TITLE:
Intervertebral Disc Degeneration: A Comprehensive Review of Pathophysiological Mechanisms, Diagnostic Advances, and Evolving Clinical Management Protocols
AUTHORS:
Arjun Sinkemani, Shuang Zhang
KEYWORDS:
Intervertebral Disc Degeneration, Cellular Senescence, Mitophagy, Inflammation, Extracellular Matrix, Mechanotransduction, Stem Cell Therapy, Hydrogels, Spinal Fusion, Regenerative Medicine
JOURNAL NAME:
International Journal of Clinical Medicine,
Vol.17 No.10,
October
22,
2026
ABSTRACT: Intervertebral disc degeneration (IVDD) is a progressive, multifactorial condition in which the cellular and extracellular matrix architecture of the disc deteriorates. It is a leading global cause of chronic low back pain and disability. Its pathophysiology involves a complex interplay among cellular senescence, inflammatory signaling, oxidative stress, mitochondrial dysfunction, and impaired mechanotransduction. Recent studies have clarified the roles of mitophagy and programmed cell death pathways such as pyroptosis and ferroptosis, as well as the critical influence of the disc microenvironment on disease progression. Diagnosis depends mainly on magnetic resonance imaging, although emerging biomarkers and advanced imaging techniques may allow earlier detection. Clinical management follows a stepwise approach, starting with conservative measures and advancing to surgery for refractory cases. Traditional treatments focus on symptom relief, whereas emerging regenerative strategies including stem cell therapies, senolytics, and biomaterial innovations aim to modify the degenerative cascade at the molecular level. This review summarizes current knowledge of IVDD pathogenesis and assesses contemporary clinical management protocols together with promising biological therapies.