Longitudinal changes of serum COMP and urinary CTX-II predict X-ray defined knee osteoarthritis severity and stiffness in women.

OBJECTIVE: To ascertain the predictive role of longitudinally acquired biochemical measures of cartilage turnover in relation to X-ray defined knee osteoarthritis (OAK), knee pain and functioning. METHODS: This is a feasibility study based on 72 enrollees of the Michigan site of Study of Women's Health Across the Nation (SWAN), a longitudinal, population-based cohort study with 11 annual visits to characterize health at the mid-life. At visits in 1996, 1998 and 2007, radiographs were evaluated for the presence of OAK [>or=2 on the Kellgren and Lawrence (K-L) scale]. Knee pain and stiffness were assessed by interview. Functioning was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Cartilage oligomeric matrix protein (COMP) and Type II collagen telopeptides (CTX-II) were assayed in serum and urine samples collected on alternate years from 1997 to 2006. We related trajectories of the cartilage biochemical markers from these five time points to OAK severity (no OAK, K-L score<2; mild OAK, K-L score=2; moderate/severe OAK, K-L score=3 or 4), pain, stiffness, or functioning, using longitudinal non-linear mixed modeling. RESULTS: The 2007 prevalence of X-ray defined OAK was 50% in these 72 women. Upward trajectories of COMP (P=0.02) and CTX-II (P=0.006) were associated with increased OAK severity and body size. COMP trajectories were associated with pain and stiffness, but not functioning. CTX-II trajectories were associated with stiffness scores, but not knee pain or functioning scores. CONCLUSION: Multiple, biennial measures of COMP or CTX-II taken over a 10-year period were predictive of subsequent OAK and knee stiffness.

The reproducibility of ultrasound bone measures in a triethnic population of pregnant adolescents and adult women.

We used bone ultrasound technology with its measurement of attenuation (broadband ultrasound attenuation [BUA] as dB/MHz) and sound velocity (speed of sound as m/s) for assessing the quantitative ultrasound index (QUI) summary measure in a triethnic population of 280 pregnant women. The study purpose was to describe the reproducibility of the ultrasound technology and determine if the correlations of age, weight, and ethnicity with the bone status measures in this population are consistent with the correlations of age, weight, and ethnicity that have been reported with other technologies that measure bone mass. We evaluated the first 280 women enrolled in our longitudinal study of lead turnover from maternal bone during pregnancy and lactation. Enrollees were pregnant, aged 12-29 years, and self-classified as black, white, or Hispanic. Bone ultrasound was measured twice at entry to prenatal care, which, on average, was at 14 weeks gestation. Reproducibility was described with intraclass correlations and the standard error of measurement. Age, weight, and ethnicity were associated with bone status measures using Spearman correlations and generalized linear models. The reproducibility of the summary bone measure, QUI, was high (96-97%). Variation in age and ethnicity did not alter reproducibility; however, the reproducibility of the attenuation measure (BUA as dB/MHz) lessened with increasing weight, declining from 95% to 89%. Since this attenuation is included in the summary QUI measure, there was a slight, and nonsignificant, decline in QUI reproducibility (from 97% to 96%) as women increased in size. There were no statistically significant differences in mean bone ultrasound measures according to age, where ages ranged from 12-29 years. Women who categorized themselves as black had, on average, an 8.5% greater QUI than did women who classified themselves as Hispanic or white. There were no significant pair-wise differences in mean ultrasound measures of bone between women classifying themselves as Hispanic or white. The use of ultrasound is a highly reproducible measure to assess bone characteristics in a population of pregnant adolescent and young adult women and its summary measure of bone mass is correlated with ethnic as well as body size characteristics.

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.

Genetic markers, bone mineral density, and serum osteocalcin levels.

