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Vertebral Endplate Defect as Initiating Factor in Intervertebral Disc Degeneration

Strong Association Between Endplate Defect and Disc Degeneration in the General Population

Rade, Marinko, PhD∗,†; Määttä, Juhani H., MD, PhD‡,§,¶; Freidin, Maxim B., PhD; Airaksinen, Olavi, MD, PhD; Karppinen, Jaro, MD, PhD‡,||; Williams, Frances M. K., PhD, FRCP(E)

doi: 10.1097/BRS.0000000000002352

Study Design. Cross-sectional study of spine magnetic resonance in a population, predominantly female, sample.

Objective. To determine the relationship between vertebral endplate defect and intervertebral disc degeneration (DD) in general population.

Summary of Background Data. Precise understanding of the mechanisms leading to DD development is lacking. In a degenerating disc, mechanical and structural changes lead to further worsening of disc integrity. Increasing attention has been paid to vertebral endplate defects as having a possible role in the etiopathogenesis of DD.

Methods. The study population comprised 831 twin volunteers from TwinsUK (mean age 54 ± 8 yr, 95.8% female). Lumbar T2-weighted magnetic resonance images were coded for endplate defects from 8310 endplates into six grades. Total endplate score (TEP score) was achieved by summing both endplate defect grades from the same disc level. DD was evaluated using two different classifications; Pfirrmann grading, and a quantitative trait for DD based on a 4-point grading system. Multivariable regression analysis was used to determine relationships between the traits of interest and the known risk factors for DD, age, and body mass index (BMI). A receiver operator curve for TEP score predicting DD was generated, and survival analysis paired with Cox proportional hazards models analysis performed.

Results. There was statistically significant association between DD and age and BMI. These associations lost significance when TEP score was included as predictor in multivariable model. TEP score was strongly and independently associated at every lumbar disc level with DD (Pfirmann P≤0.001; 4-point grading systems P < 1e-16). A cut-off point score of 5 for TEP score was found above which there was a higher DD prevalence. Across all age subgroups, probabilities of having DD were significantly increased in those considered TEP score positive (≥5).

Conclusion. Our large, population-based study has shown that endplate defect was strongly and independently associated with DD at every lumbar disc level. These results provide a mechanism by which increasing age and BMI predispose to DD.

Level of Evidence: 2

Department of Physical and Rehabilitation Medicine, Kuopio University Hospital, Kuopio, Finland

Faculty of Medicine, Orthopaedic and Rehabilitation Hospital “Prim. dr.Martin Horvat”, Josip Juraj Strossmayer University of Osijek, Rovinj, Croatia

Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland

§Orton Rehabilitation Centre, Helsinki, Finland

Department of Twin Research and Genetic Epidemiology, King's College London, London, UK

||Finnish Institute of Occupational Health, Oulu, Finland.

Address correspondence and reprint requests to Frances M. K. Williams, PhD, FRCP(E), Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK; E-mail:

Received 2 November, 2016

Revised 19 June, 2017

Accepted 22 June, 2017

The manuscript submitted does not contain information about medical device(s)/drug(s).

The EU FP7 project Pain_omics, the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007–2013), and the National Institute for Health Research funds were received in support of this work.

Relevant financial activities outside the submitted work: board membership, payment for lectures, stocks.

MR and JHM contributed equally to this work.

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