Relationship of blood and bone lead to menopause and bone mineral density among middle-age women in Mexico City. (Environmental Medicine).To describe the relationship of blood lead levels to menopause and bone lead levels, we conducted a cross-sectional study cross-sectional study n. See synchronic study. cross-sectional study, n the scientific method for the analysis of data gathered from two or more samples at one point in time. on 232 pre- or perimenopausal perimenopausal adjective Referring to a period of a ♀'s life–age 45 to 55-ish–in which menstrual periods become irregular; perimenopause is immediately before, during and after menopause. See Menopause. (PreM) and postmenopausal post·men·o·paus·al adj. Of or occurring in the time following menopause. postmenopausal Change of life Gynecology adjective Referring to the time in ♀ when menstrual periods stop for ≥ 1 yr (PosM) women who participated in an osteoporosis-screening program in Mexico City Mexico City Spanish Ciudad de México City (pop., 2000: city, 8,605,239; 2003 metro. area est., 18,660,000), capital of Mexico. Located at an elevation of 7,350 ft (2,240 m), it is officially coterminous with the Federal District, which occupies 571 sq mi during the first quarter of 1995. Information regarding reproductive characteristics and known risk factors for blood lead was obtained using a standard questionnaire by direct interview. The mean age of the population was 54.7 years (SD = 9.8), with a mean blood lead level of 9.2 [micro]g/dL (SD = 4.7/dL) and a range from 2.1 to 32.1[micro]g/dL. After adjusting for age and bone lead levels, the mean blood lead level was 1.98 [micro]g/dL higher in PosM women than in PreM women (p = 0.024). The increase in mean blood lead levels peaked during the second year of amenorrhea amenorrhea (āmĕn'ərē`a, əmĕn'–), cessation of menstruation. Primary amenorrhea is a delay in or a failure to start menstruation; secondary amenorrhea is an unexpected stop to the menstrual cycle. with a level (10.35 [micro]g/dL) that was 3.51 [micro]/dL higher than that of PreM women. Other important predictors of blood lead levels were use of lead-glazed ceramics, schooling, trabecular bone trabecular bone n. See spongy bone. lead, body mass index, time of living in Mexico City, and use of hormone replacement therapy Hormone Replacement Therapy Definition Hormone replacement therapy (HRT) is the use of synthetic or natural female hormones to make up for the decline or lack of natural hormones produced in a woman's body. . Bone density was not associated with blood lead levels. These results support the hypothesis that release of bone lead stores increases during menopause and constitutes an internal source of exposure possibly associated with health effects in women in menopause transition. Key words: blood lead, bone lead, bone mineral density bone mineral density n. See bone density. bone mineral density A measurement of bone mass, expressed as the amount of mineral–in grams divided by the area scanned in cm2. See Bone densitometry. , menopause, Mexico. ********** For decades the population of Mexico City was exposed to high environmental lead levels because of the combustion of leaded gasoline and poor environmental control of industrial activities. However, this situation changed in 1986 with regulatory actions that reduced the lead emissions and lead content of gasoline, culminating in its elimination in 1997 (Hernandez-Avila et al. 2000). Similar regulatory actions were established for other sources of lead exposure such as paints, solders in canned food canned food food sterilized by heat in a closed, durable container such as tin and aluminum cans, flexible aluminum foil and thermoplastic containers including squeeze tubes. Technically, the processes used are highly efficient and used universally. , and cosmetics. In addition, in 1995 the Mexican government initiated the search for alternative substitute for lead used in low-temperature hand-made ceramics, but at present this type of ceramic remains the main non-occupational source of lead exposure in Mexico (Hernandez-Avila and Romieu 1991; Romieu et al. 1994). Lead from environmental and occupational sources enters the body through inhalation of particles or intake of lead-contaminated food (Lockitch 1993). It is transported by blood to soft tissues, where it remains for short periods and is finally deposited in bone tissue (Barry and Mossmann 1970). More than 90% of the lead present in the body is stored in bones throughout life, where it may remain for decades (Barry and Mossmann 1970). Nevertheless, bone tissue does not represent a site of permanent sequestration sequestration In law, a writ authorizing a law-enforcement official to take into custody the property of a defendant in order to enforce a judgment or to preserve the property until a judgment is rendered. of lead but rather a source of continuous internal exposure that may increase as a result of the changes in bone turnover observed at different life stages (Gulson et al. 1995; Pounds et al. 1991). This may be the case with menopause, where bone mass loss is a frequent phenomenon that typically starts in the perimenopausal years and continues with an accelerated loss in the early postmenopausal years (Cummings et al. 1985; Elders et al. 1988; Nilas and Christiansen 1988; Riggs and Melton mel·ton n. A heavy woolen cloth used chiefly for making overcoats and hunting jackets. [After Melton Mowbray, an urban district of central England.] 1986; Ruegsegger et al. 1984; Silbergeld et al. 1993). Although previous studies demonstrated the blood lead increase during this stage of life (Muldoon et al. 1994; Silbergeld et al. 1988; Symansky and Hertz-Picciotto 1995; Weyerman and Brenner 1998), only one study recently published simultaneously measured lead levels in blood and bone among perimenopausal women (Korrick et al. 2002). The objective of this study was to examine the relationship between blood and bone lead during menopause under the hypothesis that postmenopausal (PosM) women have higher blood lead levels in comparison with pre-menopausal women after controlling for bone lead content, age, and exposure to environmental sources. A second hypothesis is that higher bone remodeling bone remodeling See Remodeling. rates among PosM women--using bone mineral density (BMD BMD In currencies, this is the abbreviation for the Bermudian Dollar. Notes: The currency market, also known as the Foreign Exchange market, is the largest financial market in the world, with a daily average volume of over US $1 trillion. ) as an indicator--is associated with higher blood lead levels after controlling for age and bone lead among other variables. Materials and Methods The study population was recruited from women attending an osteoporosis-screening program carried out by the Mexican Committee for Osteoporosis Research in Mexico City. Women were recruited through conferences given live during a radio program aimed at women. During the program, one of us (J.T.O.), an expert in osteoporosis, explained to the audience a set of actions to prevent osteoporosis and provided information regarding its diagnosis and treatment and the screening program. The radio programs were broadcast during the first quarter of 1995, and a total of 961 women were recruited. Once the clinical procedures necessary for osteoporosis diagnosing were carried out, all participants were invited for complimentary measurements of blood and bone lead levels. A total of 653 women consented to the blood lead test, and 35% of these (n = 232) completed measurements of both blood and bone lead. The primary reason for not completing