Assessment of bone lead during pregnancy: a pilot study.

More than 85% of American children raised in the 1970s had blood lead (BPb) levels >/=10 microg/dL, the level that currently defines childhood Pb poisoning. With exposure and absorption Pb accumulates in bone. Bone Pb release back to blood also occurs, particularly when kinetic rates of bone turnover are elevated. We examined a group of childbearing age, urban African American and Hispanic women to determine whether they had measurable bone Pb and whether bone Pb levels changed during pregnancy. Tibial bone Pb content was assessed sequentially 3 times over 4 months by L-line X-ray fluorescence (LXRF); for pregnant enrollees this occurred during the second and third trimesters and 1-2 months postpartum. LXRF is a noninvasive, low-dose radiation technique that measures superficial cortical bone Pb. Other measures included age, years living in New York City, BPb and a home Pb assessment employing KXRF methodology. Of 53 women evaluated 34 were pregnant. Of these 34, 2 had blood Pb levels >/=10 microg/dL; 2 had bone Pb levels above the minimum detection limit of the instrumentation at the time of enrollment. A case report is presented in which a declining bone Pb level was accompanied by an increase in BPb concentration. We surmise that the prevalence of elevated bone Pb levels will be low in Bronx women despite long-term exposure to leaded paint. However, fetuses of those with elevated bone Pb are at risk of excessive in-utero Pb exposure.

Low-level lead-induced neurotoxicity in children: an update on central nervous system effects.

The neurotoxicity of low-level long-term exposure to lead has a special relevance in children. An extensive database has provided a direct link between low-level lead exposure and deficits in the neurobehavioral-cognitive performance evidenced in childhood through adolescence. Electrophysiological studies showed that neurosensory processing may be affected by lead, with consequent decrease in auditory sensitivity and visuomotor performance. Lead disrupts the main structural components of the blood-brain barrier by primary injury to astrocytes with a secondary damage to the endothelial microvasculature. Within the brain, lead-induced damage occurs preferentially in the prefrontal cerebral cortex, hippocampus and cerebellum. Some characteristic clinical features of lead poisoning may be attributed to this specific anatomical pattern. The cellular, intracellular and molecular mechanisms of lead neurotoxicity are numerous, as lead impacts many biological activities at different levels of control: at the voltage-gated channels and on the first, second and third messenger systems. These effects could be related to lead's ability to interfere with the regulatory action of calcium in cell functions. Consequently, it may be assumed that lead acts as a chemical stressor and causes breakdown of the homeostatic cellular mechanisms. This is expressed in both the anatomical site and the neurotransmitter systems which are crucial in modulating emotional response, memory and learning. There is no threshold below which lead remains without effect on the central nervous system; thus, symptoms could simply be a clinical reflection of the brain regions preferentially involved. In integrating these physiological and clinical data, it may be suggested that the different mechanisms of low level lead neurotoxicity have a final common functional pathway.

Children with moderately elevated blood lead levels: a role for other diagnostic tests?

In this study we examined potential limitations of relying exclusively on blood lead (BPb) levels to evaluate children with moderately elevated BPb levels (1.21-2.12 micromol/l, or 25-44 microg/dl). We tested the following hypotheses: 1) such children without elevated erythrocyte protoporphyrin (EP) levels (>=0.62 micromol/l or >/= 35 microg/dl) are unlikely to respond to a chelating agent with a brisk urinary Pb diuresis; 2) those with elevated EP levels, but low hematologic indices consistent with iron deficiency, are also unlikely to respond to a chelating agent with a robust urinary Pb diuresis; and 3) those with elevated EP levels and iron sufficiency are more likely to respond to a chelating agent. To test these hypotheses, we performed retrospective analyses of the relationships between EP concentrations, hematologic indices, and urinary Pb excretion ratios (uPbr) in moderately Pb-poisoned children undergoing the CaNa2EDTA lead mobilization test (Pb-MT). Data from 122 children were available. Urinary Pb excretion was limited in children with an EP <0.62 micromol/l (<35 microg/dl); only 5% (1/21) of Pb-MTs were positive (uPbr >=0.6). In children with an EP >=0.62 micromol/l, low hematologic indices, such as a mean corpuscular hemoglobin (MCH) <23 pg, were associated with relatively little Pb excretion (0/14 positive Pb-MTs). In contrast, 32% (28/87) of Pb-MTs were positive in children with an EP >/= 0.62 micromol/l and iron sufficiency (p<0.01 by chi-square comparison between groups with EP >/= 0.62 micromol/l and either MCH <23 pg or MCH >/= 23 pg). We conclude that only a minority of moderately Pb-poisoned children will demonstrate enhanced urinary Pb excretion in response to chelation therapy. Some of the predicted nonresponders can be readily identified by adding the EP and complete blood count to the panel of tests performed.