We evaluated five genetic markers for products that contribute to skeletal mineralization including the Sp1 polymorphism for type I collagen Ai (COLIA1), the vitamin D receptor (VDR) translation initiation site polymorphism, the promoter of the osteocalcin gene containing a C/T polymorphism, the estrogen receptor (ER) gene containing a TA repeat, and the polymorphic (AGC)n site in the androgen receptor. These markers were evaluated for their potential relationship with bone mineral density (BMD), measured by dual-energy X-ray densitometry, or its 3-year change. Additionally, potential associations of these genotypes and with baseline osteocalcin concentration or its 3-year change (assessed using radioimmunoassay) were evaluated. The study was conducted in 261 pre- and perimenopausal women of the Michigan Bone Health Study, a population-based longitudinal study of musculoskeletal characteristics and diseases. The polymorphic (AGC)n site in the androgen receptor showed a strong association with BMD of the femoral neck (FN) and lumbar spine and remained highly significant after adjusting for body mass index (BMI), oophorectomy/hysterectomy, oral contraceptive (OC) use and hormone replacement use (p < 0.001). The TA repeat at the 5' end of the ER gene was associated with total body calcium (p < 0.05) after adjusting for BMI, oophorectomy and hysterectomy, and OC use. The frequency of oophorectomy and hysterectomy within selected genotypes explained much of the statistically significant association of the ER genotypes with BMD of the FN and spine. There was no association of measures of BMD or bone turnover with the Sp1 polymorphism for COLIA1, the VDR translation initiation site polymorphism, or the C/T promoter polymorphism of the osteocalcin gene. These findings suggest that sex hormone genes may be important contributors to the variation in BMD among pre- and perimenopausal women.

Bone mineral density and its change in pre-and perimenopausal white women: the Michigan Bone Health Study.

There is a need to better understand potential bone mineral density (BMD) loss during the menopausal transition since this period may include the initiation of interventions. The study purpose was to determine if there was BMD loss at the femoral neck, lumbar spine, or total body bone sites in a population-based study of women approaching or transitioning the midlife. The 583 enrollees were 25-45 years of age at the first of four annual measurements from 1992 through 1996. Bone mineral content and bone width were measured using dual-energy X-ray absorptiometry. Considering all enrollees collectively, there was a significant 3-year decline (1%) in BMD at the femoral neck over the 3-year period (p = 0.076). There was no significant annual change in the lumbar spine (p = 0.11), and a significant annual increase in the total body BMD (p = 0.0003). Within subgroups and cross-sectionally, BMD values of the femoral neck were 5% lower in women classified as perimenopausal compared with premenopausal enrollees; BMD was 3% and 1% lower at the lumbar spine and total body site, respectively. Longitudinally, among perimenopausal women, a double oophorectomy was associated with BMD loss in the spine (p = 0.0003), even though 75-85% of these women had a hormone replacement prescription at some time during the study period. In summary, the site with evidence of loss was the femoral neck, specifically among perimenopausal women. There was little evidence of substantial total body or lumbar spine BMD loss in premenopausal women with ovaries who maintained follicle-stimulating hormone levels < 20 mIU/l in the early follicular period. Double oophorectomy, even with hormone replacement, was associated with bone loss.

Urinary ovarian and gonadotropin hormone levels in premenopausal women with low bone mass.

