Biomarker Commons

Predicting OA progression to total hip replacement: can we do better than risk factors alone using active shape modelling as an imaging biomarker?

Rheumatology (Oxford). 2012 Mar;51(3):562-70

Authors: Barr RJ, Gregory JS, Reid DM, Aspden RM, Yoshida K, Hosie G, Silman AJ, Alesci S, Macfarlane GJ

Abstract
OBJECTIVE: Previously, active shape modelling (ASM) of the proximal femur was shown to identify those individuals at highest risk of developing radiographic OA. Here we determine whether ASM predicts the need for total hip replacement (THR) independent of Kellgren-Lawrence grade (KLG) and other known risk factors.
METHODS: A retrospective cohort study of 141 subjects consulting primary care with new hip pain was conducted. Pelvic radiographs taken on recruitment were assessed for KLG, centre-edge angle, acetabular depth and femoral head migration. Clinical factors (duration of pain, use of a stick and physical function) were collected by self-completed questionnaires. ASM differences between shape mode scores at baseline for individuals who underwent THR during the 5-year follow-up (n = 27) and those whose OA did not progress radiographically (n = 75) were compared.
RESULTS: A 1 s.d. reduction in baseline ASM mode 2 score was associated with an 81% reduction in odds of THR (OR = 0.19, 95% CI 0.52, 0.70) after adjustment for KLG, radiographic and clinical factors. A similar reduction in odds of THR was associated with a 1 s.d. reduction in mode 3 (OR = 0.45, 95% CI 0.28, 0.71) and a 1 s.d. increase in mode 4 score (OR = 2.8, 95% CI 1.7, 4.7), although these associations were no longer significant after adjustment for KLG and clinical factors.
CONCLUSION: ASM of the hip joint is a reliable early biomarker of radiographic OA severity, which can improve the ability to identify patients at higher risk of rapid progression and poor outcome even when KLG and clinical risk factors are taken into account.

PMID: 22139532 [PubMed - indexed for MEDLINE]

Synovial infiltration with CD79a-positive B cells, but not other B cell lineage markers, correlates with joint destruction in rheumatoid arthritis.

J Rheumatol. 2011 Nov;38(11):2301-8

Authors: Mo YQ, Dai L, Zheng DH, Zhu LJ, Wei XN, Pessler F, Shen J, Zhang BY

Abstract
OBJECTIVE: The efficacy of B cell depletion in the treatment of patients with rheumatoid arthritis (RA) has revitalized interest in the pathogenic role(s) of B cells in RA. We evaluated the distribution of synovial B lineage cells and their correlation with histologic disease activity and joint destruction in RA.
METHODS: Synovial tissue samples were obtained by closed-needle biopsy from 69 Chinese patients with active RA, from 14 patients with osteoarthritis (OA), and from 15 with orthopedic arthropathies (OrthA) as disease controls. Serial tissue sections were stained immunohistochemically for CD79a (pro-B cell to plasma cell), CD20 (B cells), CD38 (plasma cells), CD21 (follicular dendritic cells), CD68 (macrophages), CD3 (T cells), and CD34 (endothelial cells). Densities of positive-staining cells were determined and correlated with histologic disease activity (Krenn 3-component synovitis score) and radiographic joint destruction (Sharp score).
RESULTS: Mean sublining CD79a-positive cell density was significantly higher in RA than in OA (p <0.001) or OrthA (p = 0.003). Receiver operating characteristic curve analysis showed that CD79a-positive cell density differentiated RA well from OA [area under the curve (AUC) = 0.79] or OrthA (AUC = 0.75). Spearman's rank order correlation showed significant correlations between sublining CD79a-positive cell density and the synovitis score (r = 0.714, p < 0.001), total Sharp score (r = 0.490, p < 0.001), and the erosion subscore (r = 0.545, p < 0.001), as well as the joint space narrowing subscore (r = 0.468, p = 0.001) in RA.
CONCLUSION: Synovial CD79a-positive B cells may be a helpful biomarker for histologic disease activity in RA and may be involved in the pathogenesis of joint destruction in RA.

