Vol. 147, No. 5
Printed in U.SA.
American Journal of Epidemiology
Copyright O 1998 by The Johns Hopkins University School of Hygiene and Public Health
All rights reserved
Calcitropic Hormones and Occupational Lead Exposure
Estela Kristal-Boneh,1 Paul Froom,1i 2 Noga Yerushalmi,1Gil Harari,1 and Joseph Ribak1'
2
The authors sought to clarify in a cross-sectional study the possible associations between homeostatic
regulators of calcium and occupational exposure to lead. Subjects were 146 industrial male employees, 56
with and 90 without occupational lead exposure. The main outcome measures were serum concentration of
parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (calcitriol). The median values of blood lead were
40.5 jxg/dl in the exposed group and 4.0 piQ/dl in the controls. There were no differences between groups in
dietary history and serum calcium levels. PTH and calcitriol levels were significantly higher in the exposed than
in the nonexposed subjects (42.0 ± 24.2 vs. 33.6 ± 14.9 pg/ml, p <0.05; and 83.8 ± 27.0 vs. 67.9 ± 17.6
pmol/liter, p <0.001, respectively). Multivariate analyses showed that after controlling for possible confounders, occupational lead exposure (no/yes) was independently associated with PTH level (pg/ml) (/3 = 7.81, 95%
confidence interval (Cl) 3.7-11.5) and with calcitriol (pmol/liter) (/3 = 12.3, 95% Cl 3.84-20.8). It is concluded
that subjects occupationally exposed to lead show a substantial compensatory increase in PTH and calcitriol
activities which keep serum calcium levels within normal range. This may be of clinical significance since a
sustained increase in calcitropic hormones in susceptible subjects may eventually increase the risk of bone
disorders. Am J Epidemiol 1998;147:458-63.
lead; occupational exposure; parathyroid hormones; vitamin D
Significant efforts have been invested in studying
the association between blood lead levels and blood
pressure, between calcitropic hormones and blood
pressure, and the close and complex relation between
calcium and lead metabolism.
Lead exposure affects calcium metabolism in various ways. Toxic lead levels can impair the synthesis
of the most important vitamin D metabolite, 1,25dihydroxyvitamin D (calcitriol), by inhibiting renal
1 a-hydroxylation of 25-hydroxyvitamin D (1-3),
thereby decreasing calcium absorption. Lead can also
directly compete for and inhibit calcium absorption
from the gastrointestinal tract (4). Conversely, dietary
vitamin D and calcium have complex and interrelated
effects on lead absorption (5). Increasing the concentration of calcitriol, either exogenously or endogenously, increases gastrointestinal lead absorption (5),
whereas increasing dietary calcium may decrease lead
absorption.
Current knowledge on the effects of lead on calcitropic hormones is based mainly on experimental studies and studies on children, who have higher calcium
requirements than adults. The overall effect of occupational lead exposure on the parathyroid hormone
(PTH)-vitamin D-calcium axis remains unclear. On
the one hand, kidney damage may lead to reduced
levels of circulating calcitriol; on the other, decreased
absorption of calcium may lead to compensatory elevations in PTH and, hence, in calcitriol levels. This
may have important clinical implications, since perturbations of the axis have been related to hypertension
(6-10) and may increase the risk of osteoporosis (11).
We are unaware of previous studies of the entire
PTH-vitamin D-calcium axis in healthy adults occupationally exposed to lead. To clarify the possible
associations between homeostatic regulators of calcium and occupational exposure to lead, we examined
PTH, calcitriol, 25-hydroxyvitamin D, and serum calcium levels, as well as dietary intake in 56 employees
exposed to lead, and compared them with an agematched control group. We hypothesized that we
would find disturbances in the calcitropic axis which
would result in either increases or decreases in calcitriol.
MATERIALS AND METHODS
Received for publication April 11, 1997, and accepted for publication August 11, 1997.
Abbreviations: Cl, confidence interval; EDTA, ethylenediaminetetraacetic acid; PTH, parathyroid hormone.
1
2
Study population
The study population was chosen from factories in
the central area of Israel which were required by law
to undergo periodic air lead monitoring. Two factories
0ccupational Hearth and Rehabilitation Institute, Raanana, Israel.
Sackler Faculty of Medicine, Tel Avfv University, Tel Aviv, Israel.
