Clinical Chemistry 46: 1171-1178, 2000;
(Clinical Chemistry. 2000;46:1171-1178.)
© 2000 American Association for Clinical Chemistry, Inc.
Bone Lead Concentrations Assessed by in Vivo X-Ray Fluorescence
Theresa M. Ambrose1,
Muhammad Al-Lozi2 and
Mitchell G. Scott1,a
Departments of
1
Laboratory Medicine and
2
Neurology, Washington University School of Medicine, 660 S. Euclid St., St. Louis, MO 63110-1093.
a Author for correspondence. Fax 314-362-1461; e-mail mscott{at}pathbox.wustl.edu
 |
Abstract
|
|---|
The assessment of past chronic lead exposure is difficult. Chronic lead
burden is not always correctly assessed using laboratory-based tests
that are useful for acute or recent exposures. We describe a case of
suspected chronic lead exposure that illustrated the need for improved
and possibly noninvasive methods to determine cumulative lead body
burden. X-Ray fluorescence (XRF) is discussed as a method to obtain in
vivo bone lead measurements. We discuss the potential of such
measurements as accurate biomarkers of cumulative exposure and whether
XRF can be used for retroactive exposure assessment or to predict risk
of future health problems.
|
Case
|
|---|
A 53-year-old male was referred to a neurologist with an 8-year
history of numbness in his hands and feet that was originally diagnosed
as carpal tunnel syndrome. He complained of progressive weakness in his
hands and pain in his elbows, neck, and shoulders. Exam findings
included a mild peripheral neuropathy involving both motor and sensory
components. A loss of pain sensation in the hands and feet as well as a
loss of vibratory sensation in the toes was demonstrated. The patient
claimed that his reading speed and language skills began to regress in
his mid-20s. Since then he had complained of slowed thinking and had
experienced some memory loss and mild dementia. The patient also had a
14-year history of hypertension, but he did not smoke or drink. Other
conditions that could cause cognitive defects together with peripheral
neuropathy, including stroke, Alzheimer disease, vitamin E or
B12 deficiency, and hypothyroidism, were ruled
out.
Between the ages of 22 and 42, the patient was employed at a lead
smelter. During the course of his employment, blood lead values were
monitored periodically and on more than one occasion were high enough
to warrant temporary removal from the work site. Although the records
are unavailable, the blood lead values may have approached or exceeded
the maximum permissible occupational exposure limits, which at that
time were 3.5–4 µmol/L (70–80 µg/dL) (1). It was felt
that his medical history and current symptoms could have been caused by
occupational exposure to lead.
Because the exposure had ended 12 years previously, the usual
laboratory measurements of recent lead exposure were unlikely to be
useful in the assessment of his total lead body burden (see below).
Indeed, blood lead values were within the reference interval at
0.25 µmol/L [5 µg/dL; reference interval <1 µmol/L (<20
µg/dL)], and urine lead was undetectable [<0.25 µmol/24 h (<5
µg/24 h); reference interval, 0–4 µmol/L (0–80 µg/24 h)].
Blood lead concentrations measured before admission were normal and
were not repeated in light of the urine lead findings. Protoporphyrin
measurements were not performed. Because lead accumulates in the bone
where it remains for long periods of time, the laboratory was contacted
to investigate measurements of lead in bone or other means to determine
past exposure.
|
Lead Health Risks, Metabolism, and Storage
|
|---|
Lead exposure causes numerous health problems, affecting nearly
every system of the body (2)(3). As laboratory
and epidemiological research into lead toxicity has progressed,
evidence has accumulated associating chronic low-level lead exposure
with a variety of health problems
(1)(3)(4). Because lead is
especially toxic to the developing central nervous system of young
children (3), considerable attention has been given to the
problem of early childhood lead exposure. Early studies that focused
mainly on children with known histories of high lead exposure reported
associations between increased blood lead concentrations and impairment
of fine motor skills as well as a variety of neurobehavioral and
cognitive defects, including behavioral problems and decreased IQ
(1)(5)(6). Particular concern over
the effect of lead on IQ spurred several large-scale prospective
studies. Blood lead concentrations were monitored from birth through
school age, and children were evaluated using a variety of standardized
IQ tests designed for children. Results were controlled for
socioeconomic status, maternal IQ, and other factors that correlate
with IQ. A meta-analysis of these studies concluded that an increase in
blood lead concentrations from 0.5 to 1 µmol/L (10 to 20 µg/dL)
lowered IQ by 2.2 points (7). These and other
studies led to the initiation of federally mandated lead screening
programs. In addition, the maximum permissible lead concentration for
children has been progressively lowered by the Centers for Disease
Control and Prevention from 2 µmol/L (40 µg/dL) in the early 1970s
to the current action concentration of 0.5 µmol (10 µg/dL)
(1). More recently, chronic subclinical lead exposure has
been linked with several health problems in adults, including anemia
(8), chronic progressive renal dysfunction
(4)(9)(10), peripheral neuropathy
(3)(4)(11), hypertension
(12), and various reproductive problems
(3)(4)(13). Acute lead poisoning,
characterized by persistent high blood lead concentrations [4 µmol/L
(80 µg/dL) in children, 4–5 µmol/L (80–100 µg/dL) in adults]
can lead to renal failure, encephalopathy, and death.