We hypothesized that lower ovarian and gonadotropin hormone concentrations would be associated with lower levels of peak bone mineral density (BMD) in apparently normally menstruating women who did not exercise intensively and did not report anorexia or bulimia. This hypothesis was evaluated using a case-with-control study design (n = 65) which was nested within a population-based longitudinal study of peak bone mass (Michigan Bone Health Study) with annual assessment in women aged 25-45 years (n = 582). Cases were 31 premenopausal women with BMD of the lumbar spine, femoral neck, and total body less than the 10th percentile of the distribution, where controls were 34 premenopausal women with BMD between the 50th and 75th percentile. BMD was measured by dual-energy X-ray absorptiometry. In addition to their annual measurement, these 65 participants collected first-voided morning urine specimens daily through two consecutive menstrual cycles. The urine from alternating days of this collection was analyzed for estrone-3-glucuronide (E1G), pregnanediol glucuronide (PdG), testosterone, and follicle-stimulating hormone by radioimmunoassay and these values adjusted for daily creatinine excretion levels. Additionally, analyses of daily urine specimens for luteinizing hormone (uLH) was undertaken to better characterize the possible uLH surge. Cases had significantly lower amounts of E1G (p = 0.009) and PdG (p = 0.002) than did controls, whether amounts were characterized by a mean value, the highest value, or the area under the curve, and after statistically controlling for body size. Further, when B-splines were used to fit lines to the E1G and PdG data across the menstrual cycle, the 95% confidence intervals (CIs) about the line for the controls consistently excluded and excluded and exceeded the 95% confidence bands for the cases in the time frame associated with the luteal phase in ovulatory cycles. Likewise, 95% CIs for the LH surge in controls exceeded the fitted line for cases around the time associates with the LH surge. The cases and controls were not different according to dietary intake (energy, protein, calcium), family history of osteoporosis, reproductive characteristics (parity, age at menarche, age of first pregnancy), follicular phase serum hormone levels, calciotropic hormone levels, or by evidence of perimenopause. We conclude that these healthy, menstruating women with BMD at the lowest 10th percentile from a population-based study had significantly lower urinary sex steroid hormone levels during the luteal phase of menstrual cycles as compared with hormone levels in premenopausal women with BMD between the 50th and 75th percentile of the same population-based study, even after considering the role of body size. These data suggest that subclinical decreases in circulating gonadal steroids may impair the attainment and/or maintenance of bone mass in otherwise reproductively normal women.

Bone mineral density and its change in white women: estrogen and vitamin D receptor genotypes and their interaction.

Low bone mineral density (BMD) is a major risk factor for development of osteoporosis; increasing evidence suggests that attainment and maintenance of peak bone mass as well as bone turnover and bone loss have strong genetic determinants. We examined the association of BMD levels and their change over a 3-year period, and polymorphisms of the estrogen receptor (ER), vitamin D receptor (VDR), type I collagen, osteonectin, osteopontin, and osteocalcin genes in pre- and perimenopausal women who were part of the Michigan Bone Health Study, a population-based longitudinal study of BMD. Body composition measurements, reproductive hormone profiles, bone-related serum protein measurements, and life-style characteristics were also available on each woman. Based on evaluation of women, ER genotypes (identified by PvuII [n = 253] and XbaI [n = 248]) were significantly predictive of both lumbar spine (p < 0.05) and total body BMD level, but not their change over the 3-year period examined. The VDR BsmI restriction fragment length polymorphism was not associated with baseline BMD, change in BMD over time, or any of the bone-related serum and body composition measurements in the 372 women in whom it was evaluated. Likewise, none of the other polymorphic markers was associated with BMD measurements. However, we identified a significant gene x gene interaction effect (p < 0.05) for the VDR locus and PvuII (p < 0.005) and XbaI (p < 0.05) polymorphisms, which impacted BMD levels. Women who had the (-/-) PvuII ER and bb VDR genotype combination had a very high average BMD, while individuals with the (-/-) PvuII ER and BB VDR genotype had significantly lower BMD levels. This contrast was not explained by differences in serum levels of osteocalcin, parathyroid hormone, 1,25-dihydroxyvitamin D, or 25-dihydroxyvitamin D. These data suggest that genetic variation at the ER locus, singly and in relation to the vitamin D receptor gene, influences attainment and maintenance of peak bone mass in younger women, which in turn may render some individuals more susceptible to osteoporosis than others.

IGF-I, osteocalcin, and bone change in pregnant normotensive and pre-eclamptic women.

