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      Serum biomarkers in patients with ossification of the posterior longitudinal ligament (OPLL): Inflammation in OPLL

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          Abstract

          Backgroud

          Ossification of the posterior longitudinal ligament (OPLL) is characterized by replacement of ligamentous tissue by ectopic new bone formation. OPLL causes narrowing of the spinal canal, resulting in neurological impairment. However, the pathogenesis of OPLL has not been fully elucidated. We investigated whether inflammation occurs in OPLL or not using high-sensitivity CRP (hs-CRP) in a case-control study.

          Methods and findings

          This study included 103 patients with OPLL in the patient group and 95 age- and sex-matched volunteers with degenerative spinal disease in the control group. Of the 103 OPLL patients, 88 patients who were available for more than 2 years follow-up were checked for OPLL progression. A blood sample was obtained and Hs-CRP, and other routine data, including total protein (TP), albumin (ALB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), glucose (Glu), calcium (Ca), inorganic phosphate (Pi), white blood cell count (WBC), hemoglobin (Hb) and platelet (PLT), were analyzed. The data were compared between the patients with OPLL and the controls. The severity of the ossified lesions in the whole spine were evaluated by the ossification index (OS index) in patients with OPLL. The data were also compared between the patients with OPLL progression (the progression group) and the patients without OPLL progression (the non-progression group). In the results, the mean hs-CRP in the OPLL group was higher than that in the controls. The Pi in the OPLL group was lower than that in the control group. A negative correlation was found between the Pi and the OS index. The mean hs-CRP in the progression group was higher than that in the non-progression group. There was a positive correlation between the average length of the OPLL progression per year and the hs-CRP.

          Conclusions

          The results may suggest the occurrence of local inflammation in OPLL and the inflammation might cause OPLL progression. These facts are important for understanding the pathology of OPLL.

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          Most cited references45

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          C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992.

          W. Koenig, M Sund, M. Fröhlich … (1999)
          Inflammatory reactions in coronary plaques play an important role in the pathogenesis of acute atherothrombotic events; inflammation elsewhere is also associated with both atherogenesis generally and its thrombotic complications. Recent studies indicate that systemic markers of inflammation can identify subjects at high risk of coronary events. We used a sensitive immunoradiometric assay to examine the association of serum C-reactive protein (CRP) with the incidence of first major coronary heart disease (CHD) event in 936 men 45 to 64 years of age. The subjects, who were sampled at random from the general population, participated in the first MONICA Augsburg survey (1984 to 1985) and were followed for 8 years. There was a positive and statistically significant unadjusted relationship, which was linear on the log-hazards scale, between CRP values and the incidence of CHD events (n=53). The hazard rate ratio (HRR) of CHD events associated with a 1-SD increase in log-CRP level was 1.67 (95% CI, 1.29 to 2. 17). After adjustment for age, the HRR was 1.60 (95% CI, 1.23 to 2. 08). Adjusting further for smoking behavior, the only variable selected from a variety of potential confounders by a forward stepping process with a 5% change in the relative risk of CRP as the selection criterion, yielded an HRR of 1.50 (95% CI, 1.14 to 1.97). These results confirm the prognostic relevance of CRP, a sensitive systemic marker of inflammation, to the risk of CHD in a large, randomly selected cohort of initially healthy middle-aged men. They suggest that low-grade inflammation is involved in pathogenesis of atherosclerosis, especially its thrombo-occlusive complications.
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            Diffuse idiopathic skeletal hyperostosis (DISH): Forestier's disease with extraspinal manifestations.

            Michael Resnick, Paul M Robins, S Shaul (1975)
            The extraspinal manifestations of Forestier's disease are described in 21 consecutive cases; diffuse idiopathic skeletal hyperostosis (DISH) is suggested as a more appropriate description of this ossifying diathesis. Characteristic roentgen abnormalities of the spine were present in all individuals and associated with significant axial clinical complaints. In extraspinal locations, hyperostosis at ligament attachments usually occurs in the pelvis, calcaneus, tarsal bones, ulnar olecranon and patella, and is occasionally associated with clinical signs and symptoms requiring surgery. The radiographic appearance in the peripheral skeleton is frequently distinctive and allows the radiologist to suggest the correct diagnosis, even in the absence of axial radiographs.
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              Clinical efficacy of an automated high-sensitivity C-reactive protein assay.

