percent changes in BMD among ACEi and BB users were similar to rates in nonusers. In comparison with BB, THZD use was associated with a trend toward less annualized BMD loss at the spine (-0.35% vs -0.60%; p = 0.08) and a similar trend at the FN (-0.39% vs -0.64%; p = 0.08); in comparisons with ACEi, THZD was also associated with less loss at the FN (-0.48% vs -0.82%; p = 0.02), but not at the spine (-0.40% vs -0.56%; p = 0.23). CONCLUSIONS: Neither ACEi nor BB was associated with improvements in BMD. THZD use was associated with less annualized loss of BMD compared with nonusers, as well as compared with ACEi and BB.

Adult bone strength of children from single-parent families: the Midlife in the United States Study.

UNLABELLED: Bone health may be negatively impacted by childhood socio-environmental circumstances. We examined the independent associations of single-parent childhood and parental death or divorce in childhood with adult bone strength indices. Longer exposure to a single-parent household in childhood was associated with lower bone strength in adulthood. INTRODUCTION: Because peak bone mass is acquired during childhood, bone health may be negatively impacted by childhood socio-environmental disadvantage. The goal of this study was to determine whether being raised in a single-parent household is associated with lower bone strength in adulthood. METHODS: Using dual-energy X-ray absorptiometry data from 708 participants (mean age 57 years) in the Midlife in the United States Biomarker Project, we examined the independent associations of composite indices of femoral neck bone strength relative to load (in three failure modes: compression, bending, and impact) in adulthood with the experience of single-parent childhood and parental death or divorce in childhood. RESULTS: After adjustment for gender, race, menopause transition stage, age, and body mass index, each additional year of single-parent childhood was associated with 0.02 to 0.03 SD lower indices of adult femoral neck strength. In those with 9-16 years of single-parent childhood, the compression strength index was 0.41 SD lower, bending strength index was 0.31 SD lower, and impact strength index was 0.25 SD lower (all p values < 0.05). In contrast, parental death or divorce during childhood was not by itself independently associated with adult bone strength indices. The magnitudes of these associations were unaltered by additional adjustment for lifestyle factors and socioeconomic status in childhood and adulthood. CONCLUSIONS: Independent of parental death or divorce, growing up in a single-parent household is associated with lower femoral neck bone strength in adulthood, and this association is not entirely explained by childhood or adult socioeconomic conditions or lifestyle choices.

Bleeding patterns during the menopausal transition in the multi-ethnic Study of Women's Health Across the Nation (SWAN): a prospective cohort study.

OBJECTIVE: Previous studies describing menses duration and heaviness of flow during the menopausal transition (MT) have been short in duration and limited to white women. We estimated the frequency of and risk factors for prolonged bleeding, spotting and heavy bleeding during the MT in an ethnically diverse population. DESIGN: Prospective community-based cohort study. SETTING USA: southeastern Michigan, northern California and Los Angeles, California. POPULATION: A total of 1320 midlife women who participated in the Study of Women's Health Across the Nation (SWAN) Menstrual Calendar Substudy. Participants included African-American, white, Chinese, and Japanese women. METHODS: Women completed daily menstrual calendars from 1996 to 2006, and provided information on hormone therapy, smoking and physical activity. Annual measures included height and weight. Kaplan-Meier survival analysis and multivariable regression were used to analyse the data. MAIN OUTCOME MEASURES: Menses of 10+ days, spotting of 6+ days, heavy bleeding of 3+ days. RESULTS: At least three occurrences of menses 10+ days was reported by 77.7% (95% confidence interval [95% CI] 56.7-93.2), of 6+ days of spotting by 66.8% (95% CI 55.2-78.0) and of 3+ days of heavy bleeding by 34.5% (95% CI 30.2-39.2) of women. Menses of 10+ days, 6+ days of spotting, and 3+ days of heavy bleeding were associated with MT stage, uterine fibroids, hormone use and ethnicity. Body mass index was associated with 3+ days of heavy bleeding. CONCLUSIONS: These data provide clinicians and women with important information about the expected frequency of prolonged and heavy bleeding and spotting during the menopausal transition that may facilitate clinical decision making.

Socioeconomic status in relation to incident fracture risk in the Study of Women's Health Across the Nation.