PMID: 22002013 [PubMed - indexed for MEDLINE]

Protein modification by deamidation indicates variations in joint extracellular matrix turnover.

J Biol Chem. 2012 Feb 10;287(7):4640-51

Authors: Catterall JB, Hsueh MF, Stabler TV, McCudden CR, Bolognesi M, Zura R, Jordan JM, Renner JB, Feng S, Kraus VB

Abstract
As extracellular proteins age, they undergo and accumulate nonenzymatic post-translational modifications that cannot be repaired. We hypothesized that these could be used to systemically monitor loss of extracellular matrix due to chronic arthritic diseases such as osteoarthritis (OA). To test this, we predicted sites of deamidation in cartilage oligomeric matrix protein (COMP) and confirmed, by mass spectroscopy, the presence of deamidated (Asp(64)) and native (Asn(64)) COMP epitopes (mean 0.95% deamidated COMP (D-COMP) relative to native COMP) in cartilage. An Asp(64), D-COMP-specific ELISA was developed using a newly created monoclonal antibody 6-1A12. In a joint replacement study, serum D-COMP (p = 0.017), but not total COMP (p = 0.5), declined significantly after replacement demonstrating a joint tissue source for D-COMP. In analyses of 450 participants from the Johnston County Osteoarthritis Project controlled for age, gender, and race, D-COMP was associated with radiographic hip (p < 0.0001) but not knee (p = 0.95) OA severity. In contrast, total COMP was associated with radiographic knee (p < 0.0001) but not hip (p = 0.47) OA severity. D-COMP was higher in soluble proteins extracted from hip cartilage proximal to OA lesions compared with remote from lesions (p = 0.007) or lesional and remote OA knee (p < 0.01) cartilage. Total COMP in cartilage did not vary by joint site or proximity to the lesion. This study demonstrates the presence of D-COMP in articular cartilage and the systemic circulation, and to our knowledge, it is the first biomarker to show specificity for a particular joint site. We believe that enrichment of deamidated epitope in hip OA cartilage indicates a lesser repair response of hip OA compared with knee OA cartilage.

PMID: 22179616 [PubMed - indexed for MEDLINE]

[Research progress of C terminal propeptide of collagen type II].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 Jan;25(1):66-9

Authors: Bai L, Wang Y, Ba G

Abstract
OBJECTIVE: To review the research progress of C terminal propeptide of collagen type II (CTX-II), a osteoarthritis (OA) biomarker.
METHODS: Domestic and international literature about CTX-II was reviewed extensively and summarized.
RESULTS: CTX-II is investigated broadly and has the best performance of all currently available biomarkers. CTX-II is a truly useful biomarker for early diagnosis, prognosis, and measurement of treatment response in OA.
CONCLUSION: Single CTX-II may be not sufficient for early diagnosis and prognosis of OA, so a combination of CTX-II and other biomarkers or diagnosis methods is needed.

PMID: 21351613 [PubMed - indexed for MEDLINE]

Association of plasma and synovial fluid interferon-γ inducible protein-10 with radiographic severity in knee osteoarthritis.

Clin Biochem. 2011 Oct;44(14-15):1218-22

Authors: Saetan N, Honsawek S, Tanavalee A, Tantavisut S, Yuktanandana P, Parkpian V

Abstract
OBJECTIVES: The objective of this study was to investigate interferon-γ inducible protein-10 (IP-10) concentrations in plasma and synovial fluid of patients with knee osteoarthritis (OA) and to analyze their relationship with disease severity.
DESIGN AND METHODS: Forty OA patients and 15 healthy controls were enrolled in this study. OA grading was performed according to the Kellgren-Lawrence criteria. IP-10 levels in plasma and synovial fluid were assessed using enzyme-linked immunosorbent assay.
RESULTS: Plasma IP-10 levels in the knee OA patients were significantly lower than those of controls (P=0.006). IP-10 levels in plasma were markedly higher with regard to paired synovial fluid (P<0.001). Furthermore, IP-10 concentrations in plasma and synovial fluid displayed significant inverse correlation with radiographic severity (r=-0.713, P<0.001 and r=-0.561, P<0.001, respectively). Subsequent analysis revealed that plasma IP-10 levels were positively correlated with synovial fluid IP-10 levels (r=0.424, P=0.006).
CONCLUSIONS: IP-10 levels in both plasma and synovial fluid were inversely associated with the severity of knee OA. Accordingly, IP-10 could serve as a biomarker for determining disease severity and might play a possible role in the pathophysiology of osteoarthritis.

