Inflammatory, Structural, and Pain Biochemical Biomarkers May Reflect Radiographic Disc Space Narrowing: The Johnston County Osteoarthritis Project.

The purpose of this work is to determine the relationship between biomarkers of inflammation, structure, and pain with radiographic disc space narrowing (DSN) in community-based participants. A total of 74 participants (37 cases and 37 controls) enrolled in the Johnston County Osteoarthritis Project during 2006-2010 were selected. The cases had at least mild radiographic DSN and low back pain (LBP). The controls had neither radiographic evidence of DSN nor LBP. The measured analytes from human serum included N-cadherin, Keratin-19, Lumican, CXCL6, RANTES, IL-17, IL-6, BDNF, OPG, and NPY. A standard dolorimeter measured pressure-pain threshold. The coefficients of variation were used to evaluate inter- and intra-assay reliability. Participants with similar biomarker profiles were grouped together using cluster analysis. The binomial regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) in propensity score-matched models. Significant associations were found between radiographic DSN and OPG (RR = 3.90; 95% CI: 1.83, 8.31), IL-6 (RR = 2.54; 95% CI: 1.92, 3.36), and NPY (RR = 2.06 95% CI: 1.62, 2.63). Relative to a cluster with low levels of biomarkers, a cluster representing elevated levels of OPG, RANTES, Lumican, Keratin-19, and NPY (RR = 3.04; 95% CI: 1.22, 7.54) and a cluster representing elevated levels of NPY (RR = 2.91; 95% CI: 1.15, 7.39) were significantly associated with radiographic DSN. Clinical Significance: These findings suggest that individual and combinations of biochemical biomarkers may reflect radiographic DSN. This is just one step toward understanding the relationships between biochemical biomarkers and DSN that may lead to improved intervention delivery. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1027-1037, 2020.

Serum periostin is associated with prevalent knee osteoarthritis and disease incidence/progression in women: the OFELY study.

OBJECTIVE: Our aim was to investigate the relationships between serum periostin (POSTN) and both prevalence and incidence/progression of knee osteoarthritis (OA) in women. METHODS: We investigated 594 women (62.7 ± 11.2 yr) from the OFELY cohort. Knee radiographs were scored according to the Kellgren & Lawrence (KL) grading system at baseline and 4 years later. Spine, hip and hand OA were assessed at baseline. Prevalent knee OA was defined by a KL score higher or equal in 2. Progression of KL was defined as an increase of the KL score ≥1 during the 4 years follow-up. Serum POSTN was measured at baseline by ELISA. RESULTS: By non-parametric tests, POSTN was significantly lower in 83 women with a KL score ≥2 at baseline, compared to those with a KL score <2 (n = 511; 1101 ± 300 vs 1181 ± 294 ng/ml, P = 0.002) after adjustment for age, body mass index (BMI), treatments and diseases, prevalent hand OA and prevalent lumbar spine OA. By logistic regression analyses, the odds-ratio of knee OA incidence/progression was significantly reduced by 21% (P = 0.043) for each quartile increase in serum POSTN at baseline, after adjustment for age, BMI, prevalent knee OA, prevalent hand OA and prevalent lumbar spine OA. CONCLUSIONS: We show for the first time that serum POSTN is associated with prevalence and the risk of development/progression of knee OA in women.

Associations between serum biomarkers and pain and pain-related function in older adults with low back pain: a pilot study.

OBJECTIVES: To examine the relationship between serum biomarkers and self-reported pain intensity and pain-related function, in addition to the contribution of magnetic resonance imaging (MRI) findings of lumbar spine degenerative changes, in older adults with chronic low back pain. DESIGN: Single-center cross-sectional cohort study. SETTING: Academic medical center. PARTICIPANTS: Individuals aged 60 and older with axial low back pain without radiculopathy or previously diagnosed osteoarthritis of the knee or hip or pain outside the low back that is more severe than the back pain (n = 43). MEASUREMENTS: To examine pain-related impairment, pain was measured on a pain thermometer and the McGill Pain Questionnaire Short Form was administered. To examine pain-related function or activity limitation, the Roland Morris Disability Questionnaire, Short Physical Performance Battery (SPPB), and repetitive trunk rotation were used. Single plasma samples were obtained before and after physical performance tests and analyzed for inflammatory markers (E-selectin and regulated on activation, normal T cell expressed and secreted (RANTES)), inhibitors of catabolic enzymes (tissue inhibitor of metalloproteinases-1 (TIMP-1)), markers of matrix turnover (C- telopeptide of type II collagen (CTX-II) and aggrecan chondroitin sulfate 846 (CS846)), and stress biomarkers (neuropeptide Y (NPY)). Conventional nongadolinium lumbar MRI was performed and analyzed quantitatively and clinically. RESULTS: Composite MRI measurements did not show significant correlation with pain or pain-related function. Basal levels and changes in serum biomarkers in response to activity, particularly NPY and RANTES, demonstrated associations with pain and pain-related function in addition to the explanatory power of MRI-based results. CONCLUSION: Serum biomarkers may be a metric for assessment of active disease in older adults, in whom imaging changes are ubiquitous. In addition, changing levels of biomarkers in response to activity suggests that they may be useful as metrics to measure treatment responses in future studies and may reflect potential targets for use in designing personalized treatment for older adults with low back pain.

Relationship between spine osteoarthritis, bone mineral density and bone turn over markers in post menopausal women.

BACKGROUND: Several studies have observed an inverse relationship between osteoporosis and spinal osteoarthritis, the latter being considered as possibly delaying the development of osteoporosis. The aim of this study was to determine the association between individual radiographic features of spine degeneration, bone mineral density (BMD) and bone-turn over markers. METHODS: It was a cross sectional study of 277 post menopausal women. BMD of all patients was assessed at the spine and hip using dual-energy X-ray absorptiometry. Lateral spinal radiographs were evaluated for features of disc degeneration. Each vertebral level from L1/2 to L4/5 was assessed for the presence and severity of osteophytes and disc space narrowing (DSN). For Bone turn-over markers, we assessed serum osteocalcin and C-terminal cross-linking telopeptide of type I collagen (CTX). Linear regressions and partial correlation were used respectively to determine the association between each of disc degeneration features, BMD, and both CTX and osteocalcin. RESULTS: Mean age of patients was 58.7 +/- 7.7 years. Eighty four patients (31.2%) were osteoporotic and 88.44% had spine osteoarthritis. At all measured sites, there was an increase in BMD with increasing severity of disc narrowing while there was no association between severity of osteophytes and BMD. After adjustment for age and BMI, there was a significant negative correlation between CTX and DSN. However, no significant correlation was found between CTX and osteophytes and between osteocalcin and both osteophytes or DSN. CONCLUSION: In post menopausal women the severity of disc narrowing, but not osteophytes, is associated with a generalized increase in BMD and a decreased rate of bone resorption. These results are consistent with the hypothesis that osteoarthritis, through DSN, has a protective effect against bone loss, mediated by a lower rate of bone resorption. However, spine BMD is not a relevant surrogate marker for the assessment of osteoporosis in the spine in patients with osteoarthritis and debate as to the relationship between OA and OP is still open because of the contradictory data in the literature.