Pre-eclampsia is a pregnancy disorder of uncertain etiology that affects 5-10% of all pregnancies, with symptoms typically presenting around or after 20 wk gestation. We hypothesized that IGF-I, osteocalcin, and bone loss would be different among women with pre-eclampsia compared with normotensive pregnant women. There were 962 pregnant healthy women, aged 12-35, who were assessed at entry to care, at 28 wk, and at delivery for osteocalcin and IGF-I concentrations. Bone ultrasound was measured at entry to care and at 6 wk postpartum, whereas bone mineral density was measured by dual x-ray densitometry at delivery. There were 64 women (6.7%) among the women being followed who developed pre-eclampsia. In women with pre-eclampsia, IGF-I concentrations were 74% greater in the third trimester compared with the first trimester, whereas there was little change in osteocalcin concentrations. In contrast, normotensive women had an average increase of 43% in IGF-I concentrations accompanied by a 63% decline in osteocalcin concentrations. In women with pre-eclampsia, IGF-I and osteocalcin concentrations were significantly correlated (r = 0.48 and 0.43) at both the first and third trimester time points, but only in the third trimester among normotensive women (r = 0.27). The bone change difference between the two groups was not statistically significant. Women with pre-eclampsia appear to have an exaggerated IGF-I responsiveness compared with women who are normotensive; however, the strong correlation between IGF-I and osteocalcin in women with pre-eclampsia suggests that the IGF-I is able to retain its role as a local regulator of bone remodeling, as indicated by the osteocalcin concentrations.

Biochemical markers of bone turnover in lactating and nonlactating postpartum women.

We measured two bone-formation markers, osteocalcin and bone-specific alkaline phosphatase, and one bone-resorption marker, N-telopeptide, in a longitudinal study in order to describe levels of these markers in lactating and nonlactating women after parturition. This 18-month postpartum period included an initial 6 months in which a 5% short-term bone loss occurred at both spine and femoral neck among breast-feeding women. The second part of the 18-month period was characterized by bone recovery among women who had lost bone. These bone-change characteristics provided an opportunity to evaluate the performance of biochemical markers during both bone loss and recovery and to identify environmental exposures during lactation associated with bone turnover. The eligible population comprised 115 women whose bone-turnover markers were measured at 2 weeks (baseline) and at 2, 4, 6, 12, and 18 months after parturition. Participants reported reproductive characteristics, diet, physical activity, use of medications, and infant-feeding practices at each contact. Women were grouped according to lactation duration: 0-1 months, 2-5 months, and 6 months or more. Women who breast-fed for at least 6 months had significantly different levels of all three bone-turnover markers compared with the levels in bottle-feeding controls, which were indicative of substantially increased bone turnover. Factors that predicted the difference in biochemical markers from baseline to 6-month values by regression analysis were lactation of 2-6 months duration and lactation for 6 months or more. Dietary calcium intake, physical activity level, and body size did not explain the differences in the change from the baseline level to the 6-month level, a period of time that corresponded with bone loss in the lactating women. Factors that predicted the differences in bone-turnover markers between 6 and 18 months (the time of bone-mass recovery) were lactation status and number of months to resumption of menses. By the 18-month observation, there was no difference in the mean values for the measured bone-turnover markers among the three lactation groups. This suggests that menstrual activity, rather than diet or physical activity, is the primary factor in bone-mass recovery after the bone loss of lactation.

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.

A prospective study of bone density and pregnancy after an extended period of lactation with bone loss.

OBJECTIVES: To determine if pregnancy after an extended period of lactation curtails the recovery of maternal bone mineral density. METHODS: Twenty-five women who fully breast-fed their infants for at least 6 months and had a subsequent pregnancy within 18 months of initiating lactation were studied longitudinally. Twenty controls breast-fed similarly, but had no subsequent pregnancy. The women were healthy, well-nourished, and between 20-40 years old. Bone mineral density was measured by dual x-ray energy absorptiometry at the spine and hip. RESULTS: Both cases and controls lost bone mineral density with extended lactation. The case group had a bone mineral density recovery comparable to the controls. CONCLUSION: Women with the dual calcium demands of extended lactation and a subsequent pregnancy are not at risk for failure of bone recovery to pre-lactation levels.

A prospective evaluation of bone mineral change in pregnancy.