The total body burden of lead in 20th century humans peaked at
concentrations ~1000-fold higher than those measured in
pre-industrial society (14). Industrial activity has
increased the environmental availability of lead. Although use of lead
paint and leaded gasoline has been largely discontinued, leading to
markedly lower population blood lead values
(15)(16), substantial amounts of lead have
accumulated in the soil and dust near roadways and lead-painted homes.
The resulting lead-containing dust can be inhaled and absorbed through
the lungs or ingested and absorbed through the gastrointestinal tract.
Lead is excreted primarily through the feces but also in the urine and,
to a very minor extent, in sweat and saliva (3). Because
lead excretion is rather inefficient, most of an absorbed lead dose
will be stored in the body.
As shown in Fig. 1
, there are three main compartments where lead distributes:
blood, soft tissue, and bone. After being absorbed from the lungs or
gastrointestinal tract, lead first enters the red blood cells
(RBCs),1
where it displaces zinc from the active site of various
hematopoietic enzymes. Blood lead represents only 1–5% of the total
body burden of lead (4)(17). At lower lead
concentrations, 95–99% of blood lead is bound to RBCs and only 1% is
found in the ionized form in plasma. At higher concentrations, the
binding sites in the RBCs become saturated and more lead can be found
in the plasma. Plasma lead can easily exchange into soft tissues,
primarily the kidney and brain, where it exerts its most toxic effects.
It binds to cell membranes, alters protein structure, and may interfere
with gene translation (2). Plasma lead is also available for
exchange into bone mineral, where lead replaces the calcium in
hydroxyapatite crystals (18). Bone lead comprises 70–80%
of the total body burden of lead in children and 90–95% of the total
body burden in adults (3)(7). Because of bone’s
relatively slow metabolic turnover, deposited lead persists for years,
and bone lead stores accumulate slowly throughout life; therefore, bone
lead may represent a more accurate cumulative biomarker of lead body
burden than either blood or soft tissue lead.
View larger version (20K):
[in this window]
[in a new window]
|
Figure 1. Three-compartment model of human lead metabolism, showing
the mean lead content, mean lifetime, and rates of lead movement
( ) between pools.
Reproduced with permission from the Journal of Clinical
Investigations 1976;58:260–70 (49).
|
|
Bone lead acts as an endogenous source of lead, and by continuous
release to other tissues it can represent a health risk long after
exposure has ended. Release of lead from the bones will increase in
settings of increased bone turnover, such as osteoporosis, pregnancy,
lactation, and certain hyperendocrine states. Indeed, there have been
reports in the literature of acute lead poisoning (in the absence of
recent exposure) associated with hyperthyroidism
(19)(20), and skeletal lead release has been
quantitatively demonstrated in pregnant and lactating women
(21). Even in normal metabolic states, slow release of lead
from bone can maintain chronically increased blood lead values in a
heavily exposed individual long after external exposure has ceased
(22). In light of this observation, several studies have
been aimed at determining whether bone lead constitutes an independent
risk factor for conditions associated with chronic lead exposure.
|
Methods for Measuring Lead Body Burden
|
|---|
The usual clinical laboratory-based methods for assessing lead
exposure include direct determinations of lead in blood and in urine as
well as measurements of various components of the heme biosynthetic
pathway, which is inhibited by lead. To guide their treatment
decisions, clinicians ultimately rely on whole blood lead values, which
are quantified by atomic absorption-based or voltammetric methods
(23). Because of the sensitivities of these methods and the
fact that lead is ubiquitous in the environment, especially in dust
particles, great care must be taken to avoid contamination during
sample collection to avoid false positives (23). Special
blood collection tubes designed specifically for trace metal analysis
should be used in preference to other tubes (23).
Measurements of the heme precursors free erythrocyte protoporphyrin
(FEP) and erythrocyte zinc protoporphyrin (ZnP) have also been used for
screening purposes. Because these heme precursors are not sensitive
indicators of blood lead concentrations <1.25 µmol/L (25 µg/dL)
(24) and can be increased in other conditions, such as iron
deficiency (23), blood lead measurements remain the
preferred screening tool. Increased concentrations of FEP or ZnP denote
impairment of the heme biosynthetic pathway and therefore may indicate
a more prolonged recent exposure to lead. From a practical point of
view, FEP and ZnP measurements are less prone to sample contamination
and can be performed using a relatively inexpensive hematofluorometer
(3)(23)(25), but because of the
finite lifetime of affected erythrocytes and the resulting short
half-life of lead in blood, these laboratory-based measurements can
assess only ongoing or recent lead exposure, within a period of a few
weeks to months.
