Methodologic issues in clinical trials for prevention or risk reduction in osteoarthritis.

The design and execution of prevention trials for OA have methodological issues that are distinct from trials designed to impact prevalent disease. Disease definitions and their precise and sensitive measurement, identification of high-risk populations, the nature of the intervention (pharmaceutical, nutraceutical, behavioral) and its potential pleiotropic impacts on other organ systems are critical to consider. Because prevention trials may be prolonged, close attention to concomitant life changes and co-morbidities, adherence and participant retention in the trial is of primary importance, as is recognition of the potential for "preventive misconception" and "behavioral disinhibition" to affect the ability of the trial to show an effect of the intervention under study. None of these potential pitfalls precludes a successful and scientifically rigorous process and outcome. As technology improves the means to measure and predict the OA process and its clinical consequences, it will be increasingly possible to screen individuals for high-risk phenotypes, combining clinical factors with information from imaging, genetic, metabolic and other biomarkers and to impact this high-risk condition to avoid or delay OA both structurally and symptomatically.

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.

Testosterone, sex hormone-binding globulin and free androgen index among adult women: chronological and ovarian aging.

BACKGROUND: In this study, levels and rates of change in total testosterone (T), sex hormone-binding globulin (SHBG) and free androgen index (FAI) were related to chronological age and to the final menstrual period (FMP) as an indicator of ovarian aging. METHODS: Data were annually acquired over a 15-year period in 629 women of the Michigan Bone Health and Metabolism Study cohort. Data were censored for hormone therapy use. Endogenous androgen patterns over time were described with stochastic processes and bootstrapping. RESULTS: With ovarian aging, T levels rose from a mean of 18 ng/dl commencing 10 years prior to the FMP to 27 ng/dl at the FMP. Over the 20-year period encompassing the FMP, modeled mean SHBG levels changed from 58 to 34 nM and the FAI ratio increased from 1.6 to 2.9 in a non-linear manner. With chronological aging, total T levels increased (P < 0.0001) from 43 to 50 years, but not thereafter. SHBG declined steadily with age with a modestly greater rate of change between 49 and 54 years. The FAI increased from 1.3 to 2.5 from 34 to 58 years. CONCLUSIONS: T increased from approximately age 40 until the FMP whereas SHBG had rate of change patterns reflecting both chronological and ovarian aging components. These data provide new insight into the endogenous androgen patterns at mid-life.

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.

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.

Effects of smoking on the development of female reproductive cancers.

The effect of smoking on the development of breast, endometrial, and ovarian cancers is evaluated among cases identified between November 1980 and July 1982 in the Iowa Surveillance, Epidemiology, and End Results Cancer Registry. Population-based, age-frequency matched controls were also evaluated, adjusting for potential confounders: Age, age of menarche, age of menopause, duration of menses, female family reproductive cancer history, obesity, parity, infertility, and lifetime steroid hormone use. Logistic regression analyses of total pack-years of cigarette exposure indicate that smoking is not significantly related to the development of breast cancer [relative risk (RR) = .99; confidence interval (CI) = .97, 1.02] or ovarian cancer (RR = 1.00; CI = 1.00, 1.00). Among women with endometrial cancer, the risk for those who smoke is increased among premenopausal women (RR = 1.27; CI = .65, 2.59) and decreased among postmenopausal women (RR = .41; CI = .16, 1.04).

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.

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.

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.

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.

Lactose intolerance among Mexican Americans.

Thirty-three Mexican Americans between the ages of 9 and 60 were interviewed and tested for lactose intolerance. The participants of the study included 16 children and 17 persons not related by birth, including the parents of the children. Determination of lactose intolerance was based on a rise of less than 25mg/100 ml of blood glucose as measured by an Ames Dextrostix/Reflectance Meter following consumption of a lactose load. Forty-seven percent of the 17 nonrelated Mexican Americans were lactose intolerant. There was a marked relationship between low rise in blood glucose and symptoms of diarrhea, flatulence, and distention. Sixteen children from four families had an incidence of 50 per cent intolerance. The findings of intolerance in two successive generations of three families and in both sexes of the families adds support to the contention that lactose intolerance has a genetic basis, without sex predilection.

Lactation and weight retention.