the bone lead measurement was the inconvenience of particiants visiting a different clinic far from the initial enrollment and screening center. For the analyses, the final sample was made up of these 232 women, of whom 36 were pre- or peri-menopausal (PreM) and 196 were PosM. The research protocol was approved by the Human Subjects Committee of the National Institute of Public Health of Mexico. All participants gave their informed consent and received a detailed explanation of the study and procedures used, as well as counseling on how to reduce lead exposure. We used a structured questionnaire that collected information on sociodemographics, life styles, reproductive history reproductive history Obstetrics A set of 4 numbers that may be used to define a woman's obstetric Hx–eg, 4-3-2-1, would mean 4 term infants delivered, 3 preterm infants, 2 abortions, 1 child currently living , and sources of environmental exposure to lead. The education level of the subjects was grouped in the following three categories: less than primary school, primary and secondary school, and high school or more. We also asked about tobacco consumption, alcohol consumption, and physical exercise. With regard to tobacco, the subjects were classified according to according to prep. 1. As stated or indicated by; on the authority of: according to historians. 2. In keeping with: according to instructions. 3. current smoking habits. Alcohol consumption was analyzed according to frequency (abstainers, less then once a month but at least once a year, from two to three times a month, and one or more times a weed and the number of drinks consumed per occasion. Regarding physical activity, participants were asked whether they currently exercised on a regular basis. In the section of reproductive characteristics, we collected information on the use of exogenous Exogenous Describes facts outside the control of the firm. Converse of endogenous. hormones and the time of their use, either for family planning family planning Use of measures designed to regulate the number and spacing of children within a family, largely to curb population growth and ensure each family’s access to limited resources. purposes or to treat symptoms associated with menopause. Other variables included the number of pregnancies overall, the number of deliveries, total period of breastfeeding (in months), type of menopause (natural or surgical), and years since menopause. Women were classified as menopausal according to their answers to the following questions: Do you continue menstruating men·stru·ate intr.v. men·stru·at·ed, men·stru·at·ing, men·stru·ates To undergo menstruation. [Late Latin m (yes/no)? If you have stopped menstruating, how long have you not been menstruating (number of months)? Have you stopped menstruating in the natural way, because of some disease, pregnancy or lactation lactation Production of milk by female mammals after giving birth. The milk is discharged by the mammary glands in the breasts. Hormones triggered by delivery of the placenta and by nursing stimulate milk production. , or because you underwent surgery? The menopause event was considered positive when the subjects were in amenorrhea for 12 months not due to pregnancy, lactation, or any disease or surgical procedure. Finally, menopause was classified as natural or surgical. Years since menopause was calculated as the time since the last menstrual period last menstrual period Gynecology The most recent time that a ♀ notes menstruation, a datum recorded in a chart during a routine gynecologic visit. See Menstruation. or time since hysterectomy hysterectomy (hĭstərĕk`təmē), surgical removal of the uterus. A hysterectomy may involve removal of the uterus only or additional removal of the cervix (base of the uterus), fallopian tubes (salpingectomy), and ovaries . The questionnaire also included a section to identify sources of environmental and indoor exposure to lead. Among them, the following were identified: type of vehicular traffic next to the place of residence (intense, intermediate, or low), residence time (in years) in Mexico City, and overall time spent in preparing and storing food in lead-glazed ceramics. These characteristics represent the most important sources of lead exposure previously identified in our population (Hernandez-Avila and Romieu 1991; Romieu et al. 1994). Lead measurements. Blood samples were analyzed with a graphite furnace atomic absorption Graphite furnace atomic absorption spectrometry (GFAAS) (also known as Electrothermal Atomic Absorption Spectrometry (ETAAS)) is a type of spectrometry that uses a graphite-coated furnace to vaporize the sample. spectrophotometry spectrophotometry Branch of spectroscopy dealing with measurement of radiant energy transmitted or reflected by a body as a function of wavelength. The measurement is usually compared to that transmitted or reflected by a system that serves as a standard. instrument (Perkin Elmer 3000; Perkin Elmer, Norwalk, CT) at the metals laboratory of the American British Cowdray Hospital in Mexico City. The laboratory standardization program of the Wisconsin State Laboratory of Hygiene (Madison, WI) provided external quality control specimens varying from 2 to 88 [micro]g/dL. Our laboratory maintained acceptable precision and accuracy during the study time (correlation = 0.98; mean difference, 0.71 [micro]g/dL; SD = 0.68). Bone lead measurements were taken of each subject's midtibial shaft (cortical bone cortical bone n. See cortical substance. ) and patella patella (pətĕl`ə): see kneecap. (trabecular) using a spot-source [sup.109]Cd KXRF instrument constructed at Harvard University Harvard University, mainly at Cambridge, Mass., including Harvard College, the oldest American college. Harvard College Harvard College, originally for men, was founded in 1636 with a grant from the General Court of the Massachusetts Bay Colony. and installed in a research facility at the American British Cowdray Hospital. Physical principles, technical specifications, validation, and use of this and other KXRF instruments have been described in detail elsewhere (Aro et al. 1994; Hu et al. 1995). In brief, the instrument uses a [sup.109]Cd [gamma]-ray source to provoke the emission of fluorescent photons from target tissue that are then detected, counted, and arrayed on a spectrum. Net lead signal is determined after subtraction subtraction, fundamental operation of arithmetic; the inverse of addition. If a and b are real numbers (see number), then the number a−b is that number (called the difference) which when added to b (the subtractor) equals of Compton background counts by a linear least-squares algorithm. The lead fluorescent signal is then normalized to the elastic or coherently scattered y-ray signal, which arises predominantly from the calcium and phosphor A rare earth material used to coat the inside face of a CRT. When struck by an electron beam, the phosphor emits a visible light for a few milliseconds. In color displays, red, green and blue phosphor dots are grouped as a cluster. See screen burn. present in bone mineral. For the present study, 30-min measurements were taken at the midshaft of the left tibia tibia: see leg. (cortical bone) and at the left patella (trabecular bone) after each region had been washed with a 50% solution of isopropyl alcohol isopropyl alcohol: see isopropanol. . The instrument provides an estimate of the uncertainty associated with each measurement; for purposes of quality control of bone lead measurements, we excluded 14 individuals with questionable values either because the movement of the limb being measured was out of the