Adipocytokine and ghrelin levels in relation to cardiovascular disease risk factors in women at midlife: longitudinal associations.

BACKGROUND: There are limited data concerning the relationships between changes in adipocytokines and cardiovascular disease (CVD) risk factors. OBJECTIVE: To examine the longitudinal associations between leptin, adiponectin, resistin and ghrelin levels and CVD risk factor levels in women at midlife. DESIGN: Prospective, observational study. SUBJECTS AND MEASUREMENTS: Leptin, adiponectin, resistin, ghrelin levels and CVD risk factors were measured in specimens collected from 40 women at 3 points in time corresponding to the pre-, peri- and postmenopause stages of their natural menopause transition. RESULTS: In longitudinal analyses adjusted for CVD risk factors and leptin at the previous menopausal stage, aging, education, smoking and physical activity, greater increases in leptin over the menopause transition were associated with greater decreases in high-density lipoprotein cholesterol (HDL-c) and greater increases in diastolic blood pressure, glucose, insulin and insulin resistance (all P < 0.05). Larger decreases in adiponectin over the menopause transition were associated with greater increases in systolic blood pressure, insulin and insulin resistance and with greater decreases in HDL-c. Greater increases in ghrelin levels over the menopausal transition were associated with greater low-density lipoprotein cholesterol increases (P = 0.014). Resistin was not associated with CVD risk factor changes. CONCLUSION: There were significant adverse associations of adipocytokines and ghrelin with multiple CVD risk factor changes in women across midlife. Given that this time period is dynamic for CVD risk, these data underscore the need for additional prospective studies.

Carbonated soft drinks and dental caries in the primary dentition.

We analyzed fluid intake data among children aged 2-10 years from a 24-hour dietary recall interview in the NHANES III (1988-94) to investigate the effect of high consumption of carbonated soft drinks on caries in the primary dentition. We used cluster analysis to determine fluid consumption patterns. Four distinct fluid consumption patterns were identified: high carbonated soft drinks, high juice, high milk, and high water. About 13% of children had a high carbonated soft drink consumption pattern; they also had a significantly higher dental caries experience in the primary dentition than did children with other fluid consumption patterns. A fluid intake pattern comprised mainly of milk, water, or juice was less likely to be associated with dental caries. Findings of this study suggest that high consumption of carbonated soft drinks by young children is a risk indicator for dental caries in the primary dentition and should be discouraged.

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.

The association of endogenous hormone concentrations and bone mineral density measures in pre- and perimenopausal women of four ethnic groups: SWAN.

We evaluated bone mineral density (BMD), hormone concentrations and menstrual cycle status to test the hypothesis that greater variations in reproductive hormones and menstrual bleeding patterns in mid-aged women might engender an environment permissive for less bone. We studied 2336 women, aged 42-52 years, from the Study of Women's Health Across the Nation (SWAN) who self-identified as African-American (28.2%), Caucasian (49.9%), Japanese (10.5%) or Chinese (11.4%). Outcome measures were lumbar spine, femoral neck and total hip BMD by dual-energy X-ray densitometry (DXA). Explanatory variables were estradiol, testosterone, sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) from serum collected in the early follicular phase of the menstrual cycle or menstrual status [premenopausal (menses in the 3 months prior to study entry without change in regularity) or early perimenopause (menstrual bleeding in the 3 months prior to study entry but some change in the regularity of cycles)]. Total testosterone and estradiol concentrations were indexed to SHBG for the Free Androgen Index (FAI) and the Free Estradiol Index (FEI). Serum logFSH concentrations were inversely correlated with BMD (r = -10 for lumbar spine [95% confidence interval (CI): -0.13, -0.06] and r = -0.08 for femoral neck (95% CI: -0.11, -0.05). Lumbar spine BMD values were approximately 0.5% lower for each successive FSH quartile. There were no significant associations of BMD with serum estradiol, total testosterone, FEI or FAI, respectively, after adjusting for covariates. BMD tended to be lower (p values = 0.009 to 0.06, depending upon the skeletal site) in women classified as perimenopausal versus premenopausal, after adjusting for covariates. Serum FSH but not serum estradiol, testosterone or SHBG were significantly associated with BMD in a multiethnic population of women classified as pre- versus perimenopausal, supporting the hypothesis that alterations in hormone environment are associated with BMD differences prior to the final menstrual period.

