UCSF

Back pain is the most common musculoskeletal condition, affecting 80% of Americans during their lifetimes. Irregularities of the spinal disc-vertebra interface are associated with back pain and over 60% of disc herniation injuries. Despite the vulnerability of this interface, its structure and function are not well characterized. This dissertation explores the structural and biomechanical features of the disc-vertebra interface, with the goal of motivating improved diagnostics and treatments for back pain patients.

Towards this goal, this dissertation is broken into four studies. In the first, we show that bending strength and flexibility of the disc-vertebra interface in murine spines are reduced following spaceflight. This coincides with bone loss, and suggests that lowered bone density may lead to the increased risk of disc herniation seen in astronauts. This work translates to humans on Earth, suggesting that strategies that maintain bone health may help prevent disc herniation. In the second study, we identify failure mechanisms, quantify mechanical properties, and measure architectural features at the disc-vertebra interface in human cadaver spine specimens tested in tension. The majority of specimens failed at the disc-vertebra interface, as explained by a lack of structural integration observed with high-resolution microscopy. We also found that disc degeneration and lowered bone density in the vertebral endplate led to decreased interface strength. In the third study, we present a histological classification system for endplate irregularities. During this work, we discovered a highly prevalent irregularity in which the disc separates from the vertebra at the tidemark – the mineralization front between the annulus fibrosus and calcified cartilage layer. We show that even small separations at the tidemark may be clinically relevant, as they are visible as high-intensity zones (HIZs) using MRI. In the last study, we present a novel Matlab algorithm for quantifying cartilage endplate morphology using MRI, and show that variation in endplate thickness is correlated with disc degeneration.

Collectively, the work presented in this dissertation emphasizes the vulnerability of the disc-vertebra interface and uncovers potential risk factors for injury. These findings will motivate new specialized diagnostics, preventive strategies, and treatments for many patients suffering from low back pain.