Bone Lead Research Articles

Prenatal Lead Exposure and Weight of 0- to 5-Year-Old Children in Mexico City

Background: Cumulative prenatal lead exposure, as measured by maternal bone lead burden, has been associated with smaller weight of offspring at birth and 1 month of age, but no study has examined whether this effect persists into early childhood.Objective: We investigated the association of perinatal maternal bone lead, a biomarker of cumulative prenatal lead exposure, with children’s attained weight over time from birth to 5 years of age.Methods: Children were weighed at birth and at several intervals up until 60 months. Maternal tibia and patella lead were measured at 1 month postpartum using in vivo K-shell X-ray fluorescence. We used varying coefficient models with random effects to assess the association of maternal bone lead with weight trajectories of 522 boys and 477 girls born between 1994 and 2005 in Mexico City.Results: After controlling for breast-feeding duration, maternal anthropometry, and sociodemographic characteristics, a 1-SD increase in maternal patella lead (micrograms per gram) was associated with a 130.9-g decrease in weight [95% confidence interval (CI), –227.4 to –34.4 g] among females and a 13.0-g nonsignificant increase in weight among males (95% CI, –73.7 to 99.9 g) at 5 years of age. These associations were similar after controlling for concurrent blood lead levels between birth and 5 years.Conclusions: Maternal bone lead was associated with lower weight over time among female but not male children up to 5 years of age. Given that the association was evident for patellar but not tibial lead levels, and was limited to females, results need to be confirmed in other studies.

THE INFLUENCE OF BONE-DENSITY ON IN VIVO K X-RAY FLUORESCENCE BONE-LEAD MEASUREMENTS

Mathematical simulations and benchmark measurements were performed to assess the impact that normal variations in human calcium content have on in vivo K x-ray fluorescence measurements of lead in bone. Four sets of cortical bone tissue simulants were fabricated containing from 20.8% to 23.8% calcium (by weight) for measurement in a surrogate (phantom) of the human leg. The net counts detected in the coherent backscatter peak at 88.034 keV using a Cd source indicate a positive trend, with a variability of up to 17% over the range of assessed calcium content. Mathematical simulations confirm this trend and also demonstrate that the contribution of 87.3 keV Pb Kβ2 counts, which are unresolved in measurements, do not contribute significantly to the coherent peak at low levels of bone-lead content. Both measurements and simulations confirm that calcium is a statistically significant parameter in predicting the K-XRF response and suggest that lead levels may be over-predicted for individuals having low bone density compared to the calibration matrix. Simulations identify a 4.5% negative bias in measured lead values for each 1% increase in calcium weight percent in the bone matrix as compared to the calibration matrix. It is therefore important to accommodate this uncertainty when performing epidemiological studies of populations having a wide range of bone densities.

Prospective Cohort Study of Lead Exposure and Electrocardiographic Conduction Disturbances in the Department of Veterans Affairs Normative Aging Study

Background: No studies have examined the association between cumulative low-level lead exposure and the prospective development of electrocardiographic conduction abnormalities, which may mediate the association between lead and several cardiovascular end points.Objective: We prospectively examined the association between lead exposure and the development of electrocardiographic conduction abnormalities.Methods: We assessed blood lead, bone lead—a biomarker of cumulative lead exposure—measured with K-shell X-ray fluorescence, and electrocardiographic end points among 600 men in the Normative Aging Study who were free of electrocardiographic abnormalities at the time of the baseline ECG. Of these men, we had follow-up data from a second electrocardiogram for 496 men 8.1 (SD = 3.1) years later, on average. We used repeated measures linear regression to analyze change in electrocardiographic conduction timing and logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for developing specific conduction disturbances and adjusted for potential confounders.Results: Mean (± SD) blood (5.8 ± 3.6), patella bone (30.3 ± 17.7), and tibia bone (21.6 ± 12.0) lead concentrations were similar to those found in samples from the general U.S. population and much lower than those reported in occupationally exposed groups. Compared with those in the lowest tertile of tibia lead, those in the highest had a 7.94-ms (95% CI, 1.42–14.45) increase in heart rate–corrected QT (QTc) interval and a 5.94-ms increase in heart rate–corrected QRS (95% CI, 1.66–10.22) duration > 8 years. Those in the highest tertile of tibia lead also had increased odds of QT prolongation (QTc ≥ 440 msec; OR = 2.53; 95% CI, 1.22–5.25) and JT prolongation (heart rate–corrected JT > 360 msec; OR = 2.53; 95% CI, 0.93–6.91). Results were weaker for patella lead. No associations were identified with blood lead.Conclusions: This study suggests that low-level cumulative exposure to lead is associated with worse future cardiac conductivity in the ventricular myocardium, as reflected in QT interval characteristics.

