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The association between environmental lead exposure and bone density in children.

Osteoporosis is a decrease in bone mineral density (BMD) that predisposes individuals to fractures. Although an elderly affliction, a predisposition may develop during adolescence if a sufficient peak BMD is not achieved. Rat studies have found that lead exposure is associated with decreased BMD. However, human studies are limited. We hypothesized that the BMD of children with high lead exposure would be lower than the BMD of children with low lead exposure. We collected data on 35 subjects; 16 had low cumulative lead exposure (mean, 6.5 [micro]g/dL), and 19 had high exposure (mean, 23.6 [micro]g/dL). All were African American; there was no difference between the groups by sex, age, body mass index, socioeconomic status, physical activity, or calcium intake. Significant differences in BMD between low and high cumulative lead exposure were noted in the head (1.589 vs. 1.721 g/[cm.sup.2]), third lumbar vertebra (0.761 vs. 0.819 g/[cm.sup.2]), and fourth lumbar vertebra (0.712 vs. 0.789 g/[cm.sup.2]). Contrary to our hypothesis, subjects with high lead exposure had a significantly higher BMD than did subjects with low lead exposure. This may reflect a true phenomenon because lead exposure has been reported to accelerate bony maturation by inhibiting the effects of parathyroid hormone-related peptide. Accelerated maturation of bone may ultimately result in a lower peak BMD being achieved in young adulthood, thus predisposing to osteoporosis in later life. Future studies need to investigate this proposed model. Key words: blood lead levels, bone mineral density, dual-energy X-ray absorptiometry, parathyroid hormone-related peptide. Environ Health Perspect 112:1200-1203 (2004). doi:10.1289/ehp.6555 available via http://dx.doi.org/[Online 7 April 2004]

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Research on the adverse effects of lead exposure on humans has focused on neurocognitive outcomes among children [Canfield et al. 2003; National Research Council (NRC) 1993]. However, a growing body of literature reports that the effects of childhood lead exposure continue into adolescence and adulthood. These include delinquent behavior (Dietrich et al. 2001; Needleman et al. 2002), dental caries (Moss et al. 1999), hypertension (Hu et al. 1996; Nash et al. 2003), cardiac arrhythmias (Cheng et al. 1998), and renal dysfunction (Kim et al. 1996). Research also demonstrates another potential late effect of childhood lead exposure: osteoporosis. Studies on rats have found that increased lead exposure is associated with decreased bone density (Escribano et al. 1997; Gruber et al. 1997; Puzas et al. 1999) and decreased bone strength (Ronis et al. 2001). Additional studies have found that lead exposure inhibits the function of osteoblasts (Klein and Wiren 1993; Puzas et al. 1999; Ronis et al. 2001), the cells that make bone.

However, human studies on this association are limited. In a study of children, Laraque et al. (1990) found no association between bone density and lead exposure. However, because the comparison group was made up of children with moderate-level lead exposure (i.e., blood lead level 12-29 [micro]g/dL), such a study cannot exclude the possibility that lead exposure has an effect at lower levels. In addition, because the children were examined at a young age (range, 18-47 months), sufficient time may not have elapsed for the adverse effects on the bone to become manifest. A study by Alfven et al. (2002) also found no association between lead exposure and bone mineral density (BMD) in a cross-sectional study of adults. However, the authors used concurrent blood lead level to define lead exposure and acknowledged that such a measure may be inadequate to measure body lead burden. In addition, subjects did not have high blood lead levels [the mean blood lead level was 3.1 [micro]g/dL (Alfven T, personal communication)]; thus, the lack of an association may be due to low lead exposure among the subjects.

Our objective was to determine whether an association between lead exposure and bone density exists in children. We hypothesized that the bone density of children with high lead exposure would be lower than the bone density of children with low lead exposure.

