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.
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.
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.
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.