Lead and Calcium Content in the Human Hip Joint

Concentration of lead in bone, unlike in soft tissues, increases during the lifetime and reflects severity of exposure to this element. The main aim of the study was to determine concentrations of lead and calcium and to find possible relationship between calcium and lead in the tissues of the hip joints obtained from inhabitants of the Upper Silesian Industrial Area. We also attempted to identify factors that might affect this relationship. The samples were harvested intraoperatively during total hip replacement procedures; in most cases, the indication for the surgery was hip osteoarthritis. Concentrations of lead and calcium were measured with a Pye Unicam SP-9 acetylene-oxygen flame atomic absorption spectrometer. The highest mean concentration of lead was found in the cancellous bone from the femoral head, followed by articular cartilage, cortical bone and the intertrochanteric cancellous bone (0.75μg/g). The smallest concentration was found in the joint capsule (0.19μg/g). The highest mean concentration of calcium was found in cancellous bone from the femoral head, followed by cancellous bone from the intertrochanteric area, cortical bone, articular cartilage and joint capsule. The concentration of lead showed no correlation with sex. The bone concentration of calcium decreased with age. In the analysed hips, this finding was true in the cortical bone, as well as in the cancellous bone of the intertrochanteric area. Statistically significant correlation between calcium and lead was found only in the hip articular cartilage.

Assessment of lead exposure in Spanish imperial eagle (Aquila adalberti) from spent ammunition in central Spain

The Spanish imperial eagle (Aquila adalberti) is found only in the Iberian Peninsula and is considered one of the most threatened birds of prey in Europe. Here we analyze lead concentrations in bones (n=84), livers (n=15), primary feathers (n=69), secondary feathers (n=71) and blood feathers (n=14) of 85 individuals collected between 1997 and 2008 in central Spain. Three birds (3.6%) had bone lead concentration>20μg/g and all livers were within background lead concentration. Bone lead concentrations increased with the age of the birds and were correlated with lead concentration in rachis of secondary feathers. Spatial aggregation of elevated bone lead concentration was found in some areas of Montes de Toledo. Lead concentrations in feathers were positively associated with the density of large game animals in the area where birds were found dead or injured. Discontinuous lead exposure in eagles was evidenced by differences in lead concentration in longitudinal portions of the rachis of feathers.

In vivo quantification of lead in bone with a portable x-ray fluorescence system—methodology and feasibility

This study was conducted to investigate the methodology and feasibility of developing a portable x-ray fluorescence (XRF) technology to quantify lead (Pb) in bone in vivo. A portable XRF device was set up and optimal settings of voltage, current, and filter combination for bone lead quantification were selected to achieve the lowest detection limit. The minimum radiation dose delivered to the subject was calculated by Monte Carlo simulations. An ultrasound device was used to measure soft tissue thickness to account for signal attenuation, and an alternative method to obtain soft tissue thickness from the XRF spectrum was developed and shown to be equivalent to the ultrasound measurements (intraclass correlation coefficient, ICC = 0.82). We tested the correlation of in vivo bone lead concentrations between the standard KXRF technology and the portable XRF technology. There was a significant correlation between the bone lead concentrations obtained from the standard KXRF technology and those obtained from the portable XRF technology (ICC = 0.65). The detection limit for the portable XRF device was about 8.4 ppm with 2 mm soft tissue thickness. The entrance skin dose delivered to the human subject was about 13 mSv and the total body effective dose was about 1.5 µSv and should pose minimal radiation risk. In conclusion, portable XRF technology can be used for in vivo bone lead measurement with sensitivity comparable to the KXRF technology and good correlation with KXRF measurements.

In vivo measurement of lead in the bones of smelter workers using the four-element ‘clover-leaf’ geometry detector system

A total of 497 smelter employees from New Brunswick participated in a bone lead survey conducted by McMaster University in 2008 to examine the efficiency of lead exposure control programmes and a four-element ‘clover-leaf’ geometry detector system. Nearly 42% of the subjects had participated in both the previous surveys performed in 1994 and 1999. After developing the clover-leaf geometry system in 2006, the reliability of the system based on examining the consistency of four detectors and improving the minimum detection limit (MDL) was tested for the first time in 2008 by measuring lead levels of a large population that was occupationally exposed to lead. The Z test was used to study the distribution of the lead concentration calculated based on Kα and Kβ lead x-rays, where the results were broadly consistent with a normal distribution criterion, with relatively small means and standard deviations of between 1 and 2. The MDL of the clover-leaf geometry system was improved on average for tibia and calcaneus by a factor of 3.1 compared to the 1999 and 1994 surveys in which a conventional system (one detector) was used. Furthermore, by comparing the results of the three mentioned surveys, the 2008 results were found to represent the highest precision.