458
PTH, Vitamin D, and Lead
were found with high air lead levels (battery and
recycling factories) and their workers were recruited
for the study. The control group included workers
from three other factories selected for similar physical
work demands and environmental conditions yet with
only negligible air lead levels. All subjects in a single
work section were examined in order to prevent discrimination, though not all fit our inclusion criteria:
male blue collar production workers, aged 25-64
years, no history of chronic disease, at least 1 year of
tenure, no use of medication (other than analgesics)
during the month preceding data collection, and no
other activity involving the possibility of occupational
exposure to other chemicals. Every employee was
offered the examination free of charge. The response
rate was 95 percent. Complete data were available for
56 eligible exposed and 90 nonexposed subjects. Prior
to their enrollment, all subjects were informed about
the risks and discomfort involved in participating in
the study. It was explained that they were being asked
to volunteer for research purposes only and that their
sole compensation would be the receipt of the results
of the medical tests. The study was approved by the
local Research on Human Subjects Committee.
Study design
The study was cross-sectional in design and carried
out on-site during regular working days. To account
for possible seasonal effects on lead levels and for
other exposure and blood variables, all data collection
and blood sampling were carried out during the summer, and not after vacation. Blood samples were taken
in a single day for 20 employees in a given workstation. Physical examinations were performed on different days, five subjects each day, together with the field
tests and personal interview.
Measurements
Height and weight were measured between 6:00 and
9:00 a.m., without shoes, with the subject wearing
only light industrial clothes. Body weight was measured with the Seca electronic scale (Alpha model
770), (Seca, Hamburg, Germany), accurate to 100 g.
Quetelet's index (weight (kg)/height (m2)) was used as
a measure of body mass index.
Field tests included an examination of the working
conditions by an expert hygienist and monitoring of
environmental lead levels.
Subjects were interviewed about health-related habits, medical history, demographic information, personal hygiene, and occupational factors. Smoking habits were determined by a special comprehensive
questionnaire and daily dietary intake of calcium by a
Am J Epidemiol
Vol. 147, No. 5, 1998
459
semiquantified dietary questionnaire designed for this
study. The latter covered 112 food items. In addition,
there was also space at the end of each food subgroup
list for additional volunteered information of foods
consumed that were not listed. The list of food items
was selected on the basis of a more extensive quantified dietary history questionnaire covering 260 food
items, used in an evaluation of nutritional intake of a
stratified random sample of the Israeli population (12),
as the items more frequently eaten in our population
(above 80 percent). Semiquantified dietary questionnaires have been successfully used previously (12, 13).
Participants reported how often, on average, over the
present season they had eaten the specified portion of
each food. We also sought information about nutritional supplements. We computed nutrient intake by
multiplying the frequency of intake of each unit of
food by the nutrient composition of the specified portion size. Several types of units were used to quantify
portion size, such as standard units, commercial containers, and natural units such as fruits and vegetables.
The interview was personal, conducted by a trained
interviewer, and lasted about 40 minutes.
Venous blood samples were taken in a climatecontrolled room before the beginning of a regular
workday (between 7:00 and 9:00 a.m.), after a 10-hour
fast (subjects were encouraged to drink water during
the fasting period), with the subject seated. The tourniquet was released immediately after blood began to
enter the tube to avoid venostasis. The samples were
placed in vacuum test tubes without additives, with K3
ethylenediaminetetraacetic acid (EDTA) (for blood
counts) and with sodium heparin (for lead measures).
Serum was separated from whole blood in the tubes
without additive within 30 minutes of being drawn,
and the tube for endocrine measures was covered with
tinfoil and stored at -20°C. Blood with EDTA was
stored for 2 hours at 4°C until the blood count. The
blood count was carried out in an automatic counting
device (Cell-Dyn 3000, Abbott Diagnostics, Mountain
View, CA). Quality control and system testing were
performed every morning using the control material
(CBC-3K Haematology Controls, R & D Systems,
Inc., Minneapolis, MN). Fresh serum samples were
analyzed in the Kodak Ektachem Automated Clinical
Chemistry Analyzer (Eastman Kodak, Rochester, New
York). Total protein was estimated by the Biuret
method (14). Albumin was determined by the bromcresol green method (15). Total calcium was determined by spectrophotometry (16). Blood samples
were sent to The Bio-Rad Laboratories (Richmond,
California) for external control, and a satisfactory rating was obtained. In addition, every 3 months samples
were sent to the College of American Pathologists
460
Kristal-Boneh et al.