Moderate lead poisoning: trends in blood lead levels in unchelated children.

The appropriate clinical management of children who are moderately poisoned with lead (Pb) is under active investigation. To determine the pattern of change in blood Pb (BPb) levels in the absence of chelation therapy, we followed moderately Pb-poisoned children (initial blood Pb levels 1.21-2.66 mumol/l or 25-55 micrograms/dl) for 6 months with repeated BPb level measurements. Chelation therapy was not administered because all the children had negative lead mobilization tests indicating limited response to the chelating agent, calcium disodium edetate (CaNa2EDTA). Eligible children received the following interventions: notification of the health department to remediate lead hazards; reinforced educational efforts about the toxicity sources and treatment of Pb during 10 clinic and 3 home visits; and iron therapy for children with ferritin levels less than 16 micrograms/l. To quantify the lead paint hazards in the home, we combined a visual rating of the surfaces (intact to peeling) with an X-ray fluorescence (XRF) measurement of the lead content of the painted surface. The sum of these assessments is termed the home environmental score (HES). Data were analyzed from 79 children. BPb levels declined by 27%, on average, over 6 months. HES was correlated with BPb at enrollment, but neither the initial nor later HES measurements predicted BPb at other time points. The HES was highest at enrollment and declined by 50% and 75% at the second and third home visits, respectively. However, only a minority of the children (20%) achieved an HES of 0, indicating no lead paint hazards at home. Despite some ongoing Pb exposure, a parallel fall in BPb levels was observed in subgroups of children with either initially low or high HES (above or below the median HES of 37). Iron status did not account for the change in BPb levels. These data provide evidence that our measure, the HES, is quantifiably related to BPb levels in children, that this correlation is significant only prior to intervention; and that BPb levels decline in children who are moderately poisoned with Pb after they are enrolled in a comprehensive intervention program, even in the absence of chelation therapy and in the presence of ongoing lead paint exposure and Fe deficiency.

Relationships among blood lead levels, iron deficiency, and cognitive development in two-year-old children.

The goals of this study were to explore the relationship of declining blood lead levels and cognitive development in 42 moderately lead poisoned children around 2 years of age and to investigate the potential interaction between iron and lead levels in the course of development. The cognitive functioning of children was assessed upon enrollment into a comprehensive intervention and 6 months later. The intervention consisted of chelation treatment, if appropriate, iron supplementation, if needed, and steps to eliminate the source of lead in the home environment. The children were referred because of blood lead levels between 25 and 55 mu g/dl; they were also selected on the basis of age between 18 and 30 months. The outcome measures were the global score on a standardized test of cognitive development and subscale scores for perceptual-motor and language functioning. Cognitive change over 6 months was related to an interaction between change in blood lead and initial iron status. Specifically, the change in standardized score (particularly change in perceptual-motor performance) was strongly related to change in blood lead in children who were iron sufficient at the outset: there was an increase of 1.2 points for every 1 mu g/dl decrease in blood lead. There was no such relationship in iron-deficient children. Secondary analyses suggested that 1) the change in cognitive functioning of iron-deficient children was related to change in hemoglobin, and 2) the decline in blood lead was less in iron-deficient than in iron-sufficient children. Thus, when iron is sufficient, changes in blood lead and changes in cognition are inversely related. When iron is deficient, other processes affect the outcome.

