Analysis of serum biomarkers in patients with spinal ossification

• Project/Area Number: 16K10815
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: University of Toyama
• Principal Investigator: KAWAGUCHI Yoshiharu 富山大学, 大学院医学薬学研究部(医学), 准教授 (00262527)
• Co-Investigator(Kenkyū-buntansha): 北島 勲 富山大学, 大学院医学薬学研究部(医学), 教授 (50214797) ; 箭原 康人 富山大学, 附属病院, 医員 (60456390)
• Research Collaborator: YASUDA taketoshi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 脊椎脊髄病学 / 脊柱靭帯骨化症 / 骨化関連因子

Outline of Final Research Achievements

We have investigated the serum biomarkers which might be related to the pathology of spinal ossification. Hyper-sensitive C-reactive protein (hs-CRP) in patients with the spinal ossification was higher than that in the control. Hs-CRP had a positive correlation with the progression of the spinal ossification. Serum inorganic phosphate (IP) was lower in patients with the spinal ossification, compared to the control. IP had a negative correlation with the extent of the spinal ossification. Serum FGF-23 was higher in patients with the spinal ossification. Based on these studies, we wrote a review paper regarding the relationship between the serum biomarkers and spinal ossification. These results are important to understand the pathology of spinal ossification.

Academic Significance and Societal Importance of the Research Achievements

脊柱靭帯骨化症は原因不明の疾患である。本研究はこの病因についてバイオマーカーを用いて検討し、以下の２つの知見を得た。１）脊柱靭帯骨化には炎症が関与し、特に骨化巣の伸展と正の相関があること、２）脊柱靭帯骨化では血清リン値が低下し、骨化巣の広がりと負の相関があること。またこれらのデータを基に文献的にレビューを行い、脊柱靭帯骨化症に関わるバイオマーカーを調べまとめた。以上の結果は脊柱靭帯骨化症の病因の解明のみならず、治療の糸口を探るために重要であると考えられた。