Materials and Methods

Subject identification and enrollment. To identify potential subjects who had an adequate number of blood lead levels to define past lead exposure, we obtained a comprehensive database of blood lead levels from the local county health department (Department of Health, Monroe County, New York State). To minimize the effect of age on BMD, we limited the database to children 8-10 years of age. In the database, we excluded capillary blood lead levels [greater than or equal to] 10 [micro]g/dL, because of the possibility that these represent contaminated specimens [Centers for Disease Control and Prevention (CDC) 1991], and children who did not have at least one blood lead level at each of four age groups (13-24 months, 25-36 months, 37-48 months, and 49-60 months). For the remaining children, we calculated each child's cumulative lead exposure (defined below) and created a list with the following information: child's name, date of birth, race, and cumulative lead exposure. From the list, we identified children who attended the principal investigator's (J.R.C.) pediatric practice or whom the principal investigator had medically managed for lead toxicity. To eliminate the effect of race, we contacted only subjects who were African American. The principal investigator (J.R.C.) subsequently called the parents of the potential subjects to ask if they would be interested in having the child enrolled. If a parent agreed, a short questionnaire was administered to determine whether exclusionary criteria existed. We excluded children who had medical conditions that affected bone density (metabolic bone disease, renal disease, sickle cell disease), used certain medications (corticosteroids, anticonvulsants, diuretics), had evidence of sexual maturation (i.e., Tanner stage [greater than or equal to] 2), or had a parent who was not African American. If no exclusionary criteria existed, the study coordinator (L.N.) called the parent to schedule an appointment for the bone density procedure. At the appointment, the study coordinator obtained informed consent, completed a questionnaire to collect covariate date, and measured the child's height and weight. Subsequently, one technician conducted the bone density measurement. The study coordinator and technician were blinded to the subject's cumulative lead exposure status.

The Human Subjects Committee of the Monroe County Health Department, the Human Subjects Review Board of the University of Rochester Medical Center, and the Clinical Investigation Committee of Rochester General Hospital approved this study.

Measure of lead exposure. The measure of lead exposure used in this study is termed the cumulative lead exposure. To compute it, we identified all blood lead levels collected during four age strata (i.e., 12-23 months, 24-35 months, 36-47 months, and 48-60 months) from the local health department database. Subsequently, we calculated the arithmetic mean of all blood lead levels for each of the four age strata. Finally, the cumulative lead exposure was calculated by computing the arithmetic mean of the four age strata means. Subjects were dichotomized as having high versus low cumulative lead exposure at a cutoff of 15 [micro]g/dL.

There is a strong correlation (i.e., 0.92-0.95) between any single blood lead level in children between 2 and 4 years of age and cumulative lead exposure measure based on 24 serial blood lead levels in children between 3 months and 10 years of age (Dietrich K, personal communication); therefore, we conclude that our measure of cumulative lead exposure is a valid measure of the overall lifetime lead exposure for a school-age child.

Measure of bone density. We used a fan-beam dual-energy X-ray absorptiometry (DEXA) scanner (Prodigy; GE/Lunar Corporation, Madison, WI) to measure BMD (Mazess et al. 1990). BMD was determined at various body regions (e.g., total body, arms, legs, trunk), the lumbar vertebrae, and hip regions (total hip, femoral neck, trochanter, femoral shaft).

Measure of covariates. Variables associated with changes in bone density include age (Boot et al. 1997; Maynard et al. 1998), race (Nelson et al. 1997; Pollitzer and Anderson 1989), weight (Boot et al. 1997), physical activity (Cooper et al. 1988), and calcium intake (Johnston et al. 1992). Bone density does not vary by sex among children < 13 years of age (Maynard et al. 1998).

To minimize the effect of age, we enrolled only subjects within a narrow age range: 8-10 years. To eliminate the effect of race, we enrolled only subjects who were African American (and whose parents were both African American). We measured subject weight and height at the time of the BMD measurement. A parental questionnaire collected data on physical activity (i.e., the number of hours a day the child is physically active and inactive), calcium intake (i.e., current milk and milk-product intake and frequency), and socioeconomic status [head of household Hollingshead occupational level and socioeconomic score (Hollingshead 1958)].