The effects of succimer on the absorption of lead in adults determined by using the stable isotope 204Pb.

The chelating agent succimer (meso-2,3-dimercaptosuccinic acid) is orally effective at inducing a urinary lead diuresis and a decrease in blood lead levels in lead poisoned children and adults. However, there are concerns that succimer may increase the absorption of lead from the gastrointestinal (GI) tract during treatment, particularly in cases of continuing lead exposure, which would compromise its effectiveness in reducing whole body lead stores. This preliminary study investigated the effects of succimer on the absorption of lead in adults using a stable lead isotopic tracer (204Pb). Twelve male subjects were divided into control (no succimer), 10, and 30 mg succimer/kg body wt treatment groups of 4 individuals each. All subjects ingested a single tracer dose (200 micrograms) of 204Pb, followed by a single oral dose of placebo (control) or succimer. Whole blood was collected at intervals of 0, 2, 4, and approximately 26 hr following ingestion of the 204Pb tracer, and composite urine and feces samples were collected over the duration of the study (approximately 26 hr). Mean intestinal excretion of 204Pb was reduced in the succimer-treated groups compared to the control (placebo), whereas urinary diuresis of 204Pb was higher in the succimer groups. The amount of lead 204Pb tracer accounted for at the end of the study was lower in the succimer-treated groups. These results suggest that GI lead absorption was enhanced by succimer and that succimer mediated the redistribution of lead from the circulation to other tissues. However, none of the differences between treatment groups were statistically significant (P < 0.05, t test) because of the relatively large within-group variability. This study demonstrates the utility of microgram doses of a stable lead isotopic tracer to assess the efficacy of clinical chelating agents in humans. Future studies are necessary to further clarify the effects of succimer on the absorption and retention of lead in adults and children. Although, based upon these preliminary data, it appears advisable that patients be maintained in a lead-safe environment while being treated with succimer.

Effects of calcium disodium versenate (CaNa2EDTA) chelation in moderate childhood lead poisoning.

BACKGROUND: For children with asymptomatic moderate lead poisoning (Blood lead level [BPb] 25 to 55 micrograms/dL [1.21 to 2.66 mumol/L]), treatment with the chelating agent calcium disodium versenate (CaNa2EDTA) is recommended for all those children with a BPb level > 45 micrograms/dL (2.17 mumol/L) and for those with a BPb level of 25 to 44 micrograms/dL (1.21 to 2.13 mumol/L) who also have a positive lead mobilization test. However, controlled studies demonstrating its efficacy at inducing a sustained reduction in BPb level or lead-related toxicity have not been performed in children with moderate lead poisoning. This study assesses the relationship between CaNa2EDTA chelation and measures of lead burden and toxicity in children with moderate lead poisoning. METHODS: Two hundred one children with moderate lead poisoning were enrolled. Sequential changes in BPb concentrations, bone lead level as measured by L alpha-x-ray fluorescence, and lead-induced toxicity as assessed by erythrocyte protoporphyrin levels were determined over a 7-week period. From this group, children with a positive lead mobilization test received CaNa2EDTA chelation therapy. RESULTS: Children with positive lead mobilization tests had on average higher initial BPb, bone lead, and erythrocyte protoporphyrin concentrations. The chelated children decreased approximately 4.7 micrograms/dL (0.23 mumol/L), 41 corrected net counts, and 24 micrograms/dL (0.46 mumol/L) more than the unchelated children on BPb, bone lead, and erythrocyte protoporphyrin values, respectively. However, children with higher initial levels decreased the most, whereas children with lower initial levels showed the least decline, with or without treatment. When the initial values on the measures were controlled analytically, or when subgroups matched on initial levels were compared, there were no significant differences between the chelated and unchelated children. CONCLUSIONS: The apparent effectiveness of CaNa2EDTA at reducing lead burden and toxicity is no longer observed when the pretreatment levels are considered. The findings suggest that sufficient doubt about CaNa2EDTA efficacy now exists to warrant a randomized controlled trial of chelation therapy in moderately lead-poisoned children. However, until such studies are performed, it would be premature to withhold chelation treatment on the basis of this study alone.