UNLABELLED: We examined baseline and annual follow-up data (through annual follow-up visit 9) from a cohort of 2,234 women aged 42 to 52 years at baseline. Independent of financial status, higher educational level was associated with lower fracture incidence among non-Caucasian women but not among Caucasian women. INTRODUCTION: This study was conducted to determine the associations of education and income with fracture incidence among midlife women over 9 years of follow-up. METHODS: We examined baseline and annual follow-up data (through annual follow-up visit 9) from 2,234 participants of the Study of Women's Health Across the Nation, a cohort of women aged 42 to 52 years at baseline. We used Cox proportional hazards regression models to examine the associations of socioeconomic predictors (education, family-adjusted poverty-to-income ratio, and difficulty paying for basics) with time to first incident nontraumatic, nondigital, noncraniofacial fracture. RESULTS: Independent of family-adjusted poverty-to-income ratio, higher educational level was associated with decreased time to first incident fracture among non-Caucasian women but not among Caucasian women (p(interaction) 0.02). Compared with non-Caucasian women who completed no more than high school education, non-Caucasian women who attained at least some postgraduate education had 87% lower rates of incident nontraumatic fracture (adjusted hazard ratio 0.13, 95% confidence interval [CI] 0.03-0.60). Among non-Caucasian women, each additional year of education was associated with a 16% lower odds of nontraumatic fracture (adjusted odds ratio 0.84, 95% CI 0.73-0.97). Income, family-adjusted poverty-to-income ratio, and degree of difficulty paying for basic needs were not associated with time to first fracture in Caucasian or non-Caucasian women. CONCLUSIONS: Among non-Caucasian midlife women, higher education, but not higher income, was associated with lower fracture incidence. Elucidation of the mechanisms underlying the possible protective effects of higher educational level on nontraumatic fracture incidence may allow us to better target individuals at risk of future fracture.

Marital histories, marital support, and bone density: findings from the Midlife in the United States Study.

UNLABELLED: We examined the association between marital life history and bone mineral density (BMD) in a national sample from the US. In men, being stably married was independently associated with better lumbar spine BMD, and in women, more spousal support was associated with better lumbar spine BMD. INTRODUCTION: Adult bone mass may be influenced by stressors over the life course. We examined the association between marital life history and bone mineral density (BMD) net socioeconomic and behavioral factors known to influence bone mass. We sought evidence for a gender difference in the association between marital history and adult BMD. METHODS: We used data from 632 adult participants in the Midlife in the United States Study to examine associations between marital history and BMD, stratified by gender, and adjusted for age, weight, menopausal stage, medication use, childhood socioeconomic advantage, adult financial status, education, physical activity, smoking, and alcohol consumption. RESULTS: Compared to stably married men, men who were currently divorced, widowed, or separated, men who were currently married but previously divorced, widowed, or separated, and never married men had 0.33 (95% CI: 0.01, 0.65), 0.36 (95% CI: 0.10, 0.83), and 0.53 (95% CI: 0.23, 0.83) standard deviations lower lumbar spine BMD, respectively. Among men married at least once, every year decrement in age at first marriage (under age 25) was associated with 0.07 SD decrement in lumbar spine BMD (95% CI: 0.002, 0.13). In women, greater support from the spouse was associated with higher lumbar spine BMD. CONCLUSIONS: Our findings suggest that marriage before age 25 and marital disruptions are deleterious to bone health in men, and that marital quality is associated with better bone health in women.

Physical activity as determinant of femoral neck strength relative to load in adult women: findings from the hip strength across the menopause transition study.

UNLABELLED: Our objective was to examine associations of physical activity in different life domains with peak femoral neck strength relative to load in adult women. Greater physical activity in each of the domains of sport, active living, home, and work was associated with higher peak femoral neck strength relative to load. INTRODUCTION: Our objective was to examine the associations of physical activity in different life domains with peak femoral neck strength relative to load in adult women. Composite indices of femoral neck strength integrate body size with femoral neck size and bone mineral density to gauge bone strength relative to load during a fall, and are inversely associated with incident fracture risk. METHODS: Participants were 1,919 pre- and early perimenopausal women from the Study of Women's Health Across the Nation. Composite indices of femoral neck strength relative to load in three failure modes (compression, bending, and impact) were created from hip dual-energy X-ray absorption scans and body size. Usual physical activity within the past year was assessed with the Kaiser Physical Activity Survey in four domains: sport, home, active living, and work. We used multiple linear regression to examine the associations. RESULTS: Greater physical activity in each of the four domains was independently associated with higher composite indices, adjusted for age, menopausal transition stage, race/ethnicity, Study of Women's Health Across the Nation study site, smoking status, smoking pack-years, alcohol consumption level, current use of supplementary calcium, current use of supplementary vitamin D, current use of bone-adverse medications, prior use of any sex steroid hormone pills or patch, prior use of depo-provera injections, history of hyperthyroidism, history of previous adult fracture, and employment status: standardized effect sizes ranged from 0.04 (p < 0.05) to 0.20 (p < 0.0001). CONCLUSIONS: Physical activity in each domain examined was associated with higher peak femoral neck strength relative to load in pre- and early perimenopausal women.