PMID: 21819974 [PubMed - indexed for MEDLINE]

Serum cartilage oligomeric matrix protein (sCOMP) is elevated in patients with knee osteoarthritis: a systematic review and meta-analysis.

Osteoarthritis Cartilage. 2011 Dec;19(12):1396-404

Authors: Hoch JM, Mattacola CG, Medina McKeon JM, Howard JS, Lattermann C

Abstract
OBJECTIVE: To be used in diagnostic studies, it must be demonstrated that biomarkers can differentiate between diseased and non-diseased patients. Therefore, the purpose of this study was to answer the following questions: (1) Is serum cartilage oligomeric matrix protein (sCOMP) elevated in patients with radiographically diagnosed knee osteoarthritis (OA) compared to controls? (2) Are there differences in sCOMP levels when comparing differing radiographic OA severities to controls?
METHODS: Systematic review and meta-analysis. Data Sources: A systematic search of CINAHL, PEDro, Medline, and SportsDiscus was completed in March 2010. Keywords: knee, osteoarthritis, sCOMP, radiography. Study inclusion criteria: Studies were written in English, compared healthy adults with knee OA patients, used the Kellgren Lawrence (K/L) classification, measured sCOMP, and reported means and standard deviations for sCOMP.
RESULTS: For question 1, seven studies were included resulting in seven comparisons. A moderate overall effect size (ES) indicated sCOMP was consistently elevated in those with radiographically diagnosed knee OA when compared to controls (ES = 0.60, P < 0.001). For question 2, four studies were included resulting in 13 comparisons between radiographic OA severity levels and controls. Strong ESs were calculated for K/L-1 (ES = 1.43, P = 0.28), K/L-3 (ES = 1.05, P = 0.04), and K/L-4 (ES = 1.40, P = 0.003). A moderate ES was calculated for K/L-2 (ES = 0.60, P = 0.01).
CONCLUSIONS: These results indicate sCOMP is elevated in patients with knee OA and is sensitive to OA disease progression. Future research studies with a higher level of evidence should be conducted to investigate the use of this biomarker as an indicator for OA development and progression.

PMID: 22001901 [PubMed - indexed for MEDLINE]

Identification of a panel of novel serum osteoarthritis biomarkers.

J Proteome Res. 2011 Nov 4;10(11):5095-101

Authors: Fernández-Puente P, Mateos J, Fernández-Costa C, Oreiro N, Fernández-López C, Ruiz-Romero C, Blanco FJ

Abstract
Osteoarthritis (OA) is the most common rheumatic pathology. Because currently available diagnostic methods are limited and lack sensitivity, the identification of new specific biological markers for OA has become a focus. The purpose of this study was to identify novel protein biomarkers for moderate and severe OA in serum. Sera were obtained from 50 moderate OA patients, 50 severe OA patients, and 50 nonsymptomatic controls. Serum protein levels were analyzed using isobaric tags for relative and absolute quantitation (iTRAQ) and matrix-assisted laser desorption/ionization (MALDI)-TOF/TOF mass spectrometry. We identified 349 different proteins in the sera, 262 of which could be quantified by calculation of their iTRAQ ratios. Three sets of proteins were significantly (p < 0.05) changed in OA samples compared to controls. Of these, 6 were modulated only in moderate OA, 13 only in severe OA and 7 in both degrees. Although some of these proteins, such as cartilage oligomeric matrix protein, have a previously reported putative biomarker value for OA, most are novel biomarker candidates for the disease. These include some complement components, lipoproteins, von Willebrand factor, tetranectin, and lumican. The specificity and selectivity of these candidates need to be validated before new molecular diagnostic or prognostic tests for OA can be developed.