Analyses. We initially compared the covariates between subjects by cumulative lead exposure status (i.e., low vs. high). Because age and weight are strongly associated with BMD, we decided, a priori, to introduce both into adjusted analyses. Other comparisons with p-values [less than or equal to] 0.20 were also to be introduced into adjusted analyses. The primary analysis was, for each bony site, a comparison of the mean BMD by cumulative lead exposure status. Using SPSS software (version 4.0; SPSS Inc., Chicago, IL), we conducted adjusted analyses by use of analysis of covariance between the cumulative lead exposure groups.

A sample size calculation demonstrated that 44 subjects would be required to achieve a power of 80% in discerning a 1.0-SD difference in BMD between the groups. We conducted analyses during subject recruitment, thus allowing us to discontinue enrollment after significant findings were discerned at a sample size of 35 subjects.

Results

We collected data on 36 subjects. All were African American. One subject was excluded because of obesity [body mass index (BMI) = 33]. Among the remaining subjects, 63% were male. The mean age was 109.5 months. The mean weight was 33.6 kg, and the mean height 138.6 cm; these measures are approximately at the 75th and 60th percentiles, respectively.

Among the 35 subjects analyzed, 16 had a low cumulative lead exposure and 19 had a high cumulative lead exposure; the respective mean cumulative lead exposures were 6.5 [micro]g/dL (range, 2.7-10.3 [micro]g/dL) and 23.6 [micro]g/dL (range, 15.5-43.5 [micro]g/dL) (Table 1). The groups were otherwise comparable; there were no differences (i.e., p > 0.20) between the groups on sex distribution, age, BMI, socioeconomic status, physical activity, or calcium intake (Table 2).

Table 3 shows the adjusted mean BMD by bony site and cumulative lead exposure status. Contrary to our hypothesis, we found that subjects with high cumulative lead exposure had a higher BMD than did subjects with low cumulative lead exposure. Among 17 bony sites, four were significantly different (i.e., p [less than or equal to] 0.05).

Discussion

Contrary to our hypothesis, we found that subjects with high lead exposure had a significantly higher bone density than did subjects with low lead exposure. We initially considered whether this result derived from an artificial increase in the measure of bone density by DEXA due to the presence of lead in bone. A false elevation of DEXA-based bone density is reported to occur in bone containing strontium, a heavy metal with a lower atomic weight than lead (Nielsen et al. 1999). We found, in an in vitro study using an older Lunar DPX-L pencil-beam instrument, that bone density increased by 8-11% with increasing and clinically relevant bone lead levels (i.e., 10-100 [micro]g/g) (Puzas et al. 2002). However, when this in vitro study was replicated using a newer Lunar Prodigy fan-beam instrument, the same used on the subjects of our study, the effect was minimal and within the precision of the DEXA measure (Muzytchuk et al. 2004).

The alternative interpretation of our findings is that high lead exposure is associated with truly higher bone density in childhood. Our results indicate that the magnitude of this association is clinically relevant. For example, the mean BMD of the lumbar vertebrae (L1-L4) was 0.770 g/[cm.sup.2] versus 0.720 g/[cm.sup.2] among subjects with high and low cumulative lead exposure, respectively (p = 0.03). Thus, in this study, children with high cumulative lead exposure had nearly 7% higher BMD at the lumbar vertebrae than did children with low cumulative lead exposure. This amounts to about 2 years of bone growth.