The interrelationship between body topology and body composition varies with age among women.

The purpose of this analysis was to evaluate the relationship between age and the size and distribution of the fat and lean tissue compartments in a population-based sample of women. The study population consisted of the 875 women aged 18-94 y in the Iowa Bone Health Study who reported never smoking. Fat mass and lean mass were measured using dual X-ray absorptiometry. Hip and waist circumference and height were measured using standardized protocols. Regression was used to model the associations among age, composition and topology measures. When fat mass was modeled as a function of hip and waist circumference as well as age, age(2) and height, the age x height and age x waist circumference interaction terms remained in the fitted model and collectively accounted for 91% of the variance. In contrast, the quadratic model of age alone accounted for 8% of the observed variance in fat mass. Lean mass was modeled in two segments, with age dichotomized at 58 y. Age alone did not predict lean mass in women <58 y but did predict lean mass in women >/=58 y, with the modeled relationship including interactions with waist circumference and height. These models accounted for 70% of observed variance in lean mass. Age is associated with body composition but explains <10% of variation. When measures of height and circumferences are available, amounts of lean and fat mass are highly predictable. This is particularly important for lean mass because no other surrogate measures exist for lean mass, whereas there are surrogates for fat mass, including body mass index.

Isolation of an asporogenic (spoOA) protective antigen-producing strain of Bacillus anthracis.

We found that Congo red agar allows identification of sporulation-deficient Bacillus anthracis. Using Congo red agar, we isolated an asporogenic derivative of the protective antigen-producing strain B. anthracis delta Sterne-1(pPA102). Polymerase chain reaction and Southern hybridization analyses of DNA from the asporogenic mutant revealed that a deletion was present in spoOA, an essential gene for the initiation of sporulation. The deletion also encompassed the spoIVB homologue and a portion of the recN homologue. The avirulent spoOA strain delta Sterne-1(pPA102)CR4 is suitable for the safe production of protective antigen without endospore contamination of the vaccine production facility.

Menstrual history and bone density in young women.

Adequate levels of reproductive and pituitary hormones are needed for the initiation and maintenance of regular menstrual cycles as well as for the achievement of peak bone mineral density (BMD). Therefore, in the absence of direct hormone measures, menstrual history may serve as a surrogate for the adequacy of hormonal functioning and be a marker for bone status in young women. In our cross-sectional study of white college women aged 19-26 years, we examined the association of six characteristics of menstrual history with bone density at the lumbar spine and the femoral neck. To characterize associations, we used multiple linear regression models that also accounted for the contribution of body mass index, dietary calcium intake, height, level of physical activity, smoking, and alcohol use. The associations between each of the six menstrual characteristics and BMD were stronger at the lumbar spine than at the femoral neck. Age at menarche explained the most variance at both the lumbar spine (partial r2 x 100 = 5.9%) and the femoral neck (partial r2 x 100 = 2.1%). For each year that menarche was delayed, bone density was lower by -0.023 g/cm2 (p = 0.0024) at the lumbar spine and -0.0129 g/cm2 (p = 0.0565) at the femoral neck. At the lumbar spine, a higher number of lifetime menstrual cycles was also significantly associated with increased bone density (adjusted beta = 0.0010, p = 0.0052, partial r2 x 100 = 4.4%). This association was not significant after adjusting for age at menarche. Neither reproductive years (age - age at menarche) nor a history of irregular cycles (either at menarche, in the past year, or ever) was associated with bone density at either site. Menstrual function appears to affect the bone density of these young women. Studies that include measures of reproductive and pituitary hormones are needed to further explore the role of hormones in the potential link between menstrual history and bone density.

Prevalence of renal stones in a population-based study with dietary calcium, oxalate, and medication exposures.