measurement field or because of the extreme thickness of overlying overlying suffocation of piglets by the sow. The piglets may be weak from illness or malnutrition, the sow may be clumsy or ill, the pen may be inadequate in size or poorly designed so that piglets cannot escape. tissue, which resulted in estimates of uncertainty greater than 10 [micro]g Pb/g bone mineral for the tibia or 15 [micro]g Pb/g for the patella. The mean uncertainty (and SD) for patella and tibia in our study were 8.4 (2.8) and 6.9 (3.1), respectively. BMD was measured at the lumbar spine Lumbar spine The segment of the human spine above the pelvis that is involved in low back pain. There are five vertebrae, or bones, in the lumbar spine. Mentioned in: Low Back Pain and femur neck The femur neck is a flattened pyramidal process of bone, connecting the head with the body, and forming with the latter a wide angle opening medialward. The angle is widest in infancy, and becomes lessened during growth, so that at puberty it forms a gentle curve from the with a LUNAR DEXA DEXA, n.pr See dual-energy x-ray absorptiometry. (dual energy x-ray absorptiometry Dual energy X-ray absorptiometry (DXA, previously DEXA) is a means of measuring bone mineral density (BMD). Two X-ray beams with differing energy levels are aimed at the patient's bones. ) densitometer A device that calibrates the relative strength of a color using complementary filters. Contrast with colorimeter. (GE Lunar Corp., Madison, WI). On initiating each measuring session, the equipment was calibrated cal·i·brate tr.v. cal·i·brat·ed, cal·i·brat·ing, cal·i·brates 1. To check, adjust, or determine by comparison with a standard (the graduations of a quantitative measuring instrument): by standardized mineral density devices (photons) whose coefficients of variation were lower than 4%. The results are expressed in grams per square centimeter centimeter (sĕn`tĭmē'tər), abbr. cm, unit of length equal to 0.01 meter, the basic unit of length in the metric system. The centimeter is the unit of length in the cgs system. It is approximately equal to 0. . We used the criteria established by the World Health Organization (WHO 1994) for BMD classification: a) normal, if BMD value was greater than at least 1 SD in relation to the reference group; b) osteopenia, if BMD was between -1.0 and -1.5 SD values; and c) osteoporosis, if BMD was lower than -2.5 SD values in relation to the reference group (WHO 1994). We performed an exploratory analysis of each variable included in the study by univariate statistics and distribution plots. The bivariate bi·var·i·ate adj. Mathematics Having two variables: bivariate binomial distribution. Adj. 1. analysis included test (two groups) and analysis of variance (three or more groups); linear regression Linear regression A statistical technique for fitting a straight line to a set of data points. models were used to examine the relationship between blood lead levels and variables of interest. The age effect was modeled using linear and quadratic quadratic, mathematical expression of the second degree in one or more unknowns (see polynomial). The general quadratic in one unknown has the form ax2+bx+c, where a, b, and c are constants and x is the variable. terms to account for nonlinear relationships observed between age and blood lead (Hernandez-Avila et al. 2000; Silbergeld et al. 1988). First, the relationship between each variable and log-e (natural log) transformation of blood lead levels was examined. Then, we analyzed the relationship between blood lead and all those variables that in bivariate analysis would have achieved 0.15 significance level. We defined the best model by dropping covariates one by one from a saturated model In mathematical logic, and in particular model theory, a saturated model M is one which realizes as many complete types as may be "reasonably expected" given its size. that included all variables with a p-value below 0.15. Our final multivariate The use of multiple variables in a forecasting model. model included all-important predictors with a statistically significant association defined at p < 0.10. When bone lead concentrations are very low (< 5 [micro]g/g bone mineral), the K-XRF measurements may provide negative values because of the algorithm used by equipment software (Hu et al. 1995). To test the robustness of our findings in relation to negative values, these were randomly distributed within an interval between 0 and 5 [micro]g Pb/g of bone mineral. Reanalysis using these values did not change the estimates of interest. All statistical analysis procedures were carried out with a Stata package (Stata Statistical Software, release 7.0, Stata Corp., College Station, TX). Results The study group (n = 232) showed no differences in relation to nonparticipants regarding most characteristics of interest (Table 1). Women who participated showed a lower mean blood lead concentration and a higher body weight. The group of PreM women constituted 15.5% of the total population. The age of the population ranged from 28 to 88 years, with a mean of 54.7 years (SD = 9.8). Most of these women (66.4%) had an intermediate level of schooling (6-9 years). Regarding reproductive characteristics, 92% had a history of one or more pregnancies (mean 4.3, SD = 2.6), and 81% had breast-fed breast·feed or breast-feed v. breast-fed , breast-feed·ing, breast-feeds v.tr. To feed (a baby) mother's milk from the breast; suckle. v.intr. To breastfeed a baby. their infant. The mean age of natural menopause was 47.6 years (SD = 5.8) and of surgical menopause surgical menopause Gynecology Cessation of native estrogenic activity after bilateral oophorectomy in a premenopausal woman was 42.2 years (SD = 6.7). About 46% of the participants with menopause reported the use of hormone replacement therapy (HRT HRT abbr. hormone replacement therapy Hormone replacement therapy (HRT) Also called estrogen replacement therapy, this controversial treatment is used to relieve the discomforts of menopause. ). Life-style characteristics were as follows: 18% of the participants were classified as current smokers; 55% exercised on a regular basis; 22% consumed three or more alcoholic drinks per occasion, and 23% prepared meals in lead-glazed ceramic cookware during the last week. Blood lead levels were distributed between a minimum value of 2.1 [micro]g/dL and a maximum of 32.1 [micro]g/dL, with a mean of 9.2 [micro]g/dL (SD = 4.71) and a 95% confidence interval confidence interval, n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. of 8.5-9.8 lag/dL. Lead values in trabecular and cortical bone were distributed with means of 22.7 [micro]g Pb/g of bone mineral (SD = 14.9) and 14.9 [micro]g Pb/g (SD = 10.09), respectively (Table 2). Lead levels in trabecular bone (patella) explained an important percentage of blood lead variation ([r.sup.2] = 18%). For each 1 [micro]g Pb/g of bone mineral, blood lead levels increased by 1.1% (regression coefficient Regression coefficient Term yielded by regression analysis that indicates the sensitivity of the dependent variable to a particular independent variable. See: Parameter. regression coefficient 0.011; p = 0.001). However, this association varied significantly (p < 0.01) when we stratified stratified /strat·i·fied/ (strat´i-fid) formed or arranged in layers. strat·i·fied adj. Arranged in the form of layers or strata. according to type of menopause (Figure 1). Blood lead increased by 0.3 and 1.1% per [micro]g Pb/g of bone mineral, for PreM and PosM women, respectively. According to this model, a change of 10 [micro]g Pb/g of bone mineral in PosM will be associated with an increase