If longer-term exposure is suspected, a somewhat more accurate picture
of the overall lead body burden can be provided by the provocative
chelation test (3)(26)(27). After
administration of a chelating agent such as calcium disodium
ethylenediaminetetraacetic acid (CaNa2EDTA), lead
is mobilized from the soft tissues and excreted in the urine, where it
is quantified by atomic absorption (2)(3).
Increased urine lead concentrations signify prolonged lead exposure and
indicate the need for additional treatment. Determination of lead in
hair has also been considered for assessment of chronic exposure, but
variability attributable to differing hair types and textures, as well
as the high possibility of external contamination from dust-borne lead,
can render such measurements difficult to interpret
(7)(17).
True assessment of cumulative lead body burden should use measurements
of bone lead, where most of the body lead burden is concentrated.
Historically, such measurements involve wet chemical digestion of bone
material followed by atomic absorption-based measurements and were
limited to specimens from cadavers or bone biopsy samples. Measurement
of tooth lead is possible by similar means. Like bone lead, tooth lead
increases as a function of age and exposure
(7)(28)(29). Such measurements have
been widely performed on shed primary teeth to assess lead exposure in
children (6)(30). Measurements of lead in the
permanent teeth of adults are less practical because of the highly
invasive nature of sample collection, and are rarely performed.
|
Bone Lead by X-Ray Fluorescence
|
|---|
Over the past two decades, the technique of x-ray fluorescence
(XRF) has emerged as a noninvasive method for bone lead determination,
enabling direct in vivo measurements of skeletal lead
(4)(17)(31). XRF occurs when
absorption of a high-energy photon by a heavy metal atom induces the
emission of a second x-ray photon of slightly lower energy. This
fluorescent photon has an energy characteristic of the heavy metal atom
from which it was ejected. A typical x-ray fluorometer designed for in
vivo measurements features a radioactive 109Cd
source, which emits at 88.035 keV, and a germanium crystal detector
arranged in backscatter geometry (i.e., the detector is mounted behind
the source). During a typical in vivo bone lead measurement, the bone
is irradiated for 30–60 min, and the generated photons are collected
and counted. The experimental setup and resulting spectrum are shown in
Fig. 2
. In addition to the characteristic peaks resulting from
specific electronic transitions in lead atoms, a large peak at the
energy of the incident radiation is evident. This peak results from
elastic scattering of the incident radiation by calcium atoms in the
bone sample and thus is indicative of the bone mineral density. The
first step in extracting the lead information is to curve-fit and
subtract the heavy Compton background signal that is typical of XRF
experiments. The area under one of the lead peaks, usually the Pb
K-alpha 1 transition at 74.4 keV, is then measured and normalized to
the area under the elastic scatter peak. This yields a measurement of
bone lead in units of µg lead/g of bone mineral.
View larger version (20K):
[in this window]
[in a new window]
|
Figure 2. Diagram showing measurement geometry for determination of
lead in the tibia or calcaneus and a typical XRF bone-lead spectrum.
Reproduced with permission from Environmental Health
Perspectives (17), and from the British
Journal of Industrial Medicine 1992;49:631–44, with
permission from the BMJ Publishing Group.
|
|
Calibration of x-ray fluorometers is accomplished using lead-doped
plaster of Paris phantoms. The accuracy of the method has been
established through comparison of XRF data with results from chemical
analysis of specimens from cadavers; in a representative study a linear
regression slope of 1.02 and a correlation coefficient of 0.98 were
obtained (32). The sensitivity and precision of the method
present more of an analytical challenge. In addition to the
sample-to-sample reproducibility, which has been studied using repeated
measurements of lead-doped phantoms (33), there is also a
certain amount of imprecision associated with each calculated bone lead
value. This uncertainty, estimated using goodness-of-fit statistics
from the curve-fit of the background, can range from 3 to 30 µg
lead/g of bone and can be problematic for low-level lead measurements
(11)(17)(31)(34)(35).
Treatment of low-level data varies depending on whether they are
intended for use in a clinical setting or for epidemiological research.