Atomic spectrometry update-X-ray fluorescence spectrometry

This review offers the reader a wealth of information published between April 2010 and March 2011 concerning analytical endeavours using the range of conventional and hyphenated XRF techniques that encourage the user to ensure the potential for high spectral sensitivity and, where appropriate, spatial resolution is achieved. The development of advanced micro-beam set ups and new X-ray optics driven by third generation synchrotron based XRF techniques provide nano-imaging and the detection of nano-particles on single cells whilst TXRF coupled with GIXRF and GEXRF offer great potential for non-destructive investigations of thin layers on reflecting surfaces as well as depth profiling of implants. A new portable XRF system is described as an alternative for the traditionally applied K-X-ray fluorescence technology for in vivo measurements of lead in bone. Cryogenic cooling of heat sensitive biological samples is offered as a method to mitigate possible damage by the use of the more powerful μ-XRF technique. Other new preparation methods are also reviewed for the presentation and analysis of industrial, environmental and archaeological samples. One of the more unusual contributions available this year in the characterisation and use of industrial minerals showed that a semi-precious stone, amethyst, is more effective at shielding radiation than concrete.

Effect of Increased Blood and Tibia Lead on the Change of Bone Mineral Density in Retired Male Lead Workers

PP-31-162 Background/Aims: To investigate the effect of increased blood and tibia lead on the change of bone mineral density in retired male lead workers. Methods: One hundred nine retired male lead workers who worked in 4 different lead industries and 51 nonoccupationally lead exposed male subjects were recruited from March 2004 to October 2004. Bone mineral density (BMD) was measured by broadband ultrasound attenuation (BUA) at left calcaneous bone area with broadband ultrasound attenuation method of QUS-2 (Metra Biosystems Inc, USA). Tibia bone lead was measured for skeletal bone lead with K-xray fluorescence (K-XRF) and blood lead was analyzed with flameless atomic spectrophotometer. Hemoglobin, hematocrit, serum calcium and iron were also analyzed. In addition, information for smoking and drinking status and basic personal data such as age and lead exposure were also collected using questionnaire inquiry. Results: Blood lead was correlated with tibia lead (r = 0.711) and these 2 variables were negatively correlated with BUA in bivariate analysis. BUA and tibia lead showed significant main effects on the change of blood lead after adjusting covariates. The effect modification by the level of BMD (low: lower than the median of BUA and high: higher than the median of BUA) was observed between the association of tibia lead and blood lead after adjustment of covariates. The subjects who had higher BMD seemed to have lower blood lead by the increase of tibia lead than those of lower BMD. In the multiple regression analysis of blood lead and tibia lead on BUA after adjustment of covariates, only blood lead showed statistically significant effect on BUA. Conclusion: This study confirmed that BMD and blood lead were significantly associated. To verify the causal association of BMD on blood lead and vice versa, further longitudinal studies are needed.

Lead Exposure in Female Workers Who are Pregnant or of Childbearing Age

In adults, high-level lead exposure often occurs in the lead-related industries. Acute lead poisoning has become rare, but chronic exposure to low-level lead remains a public health issue. With recent advances in our understanding of lead toxicity at low-levels, researchers have shifted their focus to studying lead at concentrations below those currently recommended as 'acceptable' in worker protection. As gender plays an important role in the storage, biokinetics, and toxicity of lead, it seems inappropriate to extrapolate findings of lead exposure in men to women. Women's bones release lead more slowly to the bloodstream, so blood levels remain increased for a long time after cessation of high exposure, reflecting the endogenous source of the lead. Particularly in pregnant women, bone lead release could influence health in pregnancy and be extremely harmful to the rapidly growing and developing fetus. Accordingly, female workers of childbearing age should avoid excessive lead exposure. However, because studies of pregnant workers encounter many difficulties and inconveniences, sufficient research has not been conducted in this area. As an alternative, a group of non-occupationally exposed women, matched as well as possible for anthropometric and reproductive variables and with almost the same levels of blood lead, could be recruited for survey.