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.

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.

Socioeconomic status, race, and bone turnover in the Midlife in the US Study.

UNLABELLED: Among a group of 940 US adults, economic adversity and minority race status were associated with higher serum levels of markers of bone turnover. These results suggest that higher levels of social stress may increase bone turnover. INTRODUCTION: To determine socioeconomic status (SES) and race differences in levels of bone turnover. METHODS: Using data from the Biomarker Substudy of the Midlife in the US (MIDUS) study (491 men, 449 women), we examined cross-sectional associations of SES and race with serum levels of bone turnover markers (bone-specific alkaline phosphatase [BSAP], procollagen type I N-terminal propeptide [PINP], and N-telopeptide [Ntx]) separately in men and women. Linear multivariable regression was used to control for body weight, menopausal transition stage, and age. RESULTS: Among men, low family poverty-to-income ratio (FPIR) was associated with higher turnover, but neither education nor race was associated with turnover. Men with FPIR <3 had 1.808 nM BCE higher Ntx (P = 0.05), 3.366 U/L higher BSAP (P = 0.02), and 7.066 higher PINP (P = 0.02). Among women, neither education nor FPIR was associated with bone turnover, but Black women had 3.688 nM BCE higher Ntx (P = 0.001), 5.267 U/L higher BSAP (P = 0.005), and 11.906 µg/L higher PINP (P = 0.008) compared with non-Black women. CONCLUSIONS: Economic adversity was associated with higher bone turnover in men, and minority race status was associated with higher bone turnover in women, consistent with the hypothesis that higher levels of social stresses cause increased bone turnover. The magnitude of these associations was comparable to the effects of some osteoporosis medications on levels of turnover.

The reliability and validity of three non-radiological measures of thoracic kyphosis and their relations to the standing radiological Cobb angle.

UNLABELLED: Hyperkyphosis is implicated in a mounting list of negative outcomes, including higher mortality. Hyperkyphosis research is hindered due to difficulties inherent in its measurement. By showing that three clinical measures of kyphosis are suitable for use in large scale, longitudinal, hyperkyphosis studies, we will facilitate much needed research in this field. INTRODUCTION: The objective of this study is to describe the reliability of three non-radiological kyphosis measures (Debrunner kyphosis angle, flexicurve kyphosis index, and flexicurve kyphosis angle) and their validity compared to the Cobb angle and to approximate a Cobb angle from non-radiological kyphosis measures. METHODS: We analyzed data from 113 participants aged ≥ 60 years with kyphosis angle ≥ 40°. Cobb angle was measured on a standing lateral thoracolumbar radiograph using bounds at T4 and T12. Non-radiological measures of kyphosis were made three times by a single rater and a 4th time by a blinded second rater. RESULTS: Intra- and inter-rater reliabilities for non-radiological assessments were high (intra-class correlations of 0.96 to 0.98) and did not differ from each other. Pearson correlations, estimating validity, ranged from 0.62 to 0.69 and did not differ. The Debrunner angle was close to the Cobb angle, with scaling factor of 1.067 and an offset of 5°. The Flexicurve kyphosis angle had to be scaled by 1.53 to obtain the equivalent Cobb angle. The scaling factor for the Flexicurve kyphosis index to Cobb angle was 315, with an offset of 5°. Compared to the measured Cobb angle, Cobb angles predicted using the non-radiological measures had similar magnitude errors (standard deviations of the differences ranging between 10.24 and 11.26). CONCLUSIONS: Each non-radiological measurement had similar reliability and validity. Low cost, ease of use, and robustness to variations in spine contour argue for the Flexicurve in longitudinal kyphosis assessments. The approximate conversion factors provided will permit translation of non-radiological measures to Cobb angles.

Menopausal bone changes and incident fractures in diabetic women: a cohort study.