Standard clinical practice mandates calculation of a minimum detectable
level (MDL) based on standard deviations of the background counts. When
interpreting low-level results for clinical purposes, any measurement
falling below the MDL is considered to be zero. The MDL varies from
instrument to instrument, but it is typically ~3–15 µg lead/g of
bone mineral. Because the bone lead concentrations for young or
unexposed patients may not be much higher than this (see Table 1
), clinical interpretation of XRF results for these individuals
may be problematic. Many epidemiologists prefer to use all estimates
generated by the instrument, including even negative values for bone
lead (17)(34)(36). Rejecting or
recoding measurements that fall below an instrument’s MDL can yield
results that are artificially biased (34). Therefore, in
epidemiological research, each bone lead value is used along with its
individual uncertainty to calculate and compare population means and
medians.
Each bone lead determination relies on the accumulation of a large
number of data points, and more photon counts will lead to better
background curve fitting and less imprecision. Experimental conditions
affecting photon count include the activity of the photon source, the
efficiency of the detector, and the measurement time. Higher photon
yield will be obtained with large, dense, well-mineralized bones
containing more calcium and lead. Photon scattering by overlying tissue
or movement of the subject during the sampling period can decrease the
photon count. Normalizing the lead signal to the calcium signal ensures
that the accuracy of the measurement is not affected by these
variables. However, the need to accumulate a large number of data
points has certain implications for sampling and renders XRF
measurements difficult in certain populations. For example, XRF
measurements are less precise in obese subjects and in children with
smaller, less well-mineralized bones.
These considerations also affect the choice of bone for XRF
measurements. From a sampling point of view, the best bone to use is a
large dense bone with very little overlying tissue; therefore, the
tibia is usually preferred for XRF measurements. However, most bones
are a mixture of two different bone types, cortical and trabecular,
which represent distinct metabolic compartments. Trabecular bone,
because of its higher surface area, has a faster rate of turnover than
denser cortical bone. The behavior of lead in each type of bone may
also differ; therefore, some researchers have chosen to measure bone
lead in two sites. The tibia and the phalanx are examples of primarily
cortical bone, whereas the patella and calcaneus are considered mainly
trabecular. Although bone lead reference intervals have not been
rigorously established, Table 1
shows some typical values of tibia lead
obtained using XRF in various populations.
|
Bone Lead as a Cumulative Exposure Marker
|
|---|
The utility of bone lead as a marker of cumulative lead exposure
has been established by studying populations of heavily exposed lead
workers. As part of an occupational exposure monitoring program, these
workers had blood lead concentrations measured and recorded throughout
their employment. A time-integrated cumulative blood lead index was
calculated from the recorded blood lead values and correlated to
measurements of bone lead (35)(37)(38)(39). The
observed correlation coefficients for four of these studies ranged from
0.67 to 0.88 (35)(37)(38)(39). Fig. 3
depicts data from one study (38).
View larger version (20K):
[in this window]
[in a new window]
|
Figure 3. Tibia lead vs time-integrated blood lead index for workers
at a lead factory.
Reproduced from the British Journal of Industrial Medicine
1988;45:174–81, with permission from the BMJ Publishing Group.
|
|
The cumulative time-integrated blood lead index reflects both the
duration and intensity of lead exposure. Erkkilla et al.
(39) showed that bone lead concentrations in the two
separate metabolic compartments are affected differently by these two
variables. A time-weighted average blood lead was calculated to
reflect the intensity of the exposure, and bone lead was measured in
the tibia and calcaneus of 91 active lead workers. It was found that
the tibia lead concentration is significantly related to both the
duration and the intensity of exposure, whereas lead in the trabecular
calcaneus bone reflects only the intensity. This suggests that
trabecular bone lead represents a relatively rapidly exchangeable bone
lead compartment, in contrast to cortical lead.
|
Bone Lead as a Retroactive Exposure Marker
|
|---|
In determining whether bone lead concentrations can be used
retroactively to assess prior exposure to lead, it is necessary to
understand what happens to bone lead concentrations after exposure
ends. Nilsson et al. (22) followed a group of 14 lead
workers for >18 years after retirement with measurements of lead in
the blood and the phalanx. The blood lead concentrations experienced an
initial rapid decline after the end of exposure and then continued to
decrease slowly over a period of years. A tri-exponential model was
used to describe this decrease, yielding half-lives of 34 days, 1.2
years, and 13 years. The shortest half-life correlates well with the
known half-life of lead in RBCs. The intermediate value is assumed to
result from lead in soft tissues and the rapidly exchangeable
trabecular compartment. The finger bone lead measurements decreased
according to a mono-exponential curve with a calculated half-life of 16
years, which was in good agreement with the longest half-life from the
blood lead measurements. Thus, the release of bone lead into blood can
maintain increased blood lead concentrations for years after the end of
occupational exposure.
A more complete model for retroactive exposure assessment, accounting
for this endogenous release of bone lead into the bloodstream, was
developed by Bergdahl et al. (35) and Borjesson et al.