Bias correction by use of errors-in-variables regression models in studies with K-X-ray fluorescence bone lead measurements

Bias correction by use of errors-in-variables regression models in studies with K-X-ray fluorescence bone lead measurements

Maternal Bone Lead Levels Are Prospectively Associated With Increased Blood Pressure in Female Offspring

Maternal Bone Lead Levels Are Prospectively Associated With Increased Blood Pressure in Female Offspring

Bias correction by use of errors-in-variables regression models in studies with K-X-ray fluorescence bone lead measurements

In-vivo measurement of bone lead by means of K-X-ray fluorescence (KXRF) is the preferred biological marker of chronic exposure to lead. Unfortunately, considerable measurement error associated with KXRF estimations can introduce bias in estimates of the effect of bone lead when this variable is included as the exposure in a regression model. Estimates of uncertainty reported by the KXRF instrument reflect the variance of the measurement error and, although they can be used to correct the measurement error bias, they are seldom used in epidemiological statistical analyzes. Errors-in-variables regression (EIV) allows for correction of bias caused by measurement error in predictor variables, based on the knowledge of the reliability of such variables. The authors propose a way to obtain reliability coefficients for bone lead measurements from uncertainty data reported by the KXRF instrument and compare, by the use of Monte Carlo simulations, results obtained using EIV regression models vs. those obtained by the standard procedures. Results of the simulations show that Ordinary Least Square (OLS) regression models provide severely biased estimates of effect, and that EIV provides nearly unbiased estimates. Although EIV effect estimates are more imprecise, their mean squared error is much smaller than that of OLS estimates. In conclusion, EIV is a better alternative than OLS to estimate the effect of bone lead when measured by KXRF.

Therapeutic efficiency of succimer used with calcium and ascorbic acid in the treatment of mild lead-poisoning

The aim of this study was to explore therapeutic efficiency of succimer used with calcium and ascorbic acid in the treatment of mildly lead-poisoned mice and preschool children. Mice were exposed to lead by drinking water, and then treated with saline solution, 50 mg/kg body weight (b.w.) succimer, 100 mg/kg b.w. succimer, or 50 mg/kg b.w. succimer plus calcium and ascorbic acid by gavage. Seventy-two children aged 48–72 months were randomly assigned into combined treatment or nutritional intervention group. Lead levels in blood and bone were analyzed by atomic absorption spectrophotometry. Activities of aminolevulinic acid dehydratase (ALAD) in blood were determined by colorimetric method. Results of animal experiment showed that succimer used alone could reduce lead levels in blood and bone and reverse activities of ALAD in blood, however, a better therapeutic efficiency in mobilizing bone lead could be achieved by succimer used with calcium and ascorbic acid. Findings from the clinical study showed that reduction of blood lead levels (BLLs) between the end and initiation of therapy in the combined treatment group was significantly greater than that in the nutritional intervention group. Percentage of children with BLLs less than 10 μg/dL at the end of therapy and the eighth week after therapy in the combined treatment group was significantly higher than that in the nutritional intervention group. In conclusion, combined use of succimer with calcium and ascorbic acid seemed to be a choice in the treatment of mildly lead poisoned children.

“Clustering Index method”: A new technique for differentiation between neurogenic and myopathic changes using surface EMG

Objective To establish a non-invasive and quantitative analysis method using single-channel surface EMG (SEMG) for diagnosing neurogenic and myopathic changes. Methods The subjects consisted of 66 healthy controls, 12 patients with neurogenic diseases, and 18 patients with myopathic diseases. The tibialis anterior muscle was examined using a belly to the adjacent bone lead. From each subject, 20–40 signals of 1 s length were collected of various strengths. A new parameter, the “Clustering Index (CI)”, was developed to quantify the uneven distribution of the SEMG signal, and was plotted against the SEMG area. The results were expressed as the Z-score of each subject calculated using linear regression from the normative data. Results When ±2.5 was used as the cut-off value of the Z-score, the specificity was 95%, whereas the sensitivity was 92% (11/12) and 61% (11/18) for the neurogenic and myopathic patients, respectively. There was no overlap of the Z-score values between the neurogenic and myopathic groups. Conclusions The CI method achieved a reasonably high diagnostic yield in detecting neurogenic or myopathic changes. Significance This is a new simple and quantitative analysis method using SEMG with good reproducibility, and is promising as a non-invasive complement to needle EMG.