Trends in the management of childhood lead poisonings.

It is unknown whether prompt medical management (with or without chelation therapy) and environmental intervention have beneficial effects other than stopping the progression towards symptomatic childhood lead poisoning. Stated differently, does prompt intervention have substantive beneficial effects or are untreated lead toxic children with blood lead values between 25-54 micrograms/dl irrevocably damaged by the time of their identification. We are carrying out a prospective treatment outcome study with CaNa2EDTA (when indicated) at our Center to hopefully answer this critical question, within the context of a multidisciplinary study. The results in 162 children indicate that environmental and medical management produce significant reductions in blood lead, erythrocyte protoporphyrin and the lead diuresis during a CaNa2EDTA provocative test. However, CaNa2EDTA treatment failed to decrease bone lead values dramatically, measured by L-line x-ray fluorescence, six months after enrollment in any patient group (treated or untreated with CaNa2EDTA). The uses of L-line x-ray fluorescence in this study and K-line x-ray fluorescence measurements of lead in bone in other reported studies open a wide time window of months to years of lead exposure, compared to 30-45 days, the time of exposure captured by blood lead levels. As with all chelating agents, DMSA should be administered to children in lead free housing, after this drug's toxicity is more widely assessed. The potential capability of DMSA to ameliorate neurobehavioral deficits produced by lead must be systematically assessed and compared with CaNa2EDTA in a randomized, controlled study before the use (s) of either drug become uncritically accepted as the treatment of choice for childhood lead poisoning, in addition to full abatement.

Need for the lead mobilization test in children with lead poisoning.

We evaluated the recommendation of the Centers for Disease Control, that children with moderate lead poisoning undergo the lead mobilization test (LMT) to determine the need for a full course of chelation treatment. Current criteria for selection for this test include a blood Pb concentration (bPb) between 25 and 55 micrograms/dl and an erythrocyte protoporphyrin level greater than 35 micrograms/dl. To determine whether the eligibility criteria could be refined to a smaller group of patients, we compared bPb determinations obtained on the day of the LMT in 198 children with moderate Pb poisoning to the results of the LMT. We found that children with bPb less than 25 micrograms/dl were unlikely to respond to the test dose of calcium disodium ethylenediamine tetraacetate with a Pb diuresis (24/25 patients had low urinary Pb excretion on the LMT). In contrast, 88% of children with bPb greater than or equal to 40 micrograms/dl were likely to excrete sufficient Pb to indicate the need for a full course of chelation. We conclude that the LMT is indicated for children with bPbs between 25 and 40 micrograms/dl. Children with bPb between 40 and 55 micrograms/dl may receive chelation therapy without having an LMT, if the performance of the LMT is not practical. Patients with levels less than 25 micrograms/dl should be followed clinically and removed from further Pb exposure.

Sequential measurements of bone lead content by L X-ray fluorescence in CaNa2EDTA-treated lead-toxic children.