(Northfield, Illinois) for control, and again satisfactory
ratings were obtained. Blood lead levels were measured by atomic absorption spectroscopy, by a modification of the method described previously (17). The
coefficient of variation was 5 percent. Assay quality control was assured by participation in the UK
National External Quality Assessment Schemes
(NEQAS) for clinical chemistry, with satisfactory results. Intact PTH levels were measured by a solidphase, two-site chemiluminescent enzyme immunometric assay (Immulite Intact PTH, Diagnostic
Products Corporation, Los Angeles, CA), with intraand interassay coefficients of variation of 5.4 percent
and 5.0 percent, respectively. Plasma levels of 25hydroxyvitamin D and calcitriol were measured by
competitive protein-binding analysis (25-Hydroxyvitamin D 3 H RIA Kit, and 1,25-Dihydroxyvitamin D
3
H RRA Kit, Incstar Corporation, Stillwater, MN).
Intra- and interassay coefficients of variation were
3.9 percent and 15.2 percent, respectively, for 25hydroxyvitamin D, and 6.9 percent and 6.9 percent,
respectively, for calcitriol.
Ionized calcium was calculated as follows: total
calcium—[8 X albumin (grams/100 ml) + 2 X globulin (grams/100 ml) + 3]. Environmental lead levels
were analyzed by atomic absorption, method US National Institute of Occupational Safety and Health
(NIOSH) 7082 (18).
Statistical analysis
Data analyses were carried out using SAS software
(19). Because blood lead concentrations are typically
skewed, analysis was performed on the natural logarithm of blood lead; arithmetic means and median
values were reported. Analyses of calcium and vitamin
D intake were controlled for age, total energy intake,
saturated fat intake, and supplements. Differences be-
tween means were analyzed by t test. Multiple linear
regression analysis was used to test the association
between occupational lead exposure (blood and environmental measurements) and calcitropic hormones
after controlling for potential confounding variables.
RESULTS
The characteristics of the study groups are shown in
table 1. The lead exposed and nonexposed subjects
were similar in age, years of formal education, body
mass index, and in energy, alcohol, and calcium consumption. There were more cigarette smokers among
the exposed subjects, although smokers in both groups
smoked similar quantities of cigarettes. Variables in
table 1 were considered possible confounders and
were included in the multivariate analyses. There were
no ethnic differences between the groups (data not
shown). Occupationally exposed subjects had higher
blood lead levels than the nonexposed subjects (table 2).
There were no differences between the groups in
dietary history: 9 percent of both groups ate less than
50 percent of the recommended daily amount of calcium, 47 percent ate between 50 and 100 percent of
the recommended daily amount of calcium, and 44
percent ate more than 100 percent.
The concentrations of calculated ionized calcium,
phosphorus, magnesium, and 25-hydroxyvitamin D
were similar in the two groups, whereas PTH and
calcitriol were significantly higher among the exposed
subjects (table 3). In univariate analyses, blood lead
level (log(p,g/dl)) was associated with PTH level (/3 =
3.48, 95 percent confidence interval (CI) 0.12-6.84,
p = 0.040) and with calcitriol level (/3 = 7.27, 95
percent CI 3.7-10.8, p <0.0001). We also used multivariate analyses to show that the observed association between blood lead level and PTH and calcitriol
was not due to potential confounders. Blood lead was
TABLE 1. Characteristics of the study groups of workers from five factories in central Israel, June
through September 1995
Occupational lead exposure
No
(n = 90)
Age (years)
BMI* (kg/mi)
Energy consumption (kcal/day)
Calcium consumption (mg/day)
Alcohol consumption
Cigarette smokers
Cigarettes/day among smokers
Seniority (years)
Education £12 years
Mean
(SD*)
41.5
26.0
2,211
774.5
(9.3)
(3.7)
(736)
(370)
Yes
%
Mean
(n=56)
(SD)
43.4
26.2
2,535
857.8
(11-2)
(3.7)
(1,218)
(423)
62
57
51
38
19.8
11.6
(13.8)
22.2
5.3
(4.3)
47
P
%
(13.3)
(4.0)
54
0.256
0.685
0.076
0.212
0.178
0.026
0.474
0.001
0.440
* SD, standard deviation; BMI, body mass index.
Am J Epidemiol
Vol. 147, No. 5, 1998
PTH, Vitamin D, and Lead
461
TABLE 2. Air and blood lead levels among occupatlonally exposed and nonexposed workerti from five
factories In central Israel, June through September 1995
Occupational lead exposure
No
(n=90)
Mean
Mean air lead (mg/m»)
Median air lead (mg/m>)
Mean blood lead (jig/dl)
Median blood lead (ug/dl)
1
0
0
4.54
4.0
Yes
(n=56)
(SD«)
Range
Mean
(SD)
(0.00)
0-0
(0.31)
(2.60)
1.4-19
0.17
0.07
42.58
40.5
(14.5)
P
Flange
0-2
20-77
0.0001
0.0001
0.0001
0.0001
SD, standard deviation.
associated with both PTH and calcitriol (table 4).