in blood lead of 1.4 [micro]g/dL, whereas a similar change among PreM women will be associated with an increase of 0.8 [micro]g/dL. [FIGURE 1 OMITTED] BMDs of lumbar spine and femur neck were distributed with means of 1.022 [micro]g/[cm.sup.2](SD = 0.177) and 0.873 [micro]g/[cm.sup.2] (SD = 0.135), respectively. We did not find any relationship between blood lead values and BMDs of lumbar spine and femur neck. Regression coefficient for BMD of lumbar spine was 0.0048 (p = 0.962), and for femur neck was 0.1561 (p = 0.217). These coefficients were not modified after adjusting for age and bone lead. No linear relationship was observed between blood lead levels and age (p = 0.23). The highest mean blood lead was observed for the 45- to 49-year-old group, corresponding to the mean age of natural menopause, when it reached a mean concentration of 10.6 [micro]g/dL and progressively decreased to values smaller than those found in PreM women. In the baseline multivariate model that adjusted for age and bone lead (Table 3), PosM women showed blood lead levels 1.98 [micro]g/dL higher than those found in PreM women (p = 0.024). This increase was apparent for women with surgical menopause (1.91 [micro]g/dL) and women with natural menopause (2.1 [micro]g/dL) compared with that for PreM women. In relation to the years since menopause, the distribution of blood lead values showed two points of inflection inflection, in grammar. In many languages, words or parts of words are arranged in formally similar sets consisting of a root, or base, and various affixes. Thus walking, walks, walker have in common the root walk and the affixes -ing, -s, and that, in the case of women with surgical menopause, corresponded to the first and fifth year after menopause (11.17 and 10.07 [micro]g/dL), which corresponded to a difference of 3.35 and 1.92 [micro]g/dL compared with those in the PreM group (p = 0.158); for women with natural menopause, the two points of inflection corresponded to the second and fourth year after menopause (10.35 and 11.43 [micro]g/dL), differences of 2.2 and 3.28 [micro]g/dL, respectively (p = 0.063). PosM women who used HRT (adjusting for age and bone lead) had lower blood lead levels than PosM women who did not use the therapy, with an estimated mean blood lead difference of-1.25 [micro]g/dL (p = 0.09). When the analysis was restricted to the group of participants with natural menopause, the mean blood lead concentration was 2.64 [micro]g/dL higher in the group of PosM women who were nonusers of replacement estrogens Estrogens Hormones produced by the ovaries, the female sex glands. Mentioned in: Acne, Polycystic Ovary Syndrome estrogens (es´trōjenz), n. (p = 0.005). The use of lead-glazed ceramics was an important predictor of blood lead levels. The women who prepared and stored food in lead-glazed ceramic cookware during the previous week showed higher blood lead compared with those who did not use it, with differences of 2.48 and 2.01 [micro]g/dL, respectively (p < 0.05). Finally, the most parsimonious par·si·mo·ni·ous adj. Excessively sparing or frugal. par  si·mo multivariate model that explained
38.7% of the variation in blood lead levels included the following
variables: age (linear and quadratic terms), time of postmenopause, body
mass index, patella lead, use of lead-glazed ceramic cookware, schooling
level greater than 6 years, and time of living in Mexico City (Table 4).Discussion Our results showed that blood lead increases significantly in the PosM period and particularly in the first 3 years of this period. Our data suggest that once these maximum levels are achieved, the blood lead decreases in the third year and afterward starts increasing again. This finding is consistent with a particular bone remodeling pattern during the first years of postmenopause that mainly depends on higher bone turnover of trabecular bone. As is well known, the trabecular bone loss increases in the perimenopausal period, which is followed by an accelerated loss in the first years of postmenopause, and then bone resorption Bone resorption is the process by which osteoclasts break down bone and release the minerals, resulting in a transfer of calcium from bone fluid to the blood. The osteoclasts are multi-nucleated cells that contain numerous mitochondria and lysosomes. decreases and becomes constant (Cummings et al. 1985; Elders et al. 1988; Nilas and Christiansen 1988; Riggs and Melton 1986; Ruegsegger et al. 1984). As reported by Muldoon et al. (1994), our study did not find high blood lead levels in women with low mineral density. Measurements of BMD in cross-sectional studies provide a snapshot of the balance between bone deposition and bone resorption rates over preceding years, whereas blood lead levels would be expected to depend more specifically on absolute rates of ongoing bone resorption. Because of this limitation Hu et al. (1998) proposed the use of bone markers bone marker Lab medicine Any protein degradation product that indicates bone breakdown. See N-telopeptides. that are specific for ongoing rates of bone resorption such as the N-telopeptide of type I collagen (urinary NTX NTX N-Telopeptide Cross-Links (bone resorption marker) NTX Navy Teletypewriter Exchange NTX Nt Extended NTX Network Terminal Accelerator ). Recent research in elderly men suggests that urinary NTX is a significant modifier (programming) modifier - An operation that alters the state of an object. Modifiers often have names that begin with "set" and corresponding selector functions whose names begin with "get". of the bone lead-blood lead relationship. The age-adjusted difference in trabecular bone lead concentrations observed between PosM and premenopausal pre·me·no·paus·al adj. Of or relating to the years or the stage of life immediately before the onset of menopause. premenopausal adjective women (difference of -5.8 [micro]g of lead per gram of bone mineral; p = 0.02) supports the hypothesis that the lead is mobilized from the bone compartments toward the circulation and contributes to the increase of blood lead levels in this stage of life. The hypothesis is also supported by our observation that the use of replacement estrogens was also associated with lower blood lead levels among PosM women. Furthermore, patella lead explained the greatest part of variations in blood lead levels, and its independent effect remained the same after controlling other important predictors of blood lead. A different pattern was found in the association between tibia lead and blood lead. These levels were marginally different between PreM and PosM women (p = 0.06). This difference suggests the existence of lead pools in the mineral tissue (trabecular represented by patella and cortical cor·ti·cal adj. 1. Of, relating to, derived from, or consisting of cortex. 2. Of, relating to, associated with, or depending on the cerebral cortex. by tibia) that follow different turnovers. In cortical bone, it is known that its turnover is much slower than that occurring in trabecular bone, so its contribution to blood lead levels is expected to be smaller. It should be noted, however, that cortical bone composes the majority of skeletal mass (~80%), making even modest resorption resorption /re·sorp·tion/ (re-sorp´shun) 1. the lysis and assimilation of a substance, as of bone. 2. reabsorption. re·sorp·tion n. of cortical bone a potentially major influence on blood lead levels. Similar results were reported by Kosnett et al. (1994) in women older than 55 years. Silbergeld et al. (1988) and Symansky and Hertz-Picciotto (1995) observed an increase of blood lead in nulliparous PosM women after comparing them with multiparous mul·tip·a·rous adj. 1. Relating to a multipara. 