We now wish to speculate on the mechanism of this finding. An in vitra study found that lead inhibits parathyroid hormone-related peptide (PTHrP) and transforming growth factor-[beta]1, proteins that decrease the rate of maturation of chondrocytes in endochondral bone formation (Zuscik et al. 2002). Further, this inhibition of PTHrP is associated with accelerated skeletal maturity. Mice homozygous for PTHrP gene deletion have advanced skeletal maturation at birth (Karaplis et al. 1994; Lee et al. 1996). Similarly, children with Blomstrand syndrome, a congenital chondrodysplasia due to nonfunctioning PTHrP receptors (Jobert et al. 1998; Karaplis et al. 1998), also have advanced skeletal maturation and higher than normal bone density at birth (Blomstrand et al. 1985; den Hollander et al. 1997; Loshkajian et al. 1997; Young et al. 1993). The inhibition of PTHrP causes premature maturation of the chondrocytes (Zuscik et al. 2002), which may result in a higher bone density.

Our findings differ from past research findings that lead exposure is associated with lower, not higher, bone density in mature animals (Escribano et al. 1997; Gruber et al. 1997; Puzas et al. 1999; Ronis et al. 2001). Nevertheless, the literature suggests that the higher bone density associated with PTHrP inhibition is transient. Although mice homozygous for PTHrP gene deletion have higher bone density at birth (Karaplis et al. 1994), mice heterozygous for PTHrP gene deletion have osteopenia as adults (Amizuka et al. 1996; He et al. 2000). The proposed mechanism is as follows: Besides its effects on endochondral bone formation, PTHrP also acts on bone remodeling in adult organisms. It promotes the differentiation of bone marrow stem cells toward osteoblasts and away from adipocytes and impedes the apoptosis of osteoblasts (Karaplis 2001). In a mature organism without endochondral bone formation, PTHrP inhibition on bone remodeling would predominate--that is, differentiation of stem cells toward adipocytes and an increased rate of osteoblast apoptosis--thus predisposing to osteoporosis (Karaplis et al. 2001). We therefore speculate that a lead-exposed individual may undergo a higher rate of bone loss when older than would individuals without lead exposure.

An alternative model for the development of osteoporosis is that a lead-exposed individual may achieve a lower peak bone mass as a young adult. Studies of children have found a negative association between blood lead level and height (Ballew et al. 1999; Schwartz et al. 1986; Selevan et al. 2003). Similarly, mice homozygous for PTHrP gene deletion, in addition to having advanced skeletal maturation, have shorter long bones and shorter vertebrae than do normal mice (Karaplis et al. 1994). These findings along with the findings described in the preceding paragraph suggest that lead targets its effects on the growth plate by inhibiting PTHrP and thus causing shorter stature in exposed children. We speculate that this inhibition of stature when young results in a lower peak bone mass being achieved, thus predisposing to osteoporosis in later life (Figure 1). Future studies axe needed to investigate whether these proposed models are valid.
Table 1. Blood lead level measures by cumulative
lead exposure status [low vs. high ([micro]g/dL)].

BLL measure Low High

Mean BLL
 12-23 months 7.3 23.8
 24-35 months 7.4 22.4
 36-47 months 5.4 24.5
 48-60 months 4.9 21.1
Mean cumulative lead exposure (a) 6.5 23.6
 Range 2.7-10.3 15.5-43.5

BLL, blood lead level.

(a) Defined in "Materials and Methods."

Table 2. Comparison of covariates by cumulative lead exposure
status (low vs. high).

Covariates Low High p-Value (a)

Demographics
 Sex (% male) 56 68 0.46
 Age (months) 109.9 109.2 0.73
 HOH Hollingshead occupation 5.6 6.3 0.30 (c)
 level (b)
 HOH Hollingshead socioeconomic 89.4 89.7 0.92
 score (b)
Body size
 Weight (kg) 34.1 33.2 0.72
 Height (cm) 137.4 139.6 0.40
 BMI (kg/[m.sup.2]) 17.9 16.9 0.28
Physical activity
 Active play (hr/day) 4.8 4.6 0.80
 Inactive play (hr/day) 3.2 3.0 0.72
 Calcium intake (portions/day) 3.6 3.6 1.00

HOH, head of household.

