title: Whole blood lead levels are associated with biomarkers of joint tissue metabolism in African American and white men and women: the Johnston County Osteoarthritis Project.
abstract: OBJECTIVE
  To examine associations between biomarkers of joint tissue metabolism and whole blood lead (Pb), separately for men and women in an African American and Caucasian population, which may reflect an underlying pathology.
  
  
  METHODS
  Participants in the Johnston County Osteoarthritis Project Metals Exposure Sub-Study (329 men and 342 women) underwent assessment of whole blood Pb and biochemical biomarkers of joint tissue metabolism. Urinary cross-linked N telopeptide of type I collagen (uNTX-I) and C-telopeptide fragments of type II collagen (uCTX-II), serum cleavage neoepitope of type II collagen (C2C), serum type II procollagen synthesis C-propeptide (CPII), and serum hyaluronic acid (HA) were measured using commercially available kits; the ratio of [C2C:CPII] was calculated. Serum cartilage oligomeric matrix protein (COMP) was measured by an in-house assay. Multiple linear regression models were used to examine associations between continuous blood Pb and biomarker outcomes, adjusted for age, race, current smoking status, and body mass index. Results are reported as estimated change in biomarker level for a 5-unit change in Pb level.
  
  
  RESULTS
  The median Pb level among men and women was 2.2 and 1.9μg/dL, respectively. Correlations were noted between Pb levels and the biomarkers uNTX-I, uCTX-II, and COMP in women, and between Pb and uCTX-II, COMP, CPII, and the ratio [C2C:CPII] in men. In adjusted models among women, a 5-unit increase in blood Pb level was associated with a 28% increase in uCTX-II and a 45% increase in uNTX-I levels (uCTX-II: 1.28 [95% CI: 1.04-1.58], uNTX-I: 1.45 [95% CI:1.21-1.74]). Among men, levels of Pb and COMP showed a borderline positive association (8% increase in COMP for a 5-unit change in Pb: 1.08 [95% CI: 1.00-1.18]); no other associations were significant after adjustment.
  
  
  CONCLUSIONS
  Based upon known biomarker origins, the novel associations between blood Pb and biomarkers appear to be primarily reflective of relationships to bone and calcified cartilage turnover among women and cartilage metabolism among men, suggesting a potential gender-specific effect of Pb on joint tissue metabolism that may be relevant to osteoarthritis.
authors.affiliation: Thurston Arthritis Research Center, Department of Radiology, University of North Carolina, 3300 Thurston Bldg, Chapel Hill, NC 27599, USA. aenelson@med.unc.edu
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Nelson
authors.forename: Sanjay
authors.initials: S
authors.lastname: Chaudhary
authors.forename: Virginia B
authors.initials: VB
authors.lastname: Kraus
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Jiu-Chiuan
authors.initials: JC
authors.lastname: Chen
authors.forename: Todd A
authors.initials: TA
authors.lastname: Schwartz
authors.forename: Xiaoyan A
authors.initials: XA
authors.lastname: Shi
authors.forename: Jordan B
authors.initials: JB
authors.lastname: Renner
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Stabler
authors.forename: Charles G
authors.initials: CG
authors.lastname: Helmick
authors.forename: Kathleen
authors.initials: K
authors.lastname: Caldwell
authors.forename: A Robin
authors.initials: AR
authors.lastname: Poole
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Jordan
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D044383:Black People; D002358:Cartilage, Articular / Q000378:metabolism*; D005260:Female; D006801:Humans; D007854:Lead / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism*; D044465:White People; D001741:Black or African American
chemical_list: D015415:Biomarkers; D007854:Lead