With the development of L X-ray fluorescence (LXRF) to measure cortical bone lead directly, safely, rapidly, and noninvasively, the present study was undertaken to a) evaluate LXRF as a possible replacement for the CaNa2EDTA test; b) quantify lead in tibial cortical bones of mildly to moderately lead-toxic children before treatment; and c) quantify lead in tibial cortical bones of lead-toxic children sequentially following one to two courses of chelation therapy. The clinical research design was based upon a longitudinal assessment of 59 untreated lead-toxic children. At enrollment, if the blood lead (PbB) was 25 to 55 micrograms/dL and the erythrocyte protoporphyrin (EP) concentration was greater than or equal to 35 micrograms/dL, LXRF measurement of tibial bone lead was carried out. One day later, each child underwent a CaNa2EDTA provocative test. If this test was positive, lead-toxic children were admitted to the hospital for 5 days of CaNa2EDTA therapy. These tests were repeated 6 weeks and 6 months after enrollment. Abatement of lead paint hazards was achieved in most apartments by the time of initial hospital discharge. The LXRF instrument consists of a low energy X-ray generator with a silver anode, a lithium-doped silicon detector, a polarizer of incident photons, and a multichannel X-ray analyzer. Partially polarized photons are directed at the subcutaneous, medial mid-tibial cortical bone. The LXRF spectrum, measured 90 degrees from the incident beam, reveals a peak in the 10.5 KeV region, which represents the lead L alpha line.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential measurements of bone lead content by L X-ray fluorescence in CaNa2EDTA-treated lead-toxic children.

With the development of L X-ray fluorescence (LXRF) to measure cortical bone lead directly, safely, rapidly, and noninvasively, the present study was undertaken to a) evaluate LXRF as a possible replacement for the CaNa2EDTA test; b) quantify lead in tibial cortical bones of mildly to moderately lead-toxic children before treatment; and c) quantify lead in tibial cortical bones of lead-toxic children sequentially following one to two courses of chelation therapy. The clinical research design was based upon a longitudinal assessment of 59 untreated lead-toxic children. At enrollment, if the blood lead (PbB) was 25 to 55 micrograms/dL and the erythrocyte protoporphyrin (EP) concentration was greater than or equal to 35 micrograms/dL, LXRF measurement of tibial bone lead was carried out. One day later, each child underwent a CaNa2EDTA provocative test. If this test was positive, lead-toxic children were admitted to the hospital for 5 days of CaNa2EDTA therapy. These tests were repeated 6 weeks and 6 months after enrollment. Abatement of lead paint hazards was achieved in most apartments by the time of initial hospital discharge. The LXRF instrument consists of a low energy X-ray generator with a silver anode, a lithium-doped silicon detector, a polarizer of incident photons, and a multichannel X-ray analyzer. Partially polarized photons are directed at the subcutaneous, medial mid-tibial cortical bone. The LXRF spectrum, measured 90 degrees from the incident beam, reveals a peak in the 10.5 KeV region, which represents the lead L alpha line.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of iron deficiency on lead excretion in children with moderate lead intoxication.

The effect of iron status on calcium disodium edetate (CaNa2EDTA)-induced lead diuresis was examined in 112 children with moderate lead intoxication. Patients whose blood lead levels were between 25 and 55 micrograms/dl and who had erythrocyte protoporphyrin concentrations greater than or equal to 35 micrograms/dl underwent provocative testing to determine the need for a full course of chelation therapy. A blood sample for lead, erythrocyte protoporphyrin, and serum ferritin determinations was obtained immediately before the intramuscular administration of CaNa2EDTA, 500 mg/m2. Determination of urinary lead level was based on an 8-hour urine collection. Blood lead and ferritin levels were significantly correlated with urinary lead excretion: r = 0.542 and 0.298, respectively, p less than 0.01 for both. Multiple regression models were tested to assess the independent effects of the variables. With blood lead level controlled, ferritin remained significantly associated with urinary lead excretion; for every 1 ng/ml increase in ferritin, urinary lead increased by 2.4 micrograms. This small effect of ferritin on urinary lead was illustrated in a discriminant analysis. Using blood lead level by itself as the independent variable resulted in a 76% correct assignment of provocative test outcomes. Knowing the ferritin level improved this assignment accuracy by only 3%. We conclude that the iron status, as measured by serum ferritin, of children with moderate lead intoxication, has a small but significant effect on CaNa2EDTA-induced lead diuresis. This effect may influence the interpretation of borderline provocative test outcomes. Although chelation therapy should not be withheld pending treatment of iron deficiency, lead stores should be reassessed after iron repletion.