Owing to the strong correlation between blood lead
level and occupational lead exposure, these two variables were analyzed in different statistical models. In
univariate analyses, occupational lead exposure (no/
yes) was associated with PTH (j3 = 8.49, 95 percent
CI 1.29-15.6, p = 0.020) and with calcitriol (/3 =
14.3, 95 percent CI 6.5-22.1, p = 0.0004). After
adjusting for possible confounders, occupational lead
exposure (no/yes) was found to be independently associated with PTH level (/3 = 7.81, 95 percent CI
3.7-11.5) and with calcitriol (j8 = 12.3, 95 percent CI
3.84-20.8).
DISCUSSION
The main finding of this study is that subjects who
are occupationally exposed to lead have higher PTH
and calcitriol levels than those who are not. This
suggests that lead exposure alters calcium metabolism.
While the close association between calcium and lead
has been recognized for years (20), to the best of our
knowledge this is the first study assessing the com-
plete PTH-vitamin D-calcium axis in occupational
lead exposure.
Lead has been shown to either decrease or increase
calcitriol levels and calcium absorption in experimental animals (21). When dietary calcium is adequate,
lead ingestion results in increased calcitriol and calcium absorption; when dietary calcium is deficient,
circulating calcitriol levels are reduced, and so is calcium absorption (21) (owing to the effect of lead on
the ability of the kidney to produce calcitriol (22)). In
our exposed cohort (all male), the mean dietary calcium intake appeared to be adequate (not below the
recommended daily amount, supporting the experimental findings that with adequate dietary calcium,
lead exposure causes an increase in calcitriol levels.
Mason et al. (23) also found elevated levels of calcitriol in 17 occupationally exposed subjects with blood
lead levels higher than 40 /xg/dl but they did not find
differences in PTH. This study, however, had a small
sample size, 25-hydroxyvitamin D was not evaluated,
the season of data collection was not given, and they
did not study dietary intake. In a much smaller study
TABLE 3. Biochemical data (crude means) compiled from workers at five factories In central Israel,
June through September 1995
Occupational lead exposure
No
Total protein (grams/dl)
Albumin (grams/dl)
Total serum calcium (mg/dl)
Calculated ionized calcium
(mg/dl)
Magnesium (mg/dl)
Phosphorus (mg/dl)
PTH* (pg/ml) (reference value:
(12-72)
25-OH-D* (ng/ml) (reference
value: 14-36)
Calcitriol (pmol/l) (reference
value: 36-96)
Mean
(n=90)
(SD*)
7.2
4.3
9.9
(0.4)
(0.3)
(0.4)
5.6
2.1
3.5
(0.2)
(0.3)
(0.5)
33.6
(14.9)
31.6
(8.2)
68.7
(17.6)
Yes
(n = 56)
Range
6.3-8.3
3.8-5.1
9-10.9
Mean
(SD)
Vol. 147, No. 5, 1998
5.9-7.8
3.4-4.6
8.9-12.0
6.9
4.1
9.7
(0.4)
(0.3)
(0.5)
5.7
2.0
3.6
(0.3)
(0.3)
(0.6)
11-72
42.0
(24.2)
(17-169)
0.042
14-^9
34.4
(10.1)
(13-68)
0.091
38-142
82.5
(27.0)
(32-156)
0.0001
* SD, standard deviation; PTH, parathyroid hormone; 25-OH-D, 25-hydroxyvltamln D.
Am J Epidemiol
P
Range
0.0001
0.0001
0.065
0.108
0.062
0.898
462
Kristal-Boneh et al.
TABLE 4. Association between blood lead level and PTH* and calcitrlol of workers from five factories
In central Israel, June through September 1995
P
Blood lead (log(ug/dl))
Age (years)
Alcohol consumption (ml/month)
Smoking (£5 to >5 cigarettes/day)
Magnesium intake (mg/day)
Calcium Intake (mg/day)
Energy intake (kcal/day)
1
PTHlnpg/d
(fl* = 0.12)
95% Cl*
4.8
0.19
-0.82
3.2
0.04
-0.08
-0.13
0.8 to 8.8
-0.19 to 0.41
-4.92 to 3.28
-1.8 to 8.2
-0.16 to 0.24
-0.14 to 0.002
-0.17 to-0.09
Calcitriol in pmol/ltter
(.f?i = 0.10)
P
95% Cl
4.8
0.18
0.84
-0.73
0.05
-O.10
0.09
2.7 to 6.9
-0.02 to 0.38
-3.46 to 1.27
-5.13 to 3.67
-0.15 to 0.25
-0.16 to-0.04
0.081 to 0.094
PTH, parathyroid hormone; Cl, confidence Interval.
by Greenberg and co-workers (24) there were no effects of lead exposure on calcitriol.