(a) By t-test, except where specified. (b) HOH Hollingshead
occupation level and socioeconomic level (Hollingshead 1958).
(c) By Mann-Whitney U-statistic.

Table 3. Adjusted BMD (g/[cm.sup.2]) by bony site and
cumulative lead exposure (low vs. high).

BMD site Low High p-Value (a)

Body regions
 Head 1.589 1.721 < 0.01 **
 Arms 0.684 0.704 0.16
 Legs 0.917 0.928 0.61
 Trunk 0.693 0.720 0.06 *
 Ribs 0.594 0.615 0.09 *
 Pelvis 0.806 0.839 0.09 *
 Spine 0.720 0.749 0.14
 Total body 0.911 0.940 0.06 *
Lumbar vertebrae
 L1 (b) 0.682 0.707 0.28
 L2 0.722 0.756 0.22
 L3 0.761 0.819 0.01 **
 L4 0.712 0.789 0.01 **
 L1-L4 0.720 0.770 0.03 **
Hip regions
 Femoral neck 0.827 0.893 0.07 *
 Trochanter 0.682 0.732 0.11
 Femoral shaft 0.939 1.006 0.11
 Total hip 0.842 0.906 0.08 *

(a) By analysis of covariance. (b) First lumbar vertebra.
* Marginally significant (i.e., 0.05 < p < 0.10).
** Significant at p [less than or equal to] 0.05 level.


REFERENCES

Alfven T, Jarup L, Elinder C-G. 2002. Cadmium and lead in blood in relation to tow bone mineral density and tubular proteinuria. Environ Health Perspect 110:699-702.

Amizuka N, Karaplis AC, Henderson JE, Warshawsky H, Lipman ML, Matsuki Y, et al. 1996. Haploinsufficiency of parathyroid hormone-related peptide (PTHrP) results in abnormal postnatal bone development. Dev Biol 175:166-176.

Ballew C, Khan LK, Kaufmann R, Mokdad A, Miller D, Gunter EW. 1999. Blood lead concentration and children's anthropometric dimensions in the Third National Health and Examination Survey (NHANES III), 1988-1994. J Pediatr 134:623-630.

Blomstrand S, Claesson I, Save-Soderbergh J. 1985. A case of lethal congenital dwarfism with accelerated skeletal maturation. Pediatr Radiol 15:141-143.

Boot AM, Ridder MA, Pols HA, Krenning EP, Keizer-Schrama SM. 1997. Bone mineral density in children and adolescents: relation to puberty, calcium intake, and physical activity. J Clin Endocrinol Metab 82:57-62.

Canfield RL, Henderson CR, Cory-Slecta DA, Cox C, Jusko TA, Lanphear BP. 2003. Intellectual impairment in children with blood lead concentrations below 10 [micro]g per deciliter. N Engl J Med 348:1517-1526.

CDC. 1991. Preventing Lead Poisoning in Young Children. Atlanta, GA:Centers for Disease Control and Prevention.

Cheng Y, Schwartz J, Vokonas PS, Weiss ST, Aro A, Hu H. 1999. Electrocardiographic conduction disturbances in association with low-level lead exposure (the Normative Aging Study). Am J Cardiol 82:594-599.

Cooper C, Barker DJP, Wickham C. 1988. Physical activity, muscular strength, and calcium intake in fracture of the proximal femur in Britain. Br Med J 297:1443-1446.

den Hollander NS, van der Harten HJ, Vermeij-Keers C, Niermeijer MF, Wladimiroff JW. 1997. First-trimester diagnosis of Blomstrand lethal osteochondrodysplasia. Am J Med Genet 73:345-350.

Dietrich KN, Ris MD, Succop PA, Berger OG, Bornschein RL. 2001. Early exposure to lead and juvenile delinquency. Neurotoxicol Teratol 23:511-518.