Effects of growth hormone therapy on circadian osteocalcin rhythms in idiopathic short stature.

The effects of GH administration on the circadian osteocalcin (Oc) rhythm were determined in four prepubertal children with idiopathic short stature (height, less than 5th percentile; growth velocity, less than 50th percentile for age). Each child underwent 24-h sequential blood sampling on three occasions: immediately before the initiation of GH treatment, 6 months later, and at the end of 12 months of treatment. The growth rate increased more than 50% over baseline in three of the four children during at least one of the 6-month periods. Insulin-like growth factor-I levels increased during treatment in all of the children. Twenty-four-hour Oc levels increased on 7 of the 8 treatment days evaluated. When mean 24-h Oc patterns for each of the 3 study days were derived by averaging across individual subjects at each time point and then compared, we noted an upward shift in the entire pattern during treatment (t = 13.2 at P less than 0.001 and t = 5.9 at P less than 0.001 for 6 and 12 month comparisons vs. the pretreatment day, respectively). This was more easily appreciated after the data were smoothed using the method of running means. There was, in addition, a progressive improvement in the shape of the Oc pattern compared to a normative model derived from a study of healthy adult men. The correlation between the model and the pre-GH day was 0.46, that between the model and the 6 months of GH day was 0.77, and that between the model and the 12 months of GH day was 0.96. Cross-correlation analyses showed that the peak correlation between the 2 treatment days and the model occurred at zero lag. In contrast, the peak correlation between the pre-GH day and the model or the pre-GH day and either of the 2 treatment days occurred when the pre-GH series was lagged by 2-3 h. Thus, an additional finding is the synchronization of the Oc series that occurred during treatment. We conclude that GH treatment increases Oc concentrations in children with idiopathic short stature by affecting its circadian rhythm. This rise in Oc values may not necessarily reflect an increase in growth velocity.

L-line x-ray fluorescence of cortical bone lead compared with the CaNa2EDTA test in lead-toxic children: public health implications.

Mild to moderate lead toxicity (blood lead, 25-55 micrograms/dl) is a preventable pediatric illness affecting several million preschool children ("lead-toxic children") in the United States. In-hospital lead-chelation treatment is predicated upon a positive CaNa2EDTA test, which is difficult to perform and impractical in large populations. After the development of an L-line x-ray fluorescence technique (LXRF) that measures cortical bone lead content safely, rapidly, and noninvasively, this study was initiated in lead-toxic children to compare LXRF with the CaNa2EDTA test. Moreover, LXRF provided the opportunity to quantify bone lead content. From blood lead and LXRF alone, 90% of lead-toxic children were correctly classified as being CaNa2EDTA-positive or -negative. In 76% of 59 lead-toxic children, bone lead values measured by LXRF were equal to or greater than those measured in normal and industrially exposed adults. These results indicate that LXRF may be capable of replacing the CaNa2EDTA test. When considered with the known neurotoxic effects on children of "low levels" of exposure to lead, these results also suggest that either an excessively narrow margin of safety or insufficient safety is provided by present U.S. guidelines, which classify an elevated blood lead concentration as 25 micrograms/dl or greater.

Temporal interrelationships between the circadian rhythms of serum parathyroid hormone and calcium concentrations.