Little is known about the epidemiology of renal stones, in spite of the relative frequency of this painful condition. This population-based study examined reported renal stone diagnosis in 1,309 women aged 20-92 years to determine whether renal stones are associated with 1) food or water exposures or 2) lower bone mineral density and an increased likelihood of fractures. Results indicated a renal stone prevalence of 3.4%. The average age at diagnosis was 42 years. Renal stone formation was not associated with community of residence, hypertension, bone mineral density, fractures, high-oxalate food consumption, or ascorbic acid from food supplements. Women with renal stones consumed almost 250 mg/day less dietary calcium (p < 0.01) than did women without stones and had a lower energy intake (p < 0.04). The authors' findings do not support the hypothesis that increased dietary calcium is associated with a greater prevalence of renal stones, nor do they identify renal stones as a risk factor for low bone mineral density. Furthermore, lack of other identifiable environmental correlates and the relatively young age at initial diagnosis suggest that genetic components of renal stone formation need further study.

Does back pain predict subsequent fracture in postmenopausal women?

This longitudinal study was undertaken to determine if back pain of postmenopausal women can well predict fragility fracture during 7-year follow-up. In 1983-84, 434 Caucasian women aged 55-80 years were examined at baseline. The incidence of fractures that occurred in the following 7 years and changes of radial bone mineral density (BMD) over 5 years were obtained. There was no significant association between baseline back pain and 7-year fracture incidence after baseline assessment (OR=1.137, [95%CI 0.674, 1.916]). However, the odds ratio in the association between 7-year fracture incidence and a prior history of back pain was 1.686, [95%CI 0.925, 3.073]. This association was statistically significant (OR=2.126, [95%CI 1.409, 2.844]) when age, baseline BMD, constitution, physical activity levels, and baseline back pain were taken into account. Although pain is subject to information bias in its reporting, it is suggested that a history of previous back pain could be a good predictor for postmenopausal fracture.

Alcohol dependence, smoking status, reproductive characteristics, and bone mineral density in premenopausal women.

Bone mineral density of the lumbar spine and femoral neck in 25 women who were alcohol dependent (case subjects) and 25 control subjects, matched for age, height, and weight was compared. Mean bone mineral density was 6.8% lower at the femoral neck and 6.9% lower at the lumbar spine in case subjects (p

Age-related hearing loss and bone mass in a population of rural women aged 60 to 85 years.

Demineralization of the cochlear capsule in conjunction with age-related bone mass loss may be one biologic factor contributing to hearing loss in the elderly. In other metabolic bone diseases, including Paget's disease of the bone and cochlear otosclerosis, demineralization of the cochlea has been associated with sensorineural hearing loss. In 1988/1989, the relation between hearing loss and bone mass of the radius and femoral neck was studied cross-sectionally in 369 women aged 60 to 85 years from three rural communities. Hearing sensitivity was measured using audiometry, and bone mineral density of the radius and femoral neck was measured using single- and dual-photon densitometry, respectively. Three variables, ascertained by interview, were associated with an increased odds for hearing loss: age, family history of hearing loss before the age of 50 years, and current use of more than two nonestrogen, nonthiazide prescription medications. After consideration of the effect of these three variables, women with femoral neck bone mass values below the mean value of 0.696 g/cm2 for this population had a 1.9 greater odds of having a hearing loss (confidence interval: 1.30, 2.50). This study demonstrated a consistent adjusted association between femoral neck bone mass and age-related hearing loss in a population of rural women aged 60 to 85 years. No consistent association was observed between radial bone mass and hearing loss.

Menopause: its epidemiology and potential association with chronic diseases.

While there are weak indications that the decline in estradiol levels with menopause has ramifications for the expression of overt disease in women, the associations are not clearly characterized with the exception of osteoporosis. The lack of well-characterized associations is undoubtedly due to the same limitations previously described: difficulty in defining the menopausal stages and difficulty in doing serum hormone sampling. Added to these limitations are other impediments. Chronic diseases will not be expressed within a few short months of the menopause, so the temporal sequence of hormone change with clinical disease expression is difficult to establish. Furthermore, it is likely that menopause is an "enabling" state that allows for the subsequent disease in women with other risk factors. Until sufficient data are available to explore the menopause as both an effect modifier and confounder, inconclusive results are likely to be reported. Future studies of the association between chronic diseases and the menopause need to consider issues similar to those that have arisen relative to studies in symptomatology. There needs to be a more concise definition of menopausal status. Potential confounders, including race/ethnicity, body size, and socioeconomic status, must be considered in both design and analysis. Studies need to be designed to separate the effects of age from those of menopause. Finally, women with medically induced menopause should be evaluated separately from those with natural menopause.