PMID: 21973172 [PubMed - indexed for MEDLINE]

Chip-based cartilage oligomeric matrix protein detection in serum and synovial fluid for osteoarthritis diagnosis.

Anal Biochem. 2012 Jan 15;420(2):139-46

Authors: Song SY, Han YD, Hong SY, Kim K, Yang SS, Min BH, Yoon HC

Abstract
We have developed a method to detect cartilage oligomeric matrix protein (COMP) as a specific biomarker of osteoarthritis (OA). In pathological conditions of the cartilage, COMP is released first into the synovial fluid (SF) and from there into the blood. Thus, measurement of COMP in the blood and SF facilitates OA diagnosis. To determine COMP, we developed a fluoro-microbead guiding chip (FMGC)-based immunoassay. The FMGC has four immunoreactive regions, each with five patterns, to allow multiple assays. A COMP-specific capture antibody was immobilized to the FMGC surface to create a self-assembled interfacial layer. SF or serum samples from patients with OA possessing the target COMP were applied to the COMP-sensing monolayer. To generate binding signal, COMP detection antibody-conjugated fluoro-microbeads were applied and the numbers of fluoro-microbeads bound specifically were counted to determine COMP concentrations. This FMGC-based immunoassay clearly distinguished immunospecific from nonspecific binding by comparing optical signals from inside and outside of the patterns. The optical signals showed linear correlations with serum and SF COMP concentrations. Optical detection and quantification of COMP using fluorescence microscopy correlated well with results from commercial enzyme-linked immunosorbent assay (ELISA). This FMGC-based immunoassay offers a new approach for detecting a clinically relevant biomarker for OA in human blood and SF.

PMID: 21982862 [PubMed - indexed for MEDLINE]

Relative percentage and zonal distribution of mesenchymal progenitor cells in human osteoarthritic and normal cartilage.

Arthritis Res Ther. 2011;13(2):R64

Authors: Pretzel D, Linss S, Rochler S, Endres M, Kaps C, Alsalameh S, Kinne RW

Abstract
INTRODUCTION: Mesenchymal stem cells (MSC) are highly attractive for use in cartilage regeneration. To date, MSC are usually recruited from subchondral bone marrow using microfracture. Recent data suggest that isolated cells from adult human articular cartilage, which express the combination of the cell-surface markers CD105 and CD166, are multi-potent mesenchymal progenitor cells (MPC) with characteristics similar to MSC. MPC within the cartilage matrix, the target of tissue regeneration, may provide the basis for in situ regeneration of focal cartilage defects. However, there is only limited information concerning the presence/abundance of CD105+/CD166+ MPC in human articular cartilage. The present study therefore assessed the relative percentage and particularly the zonal distribution of cartilage MPC using the markers CD105/CD166.
METHODS: Specimens of human osteoarthritic (OA; n = 11) and normal (n = 3) cartilage were used for either cell isolation or immunohistochemistry. Due to low numbers, isolated cells were expanded for 2 weeks and then analyzed by flow cytometry (FACS) or immunofluorescence in chamber slides for the expression of CD105 and CD166. Following immunomagnetic separation of CD166+/- OA cells, multi-lineage differentiation assays were performed. Also, the zonal distribution of CD166+ cells within the matrix of OA and normal cartilage was analyzed by immunohistochemistry.
RESULTS: FACS analysis showed that 16.7 ± 2.1% (mean ± SEM) of OA and 15.3 ± 2.3 of normal chondrocytes (n.s.) were CD105+/CD166+ and thus carried the established MPC marker combination. Similarly, 13.2% ± 0.9% and 11.7 ± 2.1 of CD105+/CD166+cells, respectively, were identified by immunofluorescence in adherent OA and normal chondrocytes. The CD166+ enriched OA cells showed a stronger induction of the chondrogenic phenotype in differentiation assays than the CD166+ depleted cell population, underlining the chondrogenic potential of the MPC. Strikingly, CD166+ cells in OA and normal articular cartilage sections (22.1 ± 1.7% and 23.6% ± 1.4%, respectively; n.s.) were almost exclusively located in the superficial and middle zone.
CONCLUSIONS: The present results underline the suitability of CD166 as a biomarker to identify and, in particular, localize and/or enrich resident MPC with a high chondrogenic potential in human articular cartilage. The percentage of MPC in both OA and normal cartilage is substantially higher than previously reported, suggesting a yet unexplored reserve capacity for regeneration.

