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

Kawaguchi, Yoshiharu; Nakano, Masato; Yasuda, Taketoshi; Seki, Shoji; Suzuki, Kayo; Yahara, Yasuhito; Makino, Hiroto; Kitajima, Isao; Kimura, Takeshi

doi:10.1371/journal.pone.0174881

Cited by 53 publications

(60 citation statements)

References 51 publications

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“…Furthermore, Kashii et al 7 found that the serum sclerostin level in men with OPLL was higher than in controls, and they identified a negative correlation between the serum sclerostin level and Dickkopf-1 level in males with OPLL. Our recent data demonstrated that hypersensitive C-reactive protein (hs-CRP) in the OPLL group was higher than in controls, 8 and serum inorganic phosphate (Pi) in the OPLL group was lower than in controls. A negative correlation was found between serum Pi and severity of ossification.…”

Section: Introductionmentioning

confidence: 97%

Increase of the Serum FGF-23 in Ossification of the Posterior Longitudinal Ligament

Kawaguchi

Kitajima

Nakano

et al. 2018

Global Spine Journal

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Study Design: Case-control study. Objectives: To determine the possible pathogenesis of ossification of the posterior longitudinal ligament (OPLL) in regard to the serum concentration of fibroblast growth factor 23 (FGF-23). Methods: The study included 95 patients with OPLL and a control group of 73 age- and sex-matched volunteers. The serum concentrations of FGF-23, creatinine (Cre), alkaline phosphatase, calcium (Ca), inorganic phosphate (Pi), and hypersensitive C-reactive protein (hs-CRP) were analyzed from blood samples, and Cre, Ca, Pi, and tubular reabsorption of phosphate were measured using urine samples. We evaluated the severity of ossified spinal lesions in patients with OPLL according to the ossification index (the OP index and the OS index). Data was compared between the OPLL and control group and between the OPLL progression and no progression group. Results: Serum FGF-23 and hs-CRP were higher, and serum Pi was lower in patients with OPLL than in the controls. There was a positive correlation between FGF-23 and hs-CRP and a negative correlation between serum Pi and the OS index; however, the correlations were very weak. Overall, 31.7% of patients had progression of OPLL during follow-up. FGF-23 and hs-CRP were higher in the progression group than in the no progression group. Conclusions: These results might indicate that FGF-23 and hs-CRP are positive markers for OPLL. Phosphate metabolism via FGF-23 might be a target for future study on the pathogenesis of OPLL.

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Section: Introductionmentioning

confidence: 97%

Increase of the Serum FGF-23 in Ossification of the Posterior Longitudinal Ligament

Kawaguchi

Kitajima

Nakano

et al. 2018

Global Spine Journal

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“…Ossification of the posterior longitudinal ligament (OPLL), which involves pathological heterotopic ossification of this region, can lead to symptoms of spinal cord compression and radiculopathy in affected patients. The disease has a marked ethnic predilection, with epidemiological studies suggesting that OPLL is found almost exclusively in Japanese, Chinese, and Korean individuals [ 1 ]. Approximately 70% of OPLL cases affect the cervical spine, whereas 15% occur in the thoracic spine [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Association of IL17RC and COL6A1 genetic polymorphisms with susceptibility to ossification of the thoracic posterior longitudinal ligament in Chinese patients

et al. 2018

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BackgroundIn our previous whole-genome sequencing study of 30 unrelated northern Chinese Han patients, we identified six single nucleotide polymorphisms (SNPs) in the interleukin 17 receptor C (IL17RC) and collagen type VI α1 chain (COL6A1) genes that were potentially associated with thoracic ossification of the posterior longitudinal ligament (T-OPLL). To determine whether these six SNPs are associated with susceptibility to T-OPLL in the northern Chinese Han population, we performed a case-control association study to confirm specific susceptible loci in the expanded samples.MethodsThe six SNPs in the IL17RC and COL6A1 genes were analyzed in 200 northern Chinese individuals (100 patients and 100 control subjects) using the Sequenom system.ResultsThe genotype distributions and allele frequencies of each SNP in the control and patient groups were compared. rs201153092, rs13051496, rs199772854, rs76999397, and rs189013166 showed potential pathogenic loci for T-OPLL in the northern Chinese Han population, whereas rs151158105 did not. At the genotype level, the differences in the genotype frequencies of rs201153092, rs13051496, rs199772854, rs76999397, and rs189013166 between T-OPLL cases and controls reached statistical significance.ConclusionsTo the best of our knowledge, this is the first association study of susceptibility genes in Han Chinese patients with T-OPLL. The results revealed five SNPs in the IL17RC and COL6A1 genes that represented potentially pathogenic mutations in patients with T-OPLL.