Escribano A, Revilla M, Hernandez ER, Seco C, Gonzalez-Riola J, Villa LF, et al. 1997. Effect of lead on bone development and bone mass: a morphometric, densitometric, and histomorphometric study in growing rats. Calcif Tissue Int 60(2):200-203.

Gruber HE, Gonick HC, Khalil-Manesh F, Sanchez TV, Motsinger S, Meyer M, et al. 1997. Osteopenia induced by long-term, low- and high-level exposure of the adult rat to lead. Miner Electrolyte Metab 23(2):65-73.

He B, Jiang Y, Jhao Y, Genant HK, Goltzman D, Karapalis AC. 2000. Quantitative assessment of three-dimensional trabecular bone microstructure in PTHrP wild type and heterogeneous-null mice using micro computed tomography [Abstract]. J Bone Miner Metab 15(S1):S186.

Hollingshead AB. 1958. Social Class and Mental Illness. New York:John Wiley.

Hu H, Ara A, Payton M, Korrick S, Sparrow D, Weiss ST, et al. 1996. The relationship of bone and blood lead to hypertension: the Normative Aging Study. JAMA 275:1171-1176.

Jobert A, Zhang P, Couvineau A, Bonaventure J, Roume J, Le Merrer M, et al. 1998. Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia. J Clin Invest 102:34-40.

Johnston CC, Miller JZ, Slemenda CW, Reister TK, Hui S, Christian JC, et al. 1992. Calcium supplementation and increases in bone density in children. N Engl J Med 327:82-87.

Karaplis AC. 2001. PTHrP: novel roles in skeletal biology. Curr Pharm Design 7:655-670.

Karaplis AC, He B, Nguyen MT, Young ID, Semeraro D, Ozawa H, et al. 1998. Inactivating mutation in the human parathyroid hormone receptor type 1 gene in Blomstrand chondrodysplasia. Endocrinology 139:5255-5258.

Karaplis AC, Luz A, Glowacki J, Bronson RT, Tybulewicz VLJ, Kronenberg HM, et al. 1994. Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone-related peptide gene. Genes Dev 8:277-289.

Kim R, Rotnitzky A, Sparrow D, Weiss ST, Wagner C, Hu H. 1996. A longitudinal study of low-level lead exposure and impairment of renal function--the Normative Aging Study. JAMA 275:1177-1181.

Klein RF, Wiren KM. 1993. Regulation of osteoblastic gene expression by lead. Endocrinology 132:2531-2537.

Laraque D, Arena L, Karp J, Gruskay D. 1990. Bone mineral content in black pre-schoolers: normative data using single photon absorptiometry. Pediatr Radiol 20:461-463.

Lee K, Lanske B, Karaplis AC, Deeds JD, Kohno H, Nissenson BA, et al. 1996. Parathyroid hormone-related peptide delays terminal differentiation of chondrocytes during endochondral bone development. Endocrinology 137:5109-5118.

Loshkajian A, Roume J, Stanescu V, Delezoide A, Stamf F, Maroteaux P. 1997. Familial Blomstrand chondrodysplasia with advanced skeletal maturation: further delineation. Am J Med Genet 71:283-266.

Maynard LM, Guo SS, Chumlea WC, Roche AF, Wisemandle WA, Zeller CM, et al. 1998. Total-body and regional bone mineral content and areal bone mineral density in children aged 8-18 y: the Fels Longitudinal Study. Am J Clin Nutr 68:1111-1117.

Mazess RB, Barden HS, Bisek JP, Hanson J. 1990. Dual energy X-ray absorptiometry for total body and regional bone mineral density and soft tissue composition. Am J Clin Nutr 51:1106-1112.

Moss ME, Lanphear BP, Auinger P. 1999. Association of dental caries and blood lead levels. JAMA 281:2294-2298.

