Adipokine dysregulation as an underlying pathology for diffuse ectopic ossification of spinal posterior longitudinal ligament in patients with obesity.

Adipokine Adiponectin Leptin Obesity Ossification of the posterior longitudinal ligament of the spine tissue necrosis factor α

Journal

The spine journal : official journal of the North American Spine Society
ISSN: 1878-1632
Titre abrégé: Spine J
Pays: United States
ID NLM: 101130732

Informations de publication

Date de publication:
26 Sep 2024
Historique:
received: 30 05 2024
accepted: 14 09 2024
medline: 29 9 2024
pubmed: 29 9 2024
entrez: 28 9 2024
Statut: aheadofprint

Résumé

Growing evidence suggests that obesity is implicated in the progression of heterotopic ossification of the posterior longitudinal ligament of the spine (OPLL), a major cause of myelopathy in Asians. However, it remains unclear whether dysregulation of adipokine production due to fat accumulation contributes to OPLL progression. To determine whether adipose-derived biochemical signals are associated with OPLL development or severity. A nationwide, multicenter, case-control study. Patients with symptomatic thoracic OPLL (T-OPLL) who received treatment between June 2017 and March 2021 and 111 controls without OPLL. OPLL severity index based on whole-spine computed tomography. Serum concentrations of adipokines, including leptin (Lep), tumor necrosis factor α (TNFα), and adiponectin (Adpn), as well as the Adpn/Lep ratio-an indicator of adipokine production dysregulation-were compared between the multiple-region OPLL and the single-region OPLL groups. Regression analysis was performed to examine the correlation between adipokine concentrations and OPLL severity index, which was calculated using whole-spine computed tomography images of 77 patients with T-OPLL within 3 years of onset. Using propensity score matching, the adipokine profiles of 59 patients with T-OPLL were compared with those of 59 non-OPLL controls. Patients with multiple-region OPLL exhibited a higher body mass index (BMI), lower serum Adpn/Lep ratio, and higher serum concentration of osteocalcin (OCN) than those with single-region OPLL. The OPLL severity index exhibited a weak positive correlation with BMI and serum Lep levels and a weak negative correlation with the Adpn/Lep ratio. Serum TNFα and OCN concentrations were significantly higher in patients with T-OPLL than in controls with similar age, sex, and BMI. Patients with diffuse OPLL over the entire spine are often metabolically obese with low Adpn/Lep ratios. In patients with OPLL, TNFα and OCN serum concentrations were essentially elevated regardless of obesity, suggesting a potential association with OPLL development. Considering the absence of therapeutic drugs for OPLL, the findings presented herein offer valuable insights that can aid in identifying therapeutic targets and formulating strategies to impede its progression.

Sections du résumé

BACKGROUND CONTEXT BACKGROUND
Growing evidence suggests that obesity is implicated in the progression of heterotopic ossification of the posterior longitudinal ligament of the spine (OPLL), a major cause of myelopathy in Asians. However, it remains unclear whether dysregulation of adipokine production due to fat accumulation contributes to OPLL progression.
PURPOSE OBJECTIVE
To determine whether adipose-derived biochemical signals are associated with OPLL development or severity.
STUDY DESIGN/SETTING METHODS
A nationwide, multicenter, case-control study.
PATIENT SAMPLE METHODS
Patients with symptomatic thoracic OPLL (T-OPLL) who received treatment between June 2017 and March 2021 and 111 controls without OPLL.
OUTCOME MEASURES METHODS
OPLL severity index based on whole-spine computed tomography.
METHODS METHODS
Serum concentrations of adipokines, including leptin (Lep), tumor necrosis factor α (TNFα), and adiponectin (Adpn), as well as the Adpn/Lep ratio-an indicator of adipokine production dysregulation-were compared between the multiple-region OPLL and the single-region OPLL groups. Regression analysis was performed to examine the correlation between adipokine concentrations and OPLL severity index, which was calculated using whole-spine computed tomography images of 77 patients with T-OPLL within 3 years of onset. Using propensity score matching, the adipokine profiles of 59 patients with T-OPLL were compared with those of 59 non-OPLL controls.
RESULTS RESULTS
Patients with multiple-region OPLL exhibited a higher body mass index (BMI), lower serum Adpn/Lep ratio, and higher serum concentration of osteocalcin (OCN) than those with single-region OPLL. The OPLL severity index exhibited a weak positive correlation with BMI and serum Lep levels and a weak negative correlation with the Adpn/Lep ratio. Serum TNFα and OCN concentrations were significantly higher in patients with T-OPLL than in controls with similar age, sex, and BMI.
CONCLUSIONS CONCLUSIONS
Patients with diffuse OPLL over the entire spine are often metabolically obese with low Adpn/Lep ratios. In patients with OPLL, TNFα and OCN serum concentrations were essentially elevated regardless of obesity, suggesting a potential association with OPLL development. Considering the absence of therapeutic drugs for OPLL, the findings presented herein offer valuable insights that can aid in identifying therapeutic targets and formulating strategies to impede its progression.

Identifiants

pubmed: 39341572
pii: S1529-9430(24)01041-6
doi: 10.1016/j.spinee.2024.09.023
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Masahiko Takahata (M)

Department of Orthopaedic Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, Shimotuga, 321-0293, Japan; Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. Electronic address: m-takahata@dokkyomed.ac.jp.

Yoshinao Koike (Y)

Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan; Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.

Tsutomu Endo (T)

Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.

Shiro Ikegawa (S)

Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.

Shiro Imagama (S)

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumaicho, Showa Ward, Nagoya, Aichi, 466-8550, Japan.

Satoshi Kato (S)

Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.

Masahiro Kanayama (M)

Department of Orthopedics, Hakodate Central General Hospital, 33-2 Hon-cho, Hakodate, Hokkaido, 040-8585, Japan.

Kazuyoshi Kobayashi (K)

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumaicho, Showa Ward, Nagoya, Aichi, 466-8550, Japan.

Takashi Kaito (T)

Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Hiroaki Sakai (H)

Department of Orthopedic Surgery, Japan Organization of Occupational Health and Safety, Spinal Injuries Center, 550-4 Igisu, Iizuka, Fukuoka, 820-8508, Japan.

Yoshiharu Kawaguchi (Y)

Department of Orthopedic Surgery, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.

Itaru Oda (I)

Department of Spine Surgery, Hokkaido Orthopedic Memorial Hospital, 7-13 Hiragishi, Toyohira-ku, Sapporo, Hokkaido, 062-0937, Japan.

Chikashi Terao (C)

Laboratory for Statistical and Translational Genetics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.

Tomoya Kanto (T)

Department of Orthopaedic Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, Shimotuga, 321-0293, Japan.

Hiroshi Taneichi (H)

Department of Orthopaedic Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, Shimotuga, 321-0293, Japan.

Norimasa Iwasaki (N)

Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.

Classifications MeSH