Mechanisms and clinical implications of intervertebral disc calcification.

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.