Body size, estrogen use and thiazide diuretic use affect 5-year radial bone loss in postmenopausal women.

Understanding factors associated with more rapid bone mineral loss among aging women is important for establishing preventive strategies for intervention. This study reports factors associated with the 5-year change in radial bone mineral density (BMD) determined prospectively in 435 women aged 55-80 years at baseline. The baseline study included measurement of radial BMD (gm/cm2) by single photon densitometry and personal interview. The baseline protocol was replicated 5 years later in a follow-up study. Women with a lower baseline weight or Quetelet index, smaller triceps skinfold and less arm muscle area had significantly greater 5-year bone loss (p = 0.001). Current users of estrogens had less radial bone loss (2.8% vs 7.3%, p = 0.0005) than women not currently using estrogens. Current users of estrogen had significantly less 5-year loss if use had been for 5 years or longer (-1.0% vs -6.9%, p = 0.05). Current users of the thiazide class of medications had less 5-year radial bone loss (5.0% vs 7.4%, p = 0.0035) than women without current thiazide use. Baseline dietary calcium, alcohol consumption and smoking were not associated with BMD change. This suggests that greater body size, and current use of estrogens or thiazide antihypertensives are associated with less radial bone mass loss in a 5-year period among postmenopausal women.

Radial bone mineral density in pre- and perimenopausal women: a prospective study of rates and risk factors for loss.

Radial bone mineral density (BMD) of 217 white women aged 22-54 years from a single rural community was evaluated in 1984 using single-photon absorptiometry. BMD was measured at a site one-third the distance from the wrist to the elbow, a site that represents predominantly cortical bone tissue. Most of these women (181; 83%) were reexamined 5 years later. The overall average 5 year radial BMD loss was -5.6%. The average rate of loss was -4.5% for women retaining positive estrogen status at follow-up (n = 108) and -7.4% for women who were in negative estrogen status at follow-up (n = 73). Baseline radial BMD measures were highly predictive of the follow-up BMD values (r = 0.80). Women with positive estrogen status and greater baseline BMD also had less BMD change. Greater baseline BMD did not predict the amount of change in women with negative estrogen status. The bone turnover markers osteocalcin and bone-specific alkaline phosphatase were significantly associated with BMD change in women with negative, but not positive estrogen status. There was no conclusive evidence of a "peak age" in the baseline and follow-up BMD measures. Based on rates of BMD change, "peak" bone mineral content appears to occur before age 25 years. Factors significantly associated with lower levels of BMD were menopause without estrogen replacement, nulliparity, smoking, and age at first pregnancy. Factors associated with more bone loss were menopause without estrogen replacement, smoking, shorter duration of oral contraceptive use, and older age. Quetelet index, muscle area, number of lost pregnancies, ever breast-feeding, or calcium intake were not associated with BMD level or its 5 year rate of loss. Physical activity and alcohol intake were not associated with BMD level or change after data were adjusted for age or estrogen status.

Consistency of perimenopausal estrogen use reporting by women in a population-based prospective study.

The authors assessed the accuracy of perimenopausal estrogen use reporting by 430 women in a prospective study of bone health risk factors. Data from two time points 5 years apart indicated that 383 (89%) women could consistently report having ever used perimenopausal estrogens or not. Of the 383, 138 reported some lifetime perimenopausal estrogen use; 97 (70%) of these consistently reported duration of use. The age-adjusted relative odds that women would misreport having ever used perimenopausal estrogens was 11.7 (1.3, 100.6) for women with 11-20 years since last use, and 22.2 (1.8, 277.4) for 21+ years. Among women who inconsistently reported ever use of perimenopausal estrogen, the relative odds of reporting use at baseline and never use at follow-up as compared to reporting the converse by women aged 70-75 was 8.1 (1.2, 53.2) times that for women aged 60-69 at follow-up, and increased to 9.6 (1.8, 49.9) for women aged 76-85. This suggests that women can consistently report perimenopausal estrogen use, but accurate report of use declines in women whose last use precedes the interview by over 10 years. Accurate report of duration or dates of perimenopausal estrogen use may be compromised in women of more advanced age.

Familiality and partitioning the variability of femoral bone mineral density in women of child-bearing age.