The temporal relationships between the circadian rhythms of serum PTH, total calcium (Cat), and phosphate (Pi) and plasma ionized calcium (Cai) concentrations were determined in 9 normal men. Blood samples were collected every half hour for 24 h. Serum PTH was measured by an RIA specific for the midregion of the molecule. The mean circadian pattern for each variable was derived by calculating the average value across all men at concurrent time points. After the data were smoothed by the method of running means, the correlations between PTH and mineral values from concurrent time points were calculated, as were cross-correlations to 12 lag periods (6 h). Spectral and cross-spectral analyses were performed on the same data set. Both statistical methods yielded consistent results: 1) at concurrent time points (0 lag), high correlations were found between serum PTH and Cat (r = -0.74), PTH and Pi (r = 0.79), and PTH and Cai (r = -0.53); and 2) when the PTH series was lagged by 2 h, the PTH/Cai correlation improved to -0.70. A direct PTH/Cai correlation of 0.50 was found when the Cai series was lagged about 4.5 h. No improvement in the correlations were found when the other series were lagged. Spectral analyses also detected significant interrelations between PTH and Cai at 2 and 3.5 h. These data describe the timing of the bidirectional interaction between serum PTH and plasma Cai under steady state conditions in normal adult men; changes in Cai concentrations precede inverse changes in PTH levels by 2 h, whereas changes in PTH precede similar directional alterations in Cai by about 4 h.

The circadian rhythm of serum osteocalcin concentrations: effects of 1,25 dihydroxyvitamin D administration.

The effects of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) administration on serum osteocalcin (Oc) concentrations were determined. 2.0 micrograms doses of 1,25(OH)2D3 were administered orally and intravenously to four healthy adult males. Blood was sampled hourly for 24 hours on four occasions: once prior to the two treatment days (i.v. and p.o.), on each of the treatment days, and during a second nontreatment day 2 years later. Mean circadian Oc rhythms of the four subjects on each study day were compared with each other and with a previously derived mathematical representation of the normative Oc rhythm, the circadian Oc rhythm model. We found overall conservation of the mean Oc pattern across time and 1,25(OH)2D3 treatment. However, 1,25(OH)2D3 administration resulted in a rapid rise (within 6 hours) in Oc concentrations that blunted or eliminated the morning fall in Oc levels. The increased Oc levels were sustained for the remainder of the 24 hour period though pattern shapes converged with those of the nontreatment days and the model. We conclude that serum Oc levels are rapidly responsive to near physiological doses of 1,25(OH)2D3 in healthy adult males and that the effects are maintained for at least 24 hours.

Effects of 1,25 dihydroxyvitamin D3 administration on circadian mineral rhythms in humans.

1,25 Dihydroxyvitamin D3 (1,25(OH)2D3) (2.0 micrograms) was given intramuscularly to 6 healthy adult males. Twenty-four circadian patterns of blood-ionized calcium (Ca2+), serum phosphate (Pi), and total calcium (CaT) were assessed pre- and posthormone administration. Correlations of mean mineral rhythms with normative models were significant for each mineral pattern on both study days. Mean Ca2+ and CaT rhythms became weakly correlated after hormone treatment (r = .39). A small but statistically significant increment in the 24 h grand mean Ca2+ concentration was observed on the treatment day compared with the baseline day. However, this increment is less than the year-to-year variability in the grand mean mineral concentrations derived from the same subjects studied under baseline conditions previously. These data indicate that acute parenteral administration of near-physiological (2.0 micrograms) doses of 1,25(OH)2D3 appears to have no major effect on circadian mineral pattern shape or mean mineral concentrations.

Circadian variations in serum zinc (Zn) concentrations: correlation with blood ionized calcium, serum total calcium and phosphate in humans.

Serum zinc (Zn) concentrations were determined in sequentially drawn blood samples from six healthy adult males. Each subject had blood sampling performed every 30 minutes for 24 hours. Mean Zn concentrations at each time point (n = 6, 48 time points) were plotted and fitted by a polynomial regression of the data against time. A "U" shaped curve was derived; we found peak Zn levels at 9:30 AM, a midtrough at 8 PM and a peak-trough difference of 19 micrograms/dl. Correlation with a similarly derived 24-h ionized calcium pattern was strikingly high, r = .923, p less than .001. An intermediate correlation between the Zn and phosphate patterns was observed, r = -.493, p less than .01; and no significant correlation occurred between Zn and total calcium rhythms, r = .167. These data conclusively demonstrate the presence of a circadian rhythm in serum Zn in healthy adult males. Furthermore, the high correlation between the Zn and ionized calcium patterns suggests a common regulator.