SUMMARY: The purpose of this study was to evaluate the rate of bone loss and incident fractures in women with diabetes mellitus (DM) across menopause. During menopause, DM women experienced bone mineral density (BMD) loss that was faster at hip and slower at spine and had a higher risk of fractures, perhaps because of their earlier menopause. The increasing DM epidemic will contribute to higher fracture burden. INTRODUCTION: Women with DM have a higher risk of fractures independent of age, body mass index (BMI), and BMD. Our objective is to evaluate if women with DM experience greater bone loss and more fractures across menopause. METHODS: Two thousand one hundred seventy one women, aged 42 to 52 years at baseline (1996), enrolled in the Study of Women's Health Across the Nation (SWAN), a prospective study, with 8 years of annual follow up. One thousand three hundred forty six (62%) completed annual visit 7 (2004). Women with baseline fasting blood glucose level of ≥126 mg/dl and those being treated for diabetes were designated as DM. Annual assessment of menopausal stage, BMD, and urinary N-telopeptide (NTx) were carried out. Rate of change in BMD across menopause and annual self-report data for risk of incident fractures by DM status were determined. RESULTS: Despite higher baseline BMD at hip (p = <0.001), and lumbar spine (p = <0.001), rate of decline in BMD was faster at hip (ß = -0.45 vs. -0.11 gm/cm(2)/year, p = <0.001) for DM women, compared to non-DM. However, lumbar spine bone loss was slower in women with DM as compared to non-DM women (ß = 0.04 vs. -0.25 gm/cm(2)/year, p = 0.004). DM women experienced menopause 3 years earlier than non-DM women (p = 0.002), and age adjusted incident fractures were two fold higher in women with DM compared to non-DM (RR = 2.20, 95% CI: 1.26-3.85, p = <0.006). CONCLUSIONS: BMD loss is greater in hip and slower at spine in DM women during menopausal transition. Women with DM have a higher risk of fractures, perhaps because of their earlier menopause.

Effects of the menopause transition and hormone use on cognitive performance in midlife women.

BACKGROUND: There is almost no longitudinal information about measured cognitive performance during the menopause transition (MT). METHODS: We studied 2,362 participants from the Study of Women's Health Across the Nation for 4 years. Major exposures were time spent in MT stages, hormone use prior to the final menstrual period, and postmenopausal current hormone use. Outcomes were longitudinal performance in three domains: processing speed (Symbol Digit Modalities Test [SDMT]), verbal memory (East Boston Memory Test [EBMT]), and working memory (Digit Span Backward). RESULTS: Premenopausal, early perimenopausal, and postmenopausal women scored higher with repeated SDMT administration (p < or = 0.0008), but scores of late perimenopausal women did not improve over time (p = 0.2). EBMT delayed recall scores climbed during premenopause and postmenopause (p < or = 0.01), but did not increase during early or late perimenopause (p > or = 0.14). Initial SDMT, EBMT-immediate, and EBMT-delayed tests were 4%-6% higher among prior hormone users (p < or = 0.001). On the SDMT and EBMT, compared to the premenopausal referent, postmenopausal current hormone users demonstrated poorer cognitive performance (p < or = 0.05) but performance of postmenopausal nonhormone users was indistinguishable from that of premenopausal women. CONCLUSIONS: Consistent with transitioning women's perceived memory difficulties, perimenopause was associated with a decrement in cognitive performance, characterized by women not being able to learn as well as they had during premenopause. Improvement rebounded to premenopausal levels in postmenopause, suggesting that menopause transition-related cognitive difficulties may be time-limited. Hormone initiation prior to the final menstrual period had a beneficial effect whereas initiation after the final menstrual period had a detrimental effect on cognitive performance.

Factors related to declining luteal function in women during the menopausal transition.

CONTEXT: Reproductive hormones are incompletely characterized during the menopause transition (MT). HYPOTHESIS: Increased anovulation and decreased progesterone accompany progress through the MT. DESIGN: The Daily Hormone Study (DHS) of the Study of Women's Health Across the Nation (SWAN) included 848 women aged 43-53 yr at baseline who collected daily urine for one cycle or up to 50 d annually for 3 yr. MAIN OUTCOME MEASURES: LH, FSH, estrone conjugates, and pregnanediol glucuronide levels were assessed. Cycles were classified by presumed luteal (ovulatory) status and bleeding. Hormones were related to time in study, age, menopausal status, and selected variables. RESULTS: Ovulatory-appearing cycles declined from 80.9% at baseline to 64.7% by the third assessment (H3). Cycles presumed anovulatory and not ending with bleeding by 50 d (anovulatory/nonbleeding) increased from 8.4 to 24% by H3 and were associated with progress to early perimenopause [odds ratio (OR) = 2.66; confidence interval (CI) = 1.17-6.04] or late perimenopause (OR = 56.21; CI = 18.79-168.12; P < 0.0001), African-American ethnicity (OR = 1.91; CI = 1.06-3.43), and less than high school education (OR = 3.51; CI = 1.62-7.62). Anovulatory cycles ending with bleeding remained at about 10% from baseline to H3; compared with ovulatory cycles, they were associated with obesity (OR = 4.68; CI = 1.33-16.52) and more than high school education (OR = 2.12; CI = 1.22-3.69; P = 0.02). Serum estradiol in both the highest and lowest categories was associated with anovulatory/nonbleeding collections. Pregnanediol glucuronide decreased 6.6% for each year on study. Insulin sensitivity measures did not relate strongly to menstrual cycle hormones. CONCLUSIONS: Anovulation without bleeding represents progression of the MT. A small but detectable decrease in luteal progesterone excretion occurs as women progress through the MT.