(37). They first mathematically modeled the flux of
lead into and out of the body, and between the skeletal and central
(blood) pools, under steady-state conditions. They then calculated
several different values for a bone-to-plasma and an overall
elimination half-life. These half-lives were then used to correct the
cumulative blood lead indices of two separate groups of actively
exposed lead workers. The resulting adjusted indices were then plotted
against the concentration of bone lead. In the study by Borjesson et
al. (37) of a group of 137 workers monitored with phalanx
lead measurements, the best correlation was observed with an
elimination half-life of 14 years. The study by Bergdahl et al.
(35) yielded a half-life of 13 years, using determinations
of tibial bone lead in 77 workers. With this information, a
three-dimensional model such as the one shown in Fig. 4
can be prepared to describe the relationship among bone lead,
blood lead, and exposure time. Assuming that exposure to lead has been
constant, this model can be used to assess retroactive exposure if the
current bone and blood lead concentrations are known. Although the
usefulness of such a model is limited by its simplicity and its
applicability only to the population from which it was derived, it
illustrates one approach to estimate retroactive exposure.
View larger version (52K):
[in this window]
[in a new window]
|
Figure 4. Three-dimensional model showing the relationship among
bone lead (Bone-Pb), concurrently obtained blood lead
(B-Pb), and exposure time under the conditions of
constant lead exposure.
Reproduced from Archives of Environmental Health
1997;52:104–12 (37), with permission from The Helen Dwight
Reid Educational Foundation, Heldref Publications.
|
|
|
Bone Lead as a Risk Factor for Disease
|
|---|
Because bone lead serves as a biomarker of cumulative lead
exposure, it may be a better predictor of adverse health effects
associated with chronic lead exposure. Several studies have been aimed
at determining whether bone lead constitutes an independent risk factor
compared with other biomarkers of lead exposure in certain disease
settings. In general, these studies involved use of multivariate
analysis and various regression techniques to search for statistically
significant associations between bone lead and some determinant of
disease condition.
At least two studies have looked for an association between renal
dysfunction and bone lead concentrations in occupationally exposed
populations of lead smelter workers (40)(41). In
both of these studies, bone lead concentrations indicated a threefold
higher body burden of lead compared with unexposed controls, but no
indicators of early tubular or glomerular damage were increased. The
study by Roels et al. (40) did find a positive correlation
between tibia lead and creatinine clearance, suggesting that lead
exposure may be associated with hyperfiltration after an oral protein
load. However, no correlation was found between markers of lead
exposure and kidney damage. In fact, the more sensitive indicators of
early tubular and glomerular damage (such as urinary microglobulin and
N-acetyl-ß-glucosaminidase) were unchanged between the
lead-exposed group and controls. Although chronic low-level lead
exposure is known to be associated with nephropathies (9),
studies using bone lead provide no evidence that occupational exposure
causes irreversible kidney damage.
Several studies have examined whether bone lead can be used to
establish a link between lead exposure and neurotoxicity. Bleecker et
al. (42) evaluated 80 active lead smelter workers with six
standardized tests of verbal memory and visuomotor function. Compared
with blood lead indices (including current, cumulative, and
time-weighted average blood lead), tibia lead was a poor predictor of
performance, being significantly associated with only one of these
tests (the Grooved Pegboard test). Two hundred eighty-one young adults
with a history of childhood lead poisoning had altered tests of
peripheral nervous function and neurobehavioral function compared with
age-matched controls (11). However, tibia lead did not
correlate significantly with any of the 26 test outcomes. High tibia
lead was found to be associated with increased reports of delinquency,
aggressive behavior, and other problems in a study of 301 11-year-old
boys assessed using the Child Behavior Checklist (43). The
association was not as strong as that found in another study using lead
concentrations in shed primary teeth (30). Studies of this
nature are limited by the inherently subjective nature of
neuropsychological tests (44), as well as the imprecision of
bone lead determinations, especially in younger subjects.
Some studies have found bone lead to be a better biomarker of lead
exposure than blood lead concentrations for predicting certain forms of
toxicity. A correlation between patella lead and decreased hemoglobin
and hematocrit was found in a study of 116 moderately lead-exposed
construction workers (8). Tibia lead was associated with
increased risk of hypertension in a study of 590 elderly men
(12). A study of 272 mother-infant pairs from Mexico City,
an area with considerable environmental lead exposure, demonstrated
decreased infant birth weight associated with high maternal tibia lead
values (45). Blood lead values were not significantly
associated with adverse outcomes in any of these three studies,
indicating that chronic and not recent exposure is responsible.