2. Giving birth to more than one offspring at a time. women. This finding suggests that pregnancy, and probably breastfeeding as well, may mobilize the lead deposited in bone simultaneously with calcium, to meet the calcium requirements observed in pregnancy and lactation, leaving smaller amounts of lead to be mobilized during the menopause transition. These results have not been confirmed by other investigators (Brown et al. 2000; Muldoon et al. 1994; Weyerman and Brenner 1998). In our study PosM women who breast-fed had higher bone lead levels (21.2 and 18.1 [micro]g of lead per gram of bone mineral; p = 0.23). These results are similar to those reported by Brown et al. (2000) and probably reflect the fact that this cohort of women breast-fed during the years of high lead concentrations in the Mexico City air and thus incorporated additional lead during the bone gain phase that is known to follow pregnancy and lactation (Kalkwarfet al 1997). HRT, alone or combined, prevents bone resorption and increases the BMD in trabecular and cortical bones of women with and without metabolic bone disease metabolic bone disease Any defect in bone absorption or deposition that alters the PTH/calcium-phosphate/vitamin D axis, often with ↑ bone fragility Etiology Fibrous dysplasia, Langerhans' cell histiocytosis/histiocytosis X, acromegaly, corticosteroid therapy, (Berlin et al. 1995; Gruber et al. 1997; Webber et al. 1995). This effect may lead to a decrease of lead mobilization from bone together with a reduction in blood lead levels. Webber et al. (1995) reported that women with HRT showed greater bone lead concentrations, especially in cortical bone, without having a simultaneous decrease in blood lead. In our study, 46.4% of the PosM women used HRT, and the blood lead levels observed among them were lower than those in nonusers (difference of 2.1 [micro]g/dL; p < 0.05). In addition, we found that trabecular and cortical bone lead levels were higher in women who used HRT (1.19 and 0.43 pg Pb/g of bone mineral for patella and tibia, respectively). This observation supports the hypothesis that HRT reduces bone resorption, and by preventing lead mobilization from bone and diminishing blood lead levels, HRT may be considered a preventive measure in PosM women with high bone lead levels. Compared with women of child-bearing age living in Mexico City (Brown et al. 2000) as well as perimenopausal women living in the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. (Korrick et al. 2002), the mean bone lead levels seen in these women were significantly higher. This finding reflects the fact that women participating in our study were living in Mexico City during the time that gasoline had a higher lead content and thus were subject to higher environmental lead exposures in the recent past. The adjusted regression coefficient of patella bone lead on blood lead predicted an increase of 0.80 pg blood lead/[micro]g bone lead for women of childbearing age and of 0.050 pg blood lead/pg bone lead for perimenopausal women, which were lower than estimated in this study (blood lead 0.135 [micro]g/[micro]g of bone lead). Our study has potential limitations that may affect the inferences derived from these data. The participants were primarily low- and middle-class women who voluntarily attended an osteoporosis program and were not a random sample of the general population. Thus, our results cannot be generalized to all women living in Mexico City. Of note, we found differences, in terms of both blood lead levels and height, between women attending the screening program and women taking part in bone lead measurements. However, the differences observed in blood lead levels decreased once we adjusted for other variables such as use of ceramics, age, and menopausal status; therefore, it is unlikely that selection bias could explain our findings. We used simple questionnaire data to characterize environmental exposure to lead-glazed ceramic ware and thus may have underestimated the contribution to blood lead levels of this major known source of environmental lead exposure in Mexico. Only 16% of our study group (n = 36) were pre-menopausal, limiting our ability to conduct a more in-depth analysis of potential interactions such as the potential modifying effect of menopausal status on other factors that determined blood or bone lead levels. The cross-sectional nature of these data also limited our ability to do more sophisticated kinetic modeling of bone lead-blood lead interrelationships. Suspicion exists that the accumulation of lead in bone itself represents a risk factor for osteoporosis. Individual cases such as the subjects reported by Berlin et al. (1995) who had occupational lead exposure, a bone fracture, and diagnosis of idiopathic idiopathic /id·io·path·ic/ (id?e-o-path´ik) self-originated; occurring without known cause. id·i·o·path·ic adj. 1. Of or relating to a disease having no known cause; agnogenic. osteoporosis provide some circumstantial evidence circumstantial evidence In law, evidence that is drawn not from direct observation of a fact at issue but from events or circumstances that surround it. If a witness arrives at a crime scene seconds after hearing a gunshot to find someone standing over a corpse and holding a of such a relationship. Other evidence supporting the hypothesis that lead can directly damage bone includes observations of fetal and neonatal growth reduction and the development of osteopenia in experimental animals exposed to lead (Gruber et al. 1997). Pounds et al. (1991) reported that bone cells, both in vitro in vitro /in vi·tro/ (in ve´tro) [L.] within a glass; observable in a test tube; in an artificial environment. in vi·tro adj. In an artificial environment outside a living organism. and in vivo in vivo /in vi·vo/ (ve´vo) [L.] within the living body. in vi·vo adj. Within a living organism. in vivo adv. , may be impaired by the presence of lead. However, additional studies are required to directly assess this hypothesis and to investigate indirect routes by which lead may be related to osteoporosis, such as the possibility that lead affects calcium absorption at the level of the digestive tract digestive tract n. See alimentary canal. Digestive tract The organs that perform digestion, or changing of food into a form that can be absorbed by the body. or that lead reduces circulating levels of 1,25-dehydrocholecalciferol, as has been noted in children by Mahaffey et al. (1982). The increase in blood lead concentrations that result from bone resorption after menopause may, in turn, be associated with health effects that have not been adequately studied in elderly women. Studies of subjects in other age groups show that relatively modest exposures to lead are associated with neurologic dysfunction, behavioral disorders behavioral disorder Psychiatry A disorder characterized by displayed behaviors over a long period of time which significantly deviate from socially acceptable norms for a person's age and situation , hypertension, renal damage, and hematologic hematological, hematologic pertaining to or emanating from blood cells. hematological tests total and differential white cell counts, hematocrit estimation, erythrocyte count. changes (Vig and Hu 2000). It may be particularly important to study the relationship between blood and bone lead levels and cognitive impairment in perimenopausal women because of the potential modifying role played by osteoporosis in these women.
Table 1. Characteristics of women participating in
the study according to their distribution in
participation groups.