During pregnancy, mineralization of the fetal skeleton creates a demand for approximately 30 g of calcium from maternal sources. We examined whether this fetal demand results in maternal femoral bone mineral loss. Femoral bone mineral density was measured twice by dual photon densitometry, once before conception and again within 15 days of parturition, in 32 white women aged 20-40 years. Femoral bone mineral density was also measured twice in 32 non-pregnant controls matched to the cases for weight, height, age, and parity. There was no significant mean bone mineral density loss in cases compared with controls (P greater than .63). Pregnant women with smaller body size, expressed as Quetelet index, were more likely to have femoral neck bone mass increase than their matched controls (P less than .03). This study provides evidence that fetal demand for calcium has a minimal effect on bone mineral density at parturition. Smaller women may experience a slight increase in femoral bone mineral density compared with controls.

Bone loss in adolescent and adult pregnant women.

OBJECTIVE: To determine the amount of change in bone ultrasound measures among pregnant adolescent girls and women and whether that change was associated with adolescence, maternal growth during pregnancy, limited weight gain during pregnancy, hypertension in pregnancy, or poor diet. METHODS: We used bone ultrasound measurements of attenuation and sound velocity to assess changes in quantitative ultrasound indices of 252 pregnant adolescent girls and women age 12-34 years. Bone ultrasound measurement of the os calcis was performed at 16 +/- 7 weeks' gestation (mean +/- standard deviation and 6 +/- 1 weeks postpartum. RESULTS: On average, the bone quantitative ultrasound index was 3.6% lower 6 weeks postpartum than at entry into care (P <.001). Nulliparous patients had significantly greater bone loss than did parous subjects. Still-growing adolescents had greater quantitative ultrasound index decreases than did grown women (-5.5% versus -1.9%, P <.02). Patients in the upper tertile of baseline quantitative ultrasound index lost more bone than did patients in the lower tertile (-5% versus 0.5%, P <.02). Pregravid weight, weight change during pregnancy, gynecologic age, and age at menarche predicted bone change in subgroups defined by parity or age; however, none of the differences in those variables were statistically significant. Greater dietary calcium intake, less physical activity, and pregnancy hypertension and preeclampsia were not associated with bone change. CONCLUSION: There has been inconsistent evidence of maternal bone loss during pregnancy. The findings of this study challenge the assumption that because of increased calcium absorption from the maternal intestine, no transitory bone loss occurs in pregnancy. The amount of bone loss among growing adolescents and nulliparous patients was consistent with the demands of fetal mineralization and the continued demands of the maternal skeleton during growth.

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.

The prevalence of hepatitis B in employees of small, rural hospitals--implications for vaccine administration.

The Centers for Disease Control Advisory Committee on Immunization Practices has based recommendations for hepatitis B vaccine for hospital employees on studies done in large urban hospitals. Data on the prevalence of hepatitis B in employees of small hospitals have been lacking. We measured hepatitis B surface and core antibody in 422 employees of six small, rural hospitals who were exposed to blood. The overall prevalence among those "high-risk" employees was 5.5%. The highest prevalence was found in General Nursing, Intensive Care Nursing, Recovery Room, IV Therapy, Laboratory, and Respiratory Therapy, although differences were seen between hospitals. Results of such testing for individual hospitals may have a major impact on the cost-effectiveness of vaccination programs for their employees.

Testosterone concentrations in women aged 25-50 years: associations with lifestyle, body composition, and ovarian status.

While there is substantial evidence of the importance of endogenous and exogenous estrogen in reproductive health and chronic disease, there is little consideration of androgens in women's health. In the Michigan Bone Health Study (1992-1995), the authors examined the correlates of testosterone concentrations in pre- and perimenopausal women (i.e., age, menopausal status, body composition, and lifestyle behaviors) in a population-based longitudinal study including three annual examinations among 611 women aged 25-50 years identified through a census in a midwestern community. Current smokers had the highest testosterone concentrations with decreasing values in former and nonsmokers (p = 0.0001). Body composition measures (body mass index, body fat (%), weight (kg), lean body mass (kg), and fat mass (kg)) were significantly and positively associated with total testosterone concentrations in a dose-response manner. Hysterectomy with oophorectomy was associated with significantly lower testosterone concentrations. Alcohol consumption, physical activity, and dietary macronutrient intake were not associated with testosterone concentrations. This is one of the first studies to examine correlates of serum testosterone concentrations in anticipation of the growing interest in the role of androgens in women's health. The greater circulating levels of testosterone in obese women and smokers suggest that testosterone concentrations should be considered in the natural history of disease conditions where obesity and smoking are risk factors, including cardiovascular disease.

