Phenotypes of pathologic vertebral endplate degeneration

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Investigator: Jeffrey C. Lotz, PhD
Sponsor: NIH Natl Inst Arthr, Musculoskel & Skin

Location(s): United States

Description

Low back pain is a significant cause of morbidity and societal expense, affecting between 65% and 80% of the population at least once in their lifetime. The intervertebral disc is thought to be a primary pain source, but mechanisms by which discs degenerate and hurt are poorly understood. There has been little attention paid to cross talk between discs and adjacent vertebra in relation to degeneration and pain. Historical data suggest that the vertebral endplate can be a significant source of pain in some 'discogenic' patients, but little is known about the pathophysiology of this process. We propose to study the endplates and discs in human cadaver spines to clarify pathologic processes and validate new imaging technologies that may serve as sensitive biomarkers for localizing painful spinal levels and directing patients toward ideal therapies. These new imaging grading schemes will be tested in patients with confirmed discogenic low back pain and control asymmetric volunteers. Three aims are proposed. In Aim 1 we will validate quantitative techniques for MR-based depictions of endplate and annular damage using fresh human cadaveric lumbar spines, and establish whether pathologic endplate phenotypes associate with intrinsic vertebral abnormalities, or rather are secondary to adjacent disc pathology. In Aim 2 we reveal structural risk factors for endplate damage and disc degeneration using high- resolution computational models. In Aim 3 we will test whether techniques developed in Aim 1 are sensitive and specific for discogenic low back pain. Through this work, we plan to clarify pathologic processes within vertebral endplates and develop more sensitive clinical imaging tools. Future studies will focus on clarifying mechanisms for the innervated disc pathologies that are linked to symptoms in patients.  Our goals are to: 1) develop and validate quantitative techniques for MR-based depictions of endplate and annular damage using fresh human cadaveric lumbar spines; 2) reveal structural risk factors for endplate damage and disc degeneration using high-resolution computational models; and 3) test whether newly- developed MRI grading schemes distinguish painful from non-painful discs in low back pain patients and asymptomatic volunteers. This research will have substantial impact by directly addressing the biggest clinical challenge (identifying why discs degenerate and hurt) in the management of patients with the most common and costly musculoskeletal condition. Data will influence patient care by identifying important degeneration and pain factors that could drive new prevention strategies, diagnostics, and therapies.