              N Rifai, R P Tracy, P Ridker (1999)
              Prospective studies have shown that C-reactive protein (CRP) can be used to predict risk of future cardiovascular events. High-sensitivity methods for CRP (hs-CRP) measurement are needed for this purpose. We compared the clinical efficacy of an automated and commercially available latex-enhanced assay (Latex) for hs-CRP (Dade Behring) to a validated in-house ELISA, previously shown to predict future peripheral arterial disease (PAD) in asymptomatic populations. Using a prospective, nested, case-control design, we measured baseline hs-CRP concentrations in 144 apparently healthy men who subsequently developed symptomatic PAD and 144 age- and smoking habit-matched controls who remained free of vascular disease over the follow-up period of 60 months. The two hs-CRP assays correlated highly (r = 0.95; P <0.001), and all but two participants were classified into concordant quartiles or varied by only one quartile. The median hs-CRP of the case group was significantly higher than that of controls when measured by either the ELISA (1.34 vs 0.99 mg/L; P = 0.034) or the Latex method (1.80 vs 1.20 mg/L; P = 0.042). Furthermore, for both ELISA and the Latex method, the calculated relative risks of developing PAD increased significantly with each increasing quartile of hs-CRP. The calculated interquartile increase in relative risk of PAD was 31% (95% confidence interval, 5.2-62.2%; P = 0.01) for ELISA and 34% (95% confidence interval, 8.2-66.1%; P = 0.007) for the Latex method. Our findings indicate that the Latex method is equally as efficacious as the validated ELISA in classifying patients into cutoff points established by prospective studies for risk stratification for coronary and cerebrovascular disease.
              Article 0 comments Cited 74 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Chunfeng Zhao: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 3 May 2017
                Publication date Collection: 2017
                Volume: 12
                Issue: 5
                Electronic Location Identifier: e0174881
                Affiliations
                [1 ]Department of Orthopaedic Surgery, University of Toyama, Toyama, Japan
                [2 ]Department of Clinical Laboratory Medicine, University of Toyama, Toyama, Japan
                Mayo Clinic Minnesota, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: YK IK TK.

                • Data curation: YK MN TY SS KS YY HM.

                • Formal analysis: YK MN TY SS.

                • Funding acquisition: YK TK.

                • Investigation: YK MN TY SS KS YY HM.

                • Methodology: YK MN TY SS KS YY HM IK.

                • Project administration: YK IK TK.

                • Resources: YK MN TY SS KS YY HM.

                • Software: YK MN TY SS.

                • Supervision: IK TK.

                • Validation: KS YY HM.

                • Visualization: YK MN TY SS.

                • Writing – original draft: YK MN TY SS.

                • Writing – review & editing: IK.

                Article
                Publisher ID: PONE-D-16-46573
                DOI: 10.1371/journal.pone.0174881
                PMC ID: 5414934
                PubMed ID: 28467440
                SO-VID: 8e44c5a9-7b0e-475a-91b2-91b34da4cd39
                Copyright © © 2017 Kawaguchi et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 23 November 2016
                Date accepted : 16 March 2017
                Page count
                Figures: 3, Tables: 4, Pages: 13
                Funding
                The work reported in this article was supported by grants from the Ministry of Health, Labour and Welfare of Japan: Committee for Study of Ossification of Spinal Ligament and Committee for Research and Development of Therapies for Ossification of Posterior Longitudinal Ligament.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Physiological Processes
                Subject: Bone Remodeling
                Subject: Ossification
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Physiological Processes
                Subject: Bone Remodeling
                Subject: Ossification
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Immune Response
                Subject: Inflammation
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Immune Response
                Subject: Inflammation
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Signs and Symptoms
                Subject: Inflammation
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Signs and Symptoms
                Subject: Inflammation
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Biological Tissue
                Subject: Connective Tissue
                Subject: Ligaments
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Biological Tissue
                Subject: Connective Tissue
                Subject: Ligaments
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Biomarkers
                Subject: Biology and Life Sciences
                Subject: Developmental Biology
                Subject: Organism Development
                Subject: Organogenesis
                Subject: Bone Development
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Signs and Symptoms
                Subject: Lesions
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Signs and Symptoms
                Subject: Lesions
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Pathogenesis
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Body Fluids
                Subject: Blood
                Subject: Blood Counts
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Body Fluids
                Subject: Blood
                Subject: Blood Counts
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Body Fluids
                Subject: Blood
                Subject: Blood Counts
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Body Fluids
                Subject: Blood
                Subject: Blood Counts
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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