The present finding of similar serum concentrations
of calculated ionized calcium in the two groups probably reflects the tight regulation of this mineral and
suggests that elevated PTH and calcitriol levels among
lead-exposed subjects is likely to be the counteracting
outcome of a tendency to systemic hypocalcemia. Total serum protein and albumin levels were significantly
lower in the exposed group. To the best of our knowledge this unexpected finding has not been reported
previously and deserves further study.
Since renal damage has been related to lead exposure (25), we cannot exclude the possibility that elevated levels of calcitropic hormones in exposed subjects may reflect a compensatory increase in PTH
secretion in response to a "renal calcium leak." However, no increase in urinary protein was found. In
addition, it is known that PTH synthesis is also stimulated by /3-adrenergic agonists, and though we cannot
rule out such a mechanism, it has been pointed out that
this is a minor effect physiologically compared with
that of ionized calcium (26).
It should be emphasized that although the levels of
calcitropic hormones were higher in the exposed than
in the nonexposed workers, they were still within the
normal range, and the health effects of such sustained
subclinical elevations are not known. Given an adequate calcium intake, the transient deficit in calcium
may be ultimately replaced from dietary sources.
However, since PTH partially corrects extracellular
fluid hypocalcemia by mobilizing bone calcium, the
maintenance of serum calcium at near-normal values
may occur at the expense of bone. It is also possible
that the higher levels of calcitriol facilitate the absorption from the gastrointestinal tract, not only of calcium
but also of lead, thus leading to further toxicity. Moreover, both calcium regulatory hormones, PTH and
calcitriol, may have blood pressure-elevating properties. PTH has the ability to stimulate cellular calcium
uptake and thereby increase intracellular calcium (27).
High intracellular calcium concentration heightens the
responsiveness of the smooth muscle cells, which in
turn, raises the blood pressure (28). PTH and calcitriol,
have both been shown to be increased in some forms
of essential hypertension (6-10). Since several reports
link blood lead levels with blood pressure levels, our
results suggest that elevated calcitropic hormones in
subjects occupationally exposed to lead may be one of
the factors involved in that relation. This may be
particularly relevant to elderly individuals with hypertension and to those with salt sensitivity, because the
age-associated decline in renal function is accompanied by an age-related rise in the level of circulating
PTH (29).
ACKNOWLEDGMENTS
This study was supported by the Committee for Preventive Action and Research in Occupational Health, The Ministry of Labor and Social Affairs, Jerusalem, Israel.
REFERENCES
1. Rosen JF. Metabolic and cellular effects of lead: a guide to
low level lead toxicity in children. In: Mahaffey KR, ed.
Dietary and environmental lead: human health effects. Topics
in environmental health, vol 7. Amsterdam, The Netherlands:
Elsevier, 1985:157-86.
2. Edelstein S, Fullmer CS, Wasserman RH. Gastrointestinal
absorption of lead in chicks: involvement of the cholecalciferol endocrine system. J Nutr 1984;114:692-700.
3. Smith CM, DeLuca HF, Tanaka Y, et al. Effect of lead
ingestion on functions of vitamin D and its metabolites. J Nutr
9 8 3 2 1 9
4. Fullmer CS. Intestinal interactions of lead and calcium. Neurotoxicology 1992;13:799-807.
5. Fullmer CS. Intestinal lead and calcium absorption: effect of
1,25-dihydroxycholecalciferol and lead status. Proc Soc Exp
Biol Med 1990;194:258-64.
6. McCarron DA, Pingree PA, Rubin RJ, et al. Enhanced parathyroid function in essential hypertension: a homeostatic response to a urinary calcium leak. Hypertension 1980;2:162-8.
7. Brickman AS, Nyby MD, von Hungen K, et al. Calcitropic
hormones, platelet calcium, and blood pressure in essential
hypertension. Hypertension 1990; 16:515-22.