Participated
in the bone lead
screening test
Variables Yes No p-Value
Age (years)
n 232 421
Mean 54.1 53.3 0.33
Blood lead ([micro]g/dL log-e)
n 232 421
Mean 9.2 10.0 0.004
Height (cm)
n 222 406
Mean 154.7 153.9 0.09
Weight (kg)
n 222 406
Mean 64.5 62.2 0.01
Lumbar spine
([micro]g/[cm.sup.2])
n 221 405
Mean 1.022 1.035 0.64
Femoral neck
([micro]g/[cm.sup.2])
n 220 402
Mean 0.873 0.881 0.46
No. of pregnancies
n 232 421
Mean 4.2 4.1 0.53
Use of lead-glazed ceramics
Yes 49 99
No 183 322 0.48
Literacy (years of school)
0-5 27 54
6-9 154 267
[greater than or equal to] 10 51 99 0.51
Smoking (%)
Yes (current) 42 64
Yes (past) 45 62 0.58
Never 145 278
Table 2. Study population according to selected variables.
Percentages or means
Variables n (a) and SD values Range
Age (years) 232 54.1 [+ or -] 9.8 28-88
Literacy (%)
0-5 years 27 11.6
6-9 years 154 66.4
[greater than or equal to]
10 years 51 22.0
Height (cm) 222 154.7 [+ or -] 5.8 1.43-1.82
Weight (kg) 222 64.5 [+ or -] 10.9 44-105
Body mass index 222 27.1 [+ or -] 4.6 17.3-35.8
Blood lead ([micro]g/dL) 232 9.2 [+ or -] 4.7 2.1-32.1
Patella lead ([micro]g Pb/g
bone mineral) 232 22.73 [+ or -] 14.9 ND-89.3
Tibia lead ([micro]g Pb/g
bone mineral) 232 14.85 [+ or -] 10.1 ND-57.8
Smoking (%)
Yes (current) 42 18.1
Yes (past) 45 19.3
Never 145 62.6
Physical activity (%)
Yes 128 55.2
No 104 44.8
No. of drinks per week (%)
One or less 127 54.7
Two 55 23.7
Three or more 50 21.6
Use of lead-glazed ceramics
Yes 49 21.1
No 183 78.8
Menarche (mean age) 232 12.7 [+ or -] 1.5 9-17
No. of pregnancies 232 4.26 [+ or -] 2.6 0-13
History of breast-
feeding (%)
Yes 187 80.6
No 26 11.2
Nulliparous 19 8.2
Premenopausal or
perimenopausal 36 15.5
Postmenopausal 196 84.5
Surgical 76 32.8
Natural 120 51.7
Age at menopause 196 45.3 [+ or -] 7.0 24-60
Years since menopause 191 11.3 [+ or -] 8.7 1-42
BMD lumbar spine
(g/[cm.sup.2]) 221 1.022 [+ or -] 0.18 0.47-1.62
BMD femoral neck
(g/[cm.sup.2]) 220 0.873 [+ or -] 0.14 0.54-1.31
(a) Some variables have missing values.
Table 3. Blood lead levels (microgram/deciliter) according to
sociodemographic, life style, and reproductive characteristics.
Variables n Mean SD
Age groups (years)
<40 12 10.5 5.5
40-44 23 9.4 4.1
45-49 41 10.6 6.0
50-54 40 9.1 3.9
55-59 49 8.5 3.0
60-64 30 8.9 5.5
65-69 19 8.3 6.4
[greater than or equal 18 7.7 3.2
to] 70
Literacy (years of school)
0-5 27 10.2 5.7
6-9 154 9.3 4.7
[greater than or equal 51 8.1 4.1
to] 10
No. of pregnancies
None 19 9.7 5.7
1-3 82 8.5 3.2
4-6 87 9.0 4.4
[greater than or equal 44 10.4 6.7
to] 7
Breast-feeding
No 26 8.2 3.2
Yes 187 9.2 4.8
Menopause
No (PreM) 36 9.4 4.9
Yes (PosM) 196 9.1 4.7
Type of menopause
PreM 36 9.4 4.9
Surgical 76 9.3 3.8
Natural 120 9.00 5.2
Time since menopause
(surgical, months)
PreM 36 9.4 4.9
12 9 11.2 4.5
13-24 6 11.1 3.9
25-36 10 7.5 2.7
37-48 9 8.9 3.6
[greater than or equal to]
49 years 42 9.1 3.7
Time since menopause
(natural, months)
PreM 36 9.4 4.9
12 15 9.3 4.3
13-24 18 9.7 4.5
25-36 12 6.8 2.5
37-48 12 11.2 7.2
[greater than or equal to]
49 years 58 8.9 5.6
HRT
Yes 91 8.5 3.5
No 105 9.7 5.5
HRT (natural menopause)
Yes 53 7.5 3.1
No 67 10.2 6.1
HRT (surgical menopause
Yes 38 9.8 3.7
No 38 8.7 3.1
Smoking
Yes (current) 42 9.1 4.9
Yes (past) 45 8.0 4.8
Never 145 9.5 4.6
Physical activity
Yes 128 9.6 5.2
No 104 8.6 3.9
No. of drinks
One or less 127 8.7 4.7
Two 55 9.9 5.6
Three + 50 9.4 3.6
Use of lead-glazed ceramics
Yes 49 10.7 6.7
No 183 8.6 3.6
Means adjusted
by age and Adjusted
Variables p-Value (a) bone lead p-value (a)
Age groups (years)
<40 0.23 9.7 0.19
40-44 9.1
45-49 10.4
50-54 9.2
55-59 9.1
60-64 8.8
65-69 8.4
[greater than or equal 7.5
to] 70
Literacy (years of school)
0-5 0.06 10.9 <0.01
6-9 9.2
[greater than or equal 8.1
to] 10
No. of pregnancies
None 0.42 9.8 0.24
1-3 8.4
4-6 9.1
[greater than or equal 10.4
to] 7
Breast-feeding
No 0.43 8.26 0.38
Yes 9.21
Menopause
No (PreM) 0.69 7.5 0.02
Yes (PosM) 9.5
Type of menopause
PreM 0.50 7.4 0.08
Surgical 9.4
Natural 9.5
Time since menopause
(surgical, months)
PreM 0.32 8.2 0.15
12 11.2
13-24 9.9
25-36 8.2
37-48 9.3
[greater than or equal to]
49 years 10.1
Time since menopause
(natural, months)
PreM 0.23 6.8 0.06
12 7.9
13-24 10.4
25-36 7.2
37-48 11.4
[greater than or equal to]
49 years 10.3
HRT
Yes 0.20 8.8 0.10
No 10.1
HRT (natural menopause)
Yes <0.01 8.4 0.01
No 10.5
HRT (surgical menopause
Yes 0.14 9.4 0.41
No 9.1
Smoking
Yes (current) 0.74 8.3 0.10
Yes (past) 8.4
Never 9.4
Physical activity
Yes 0.09 9.5 0.14
No 8.6
No. of drinks
One or less 0.112 8.9 0.20
Two 9.9
Three + 8.9
Use of lead-glazed ceramics
Yes <0.01 10.5 <0.01
No 9.2
(a) p-Value from ANOVA using log-e transformed blood lead as the
dependent variable.