Alterations in Vitamin A and E Levels in Liver and Testis of Wild Ungulates from a Lead Mining Area

In animals, exposure to metal pollution can induce oxidative stress via several mechanisms. This stress might then cause adverse effects on functions such as male reproductive capacity. Antioxidant vitamins A and E play an important role in maintaining organism functions under stressed conditions. This study assessed the effect of different metals and metalloids on levels of vitamins A and E in livers and testis (n = 67 and 36) of red deer and in livers (n = 22) of wild boar. The study compared animals residing within and outside a polluted mining area. Red deer from mined areas showed significant reductions in liver retinyl docosahexaenoate and retinyl docosapentaenoate. Free retinol, α-tocopherol, and retinyl palmitate in the testis were also lower. This might indicate that increased internal usage of these antioxidants is occurring as deer try to maintain the integrity and function of reproductive tissue. Wild boar from mined areas also showed significant reductions in liver retinyl stearate but increased free retinol levels. This might suggest that vitamin A is being mobilized to a greater degree to cope with the induced oxidative stress caused by exposure to metal pollution. Additionally, a significant negative relationship between liver α-tocopherol and bone lead (Pb) in boar might indicate some long-term effects of Pb on antioxidant levels. Results suggest that vitamin A and E status can be altered as a consequence of exposure to Pb pollution and that complex differences in this response probably exist between species.

A Self-Testing Guide to the Bony Features of the Temporal Bone

OPEN ACCESSSeptember 20, 2010A Self-Testing Guide to the Bony Features of the Temporal Bone Bob Hutchins, PhD Bob Hutchins, PhD Baylor College of Dentistry, A Member of The Texas A&M University Google Scholar More articles by this author https://doi.org/10.15766/mep_2374-8265.8169 SectionsAbout ToolsDownload Citations ShareFacebookTwitterEmail AbstractThis interactive temporal bone self-testing guide is expected to be used by novice dental or medical students learning the anatomy of the temporal bone as it relates to the convoluted nerves that pass through the bone, muscle attachments, and middle and inner ear mechanisms. Temporal bone anatomy is traditionally difficult for students to learn and few texts or atlases provide a close up view of this bone's intricate features. Lesions due to trauma, inflammation, or tumors in any part of this bone lead to clinical issues from vertigo, hearing impairment, autonomic disturbances, gustatory disorders, and more. The temporal bone module is divided into four parts; the first part provides an overview of the educational objectives. The second part gives a brief introduction on how to use this module. This is followed by an interactive table of contents and the final part is the actual bony features. The temporal bone presentation is provided anatomically first by presenting external views followed by internal views. This PowerPoint-based aid is used to supplement either traditional gross anatomy and/or neuroscience course material, as well as support case-based learning approaches. The software was tested with first-year dental students to improve the number of structures identified, their presentation, and ease of use. So far, the survey results from those using the module have been significantly in favor of using the module to learn/review the anatomy. Educational Objectives By the end of the module, the learner will be able to: Identify the external bony features of the temporal bone from the various anatomical views.Identify the middle ear bony features, muscle attachments, and the ear ossicles.Trace the entrance, path, and exit of all nerves associated with the temporal bone.Recognize how sound is transmitted from the external ear to the inner ear.Identify the components of the inner ear.Identify the relevant intracranial features associated with the temporal bone. Sign up for the latest publications from MedEdPORTAL Add your email below FILES INCLUDEDReferencesRelatedDetails FILES INCLUDED Included in this publication: Instructor's Guide.doc Final Overview of Nerves and Vessels.doc Temporal Bone Module (Proficient [faster] Review) with Lesions.pps Temporal Bone Module (Student Learner).pps To view all publication components, extract (i.e., unzip) them from the downloaded .zip file. Download editor’s noteThis publication may contain technology or a display format that is no longer in use. CitationHutchins B. A Self-Testing Guide to the Bony Features of the Temporal Bone. MedEdPORTAL. 2010;6:8169. https://doi.org/10.15766/mep_2374-8265.8169 Copyright & Permissions© 2010 Hutchins. This is an open-access publication distributed under the terms of the Creative Commons Attribution-Share Alike license.KeywordsPromontoryChudley-Mccullough syndromeCochleaEagle SyndromeJugular FossaEar OssiclesArcuate EminenceMastoid Disclosures None to report. Funding/Support None to report. Prior Presentations Hutchins B. Temporal Bone: a self-testing guide to the bony features of the temporal bone. Presented at: American Association of Clinical Anatomists Meeting; July 2008; Toronto, Ontario, Canada. Loading ...

