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Mechanisms and clinical implications of intervertebral disc calcification

Nature Reviews Rheumatology volume 18, pages 352–362 (2022)Cite this article

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Abstract

Low back pain is a leading cause of disability worldwide. Intervertebral disc (IVD) degeneration is often associated with low back pain but is sometimes asymptomatic. IVD calcification is an often overlooked disc phenotype that might have considerable clinical impact. IVD calcification is not a rare finding in ageing or in degenerative and scoliotic spinal conditions, but is often ignored and under-reported. IVD calcification may lead to stiffer IVDs and altered segmental biomechanics, more severe IVD degeneration, inflammation and low back pain. Calcification is not restricted to the IVD but is also observed in the degeneration of other cartilaginous tissues, such as joint cartilage, and is involved in the tissue inflammatory process. Furthermore, IVD calcification may also affect the vertebral endplate, leading to Modic changes (non-neoplastic subchondral vertebral bone marrow lesions) and the generation of pain. Such effects in the spine might develop in similar ways to the development of subchondral marrow lesions of the knee, which are associated with osteoarthritis-related pain. We propose that IVD calcification is a phenotypic biomarker of clinically relevant disc degeneration and endplate changes. As IVD calcification has implications for the management and prognosis of degenerative spinal changes and could affect targeted therapeutics and regenerative approaches for the spine, awareness of IVD calcification should be raised in the spine community.

Key points

  • Intervertebral disc (IVD) calcification is associated with IVD degeneration and can lead to pain.

  • IVD calcification may affect disc kinematics and degeneration severity, and can also affect adjacent vertebral endplates, which might lead to pathological non-neoplastic subchondral bone marrow lesions (Modic changes).

  • Calcification in the IVD degenerative process is comparable with mineralization of the degenerative process of cartilaginous tissues in osteoarthritis.

  • IVD calcification is a unique phenotype that is clinically relevant, that could influence personalized approaches to patient care and that warrants further investigation.

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Fig. 1: Comparison of a healthy and a degenerated intervertebral disc in the spine.
Fig. 2: Calcification in degenerated discs.
Fig. 3: Images showing presence of fissures near calcified spots.
Fig. 4: Disc calcification: mechanisms, diagnosis and clinical relevance.
Fig. 5: A conceptual overview of the initiation of Modic changes and disc degeneration.

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Acknowledgements

D.S. is supported by institutional funding from the Department of Orthopaedic Surgery at RUSH University Medical Center, Chicago, IL, USA. M.T. is supported by funding from the Dutch Arthritis Society (LLP22). F.M. is supported by the Canadian Institute of Health Research (CIHR). J.C.I. and S.I.-J. are supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH under Award Number R01 AR 069315.

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Authors and Affiliations

  1. Department of Anatomy, University of Health Sciences, Lahore, Pakistan

    Uruj Zehra

  2. Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands

    Marianna Tryfonidou

  3. Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    James C. Iatridis

  4. Emory University School of Medicine, Atlanta, GA, USA

    Svenja Illien-Jünger

  5. Lady Davis Institute for Medical Research, SMBD-Jewish General Hospital and Department of Surgery, McGill University, Montreal, QC, Canada

    Fackson Mwale

  6. Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, IL, USA

    Dino Samartzis

  7. International Spine Research and Innovation Initiative, Rush University Medical Center, Chicago, IL, USA

    Dino Samartzis

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All authors researched data for the article, made substantial contributions to discussion of the content, wrote the manuscript, and reviewed and edited the manuscript before submission. D.S. provided overall supervision and administrative support.

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Zehra, U., Tryfonidou, M., Iatridis, J.C. et al. Mechanisms and clinical implications of intervertebral disc calcification. Nat Rev Rheumatol 18, 352–362 (2022). https://doi.org/10.1038/s41584-022-00783-7

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