Am J Epidemiol
Vol. 147, No. 5, 1998
PTH, Vitamin D, and Lead
8. Resnick LM, Muller FB, Laragh JH. Calcium-regulating hormones in essential hypertension: relation to plasma renin
activity and sodium metabolism. Ann Intern Med 1986; 105:
649-53.
9. Zachariah PK, Schwartz GL, Strong CG, et al. Parathyroid
hormone and calcium: a relationship in hypertension. Am J
Hypertens 1988;l:79s-82s.
10. Grobbee DE, Hackeng WHL, Birkenhager JC, et al. Raised
plasma intact parathyroid hormone concentrations in young
people with mildly raised blood pressure. Br Med J (Clin Res
Ed) 1988;296:814-16.
11. Orwoll ES, Meier DE. Alterations in calcium, vitamin D, and
parathyroid hormone physiology in normal men with aging;
relationship to the development of senile osteopenia. J Clin
Endocrinol Metab 1986;63:1262-9.
12. Modan M, Lubin F, Lusky A, et al. Interrelationships of
obesity, habitual diet, physical activity and glucose intolerance
in the four main Israeli Jewish ethnic groups. The Israel
Glucose Intolerance, Obesity and Hypertension (GOH) Study.
In: Berry EM, Blondheim SH, Eliahou HE, et al., eds. Recent
advances in obesity research. Vol 5. London, England: J
Libbey, 1986:46-53.
13. Viskoper JR, ed. Manual of nonpharmacological control of
hypertension. Berlin, Germany: Springer-Verlag, 1990.
14. Kingsley GR. The direct biuret method for determination of
serum proteins as applied to photoelectric and visual colorimetry. J Lab Clin Med 1942;27:840-5.
15. Corcoran RM, Duman SM. Albumin determination by a modified bromcresol green method. (Letter). Clin Chem 1977;
23:765.
16. Weissman N, Pileggi VJ. Inorganic ions. In: Henry RJ,
Cannon DC, Winkelman JW, eds. Clinical chemistry principles and technics. 2nd ed. Hagerstown, MD: Harper and Row,
1974:646-53.
17. Fernandez FJ. Micromethod for lead determination in whole
blood by atomic absorption with use of the graphite furnace.
Clin Chem 1975;21:558-61.
18. Documentation of the NIOSH validation tests. Washington,
Am J Epidemiol
Vol. 147, No. 5, 1998
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
463
DC: US Department of Health, Education, and Welfare, National Institute of Occupational Safety and Health, 1977.
(DHEW publication no. (NIOSH) 77-185).
SAS language: reference, version 6. 1st ed. Cary, NC: SAS
Institute, 1985.
Aub JC, Fairhill LT, Minot AS, et al. Lead poisoning. Medicine monographs, vol 7. Baltimore, MD: Williams and
Wilkins, 1926.
Fullmer CS. Dietary calcium levels and treatment interval
determine the effects of lead ingestion on plasma 1,25-dihydroxyvitamin D concentration in chicks. J Nutr 1995; 125:
1328-33.
Rosen JF, Chesney RW, Hamstra AJ, et al. Reduction in
1,25-dihydroxy vitamin D in children with increased lead absorption. N Engl J Med 1980;302:1128-31.
Mason HJ, Somervaille LJ, Wright AL, et al. Effect of occupational lead exposure on serum 1,25-dihydroxyvitamin D
levels. Hum Exp Toxicol 1990;9:29-34.
Greenberg A, Parkinson DK, Fetterol DE, et al. Effects of
elevated lead and cadmium burdens on renal function and
calcium metabolism. Arch Environ Health 1986;41:69-76.
Goyer RA. Renal changes associated with lead exposure. In:
Mahaffey KR, ed. Dietary and environmental lead: human
health effects. Topics in environmental health, vol 7. Amsterdam, The Netherlands: Elsevier, 1985:315-35.
Kukreja SC, Hargis GK, Bowser EN, et al. Role of adrenergic
stimuli in parathyroid secretion in man. J Clin Endocrinol
Metab 1978;40:478-81.
Chausmer AB, Sherman BS, Wallach S. The effect of parathyroid hormone on hepatic cell transport of calcium. Endocrinology 1972;90:633-72.
Buhler FR, Resink TJ. Platelet membrane and calcium control
abnormalities in essential hypertension. Am J Hypertens 1988;
1:42-6.
Rudnicki M, Thode J, Jorgensen T, et al. Effects of age, sex,
season and diet on serum ionized calcium, parathyroid hormone and vitamin D in a random population. J Intern Med
1993;234:195-200.