Table 4. Results from multivariate linear regression of blood
lead levels (log-e, microgram per deciliter) on selected predictors
of study participants
Variable Coefficient p-Value 95% Cl
Age linear (years) -0.063 0.01 -0.113 to -0.013
Age squared ([years.sup.2]) 0.0005 0.04 0.0001 to 0.001
Patella lead ([micro]g Pb/g
mineral bone) 0.012 <0.01 0.008 to 0.015
Time postmenopausal
(1-24 months) (a) 0.284 <0.01 0.111 to 0.456
Time postmenopausal ([greater
than or equal to] 25 months)
(a) 0.204 0.03 0.020 to 0.388
Body mass index [(kg/height
in m).sup.2] 0.015 0.03 0.001 to 0.029
Keeps food in lead-glazed
ceramics 0.221 <0.01 0.100 to 0.342
Education level (6-9 years)
(b) -0.191 0.040 -0.373 to -0.009
Education level ([greater
than or equal to] 10 years)
(b) -0.296 <0.01 -0.506 to -0.085
Time living in Mexico City
(years) 0.007 <0.01 0.003 to 0.012
Constant 3.41 <0.01 2.03 to 4.784
(a) Years since menopause is in reference to PreM.
(b) Educational level of 0-5 years is the reference category.
REFERENCES Aro ACA ACA - Application Control Architecture , Todd AC, Amarasiriwardena C, Hu H. 1994. Improvement in the calibration of 103CD K x-ray fluorescence X-ray fluorescence (XRF) is the emission of characteristic "secondary" (or fluorescent) X-rays from a material that has been excited by bombarding with high-energy X-rays or gamma rays. systems for measuring bone lead in vivo. Phys Meal Biol 39:2263-2271. Barry PSI, Mossmann DB. 1970. Lead concentration in human tissues. Br J Ind Med 27:339-351. Berlin K, Gerhardsson L, Borjesson J, Lindh E, Lundstrom N, Schutz A, et al. 1995. Lead intoxication intoxication, condition of body tissue affected by a poisonous substance. Poisonous materials, or toxins, are to be found in heavy metals such as lead and mercury, in drugs, in chemicals such as alcohol and carbon tetrachloride, in gases such as carbon monoxide, and caused by skeletal disease. Scand J Work Environ Health 21:296-300. Brown MJ, Hu H, Gonzalez-Cossio T, Peterson K, Sannin LH, Fishbein E, et al. 2000. Determinants of bone and blood lead levels in the early postpartum period The postpartum period is the period consisting of the months or weeks immediately after childbirth or delivery. Importance to health The postpartum period is when the woman adjusts, both physically and psychologically, to the process of childbearing. . Occup Environ Med 57:535-541. Cummings SR, Kelsey JL, Nevitt MC, et al. 1985. Epidemiology of osteoporosis and osteoporotic fractures. Epidemiol Rev 7:178-208. Elders PJ, Netelenbos ac, Lips P, van Ginkel FC, van der Stelt PF. 1988. Accelerated vertebral ver·te·bral adj. 1. Of, relating to, or of the nature of a vertebra. 2. Having or consisting of vertebrae. 3. Having a spinal column. bone loss in relation to the menopause: a cross-sectional study on lumbar lumbar /lum·bar/ (lum´bar) pertaining to the loins. lum·bar adj. Of, near, or situated in the part of the back and sides between the lowest ribs and the pelvis. bone density in 286 women of 46 to 55 years of age. Bone Miner 5:11-19. Gruber H, Gonick H, Khalil-Manesh F, Sanchez T, Motsinger S, Meyer M, et al. 1997. Osteopenia induced by long-term, low-and-high-level exposure of the adult rat to lead. Miner Electrolyte electrolyte (ĭlĕk`trəlīt'), electrical conductor in which current is carried by ions rather than by free electrons (as in a metal). Metab 23:65-73. Gulson BL, Mahaffey KR, Mizon K J, Korsch M J, Cameron MA, Vimpani G. 1995. Contribution of tissue lead to blood lead in adult female subjects based on stable lead isotope methods. J Lab Clin Med 125:703-712. Hernandez-Avila M, Gonzalez VC, Palazuelos E, Hu H, Gonzalez VME (Virtual Machine Environment) An operating system from Fujitsu Services (formerly ICL) that runs on its Series 39 mainframes. Introduced in 1975, VME is a comprehensive product that provides a variety of utilities for datacenter operations. , Rivera MD. 2000. Determinants of blood lead levels across the menopausal transition. Arch Environ Health. 55:355-362. Hernandez-Avila M, Romieu I. 1991. Lead glazed glaze n. 1. A thin smooth shiny coating. 2. A thin glassy coating of ice. 3. a. A coating of colored, opaque, or transparent material applied to ceramics before firing. b. ceramics as major determinants of blood lead levels in Mexican women. Environ Health Perspect 94:117-120. Hu H, Aro A, Roknitzky A. 1995. Bone lead measured by x-ray fluorescence: epidemiological methods Texts and literature in epidemiology often make use of jargon related to epidemiological methods without reference to their actual definition. A number of basic concepts recur with particular frequency:
Hu H, Rabinowitz M, Smith D. 1998. Bone lead as a biologic marker in epidemiologic studies of chronic toxicity chronic toxicity Toxicology A condition caused by repeated or long-term exposure to low doses of a toxic substance : conceptual paradigms. Environ Health Perspect 106:1-8. Kalkwarf KJ, Specker BL, Bianchi DC, Ranz J, Ho M. 1997. The effect of calcium supplementation calcium supplementation Metabolism The addition of Ca2+ to the diet, usually in the form of calcium carbonate on bone density during lactation and after weaning weaning, n the period of transition from breast feeding to eating solid foods. weaning the act of separating the young from the dam that it has been sucking, or receiving a milk diet provided by the dam or from artificial sources. . N Engl J Med 337:523-528. Korrick SA, Schwartz J, Tsaih SW, Hunter DJ, Aro Ao Rosner B, et al. 2002. Correlates of bone and blood lead levels among middle-aged and elderly women. Am J Epidemiol 156:335-343. Kosnett MJ, Becker CE, Osterloh J, Kelly T J, Pasta DJ. 1994. Factors influencing bone lead concentration in a suburban community assessed by noninvasive K Xray fluorescence. JAMA JAMA abbr. Journal of the American Medical Association 271:197-203. Lockitch G. 1993. Perspectives on lead toxicity. Clin Biochem 26:371-381. Mahaffey KR, Rosen JF, Chesney RW, et al. 1982. Associations between age, blood lead, and serum 1,25-dihydroxycholecalciferol levels in children. Am J Clin Nutr 35:1327-1331. Muldoon SB, Cauley JA, Kuller LH, Scott J, Rohay J. 1994. Lifestyle and socidemographic factors as determinants of blood lead levels in elderly women. Am J Epidemiol 139:599-608. Nilas L, Christiansen C. 1988. Rates of bone loss in normal women: evidence of accelerated trabecular bone loss after menopause. Eur J Clin Invest 18:529-534. Pounds GJ, Long GJ, Rosen JF. 1991. Cellular and molecular toxicity of lead in bone. Environ Health Perspect 91:17-32. Riggs BL, Melton LJ III. 1986. Involutional osteoporosis.