The contributions of polygenic loci and environmental factors to femoral bone mineral density (BMD) in g/cm2) variability were estimated in modified family sets consisting of women of child-bearing age. Femoral BMDs were measured in 535 women who were members of 137 family sets consisting minimally of an index, her sister, and unrelated female control. The family set could also include multiple sisters and first cousins. Women included in these family sets were all between 20 and 40 years of age to minimize the cohort effects of maturation and menopause on measures of BMD. BMDs were measured at three femoral sites using dual photon densitometry. Values were regressed on age and Quetelet Index which explained 13-15% of the variability in BMD (dependent on site). Subsequent variance components analysis on the residuals indicated that unmeasured polygenic loci accounted for substantial additional variability: 67% for femoral neck, 58% for Wards triangle, and 45% for trochanter. These results suggest that polygenic loci account for approximately half of the variability in maximal femoral BMD.

Incidence and survival rates of children and young adults with osteogenic sarcoma.

Gender-specific and race-specific incidence and survival rates of osteogenic sarcoma over a 14-year period are presented for persons aged 0 to 24 years from eight Surveillance, Epidemiology, and End Results (SEER) registries. They were no significant gender or racial differences in age at diagnosis. There was no significant gender difference in overall incidence. Although incidence rates were slightly higher in blacks compared with whites, the difference was not significant after controlling for multiple comparisons. Females (median, 74 months) survived longer than males (median, 29 months), although this difference weakened after controlling for stage. No racial differences in survival were observed. White females survived the longest (median, 94 months), followed by black females (median, 41 months), black males (median, 34 months), and white males (median, 29 months). This striking difference in survival should be explored more fully.

Health and hormonal characteristics of premenopausal women with lower bone mass.

A study of clinical renal and endocrinologic status was undertaken to determine whether the lowest maximal bone mass observed in premenopausal women, aged 20-40 years, was a result of undiagnosed disease or represented a continuum of measurement in young adult women. A clinical sample (n = 53) was generated from an epidemiologic cross-sectional study (n = 535) designed to characterized correlates of maximal bone mass. Cases were 28 premenopausal women whose femoral bone mass as in the lowest 5th percentile of the distribution, less than 0.75 g/cm2 at the femoral neck. Controls were 25 randomly selected premenopausal women whose femoral bone mass was within 1 SD of the mean of the femoral bone mass distribution. There was no indication of increased frequency of disease among the cases as compared with the controls. No occult hypogonadism, thyrotoxicosis, hyperparathyroidism, myeloma, or renal insufficiency was observed to explain lower bone mass measurement. However, cases had significantly lower estradiol levels (75 versus 106 pg/ml, P less than 0.05) and higher luteinizing hormone levels (3.8 versus 3.1 mIU/ml, P less than 0.07) than controls. Though preliminary, these findings suggest that lower estradiol levels may contribute to significant differences in bone mass even among healthy women at the time of maximal bone accumulation.

The relationship of 1,25-dihydroxyvitamin D and radial bone mass.

We assessed the association between radial bone mass and vitamin D considering age, estrogen sufficiency and thiazide use in 373 women, aged 20-80 years in a geographically defined area. We measured cortical bone mass of the radius, using photon absorptiometry, and serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, using preliminary chromatography and protein-binding assay. We found that 1,25-dihydroxyvitamin D levels were higher in premenopausal women and postmenopausal women using estrogen replacement as compared to postmenopausal women (P less than 0.02). Users of thiazide-based antihypertensive medications had significantly lower 1,25-dihydroxyvitamin D than their age-matched peers (P less than 0.02). Dietary calcium intake was negatively associated with 1,25-dihydroxyvitamin D levels. Estimates of vitamin D intake from diet or sunlight were not associated with 1,25-dihydroxyvitamin D levels; nor were levels of 1,25-dihydroxyvitamin D related to 25-hydroxyvitamin D levels. 1,25-Dihydroxyvitamin D was negatively and significantly associated with radial bone mass, contributing approximately 6% of the explained variability of bone mass measurements. Together age, body size, thiazide use and 1,25-dihydroxyvitamin D accounted for about 47% of the explained variability in radial bone mass measurement. 1,25-Dihydroxyvitamin D was not associated with bone mass in women currently using a thiazide medication.