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

Purpose 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), and 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 1.9 µg/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.

Associations Between Biomarkers of Joint Metabolism, Hand Osteoarthritis, and Hand Pain and Function: The Johnston County Osteoarthritis Project

“…As reported previously, this well-characterized cohort includesnon-institutionalized individuals, aged 45 years and older,from six selected townships in Johnston County NC (23). The biomarkers sub-study was performed from 2003–2008 on a subset of participants (n=671) selected to represent a balance by gender (50% female) and to include a large proportion of African Americans (37%) (24). Participants with radiographic evidence of rheumatoid arthritis were excluded.…”

“…Blood for serum and second morning void urine samples were obtained and then stored at −86°C, as previously reported (24). …”

Association between serum and urine biomarkers and lumbar spine individual radiographic features: the Johnston County Osteoarthritis Project

“…This sub-study was designed to consist of 1700 consecutive individuals from T1* and from the original cohort’s first follow-up (T1) who returned for their second follow-up (T2) in 2006–2008. 29 The sample for the current analysis included participants selected from T1* who had complete biomarker analyses performed (n=555). Urinary CTX-II had missing values for 18 participants and urinary NTX-I had a single participant missing value.…”

Differential accumulation of lead and zinc in double-tidemarks of articular cartilage

“…Clinical studies indicate that exposure to Pb can lead to osteopenia 4,5 , osteoporosis 6 , impaired bone healing 7 , and even osteoarthritis 8e10 . Furthermore, it was shown that whole blood Pb levels are associated with biomarkers of joint tissue metabolism and may play a role in osteoarthritis 11 . Nelson et al found a correlation between elevated blood Pb levels and the incidence of osteoarthritis but question remained if this is the result of a direct toxic effect of Pb on the joint tissue or if Pb is released from the mineralized tissue 12 .…”