Evidence map›Paper›PMID 34337334›Full record

ArticleJOR spine2021

Development of a standardized histopathology scoring system for intervertebral disc degeneration and regeneration in rabbit models-An initiative of the ORSspine section.

Sarah E Gullbrand, Beth G Ashinsky, Alon Lai, Jennifer Gansau, James Crowley, Carla Cunha, Julie B Engiles, Marion Fusellier, Carol Muehleman, Matthew Pelletier and 7 more

Open access · goldAbstract read
In one paragraph

Article in JOR spine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 22 citations in OpenAlex.

  1. Intervertebral disc degeneration.Nature reviews. Disease primers · 2026
    Review
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  8. Lateral fenestration of lumbar intervertebral discs in rabbits: development and characterisation of an in vivo preclinical model with multi-modal endpoint analysis.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2024
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  14. Review
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  17. ISSLS Prize in Bioengineering Science 2022: low rate cyclic loading as a therapeutic strategy for intervertebral disc regeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 13 institutions in 5 countries.

Sarah E GullbrandUniversity of Pennsylvania Philadelphia Pennsylvania USA.
Beth G AshinskyUniversity of Pennsylvania Philadelphia Pennsylvania USA.
Alon LaiLeni and Peter W. May Department of Orthopaedics Ichan School of Medicine New York New York USA.
Jennifer GansauLeni and Peter W. May Department of Orthopaedics Ichan School of Medicine New York New York USA.
James CrowleySurgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School UNSW Sydney Australia.
Carla Cunhai3S - Instituto de Investigação e Inovação em Saúde, INEB - Instituto de Engenharia Biomédica Porto Portugal.
Julie B EngilesUniversity of Pennsylvania Philadelphia Pennsylvania USA.
Marion FusellierInserm, UMR 1229, RMeS, Université de Nantes, ONIRIS Nantes France.
Carol MuehlemanRush University Medical Center Chicago Illinois USA.
Matthew PelletierSurgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School UNSW Sydney Australia.
Steven PresciuttiEmory University Atlanta Georgia USA.
Jordy ScholTokai University School of Medicine Isehara Japan.
Yoshiki TakeokaBrigham and Women's Hospital Boston Massachusetts USA.
Takashi YurubeKobe University Graduate School of Medicine Kobe Japan.
Yejia ZhangUniversity of Pennsylvania Philadelphia Pennsylvania USA.
Koichi MasudaUniversity of California San Diego California USA.
James C IatridisLeni and Peter W. May Department of Orthopaedics Ichan School of Medicine New York New York USA.
Mayo Clinic in Arizona · USPhiladelphia VA Medical Center · USUniversity of Pennsylvania · USBrigham and Women's Hospital · USEmory University · USi3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto · PTKobe University · JPNantes Université · FRPrince of Wales Hospital · AURush University Medical Center · USTokai University · JPUniversity of California, San Diego · USUNSW Sydney · AU

Funding

Model of Human Disc Regeneration in the spectrum of Degenerative Disc DiseaseR01AR057397 · NIAMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI IATRIDIS, JAMES C. · 2011 to 2021
$5.1M
Mechanisms for Regenerative Healing in Intervertebral DiscsR01AR080096 · NIAMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI James C. Iatridis · 2022 to 2026
$3.8M
Role of TNFalpha in discogenic pain progression and as a treatment targetR01AR078857 · NIAMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI James C. Iatridis · 2022 to 2026
$3.2M
The Role of Disc Nutrition in the Etiology and Clinical Treatment of Disc DegenerationIK2RX003118 · VA · PHILADELPHIA VA MEDICAL CENTER · PI GULLBRAND, SARAH E · 2020 to 2024
–
NIAMS NIH HHS R01 AR057397NIAMS NIH HHS R01 AR078857NIAMS NIH HHS R01 AR080096RRD VA IK2 RX003118
6 · The paper itself

Abstract

backgroundThe rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre-clinical evaluation of regenerative therapies. Histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models.

aimsThe purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model. MATERIALS AND

methodsThe scoring system was formulated following a review of the literature and a survey of spine researchers. Validation of the scoring system was carried out using images provided by 4 independent laboratories, which were graded by 12 independent graders of varying experience levels. Reliability testing was performed via the computation of intra-class correlation coefficients (ICC) for each category and the total score. The scoring system was then further refined based on the results of the ICC analysis and discussions amongst the authors.

resultsThe final general scoring system involves scoring 7 features (nucleus pulposus shape, area, cellularity and matrix condensation, annulus fibrosus/nucleus pulposus border appearance, annulus fibrosus morphology, and endplate sclerosis/thickening) on a 0 (healthy) to 2 (severe degeneration) scale. ICCs demonstrated overall moderate to good agreement across graders. An addendum to the main scoring system is also included for use in studies evaluating regenerative therapeutics, which involves scoring cell cloning and morphology within the nucleus pulposus and inner annulus fibrosus. DISCUSSION: Overall, this new scoring system provides an avenue to improve standardization, allow a more accurate comparison between labs and more robust evaluation of pathophysiology and regenerative treatments across the field.

conclusionThis study developed a histopathology scoring system for degeneration and regeneration in the rabbit model based on reported practice in the literature, a survey of spine researchers, and validation testing.

Indexed as

histologyhistology grading scalehistopathologyintervertebral disc degenerationintervertebral disc regenerationrabbit

Identifiers

PMID34337334
PMCPMC8313151
OpenAlexW3169740039

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.