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“…Recently, a genome-wide association study of OPLL patients identified RSPO2, which encodes R-spondin 2, as a susceptibility gene for OPLL; notably, R-spondin 2 is a secreted agonist of canonical Wnt-β-catenin signaling www.nature.com/scientificreports www.nature.com/scientificreports/ and is reduced in early stages of chondrocyte differentiation 16 . In addition, Kawaguchi et al reported that serum high-sensitivity C-reactive protein was elevated in OPLL patients, compared with that in individuals without OPLL; this indicated that local inflammation was associated with the progression of OPLL 17 . In a related manner, the level of serum C-reactive protein was high in patients with heterotopic ossification who underwent total hip arthroplasty 18 .…”

Section: Discussionmentioning

confidence: 99%

Association between ossification of the longitudinal ligament of the cervical spine and arteriosclerosis in the carotid artery

Oshima

Doi

Kato

et al. 2020

Sci Rep

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Although several risk factors have been reported for cervical ossification of the longitudinal ligament (opLL), most evaluations made in the past were based on plain X-ray, not on computed tomography (ct) scan. in this study, we aimed to clarify novel risk factors for cervical opLL in asymptomatic subjects undergoing CT scan as their routine medical checkups. A total of 1789 Japanese asymptomatic subjects who underwent ct scan for the whole body as their routine medical checkups were retrospectively reviewed. the medical checkup also included laboratory examinations, bone mineral status, and ultrasound of the carotid artery. As a result, cervical OPLL was seen in 120 subjects (6.7%). As we compared the demographic and clinical data between subjects with and without opLL, opLL group showed older age, higher proportion of male sex, higher BMi, higher incidence of hypertension, higher levels of blood HbA1c and triglyceride, and higher incidence of plaques in the carotid artery. A multivariate logistic regression analysis revealed that age (Odds ratio (OR):1.03), male sex (OR: 1.91), and the presence of plaque in the carotid artery (OR: 1.71) were risk factors for OPLL. To the best of our knowledge, this is the first report to reveal an association between OPLL and arteriosclerotic lesions. Ossification of the posterior longitudinal ligament (OPLL) is a disorder characterized by progressive ectopic OPLL. Although the precise mechanisms of OPLL remain uncertain, it is considered a multifactorial disease with both environmental and genetic factors; in addition, several risk factors have been reported, including age, male sex, ethnicity, presence of diabetes mellitus, obesity, diet, sleeping time, and mechanical stimulation 1-9. Most OPLL patients are diagnosed by X-ray or computed tomography (CT) scanning when they present with radiculopathy or myelopathy. When symptoms are severe with evidence of compression to the nerve root or spinal cord, surgical intervention is often required. However, past epidemiological studies revealed that the incidence of OPLL may be higher in the general population because some patients do not present with clinical symptoms regardless of the presence of OPLL 4,10. Most epidemiological studies of OPLL have used X-rays for diagnosis; importantly, CT scans can provide more accurate diagnoses of OPLL than X-rays. There has been one study comparing the incidence of OPLL among various ethnic groups by using CT scans 11 ; however, there have been no previous reports regarding risk factors of OPLL based on diagnosis through CT scans. In this study, we aimed to investigate novel risk factors for cervical OPLL in asymptomatic subjects undergoing their routine medical checkups, which included laboratory examinations, bone mineral status evaluation, carotid artery ultrasound, and whole-body CT scans. To the best of our knowledge, this is the first study to assess the association between OPLL and arteriosclerosis.

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

Cited by 53 publications

References 51 publications

Increase of the Serum FGF-23 in Ossification of the Posterior Longitudinal Ligament

Increase of the Serum FGF-23 in Ossification of the Posterior Longitudinal Ligament

Association of IL17RC and COL6A1 genetic polymorphisms with susceptibility to ossification of the thoracic posterior longitudinal ligament in Chinese patients

Association between ossification of the longitudinal ligament of the cervical spine and arteriosclerosis in the carotid artery

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