|
Conclusion
|
|---|
In summary, XRF measurements of bone lead provide a noninvasive
measurement of total lead body burden. Studies of occupationally
exposed workers have established bone lead as a biomarker of cumulative
exposure. In some settings, bone lead concentrations can be used to
estimate retroactive blood lead concentrations. Although some evidence
suggests that bone lead may be a risk factor in various disease states
associated with chronic lead exposure, definitive correlations have not
been demonstrated. Some studies do suggest that bone lead may provide
information beyond that given by laboratory-based measurements of lead
status. For example, studies with pregnant and lactating women suggest
a possible role for screening bone lead in women of childbearing age
with prior history of lead exposure to determine the need for chelation
therapy or calcium supplementation. Many questions remain, and more
research is needed before the clinical utility of bone lead
measurements can be fully assessed. Only ~12 institutions in
North America are equipped to perform in vivo bone lead measurements on
a research basis. Whereas continued technical improvements in
instrumentation should eventually facilitate such measurements, the
clinical utility of bone lead measurements currently is limited by
experimental imprecision and poor availability.
|
Case Report
|
|---|
XRF bone lead measurements were deemed impractical in this patient
because of the need for considerable travel, expense, and
inconvenience. Two of the patient’s teeth, removed for dental health
purposes, had lead concentrations of 34.5 µg/g, which is well
above the analysis laboratory’s quoted age-independent reference limit
of <10 µg/g. Although certainly suggestive of an increased lead body
burden, this measurement is difficult to interpret in the absence of
well-defined age-specific reference intervals. Various reports have
clearly demonstrated that the concentration of tooth lead increases
with age (7)(28)(29), and values
reported for average tooth lead in a 50-year-old man range from 15 to
50 µg/g (28)(29)(46).
Although a markedly increased total lead body burden was not
conclusively demonstrated in this patient, it was nevertheless strongly
felt that lead exposure had played a significant role in his health
status. Although usually reserved for cases of recent exposure where
blood lead concentrations are demonstrably high, chelation therapy was
considered as a means to remove lead from the body. This can be
accomplished either through intramuscular injections of
CaNa2EDTA
(3)(26)(27) or by administration of
an oral chelating drug such as Chemet (2,3-dimercaptosuccinic acid)
(47). Patients with long-standing lead-induced nephropathy
have shown slight improvements in renal function in response to
prolonged EDTA chelation therapy (26)(48), but
it is unknown whether chelation therapy would also benefit patients
suffering from other manifestations of chronic lead exposure. A course
of Chemet was prescribed for this patient, and his condition continues
to be monitored.
|
Footnotes
|
|---|
1 Nonstandard abbreviations: RBC, red blood cell; FEP, free erythrocyte protoporphyrin; ZnP, zinc protoporphyrin; XRF, x-ray fluorescence; and MDL, minimum detectable level. 
|
References
|
|---|
-
Goyer RA. Lead toxicity: current concerns. Environ Health Perspect 1993;100:177-187.
[ISI][Medline]
[Order article via Infotrieve]
-
Hu H. Heavy metal poisoning. In: Wilson JD, ed.
Harrison’s principles of internal medicine. New York: McGraw-Hill,
1991:2564–6..
-
Philip AT, Gerson B. Lead poisoning. Part II. Clin Lab
Med 1994;14:651–70..
-
Todd AC, Wetmur JG, Moline JM, Godbold JH, Levin SM, Landrigan PJ. Unraveling the chronic toxicity of lead: an essential priority for environmental health. Environ Health Perspect 1996;104:141-146.
-
Needleman HL, Gastonis C. Low-level lead exposure and the IQ of children. A meta-analysis of modern studies. JAMA 1990;263:673-678.
[Abstract]
-
Needleman HL, Gunnoe C, Leviton A, Reed R, Peresie H, Maher C, et al. Deficits in psychologic and classroom performance of children with elevated dentine lead levels. JAMA 1979;300:689-695.
-
. World Health Organization. Environmental health criteria 165: inorganic lead 1995 WHO Geneva. .
-
Hu H, Watanabe H, Payton M, Korrick S, Rotnitzky A.. The relationship between bone lead and hemoglobin. JAMA 1994;272:1512-1517.
[Abstract]
-
Loghman-Adams M. Renal effects of environmental and occupational lead exposure. Environ Health Perspect 1997;105:928-938.
[ISI][Medline]
[Order article via Infotrieve]
-
Kim R, Rotnitzky A, Sparrow D, Weiss ST, Wager C, Hu H. A longitudinal study of low-level lead exposure and impairment of renal function. JAMA 1996;275:1177-1181.
[Abstract]
-
Stokes L, Letz R, Gerr F, Kolczak M, McNeill FE, Chettle DR, et al. Neurotoxicity in young adults 20 years after childhood exposure to lead: the Bunker Hill experience. Occup Environ Med 1998;55:507-516.
[Abstract]
-
Hu H, Aro A, Payton M, Korrick S, Sparrow D, Weiss ST, et al. The relationship of bone and blood lead to hypertension: the normative aging study. JAMA 1996;275:1171-1176.
