# The Vicious Cycle of Obesity and Low Back Pain: A Comprehensive Review
## 3 Low Back Pain  
LBP is the most prevalent musculoskeletal condition worldwide, impacting nearly 570 million people and representing the leading cause of disability across all age groups [2]. Notably, symptoms can begin as early as childhood, with cases reported in children as young as 10 years old [22; 23], and seemingly is on the rise in this young cohort [24]. LBP affects all populations, but certain risk factors are associated with a higher incidence and severity. These include age, genetic predisposition, obesity, smoking, and a sedentary lifestyle [25; 26]. Among workers, LBP is a leading cause of absenteeism and reduced productivity, imposing a significant economic burden on healthcare systems worldwide [2; 27]. LBP can arise from various sources, including muscular strain, ligament injuries, facet joint degeneration, and IDD [28; 29]. IDD is particularly common and often necessitates medical intervention or, in severe cases, surgical intervention. The IVDs, located between the vertebrae, are essential for spinal mobility, flexibility, and load distribution. Each IVD consists of a collagen-fibre-rich annulus fibrosus (AF) that surrounds the gel-like nucleus pulposus (NP) at its centre. These two tissues are separated from the vertebral bodies via interposition of two cartilaginous layers, namely the cartilaginous endplates (CEPs), which are essential for IVD integrity and IVD nonishment. Over time, age-related factors, mechanical stress, and metabolic changes can compromise IVD integrity, leading to IDD [28; 30]. This process is characterized by a loss of NP hydration, reduced proteoglycanand collagen content, and the formation of fissures within the AF. IDD impairs the shock absorption and force distribution capacities of the IVD, stressing NP and AF cells. This promotes IVD cells to release a plethora of enzymes, such as matrix metalloproteinases (MMPs), that facilitate ECM breakdown, leading to acceleration of disc dehydration, disc height loss, and mechanical instability [31]. Additionally, structural degeneration of the AF diminishes its ability to contain the swelling of the NP, potentially resulting in disc bulging, AF rupture, or disc herniation [30; 32]. Furthermore, pro-inflammatory cytokines (e.g., interleukin [II]-1\(\beta\), tumour necrosis factor [TNF]-\(\alpha\)) released by disc cells may exacerbate this cycle, by causing increased catabolic enzyme activity, oxidative stress, and cellular apoptosis [28; 33; 34; 35]. These cytokines may also sensitize nerve endings [36; 37; 38] and promote the influx of immunogenic cells into the otherwise largely immune-compromised IVD [39; 40; 41], further contributing to LBP. The treatment for LBP, especially chogenic LBP related to IDD, generally encompasses conservative intervention, and for most cases the condition will only present temporarily [42]. Here, conservative management typically includes physical therapy, pharmacological interventions (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs], corticosteroids, etc. ), and lifestyle modifications [43]. For patients with persistent pain who do not respond to conservative measures, surgical interventions, such as disectomy or spinal fusion, may be considered [44]. However, these surgical procedures often fail to restore full disc function and may lead to long-term complications, including reduced range of motion (ROM) and adjacent segment degeneration [45]. Moreover, long-term pain and disability benefits remain disputed [46; 47]. While current therapies aim to relieve symptoms and stabilize the spine, they do not reverse or repair the degenerative changes within the disc [48]. This lack of restoration has driven interest in regenerative medicine as a promising approach to treat IDD and LBP [49].