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.

A prospective study of bone mineral content and fracture in communities with differential fluoride exposure.

In 1983/1984, a study of bone mass and fractures was begun in 827 women aged 20-80 years in three rural Iowa communities selected for the fluoride and calcium content of their community water supplies. The control community's water had a calcium content of 67 mg/liter and a fluoride content of 1 mg/liter. The higher-calcium community had water with a calcium content of 375 mg/liter and a fluoride content of 1 mg/liter. The higher-fluoride community's water had 15 mg/liter of calcium and 4 mg/liter of fluoride naturally occurring. In 1988/1989, a follow-up study characterized the 684 women still living and available for study. Residence in the higher-fluoride community was associated with a significantly lower radial bone mass in premenopausal and postmenopausal women, an increased rate of radial bone mass loss in premenopausal women, and significantly more fractures among postmenopausal women. There was no difference in the 5-year relative risk of any fracture in the higher-calcium community versus the control community; however, the relative risk was 2.1 (95% confidence interval (CI) 1.0-4.4) in women in the higher-fluoride community compared with women in the control community. There was no difference in the 5-year risk of wrist, spine, or hip fracture in the higher-calcium community versus the control community; however, the 5-year relative risk for women in the higher-fluoride community, compared with women in the control community, was 2.2 (95% CI 1.1-4.7). Estimates of risk were adjusted for age and body size.

Prospective study of radial bone mineral density in a geographically defined population of postmenopausal Caucasian women.

The radial bone mineral density (BMD) mass of 324 Caucasian women, aged 55-80 years, from geographically defined areas was evaluated in 1983 using single photon absorptiometry; 271 of these women (86%) were reexamined 5 years later in 1988. More than 65% of women lost radial BMD in excess of 1%/year in the 5-year follow-up. Thirty percent of women lost at least 2%/year. Baseline radial BMD measures taken in 1983 were highly predictive of the 1988 radial BMD values, explaining approximately 82% of the variability. The rate of bone change, expressed as percent change or 5-year difference (g/cm2), was not associated with baseline radial BMD value. Rate of change was not strongly associated with chronologic age or years since menopause, even when data were restricted to those women who reported no previous use of perimenopausal estrogen or thiazide medication. We conclude that BMD loss in a general population may be more substantial than previously believed.

Longitudinal changes in body composition in women approaching the midlife.

This population-based longitudinal study describes the 4.5-year changes in body composition and body mass distribution in women aged 20-45 years, and characterizes predictors of these changes. Body weight, waist-to-hip ratio, Quetelet index, fat and lean body mass were measured in 404 white menstruating women aged 20-40 at baseline and 4.5 years later (follow-up). Variables considered for predicting body composition differences were hormonal status, menstrual status, parity, diet and physical activity. Average body weight increased 4.3 kg in 4.5 years (6.4 kg increase in fat and 2.1 kg decrease in lean)--a net increase of 7.1% total body fat. Measured predictors were not significantly associated with weight or Quetelet index; however, they were associated with measured amounts of lean and fat. Longitudinally, women who preserved the most lean body mass tended to be nulliparous, to be still menstruating, to have higher testosterone levels, and to smoke. Physical activity was associated with preserving lean body mass. Increasing age and higher follicle-stimulating hormone levels were associated with increasing waist-to-hip ratio. Average body weight showed a steady increase--characterized by an expanding fat compartment and a shrinking lean compartment--with the older women increasing more in waist girth relative to hip girth than younger women. Predictor variables of these changes included hormonal environment, physical activity, smoking behaviour, parity, and oophorectomy.