Abstract
BackgroundHistopathological analysis of intervertebral disc (IVD) tissues is a critical domain of back pain research. Identification, description, and classification of attributes that distinguish abnormal tissues form a basis for probing disease mechanisms and conceiving novel therapies. Unfortunately, lack of standardized methods and nomenclature can limit comparisons of results across studies and prevent organizing information into a clear representation of the hierarchical, spatial, and temporal patterns of IVD degeneration. Thus, the following Orthopaedic Research Society (ORS) Spine Section Initiative aimed to develop a standardized histopathology scoring scheme for human IVD degeneration.MethodsGuided by a working group of experts, this prospective process entailed a series of stages that consisted of reviewing and assessing past grading schemes, surveying IVD researchers globally on current practice and recommendations for a new grading system, utilizing expert opinion a taxonomy of histological grading was developed, and validation performed.ResultsA standardized taxonomy was developed, which showed excellent intra‐rater reliability for scoring nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous end plate (CEP) regions (interclass correlation [ICC] > .89). The ability to reliably detect subtle changes varied by IVD region, being poorest in the NP (ICC: .89‐.95) where changes at the cellular level were important, vs the AF (ICC: .93‐.98), CEP (ICC: .97‐.98), and boney end plate (ICC: .96‐.99) where matrix and structural changes varied more dramatically with degeneration.ConclusionsThe proposed grading system incorporates more comprehensive descriptions of degenerative features for all the IVD sub‐tissues than prior criteria. While there was excellent reliability, our results reinforce the need for improved training, particularly for novice raters. Future evaluation of the proposed system in real‐world settings (eg, at the microscope) will be needed to further refine criteria and more fully evaluate utility. This improved taxonomy could aid in the understanding of IVD degeneration phenotypes and their association with back pain.
Highlights
The intervertebral disc (IVD) is a compliant, composite tissue that separates vertebrae within the spine
We developed a survey in order to capture the needs of the wider scientific community for analyzing human IVD degeneration at the histological level and to garner the communities' opinion on important features that should be incorporated within a grading system, together with an understanding of what groups currently undertake during histology processing
When scores for each region of the IVD were pooled generating a degeneration grade per region resulting in three classifications of non-degenerate (0-3), mid-grade degeneration (4-6), and severe grade of degeneration (7-9) (Figure 14), inter-rater reliability improved with experience of grader, which was most evident for the nucleus pulposus (NP) and boney end plate (BEP) demonstrating the need for more training materials or microscope time (Figure 14)
Summary
The intervertebral disc (IVD) is a compliant, composite tissue that separates vertebrae within the spine. IVD degeneration per se has been associated with around 40% of low back pain cases[7]; other studies have contended that such IVD changes are purely coincidental with respect to pain This mismatch further underscores the need to better understand the IVD phenotype that may shed light upon its correlation with clinical features.[8] IVD degeneration is multifactorial and may start at the cellular level, including the formation of nucleus pulposus (NP) cell clusters,[9] senescent,[10,11] or apoptotic cells, caused by, for example, nutrient deprivation due to occlusion of the cartilaginous end plates (CEPs) and boney end plates (BEPs),[12] or could initiate via a structural defect for example, following injury that can cause subsequent cellular changes. Results: A standardized taxonomy was developed, which showed excellent intrarater reliability for scoring nucleus pulposus (NP), annulus fibrosus (AF), and Abbreviations: AB-PAS, Alcian blue—Periodic Acid Schiff; AF, annulus fibrosus; BEP, boney end plate; CEP, cartilaginous end plate; ECM, extracellular matrix; H&E, hematoxylin and eosin; ICC, interclass correlation coefficient; IVD, intervertebral disc; MRI, magnetic resonance imaging; NP, nucleus pulposus; ORS, Orthopaedic Research Society; UTE, ultrashort echo time
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