[Abstract]
-
Bellinger D, Leviton A, Rabinowitz M, Allred E, Needleman H, Scheonbaum S. Weight gain and maturity in fetuses exposed to low levels of lead. Environ Res 1991;54:151-158.
[Medline]
[Order article via Infotrieve]
-
Rosen JF, Pounds JG. "Severe chronic lead insult that maintains body burdens of lead related to those in the skeleton": observations by Dr. Clair Patterson conclusively demonstrated. Environ Res A 1998;78:140-151.
-
Pirkle J, Kaufmann R, Brody D, Hickman T, Gunter E, Paschal D. Exposure of the US population to lead 1991–1994. Environ Health Perspect 1998;106:745-750.
[ISI][Medline]
[Order article via Infotrieve]
-
Pirkle JL, Brody DJ, Gunter EW, Kramer RA, Paschal DC, Flegal KM, et al. The decline in blood lead levels in the United States. JAMA 1994;272:284-291.
[Abstract]
-
Hu H, Aro A, Rotnitzky A. Bone lead measured by X-ray fluorescence: epidemiologic methods. Environ Health Perspect 1995;103:105-110.
-
Wittmers LE, Wallgren J, Alich A, Aufderheide AC, Rapp G. Lead in bone. IV. Distribution of lead in the human skeleton. Arch Environ Health 1988;43:381-391.
[ISI][Medline]
[Order article via Infotrieve]
-
Goldman R, White R, Kales S, Hu H. Lead poisoning from mobilization of bone stores during thyrotoxicosis. Am J Ind Med 1994;25:417-424.
[ISI][Medline]
[Order article via Infotrieve]
-
Klein M, Barbe F, Pascal V, Weryha G, Leclere J. Lead poisoning secondary to hyperthyroidism: report of two cases. Eur J Endocrinol 1998;138:185-188.
[Abstract]
-
Gulson BL, Mahaffey KR, Jameson CW, Mizon KJ, Korsch MJ, Cameron MA, et al. Mobilization of lead from the skeleton during the postnatal period is larger than during pregnancy. J Lab Clin Med 1997;131:324-329.
-
Nilsson U, Attewell R, Christofersson J-O, Schutz A, Ahlgren L, Skerfving S, et al. Kinetics of lead in bone and blood after end of occupational exposure. Pharmicol Toxicol 1991;69:477-484.
-
Jacobs DS, Demoot WR, Grady HJ, Horvat RT, Huestis DW, Kasten BL. Laboratory test handbook 1996:195-196 Lexi-comp Hudson, OH. .
-
Burtis CA Ashwood ER eds. Tietz Textbook of clinical chemistry, 3rd ed 1999 WB Saunders London. .
-
Blumberg WE, Eisinger J, Lamola AA, Zuckerman DM. The hematofluorometer. Clin Chem 1977;23:270-274.
[Abstract/Free Full Text]
-
Wedeen RP, Mallik DK, Bautman V. Detection and treatment of occupational lead nephropathy. Arch Intern Med 1979;139:53-57.
[Abstract]
-
Tell I, Somervaille LJ, Nilsson U, Bensyrd I, Schutz A, Chettle DR, et al. Chelated lead and bone lead. Scand J Work Environ Health 1992;18:113-119.
[ISI][Medline]
[Order article via Infotrieve]
-
Manuwald O, Mey W, Herzog V, Kluge C, Reuscher G. Levels of lead in permanent teeth of the population of Erfurt and surroundings. Zentralbl Hyg Umweltmed 1991;1492:76-93.
-
Steenhout A, Pourtois M. Lead accumulation in teeth as a function of age with different exposures. Br J Ind Med 1981;38:297-303.
[ISI][Medline]
[Order article via Infotrieve]
-
Bellinger D, Levition A, Allred E, Rabinowitz M. Pre- and postnatal lead exposure and behavior problems in school-aged children. Environ Res 1994;66:12-30.
[Medline]
[Order article via Infotrieve]
-
Hu H. Bone lead as a biologic marker of lead dose: recent findings and implications for public health. Environ Health Perspect 1998;106:961-967.
-
Hu H, Milder FL, Burger DE. X-Ray fluorescence measurements of lead burden in subjects with low-level community lead exposure. Arch Environ Health 1990;45:335-341.
[ISI][Medline]
[Order article via Infotrieve]
-
Gordon C, Webber C, Chettle D. The reproducibility of 109Cd-based X-ray fluorescence measurements of bone lead. Environ Health Perspect 1994;102:690-694.
[ISI][Medline]
[Order article via Infotrieve]
-
Kim R, Aro A, Rotnitzky A, Amarasiriwardena C, Hu H. K X-Ray fluorescence measurements of bone lead concentration: the analysis of low-level data. Phys Med Biol 1995;40:1475-1485.
