Article

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

Department of Community and Family Medicine, Duke University Medical Center, USA. Electronic address: .
Osteoarthritis and Cartilage (Impact Factor: 4.66). 08/2012; 20(11):1286-93. DOI: 10.1016/j.joca.2012.08.003
Source: PubMed

ABSTRACT (1) To determine associations between radiographic features of lumbosacral (LS) spine disc space narrowing (DSN) and osteophytes (OST) and joint metabolism biomarkers (serum cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), collagen neoepitope (C2C), C-propeptide of type II procollagen (CP-II), urine C-terminal cross-linking telopeptide (CTX-II) and N-terminal telopeptide (NTX-I)). (2) To explore interactions with race, gender and low back symptoms.
Cross-sectional analysis of 547 participants enrolled in the Johnston County (JoCo) Osteoarthritis Project from 2003 to 2004. Mean biomarker levels were estimated with linear regression. Proportional and partial-proportional odds models were used to estimate associations. Interactions were tested with likelihood ratio tests at a P-value < 0.10. Biomarkers were natural log (ln) transformed.
Significant differences in mean biomarker levels were found across severity of DSN for lnHA and lnC2C and lnCTX-II across severity of both DSN and OST. Moderate-to-strong associations were found between biomarkers of type II collagen and DSN, whereas associations with OST were weak. An association between lnHA and DSN was seen in women (adjusted odds ratio [aOR] = 1.34 (95% confidence intervals (CI) 1.08, 1.65)) but no association among men (aOR = 0.90 (95% CI 0.63, 1.26)). In Caucasians there was a decreased association with NTX-I and OST (aOR = 0.67 (95% CI 0.49, 0.91)) and no association in African Americans (AAs) (aOR = 1.06 (95% CI 0.76, 1.47)). There was a positive association of lnCOMP with DSN among those with low back symptoms (aOR = 1.82 (95% CI 1.02, 3.27)), but no association in those without low back symptoms (aOR = 0.65 (95% CI 0.35, 1.20)).
Joint metabolism biomarkers suggest biological differences in the pathologic process involved in DSN and OST that may be gender (HA) and ethnicity (NTX-I) specific.

0 Followers
 · 
98 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives To assess associations between uCTX-II or uCIIM and severity of hip pain in patients with mild-moderate hip osteoarthritis (OA) over a 2-year period, and establish whether the level of these biomarkers at baseline could estimate a specific trajectory of hip pain. Design A cohort study with a 2-year follow-up and 6-monthly measurements of urinary biomarkers (uCTX-II and uCIIM) and symptom severity. Patients were recruited from general practices. The primary outcome was hip pain, measured with the Western Ontario and McMasters University Osteoarthritis Index (WOMAC) subscale and the Visual Analog Scale (VAS). Associations between hip pain and biomarkers were assessed using linear mixed-model analysis for repeated measurements. Five previously identified pain trajectories were used as outcome to investigate whether the level of biomarkers at baseline could estimate membership in one of the trajectories using multinomial regression analysis. Results LoguCTX-II and loguCIIM were not associated with WOMAC pain or VAS pain during the 2-year follow-up. Patients in the highly progressive pain trajectory and the moderate pain trajectory were more likely to have a higher loguCTX-II at baseline (OR 6.7; 95% CI 1.6-28.2 and OR 4.8; 95%CI 1.0-22.8, respectively) than patients in the mild pain trajectory. Conclusion This study shows that in patients with mild-moderate hip OA the urinary biochemical markers uCTX-II and uCIIM are not cross-sectionally associated with hip pain during the 2-year follow-up. Because the uCTX-II level estimated a progressive or moderate hip pain trajectory, this correlation needs to be confirmed in additional patients with hip OA.
    Osteoarthritis and Cartilage 04/2014; 23(1). DOI:10.1016/j.joca.2014.09.001 · 4.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In 2010, in Osteoarthritis and Cartilage, we published a comprehensive systematic review applying the consensus BIPED criteria on serum and urinary biochemical markers for knee and hip osteoarthritis (OA) using publications that were available at that time. It appeared that none of the biochemical markers at that time were sufficiently discriminating to allow diagnosis and prognosis of osteoarthritis in individual or limited numbers of patients, nor performed so consistently that they could function as primary outcome parameters in clinical trials. Also at present, almost 3 years later, this ultimate goal has not been reached (yet). Frankly, it might be questioned whether we are making the most adequate steps ahead and maybe we have to take a step back to reconsider our approaches. Some reflections are made and discussed: A critical review of molecular metabolism in osteoarthritis and validation of currently investigated marker molecules in this may be vital and may lead to new and better markers. Creating cohorts in which synovial fluid is obtained in a systematic way, together with serum and urine, may also bring the field a further step ahead. Thirdly, better understanding of different phenotypes (subtypes) of OA may facilitate identification and validation of biochemical markers. Finally, the systems biology approach as discussed in the last years OA in review on biomarkers, although very complex, might provide steps forward. Looking ahead, we are optimistic but realistic in our expectations, we believe that the field can be brought forward by critically and cautiously reconsidering our approaches, and making changes forward, one step at a time.
    Osteoarthritis and Cartilage 08/2013; 18. DOI:10.1016/j.joca.2013.08.012 · 4.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: to evaluate the role of three cartilage-derived biomarkers on osteoarthritis (OA): urinary C-terminal telopeptide (uCTX-II), serum cartilage oligomeric protein (sCOMP), and serum MMP degraded type II collagen (sC2M). and methods: Samples from 3582 individuals from the Rotterdam Study, the Genetics osteoArthritis and Progression (GARP), the Chingford Study and the TwinsUK cohort were assayed using enzyme linked immune sorbent assays. Log10 of concentration levels were correlated with risk of hip, hand and knee OA, hip and knee OA severity and incidence, and progression of knee OA, adjusting for age, gender and body mass index. Results were meta-analyzed to assess overall significance. After adjusting for covariates, sCOMP was associated with knee OA and hip and knee OA incidence. Furthermore, sC2M was associated with knee OA incidence and progression. After adjustment for multiple tests (Bonferroni p<0.002) only the association between sCOMP and knee OA remained significant (OR=3.26 (95%CI 1.63-10.1) p=0.0008 for each SD increase in biomarker levels). Levels of uCTX-II were significantly associated with risk of hand, hip and knee OA, progression and incidence of knee OA. A receiver operating characteristics analysis showed a consistent improvement in prediction of knee OA progression from an average area under the curve is 0.646 for age, sex and BMI alone to an AUC=0.668 including uCTX-II for prediction. uCTX-II is the most informative biochemical marker for prediction of OA. Both sCOMP and C2M showed some association with OA, thus indicating that they are descriptive of disease activity. {244 words}
    Osteoarthritis and Cartilage 02/2014; DOI:10.1016/j.joca.2014.02.007 · 4.66 Impact Factor