PMID: 21496249 [PubMed - indexed for MEDLINE]

The role of synovial fluid markers of catabolism and anabolism in osteoarthritis, rheumatoid arthritis and asymptomatic organ donors.

Arthritis Res Ther. 2011;13(2):R50

Authors: Kokebie R, Aggarwal R, Lidder S, Hakimiyan AA, Rueger DC, Block JA, Chubinskaya S

Abstract
INTRODUCTION: The purpose of this study was to correlate the level of anabolic and catabolic biomarkers in synovial fluid (SF) from patients with rheumatoid arthritis (RA), patients with osteoarthritis (OA) and asymptomatic organ donors.
METHODS: SF was collected from the knees of 45 OA, 22 RA patients and 20 asymptomatic organ donors. Eight biomarkers were selected and analyzed by using an enzyme-linked immunosorbent assay: interleukin (IL)-1, IL-6, IL-8 and IL-11; leukemia-inhibitory factor (LIF); cartilage oligomeric protein (COMP); osteocalcin; and osteogenic protein 1 (OP-1). Data are expressed as medians (interquartile ranges). The effects of sex and disease activity were assessed on the basis of the Western Ontario and McMaster Universities index score for patients with OA and on the basis of white blood cell count, erythrocyte sedimentation rate and C-reactive protein level for patients with RA.
RESULTS: The mean ages (± SD) of the patients were as follows: 53 ± 9 years for patients with OA, 54 ± 11 years for patients with RA and 52 ± 7 years for asymptomatic organ donors. No effect of participants' sex was identified. In the SF of patients with RA, four of five cytokines were higher than those in the SF of patients with OA and those of asymptomatic organ donors. The most significant differences were found for IL-6 and IL-8, where IL-6 concentration in SF of patients with RA was almost threefold higher than that in patients with OA and fourfold higher than that in asymptomatic donor controls: 354.7 pg/ml (1,851.6) vs. 119.4 pg/ml (193.2) vs. 86.97 pg/ml (82.0) (P < 0.05 and P < 0.05, respectively). IL-8 concentrations were higher in SF of patients with RA than that in patients with OA as well as that in asymptomatic donor controls: 583.6 pg/ml (1,086.4) vs. 429 pg/ml (87.3) vs. 451 pg/ml (170.1) (P < 0.05 and P < 0.05, respectively). No differences were found for IL-11 in the SF of patients with RA and that of patients with OA, while a 1.4-fold difference was detected in the SF of patients with OA and that of asymptomatic donor controls: 296.2 pg/ml (257.2) vs. 211.6 pg/ml (40.8) (P < 0.05). IL-1 concentrations were the highest in the SF of RA patients (9.26 pg/ml (11.1)); in the SF of asymptomatic donors, it was significantly higher than that in patients with OA (9.083 pg/ml (1.6) vs. 7.76 pg/ml (2.6); P < 0.05). Conversely, asymptomatic donor control samples had the highest LIF concentrations: 228.5 pg/ml (131.6) vs. 128.4 pg/ml (222.7) in the SF of patients with RA vs. 107.5 pg/ml (136.9) in the SF of patients with OA (P < 0.05). OP-1 concentrations were twofold higher in the SF of patients with RA than those in patients with OA and threefold higher than those in asymptomatic donor control samples (167.1 ng/ml (194.8) vs. 81.79 ng/ml (116.0) vs. 54.49 ng/ml (29.3), respectively; P < 0.05). The differences in COMP and osteocalcin were indistinguishable between the groups, as were the differences between active and inactive OA and RA.
CONCLUSIONS: Activation of selected biomarkers corresponds to the mechanisms that drive each disease. IL-11, LIF and OP-1 may be viewed as a cluster of biomarkers significant for OA; while profiling of IL-1, IL-6, IL-8, LIF and OP-1 may be more significant in RA. Larger, better-defined patient cohorts are necessary to develop a biomarker algorithm for prognostic use.