The effect of lactation on weight retention was investigated longitudinally, with data collected at 0.5, 2, 4, 6, 12, and 18 mo after parturition in 110 women aged 20-40 y who had been nulliparous or primiparous. At each evaluation women were categorized as fully breast-feeding, partly breast-feeding, or bottle-feeding including infants weaned to a bottle (bottle feeding/weaned). Postpartum weight retention was calculated by subtracting weight before pregnancy from weight at each evaluation. Lactation practices were found to be significantly associated (P < 0.05) with postpartum weight retention by longitudinal regression analysis. Women who bottle-fed their infants retained more weight over time than women who breast-fed their infants. Significantly slower rates of weight loss were observed when women ceased breast-feeding or switched from fully to partly breast-feeding. Weight retention over time was greater in women who were older, unmarried, or had greater weight gain during pregnancy (P < 0.05). A pattern of weight gain rather than weight loss was observed in unmarried women. Our findings suggest that lactation influences the pattern of postpartum weight retention; however, the effect of lactation on weight retention was sufficiently limited to warrant minimal emphasis on lactation as a means of minimizing postpartum weight retention.

The relationship of bone mass and fracture history to fluoride and calcium intake: a study of three communities.

Stimulated by the suggestion that water fluoride greater than 1 mg/L may protect against osteoporosis, we studied bone mass of women in three rural communities with differing mineral content of the water supply. Mean fluoride and calcium of community drinking waters were 4 mg/L and 16 mg/L, respectively, high fluoride community; 1 mg/L and 375 mg/L, respectively, high calcium community; and 1 mg/L and 65 mg/L, respectively, low calcium community. Bone mass was measured by single photon absorptiometry, and women were interviewed about fracture history, dietary intake, and other important covariates. We observed no protective effect with higher fluoride intake. Bone mass was lower in older women from the high fluoride community though not statistically so; these women reported significantly more fractures. There was no observed community difference in young women's bone mass or fracture history. Young women in the high fluoride community consuming calcium and vitamin D in excess of 800 mg/day and 400 IU/day, respectively, had significantly better bone mass (p less than 0.05) than their peers.

Correlates of mid-radius bone density among postmenopausal women: a community study.

We surveyed mid-radius bone density in a geographically-defined population of 324 women, 55-80 years old from two small, demographically-similar communities whose water supply provided 60 mg/l and 375 mg/l of elemental calcium. Mean community calcium intakes were 964 mg/day and 1329 mg/day respectively. Bone density, measured by photon densitometry, was correlated with physical measurements, medical history, and reported nutritional intake. Mid-radius bone density decreased with age while the following additional factors were independently and positively associated with bone density: humeral muscle area (p = 0.0001), extended estrogen use (p = 0.0004), thiazide use (p = 0.0029), and vitamin D intake (p = 0.0104). Estimated total calcium intake alone did not significantly correlate with bone density; however, mean bone density was significantly greater in persons whose calcium intake was greater than 800 mg/day, consumed concurrently with vitamin D in amounts greater than 400 IU (p = 0.0342), the Recommended Daily Allowance of these two nutrients.

The association of intakes of vitamin D and calcium with blood pressure among women.

Blood pressure and its relationship to nutritional factors, particularly intakes of calcium and vitamin D, were evaluated among 86 women, aged 20-35 yr, and 222 women, aged 55-80 yr, who were not using diuretics. Observations were based on a study of bone density among women in two communities which included blood pressure determinations, a food frequency estimate of calcium intake, a 24-h dietary recall and an extensive supplement use history. There was no significant relationship between estimated current dietary calcium consumption and blood pressure in either age group. However, in younger women, there was a significant inverse relationship between estimated dietary intake of vitamin D and systolic blood pressure which remained significant (p = 0.0016) after adjusting for age, Quetelet index, alcohol consumption and calcium intake. Older women whose consumption of both vitamin D and calcium was less than the Recommended Dietary Allowance, 400 IU/day and 800 mg/day respectively, had a significantly higher systolic blood pressure (p = 0.0371) than their counterparts whose estimated intake met the RDA for at least one of the two nutrients. Vitamin D may be related to blood pressure through its regulation of calcium absorption from the gut or its interaction with parathyroid hormone in maintaining plasma calcium homeostasis.