-N Engl J Med 314(26):1676-1986. Romieu I, Palazuelos E, Hernandez-Avila M, et al. 1994. Sources of lead exposure in Mexico City. Environ Health Perspect 102:384-389. Ruegsegger P, Dambacher MA, Ruegsegger E, Fischer JA, Anliker M. 1984. Bone loss in premenopausal women. A cross-sectional and longitudinal study longitudinal study a chronological study in epidemiology which attempts to establish a relationship between an antecedent cause and a subsequent effect. See also cohort study. using quantitative computed tomography Computed tomography (CT scan) X rays are aimed at slices of the body (by rotating equipment) and results are assembled with a computer to give a three-dimensional picture of a structure. . J Bone Surg 66:1015-1023. Silbergeld EK, Sauk J, Somerman M, Todd A, McNeill F, Fowler B, et al. 1993. Lead in bone: storage sits, exposure source, and target organ target organ n. A tissue or organ that is affected by a specific hormone. target organ, n the organ or body part whose activity levels demonstrate change in the course of biofeedback. . Neurotoxicology 14:225-236. Silbergeld EK, Schwartz J, Mahaffey K. 1988. Lead and osteoporosis: mobilization of lead from bone in postmenopausal women. Environ Res 47:79-94. Symansky E, Hertz-Picciotto I. 1995. Blood lead levels in relation to menopause, smoking and pregnancy history. Am J Epidemiol 141:1047-1058. Vig EK, Hu H. 2000 Lead toxicity in older adults. J Am Geriatr Soc 48(11):1501-1506. Webber CE, Chette DR, Bowins RJ, Beaumont LF, Gordon CL, Song X, et al. 1995. Hormone replacement therapy may reduce the return of endogenous endogenous /en·dog·e·nous/ (en-doj´e-nus) produced within or caused by factors within the organism. en·dog·e·nous adj. 1. Originating or produced within an organism, tissue, or cell. lead from bone to the circulation. Environ Health Perspect 103:1150-1153. Weyerman M, Brenner H. 1998. Factors affecting bone demineralization demineralization /de·min·er·al·iza·tion/ (de-min?er-al-i-za´shun) excessive elimination of mineral or organic salts from tissues of the body. de·min·er·al·i·za·tion n. and blood lead levels of postmenopausal women. A population-based study from Germany. Environ Res 76:1 9-25. WHO. 1994. Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis. Technical Report Series, Geneva Geneva, canton and city, Switzerland Geneva (jənē`və), Fr. Genève, canton (1990 pop. 373,019), 109 sq mi (282 sq km), SW Switzerland, surrounding the southwest tip of the Lake of Geneva. : World Health Organization. Francisco Garrido Latorre, (1) * Mauricio Hernandez-Avila, (1) Juan Tamayo Orozco, (2) Carlos A. Albores Medina, (3) Antonio Aro, (4) Eduardo Palazuelos, (5) and Howard Hu (4) (1) Instituto Nacional de Salud Publica, Cuernavaca, Morelos, Mexico; (2) Comite Mexicano para el Estudio de la Osteoporosis and Hospital Medica medica (māˑ·dē·k , Mexico City, Mexico; (3) Departamento de Toxicologia, Centro Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Mexico, DF, Mexico; (4) Channing Laboratory, Department of Medicine, Brigham and Women's Hospital Brigham and Women's Hospital (BWH) is a hospital in the Longwood Area of the Boston, Massachusetts neighborhood of Mission Hill. With Massachusetts General Hospital, it is one of the two founding members of Partners HealthCare. , Harvard Medical School Harvard Medical School (HMS) is one of the graduate schools of Harvard University. It is a prestigious American medical school located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts. and Occupational Health Program, Department of Environmental Health, Harvard School of Public Health The Harvard School of Public Health is (colloquially, HSPH) is one of the professional graduate schools of Harvard University. Located in Longwood Area of the Boston, Massachusetts neighborhood of Mission Hill, next to Harvard Medical School and Cambridge, Massachusetts, , Boston, Massachusetts “Boston” redirects here. For other uses, see Boston (disambiguation). Boston is the capital and most populous city of Massachusetts.[3] The largest city in New England, Boston is considered the unofficial economic and cultural center of the entire New , USA; (5) American British Cowdray Hospital, Mexico City, Mexico Address correspondence to M. Hernandez-Avila, Instituto Nacional de Salud Publica, Av Universidad 655, Col Sta Ma Ahuacatitlan, CP 62508, Cuernavaca, Morelos, Mexico. Telephone: 52 777 329 3003. Fax 52 777 311 1148. E-mail: mhernan@ correo.insp.mx * Current address: Evaluacion de Programa y Servicios de Salud, Reforma Juarez, Deleg. Cuauhtemoc, Mexico, DF. Support for this study came from the U.S. National Institute of Environmental Health Sciences The National Institute of Environmental Health Sciences (NIEHS) is one of 27 Institutes and Centers of the National Institutes of Health (NIH),which is a component of the Department of Health and Human Services (DHHS). The Director of the NIEHS is Dr. David A. Schwartz. (NIEHS NIEHS National Institute of Environmental Health Sciences (NIH, DHHS) ) P42-ES05947 Project 3, NIEHS R01ES07821, and NIEHS Center 2 P30 ES 00002 and from Consejo Nacional de Ciencia y Tecnologia (CONACYT CONACYT Consejo Nacional de Ciencia y Tecnología (National Board of Science and Technology; Mexico, Bolivia, Paraguay) ) grant 1233P-M Mexico. Received 8 August 2001; accepted 16 December 2002. |
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