Muzytchuk CA, Rosier R, Puzas JE. 2004. Skeletal lead interferes with BMD measurements in older generation scanners. Presented at the Conference of the International Society for Clinical Densitometry, 28-31 January 2004, Miami, FL

Nash D, Magder L, Lustberg M, Sherwin RW, Rubin RJ, Kaufmann RB, et al. 2003. Blood lead, blood pressure and hypertension in perimenopausal and postmenopausal women. JAMA 289:1523-1532.

National Research Council. 1993. Measuring Lead Exposure in Infants, Children, and Other Sensitive Populations. Washington, DC:National Academy Press.

Needleman HL, McFarland C, Ness RB, Fienberg SE, Tobin MJ. 2002. Bone lead levels in adjudicated delinquents: a case-control study. Neurotoxicol Teratol 24:711-717.

Nelson DA, Simson PM, Johnson CC, Barondress DA, Kleerekoper M. 1997. The accumulation of whole body skeletal mass in third- and fourth grade children: effects of age, gender, ethnicity and body composition. Bone 20:73-78.

Nielsen SP, Slosman D, Sorensen OH, Basse-Cathalinut B, DeCassin P, Roux C, et al. 1999. Influence of strontium on bone mineral density and bone mineral content measurements by dual X-ray absorptiometry. J Clin Densitom 2:371-379.

Pollitzer WS, Anderson JJB. 1989. Ethnic and genetic differences in bone mass: a review with hereditary vs environmental perspective. Am J Clin Nutr 69:762-770.

Puzas JE, Campbell J, O'Keefe R, Schwartz E, Rosier R. 2002. Lead in the skeleton interferes with bone mineral measurements [Abstract]. J Bone Miner Metab 17(S1):S314.

Puzas JE, Cory-Slecta DA, Rosier R, O'Keefe R, Cushing J, Pounds JG. 1999. Chronic lead intoxication may contribute to osteoporosis [Abstract]. Toxicologist 48(1-S):328.

Ronis MJ, Aronson J, Gao GG, Hogue W, Skinner RA, Badger TM, et al. 2001. Skeletal effects of developmental lead exposure in rats. Toxicol Sci 62:321-329.

Schwartz J, Angle C, Pitcher H. 1986. Relationship between childhood blood lead levels and stature. Pediatrics 77:281-288.

Selevan SG, Rice DC, Hogan KA, Euling SY, Pfahles-Hutchens A, Bethel J. 2003. Blood lead concentration and delayed puberty in gifts. N Engl J Med 348:1527-1536.

Young ID, Zuccollo JM, Broderick NJ. 1993. A lethal skeletal dysplasia with generalized sclerosis and advanced skeletal maturation: Blomstrand chondrodysplasia? J Med Genet 30:155-157.

Zuscik MJ, Pateder DB, Puzas JE, Schwarz EM, Rosier RN, O'Keefe RJ. 2002. Lead alters parathyroid hormone-related peptide and transforming growth factor-[beta]1 effects and AP-1 and NF-[kappa]B signaling in chondrocytes. J Orthoped Res 20:811-818.

James R. Campbell, (1) Randy N. Rosier, (2) Leonore Novotny, (2) and J. Edward Puzas (2) (1) Department of Pediatrics and (2) Department of Orthopedics, University of Rochester Medical Center, Rochester, New York, USA

Address correspondence to J.R. Campbell, Department of Pediatrics, MOB Suite 300, Rochester General Hospital, 1425 Portland Ave., Rochester, NY 14621 USA. Telephone: (585) 922-3919. Fax: (585) 922-3929. E-mail: James.Campbell@ViaHealth.org

We thank C. Muzytchuk for conducting the bone density measures, and R. O'Keefe, M. Zuscik, and S. Schaffer for their thoughtful commentary on the manuscript.

This work was supported by University of Rochester Environmental Health Sciences Center grants NIEHS P30 ES01247 and NIEHS PO1 ES011854.

The authors declare they have no competing financial interests.

Received 30 June 2003; accepted 7 April 2004.
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Author:Puzas, J. Edward
Publication:Environmental Health Perspectives
Date:Aug 1, 2004
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