Association of Cumulative Lead Exposure with Parkinson’s Disease

BackgroundResearch using reconstructed exposure histories has suggested an association between heavy metal exposures, including lead, and Parkinson’s disease (PD), but the only study that used bone lead, a biomarker of cumulative lead exposure, found a nonsignificant increase in risk of PD with increasing bone lead.ObjectivesWe sought to assess the association between bone lead and PD.MethodsBone lead concentrations were measured using 109Cd excited K-shell X-ray fluorescence from 330 PD patients (216 men, 114 women) and 308 controls (172 men, 136 women) recruited from four clinics for movement disorders and general-community cohorts. Adjusted odds ratios (ORs) for PD were calculated using logistic regression.ResultsThe average age of cases and controls at bone lead measurement was 67 (SD = 10) and 69 (SD = 9) years of age, respectively. In primary analyses of cases and controls recruited from the same groups, compared with the lowest quartile of tibia lead, the OR for PD in the highest quartile was 3.21 [95% confidence interval (CI), 1.17–8.83]. Results were similar but slightly weaker in analyses restricted to cases and controls recruited from the movement disorders clinics only (fourth-quartile OR = 2.57; 95% CI, 1.11–5.93) or when we included controls recruited from sites that did not also contribute cases (fourth-quartile OR = 1.91; 95% CI, 1.01–3.60). We found no association with patella bone lead.ConclusionsThese findings, using an objective biological marker of cumulative lead exposure among typical PD patients seen in our movement disorders clinics, strengthen the evidence that cumulative exposure to lead increases the risk of PD.

Cumulative lead exposure and age-related hearing loss: The VA Normative Aging Study

Although lead has been associated with hearing loss in occupational settings and in children, little epidemiologic research has been conducted on the impact of cumulative lead exposure on age-related hearing loss in the general population. We determined whether bone lead levels, a marker of cumulative lead exposure, are associated with decreased hearing ability in 448 men from the Normative Aging Study, seen between 1962 and 1996 (2264 total observations). Air conduction hearing thresholds were measured at 0.25–8 kHz and pure-tone averages (PTA) (mean of 0.5, 1, 2 and 4 kHz) were computed. Tibia and patella lead levels were measured using K X-ray fluorescence between 1991 and 1996. In cross-sectional analyses, after adjusting for potential confounders including occupational noise, patella lead levels were significantly associated with poorer hearing thresholds at 2, 3, 4, 6 and 8 kHz and PTA. The odds of hearing loss significantly increased with patella lead levels. We also found significant positive associations between tibia lead and the rate change in hearing thresholds at 1, 2, and 8 kHz and PTA in longitudinal analyses. Our results suggest that chronic low-level lead exposure may be an important risk factor for age-related hearing loss and reduction of lead exposure could help prevent or delay development of age-related hearing loss.

HFE H63D Polymorphism as a Modifier of the Effect of Cumulative Lead Exposure on Pulse Pressure: The Normative Aging Study

BackgroundCumulative lead exposure is associated with a widened pulse pressure (PP; the difference between systolic and diastolic blood pressure), a marker of arterial stiffness and a predictor of cardiovascular disease. Polymorphisms in the hemochromatosis gene (HFE) have been shown to modify the impact of cumulative lead exposure on measures of adult cognition and cardiac function.ObjectivesWe examined whether the HFE mutations modify the impact of lead on PP in community-dwelling older men.MethodsWe examined 619 participants with a total of 1,148 observations of PP from a substudy of bone lead levels (a measure of cumulative exposure, measured by in vivo K-shell X-ray fluorescence) and health in the Normative Aging Study between 1991 and 2001. Linear mixed-effects regression models with random intercepts were constructed.ResultsOf the 619 subjects, 138 and 72 carried the HFE H63D and C282Y variants, respectively. After adjusting for age; education; alcohol intake; smoking; daily intakes of calcium, sodium, and potassium; total calories; family history of hypertension; diabetes; height; heart rate; high-density lipoprotein (HDL); total cholesterol:HDL ratio; and waist circumference, baseline bone lead levels were associated with steeper increases in PP in men with at least one H63D allele (p-interaction = 0.03 for tibia and 0.02 for patella) compared with men with only the wild types or C282Y variant.ConclusionsThe HFE H63D polymorphism, but not the C282Y mutation, appears to enhance susceptibility to the deleterious impact of cumulative lead on PP, possibly via prooxidative or pro-inflammatory mechanisms.