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

Abstract

Objective 1) To determine associations between radiographic features of lumbosacral 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. Design Cross-sectional analysis of 547 participants enrolled in the Johnston County Osteoarthritis Project from 2003–2004. 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. Results 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% 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 (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)). Conclusion 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.

Biomarkers reflect differences in osteoarthritis phenotypes of the lumbar spine: the Johnston County Osteoarthritis Project

“…Details of the participants, collection and analyses of specimens of biomarkers have been described elsewhere 14 . Briefly, all participants had blood and urine collected at the clinic visit on the same day that radiographs were taken.…”

“…Relative-risk ratios (RRR) and 95% confidence intervals were the measure of association. We report models adjusted for age, BMI, race and sex separately and in combination with adjustment for knee OA, hip OA, and hand OA to overcome confounding by appendicular OA as described in our previous work 14 . Associations between each spine phenotype and potential confounding factors of clinical, demographic and knee, hip or hand OA can be found in Appendix A. Pairwise interaction terms for sex, race and low back symptoms and each biomarker individually were used to assess effect measure modification while adjusting for all other covariates, however no significant (p<0.05) interaction effects were identified.…”

“…One reason is that characterization of IVD degeneration in the spine as an OA process has been debated 14 . This is in part due to anatomical differences that exist within the IVD that do not necessarily exhibit the same pathophysiology as OA in the knee, hip or hand 7 .…”

“…Previously, using data from the Johnston County Osteoarthritis Project (JoCo OA), we identified a significant association between a broad spectrum of biomarkers and lumbar spine DSN, but most were not independently associated with vertebral OST 14 . This suggests that these radiographic features differ to some extent in their pathophysiology and associated tissue metabolism 14 . We are unaware of previous analyses that have sought to differentiate between phenotypes of spine degeneration: those with FOA only, spine OA only, or the combination of FOA and spine OA, compared to those without FOA or spine OA.…”

Association between biochemical cartilage markers and clinical symptoms in patients with hip osteoarthritis: cohort study with 2-year follow-up

“…Therefore, it would be interesting to see whether the results are different when a weighted adjustment could be done, counting the number of joints affected by OA. In addition, it would also be interesting to adjust for lower back OA, since an association has been shown between CTXII and disc space narrowing 23 . Another possible limitation is the use of glucosamine in half of the patients.…”