[ISI][Medline]
[Order article via Infotrieve]
-
Bergdahl IA, Strombergh U, Gerhardsson L, Schutz A, Chettle DR, Skerfving S. Lead concentrations in tibial and calcaneal bone in relation to the history of occupational lead exposure. Scand J Work Environ Health 1998;24:38-45.
[ISI][Medline]
[Order article via Infotrieve]
-
Hoppin JA, Aro A, Hu H, Ryan PB. In vivo bone lead measurements in suburban teenagers. Pediatrics 1997;100:365-370.
[Abstract/Free Full Text]
-
Borjesson J, Mattsson S, Stromberg U, Gerhardsson L, Schutz A, Skerfving S. Lead in fingerbone: a tool for retrospective exposure assessment. Arch Environ Health 1997;52:104-112.
[ISI][Medline]
[Order article via Infotrieve]
-
Somervaille LJ, Chettle DR, Scott MC, Tennant DR, McKiernan MJ, Skilbeck A, et al. In vivo tibia lead measurements as an index of cumulative exposure in occupationally exposed subjects. Br J Ind Med 1988;45:174-181.
[ISI][Medline]
[Order article via Infotrieve]
-
Erkkila J, Armstrong R, Riihimaki V, Chettle D, Paakkari A, Scott M, et al. In vivo measurements of lead in bone at four anatomical sites: long term occupational and consequent endogenous exposure. Br J Ind Med 1992;49:631-644.
[ISI][Medline]
[Order article via Infotrieve]
-
Roels H, Lauwerys R, Konings J, Buchet J-P, Bernard A, Green S, et al. Renal function and hyperfiltration capacity in smelter workers with high bone lead. Occup Environ Med 1994;51:505-512.
[Abstract]
-
Gerhardsson L, Chettle DR, Englyst V, Nordberg GF, Nyhlin H, Scott MC, et al. Kidney effects in long term exposed lead smelter workers. Br J Ind Med 1992;49:186-192.
[ISI][Medline]
[Order article via Infotrieve]
-
Bleeker ML, Lindgren KN, Ford DP. Differential contribution of current and cumulative indices of lead dose to neuropsychological performance by age. Neurology 1997;48:639-645.
[Abstract/Free Full Text]
-
Needleman HL, Riess JA, Tobin MJ, Biesecker GE, Greenhouse JB. Bone lead levels and delinquent behavior. JAMA 1996;275:363-369.
[Abstract]
-
Moffitt TE. Measuring children’s antisocial behaviors. JAMA 1996;275:403-404.
[ISI][Medline]
[Order article via Infotrieve]
-
Gonzalez-Cassio T, Peterson KE, Sanin L-H, Fishbein E, Palazuelos E, Aro A, et al. Decrease in birth weight in relation to maternal bone-lead burden. Pediatrics 1997;100:856-862.
[Abstract/Free Full Text]
-
Gulson BL, Gillings BR. Lead exchange in teeth and bones—a pilot study using stable lead isotopes. Environ Health Perspect 1997;105:820-824.
[ISI][Medline]
[Order article via Infotrieve]
-
Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman,
AG, eds. Heavy metals and heavy-metal antagonists. In: The
pharmacological basis of therapeutics. New York: McGraw-Hill,
1996:1666–7..
-
Lin J-L, Ho H-H, Yu C-C. Chelation therapy for patients with elevated body lead burden and progressive renal insufficiency. Ann Intern Med 1999;130:7-13.
[Abstract/Free Full Text]
-
Rabinowitz MB, Wetherill GW, Kopple JD. Kinetic analysis of lead metabolism in healthy humans. J Clin Investig 1976;58:260-270.
The following articles in journals at HighWire Press have cited this article:
|
|
|
|
 
J. A. McElroy, M. M. Shafer, R. E. Gangnon, L. A. Crouch, and P. A. Newcomb
Urinary Lead Exposure and Breast Cancer Risk in a Population-Based Case-Control Study
Cancer Epidemiol. Biomarkers Prev.,
September 1, 2008;
17(9):
2311 - 2317.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A B Engin, D Tuzun, and G Sahin
Evaluation of pteridine metabolism in battery workers chronically exposed to lead
Human and Experimental Toxicology,
July 1, 2006;
25(7):
353 - 359.
[Abstract]
[PDF]
|
|
|
|
|
|
|
E. Weir
Identifying and managing adverse environmental health effects: a new series
Can. Med. Assoc. J.,
April 1, 2002;
166(8):
1041 - 1043.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Marshall, E. Weir, A. Abelsohn, and M. D. Sanborn
Identifying and managing adverse environmental health effects: 1. Taking an exposure history
Can. Med. Assoc. J.,
April 1, 2002;
166(8):
1049 - 1055.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Case