Research Products

• [Journal Article] Clinical impact of ossification of the posterior longitudinal ligament progression after cervical laminoplasty (2019)
  • Author(s): Kawaguchi Y, Nakano M, Yasuda T, Seki S, Suzuki K, Yahara Y, Makino H, Kobayashi K, Kanamori M, Kimura T
  • Journal Title: Clinical Spine Surgery Volume: 32 Issue: 3 Pages: E133-E139
  • DOI: 10.1097/bsd.0000000000000747
  • Peer Reviewed
• [Journal Article] Co-existence of ossification of the nuchal ligament is associated with severity of ossification in the whole spine in patients with cervical ossification of the posterior longitudinal ligament -A multi-center CT study- (2019)
  • Author(s): Yoshii T, Hirai T, Iwanami A, Nagoshi N, Takeuchi K, Mori K, Yamada T, Seki S, Tsuji T, Fujiyoshi K, Furukawa M, Nishimura S,Wada K, Koda M, Furuya T, Matsuyama Y, Hasegawa T, Takeshita K, Kimura A, Abematsu M, Haro H, Ohba T, Watanabe M, Katoh H, Watanabe K, Ozawa H, Kanno H, Imagama S, Kawaguchi Y, et al.
  • Journal Title: Journal of Orthopaedic Science Volume: 24 Issue: 1 Pages: 35-41
  • DOI: 10.1016/j.jos.2018.08.009
  • Peer Reviewed / Open Access
• [Journal Article] Increase of the serum FGF-23 in ossification of the posterior longitudinal ligament (2018)
  • Author(s): Kawaguchi Y, Kitajima I, Nakano M, Yasuda T, Seki S, Suzuki K, Yahara Y, Makino H, Ujihara Y, Ueno T, Kimura T
  • Journal Title: Global Spine Journal Volume: - Issue: 5 Pages: 492-498
  • DOI: 10.1177/2192568218801015
  • Peer Reviewed / Open Access
• [Journal Article] Biomarkers of ossification of the spinal ligament (OSL) (2018)
  • Author(s): Kawaguchi Y
  • Journal Title: Global Spine Journal Volume: - Issue: 6 Pages: 650-657
  • DOI: 10.1177/2192568218791799
  • Peer Reviewed / Open Access
• [Journal Article] The effect of multiple lesions in patients with ossification of the posterior longitudinal ligament of the cervical spine (2018)
  • Author(s): Kawaguchi Y, Nakano M, Yasuda T, Seki S, Suzuki K, Yahara Y, Makino H, Kobayashi K, Kanamori M, Kimura T
  • Journal Title: Journal of Orthopaedic Science Volume: Epub ahead of print Issue: 3 Pages: 420-425
  • DOI: 10.1016/j.jos.2018.11.012
  • Peer Reviewed
• [Journal Article] Prevalence and distribution of diffuse idiopathic skeletal hyperostosis on whole-spine computed tomography in patients with cervical ossification of the posterior longitudinal ligament (2018)
  • Author(s): Nishimura S, Nagoshi N, Iwanami A, Takeuchi A, Hirai T, Yoshii T, Takeuchi K, Mori K, Yamada T, Seki S, Tsuji T, Fujiyoshi K, Furukawa M, Wada K, Koda M, Furuya T, Matsuyama Y, Hasegawa T, Takeshita K, Kimura A, Abematsu M, Haro H, Ohba T, Watanabe M, Katoh H, Watanabe K, Ozawa H, Kanno H, Kawaguchi Y, et al.
  • Journal Title: Clinical Spine Surgery Volume: 31 Issue: 9 Pages: E460-E465
  • DOI: 10.1097/bsd.0000000000000701
  • Peer Reviewed
• [Journal Article] Distribution of ossified spinal lesions in patients with severe ossification of the posterior longitudinal ligament and prediction of ossification at each segment based on the cervical OP index classification: a multicenter study (JOSL CT study). (2018)
  • Author(s): Hirai T, Yoshii T, Nagoshi N, Takeuchi K, Mori K, Ushio S, Abematsu M, Haro H, Ohba T, Watanabe M, Katoh H, Watanabe K, Ozawa H, Kanno H, Imagama S, Ando K, Fujibayashi S, Koda M, Yamazaki M, Matsumoto M, Nakamura M, Okawa A, Kawaguchi Y.
  • Journal Title: BMC Musculoskelet Disord. Volume: 19(1) Issue: 1 Pages: 107-107
  • DOI: 10.1186/s12891-018-2009-7
  • NAID: 120007133040
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Perioperative complications after surgery for thoracic ossification of posterior longitudinal ligament- nationwide multicenter prospective study (2018)
  • Author(s): Imagama S, Ando K, Takeuchi K, Kato S, Murakami H, Aizawa T, Ozawa H, Hasegawa T, Matsuyama Y, Koda M, Yamazaki M, Chikuda H, Shindo S, Nakagawa Y, Kimura A, Takeshita K, Wada K, Katoh H, Watanabe M, Yamada K, Furuya T, Tsuji T, Fujibayashi S, Mori K, Kawaguchi Y, Watanabe K, Matsumoto M, Yoshii T, Okawa A
  • Journal Title: SPINE Volume: 43 Issue: 23 Pages: E1389-E1397
  • DOI: 10.1097/brs.0000000000002703
  • Peer Reviewed
• [Journal Article] Serum biomarkers in patients with ossification of the posterior longitudinal ligament (OPLL): Inflammation in OPLL (2017)
  • Author(s): Kawaguchi Yoshiharu、Nakano Masato、Yasuda Taketoshi、Seki Shoji、Suzuki Kayo、Yahara Yasuhito、Makino Hiroto、Kitajima Isao、Kimura Tomoatsu
  • Journal Title: PLoS One Volume: 12 Issue: 5 Pages: e0174881-e0174881
  • DOI: 10.1371/journal.pone.0174881
  • Peer Reviewed / Open Access
• [Journal Article] Life expectancy after cervical en bloc laminoplasty: Analysis of data following more than 20 years. Spine. (2017)
  • Author(s): Kawaguchi Y, Nakano M, Yasuda T, Seki S, Hori T, Suzuki K, Makino H, Kimura T
  • Journal Title: Spine (Phila Pa 1976) Volume: 42 Issue: 7 Pages: 450-455
  • DOI: 10.1097/brs.0000000000001843
  • Peer Reviewed
• [Journal Article] Chracteristics of ossification of the spinal ligament; incidence of ossification of the ligamentum flavum in patients with cervical ossification of the posterior longitudinal ligament-Analysis of the whole spine using multidetector CT. (2016)
  • Author(s): Kawaguchi Y, Nakano M, Yasuda T, Seki S, Hori T, Suzuki K, Makino H, Kimura T
  • Journal Title: J Orthop Sci. Volume: 21 Issue: 4 Pages: 439-445
  • DOI: 10.1016/j.jos.2016.04.009
  • Peer Reviewed
• [Presentation] 脊椎靭帯骨化症のバイオマーカー、文献レビューの検討 Review paper regarding biomarkers for ossification of the spinal ligaments (2018)
  • Author(s): 川口善治、安田剛敏、関 庄二、鈴木賀代、牧野紘士、小林賢司、木村友厚
  • Organizer: 第33回日本整形外科基礎学術集会
• [Presentation] 全脊椎CT多施設研究によるOP index20以上の重度骨化症例における骨化局在パターンの検討 (2017)
  • Author(s): 1) 平井高志、吉井俊貴、西村空也、竹内一裕、森幹士、中村雅也、松本守雄、大川淳、川口善治
  • Organizer: 第46回日本脊椎脊髄病学会
• [Presentation] 後縦靭帯骨化症における高感度CRPの意義 (2017)
  • Author(s): 川口善治、安田剛敏、関 庄二、鈴木賀代、箭原康人、牧野紘士、木村友厚
  • Organizer: 第46回日本脊椎脊髄病学会
• [Presentation] 後縦靭帯骨化症における血清バイオマーカー (2016)
  • Author(s): 川口善治，安田剛敏，関 庄二，鈴木賀代，箭原康人，牧野紘士，北島 勲，木村友厚
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡国際会議場（福岡市）
  • Year and Date: 2016-10-13