Bone mineral density and adjuvant therapy in breast cancer survivors.

Compared to mean values from a US database, premenopausal breast cancer survivors (BCS) had significantly higher whole body bone mineral density (BMD) compared to age and ethnicity matched referents; higher whole body BMD was present in all premenopausal BCS, including those who received chemotherapy, tamoxifen+chemotherapy, or no adjuvant therapy. Postmenopausal BCS who had received no adjuvant therapy also had higher whole body BMD compared to similarly aged women. In contrast, hip and lumbar spine BMD values in BCS were similar to those of the population-based database.

Incident vertebral fractures and mortality in older women: a prospective study.

Older persons who have prevalent vertebral fractures have an increased risk of mortality. It is not known whether incident vertebral fractures are also associated with an increased risk of mortality. To determine whether older women with incident vertebral fractures have an increased risk of mortality, we conducted a prospective cohort study of 7233 community-dwelling older women aged 65 years or older who were enrolled in the Study of Osteoporotic Fractures. We measured incident vertebral fractures by radiographic morphometry of paired lateral spine X-rays taken an average of 3.7 years apart. We also collected information on baseline prevalent vertebral fractures; calcaneal bone density; anthropometric measures; and demographic, medical history, and lifestyle variables. Overall mortality was assessed and confirmed by receipt of death certificates. Over an average of 3.7 years, 389 (5.4%) women developed at least one incident vertebral fracture. During an additional 8 years of follow-up, 1617 (22%) women died. Women with at least one new fracture had an age-adjusted 32% increased risk of mortality (RH=1.32; 95% CI=1.10-1.58, P=0.003) compared to those without incident vertebral fractures. After adjustment for weight loss, physical frailty markers, and nine other predictors of mortality, there was no longer an independent association between incident vertebral fractures and mortality (RH=1.06; 95% CI=0.88 1.28). Older women with incident vertebral fractures have an increased risk of mortality that may be explained by weight loss and physical frailty.

Endogenous hormones and bone turnover markers in pre- and perimenopausal women: SWAN.

We tested the hypothesis that higher serum osteocalcin and urinary N-telopeptide of type I collagen (NTx) concentrations would be found in women with increasing cycle irregularity or increased follicle stimulating hormone concentrations. We studied 2,375 pre- and early perimenopausal women from the Study of Women's Health Across the Nation (SWAN), aged 42-52 years, who self-identified their race/ethnic origin as African-American (28.3%), Caucasian (49.4%), Japanese (10.5%) or Chinese (11.8%). Outcome measures were serum osteocalcin, a measure of bone formation, and NTx, a measure of bone resorption. The explanatory variables were menopausal status, based on self-reported regularity of menstrual bleeding, and circulating endogenous hormone concentrations including estradiol (E(2)), testosterone (T), sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) concentrations. Additionally, we evaluated the association of the bone turnover markers with the Free Androgen Index (FAI) and the Free Estradiol Index (FEI), ratios of total testosterone and estradiol concentrations to SHBG, respectively. Higher FSH concentrations were associated with higher NTx concentrations ( beta=0.003, partial r2=2.1%, p<0.0001), both before and after adjusting for other covariates (total explained variability of 9%). Higher FSH concentrations were also associated with higher osteocalcin concentrations ( beta=-0.216, partial r2=4.1%, p<0.0001, total explained variability of 15.4%). There were no significant associations of the bone turnover markers with other endogenous hormones, following adjustment for covariates. Mean osteocalcin and NTx values were not significantly different in premenopausal women compared to early perimenopausal women. In these pre- and early perimenopausal women, higher FSH concentrations, but not other serum reproductive hormone concentrations, are positively associated with greater bone turnover prior to the last menstrual period.