PMID: 21435227 [PubMed - indexed for MEDLINE]

Using animal models in osteoarthritis biomarker research.

J Knee Surg. 2011 Dec;24(4):251-64

Authors: Garner BC, Stoker AM, Kuroki K, Evans R, Cook CR, Cook JL

Abstract
Osteoarthritis (OA) is a disease that commonly affects human and veterinary patients. Animal models are routinely used for OA research, and the dog is a nearly ideal species for translational investigation of human OA biomarkers. The cytokine, chemokine, and matrix metalloprotease (MMP) profiles of synovial fluid, serum, and urine from dogs with surgically induced and naturally occurring OA were compared with dogs without OA using xMAP technology (Qiagen Inc., Valencia, CA). Markers that exhibited significant differences between groups were identified (monocyte chemoattractant protein 1 [MCP1], interleukin 8 [IL8], keratinocyte-derived chemoattractant [KC], and MMP2 and MMP3), and their sensitivities and specificities were calculated to determine their diagnostic usefulness in a future biomarker panel. Synovial fluid IL8 was the most sensitive, but MCP1 was also highly sensitive and specific. The alterations in KC suggested that it may differentiate between cruciate disease and other types of OA, and the MMPs were most sensitive and specific in the serum. This study provided additional insight to the participation of cytokines, chemokines, and MMPs in OA, and potential diagnostic biomarker candidates were identified. A brief literature review of other biomarker candidates previously examined using animal models is discussed.

PMID: 22303754 [PubMed - indexed for MEDLINE]

Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis.

Arthritis Res Ther. 2011;13(1):R22

Authors: Ishijima M, Watari T, Naito K, Kaneko H, Futami I, Yoshimura-Ishida K, Tomonaga A, Yamaguchi H, Yamamoto T, Nagaoka I, Kurosawa H, Poole RA, Kaneko K

Abstract
INTRODUCTION: We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism.
METHODS: Using Kellgren-Lawrence (K/L) grading early radiographic knee OA (K/L 2) was detected in 16 of 46 patients. These grades (K/L 1 is no OA and K/L 2 is early OA) were divided into two groups according to the presence or absence of persistent knee pain. Sera (s) and urines (u) were analysed with biomarkers for cartilage collagen cleavage (sC2C and uCTX-II) and synthesis (sCPII), bone resorption (uNTx) and synovitis (hyaluronic acid: sHA).
RESULTS: sCPII decreased and sC2C/sCPII, uCTX-II/sCPII and sHA increased with onset of OA (K/L 2 versus K/L 1) irrespective of joint pain. In contrast, sC2C and uCTX-II remained unchanged in early OA patients. Of the patients with K/L grades 1 and 2 sC2C, sCPII, sHA, uNTX and uCTX-II were all significantly increased in patients with knee pain independent of grade. Among the K/L grade 2 subjects, only uCTX-II and uCTX-II/sCPII were increased in those with knee pain. In grade 1 patients both sC2C and sCPII were increased in those with knee pain. No such grade specific changes were seen for the other biomarkers including sHA.
CONCLUSIONS: These results suggest that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain. Also K/L grade 1 patients with knee pain exhibit biomarker features of early OA.

PMID: 21320321 [PubMed - indexed for MEDLINE]

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.

Environ Res. 2011 Nov;111(8):1208-14

Authors: Nelson AE, Chaudhary S, Kraus VB, Fang F, Chen JC, Schwartz TA, Shi XA, Renner JB, Stabler TV, Helmick CG, Caldwell K, Poole AR, Jordan JM

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), 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.

PMID: 21839992 [PubMed - indexed for MEDLINE]