Clinical Research Directory

The Effect of NSAID on Serum Periostin

Low back pain (LBP) is one of the most prevalent musculoskeletal disorders worldwide and constitutes a major source of disability and socioeconomic burden. Intervertebral disc degeneration (IVDD) is recognized as one of the primary etiological contributors to LBP, and its prevalence increases substantially with age. The intervertebral disc (IVD) is a complex fibrocartilaginous structure composed of a central gelatinous nucleus pulposus (NP), a surrounding annulus fibrosus (AF), and superior and inferior cartilaginous endplates. The NP and AF cells synthesize a water-rich extracellular matrix (ECM) that confers the disc with its biomechanical properties, enabling load distribution and flexibility of the spinal column. Under physiological conditions, ECM homeostasis within the IVD is tightly regulated; however, various intrinsic and extrinsic stimuli can disrupt this balance and initiate the degenerative cascade. IVDD has been attributed to a multitude of factors, including aging, obesity, genetic predisposition, mechanical overload, degeneration of the multifidus and psoas muscles, osteoporosis, oxidative stress, and chronic low-grade inflammation. Dysfunction of NP and AF cells, compounded by excessive endplate metabolic activity, leads to progressive endplate calcification, loss of disc hydration, structural failure of the AF, and ultimately irreversible IVDD. Among these contributing factors, elevated oxidative stress and increased secretion of pro-inflammatory cytokines-such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)-have been shown to markedly accelerate the progression of IVDD by promoting ECM catabolism and suppressing anabolic repair processes. Periostin (gene symbol: POSTN) is a matricellular ECM protein originally identified in the periosteum and periodontal ligament. It belongs to the fasciclin superfamily and plays a critical role in ECM assembly, tissue remodeling, and cell-matrix interactions. Periostin has been identified as a key mediator of mechanical stress responses, inflammatory signaling, and aging-related tissue changes, and is increasingly recognized as an important contributor to musculoskeletal pathology. Within the IVD, periostin binds to structural ECM molecules-including fibronectin, tenascin-C, and collagens-and participates in disc maintenance and repair. Conversely, dysregulated periostin expression promotes excessive ECM turnover and accelerates IVD degeneration through both mechanosensory and pro-inflammatory pathways. Importantly, serum periostin levels have been reported to be significantly elevated in patients with severe IVDD, and a recent clinical study demonstrated a strong positive correlation between serum periostin concentration and the Pfirrmann grading system, the most widely used MRI-based classification of disc degeneration severity. Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed pharmacological treatments for LBP, recommended in current clinical guidelines as first-line analgesic therapy. NSAIDs exert their primary effects through inhibition of cyclooxygenase (COX) enzymes, thereby suppressing prostaglandin synthesis and attenuating the inflammatory cascade. Beyond analgesia, NSAIDs may modulate the systemic inflammatory milieu in patients with IVDD by reducing circulating pro-inflammatory cytokine levels. Periostin expression is known to be upregulated by inflammatory mediators, including IL-4, IL-13, and TNF-α, and is closely linked to the overall inflammatory burden. It is therefore plausible that NSAID use may indirectly attenuate serum periostin elevation in patients with IVDD-related LBP; however, direct evidence for this hypothesis is currently lacking. To date, no study has systematically compared serum periostin and inflammatory cytokine concentrations among patients with IVDD-related LBP who are using NSAIDs, those who are not using NSAIDs, and healthy controls without LBP. Elucidating these differences would not only advance our understanding of the role of systemic inflammation and ECM remodeling in IVDD pathophysiology, but would also help clarify whether NSAID use influences the biomarker profile of affected patients-with important implications for patient stratification and biomarker-guided management.

Relationship of Periostin and ODI, EQ-5D

The intervertebral disc degeneration (IVDD) is a widely recognized musculoskeletal disorder that impose a substantial socioeconomic burden and respresents one of the most important causes of low back pain. IVDD can result from a variety of factors, including aging, obesity, genetic predispositioin, degeneration of of the multifidus and psoas muscles, osteoporosis, inflammation, and oxidative stress. The IVD consists of a central gelatinous nucleus pulposus (NP), an outer annulus fibrosus (AF), and superior and inferior cartilaginous endplates. The NP and AF produce a water-rich extracellular matrix (ECM), which is essential for normal trunk function. Dysfunction of the NP and AF, together with excessive metabolic activity of the enplates triggered by various intrinsic and extrinsic stimuli, leads to endplate degeneration and calcification, and ultimately to IVDD. In addition to aging and mechanical overload, increased oxidative stress and pro-inflammatrory cytokine secretion further accelerate the progression of IVDD. Periostin is an ECM protein which is associated with mechanical stress, inflammation, and aging, and is known to be closely involved in the development and progression of IVDD. Periostin binds to ECM molecule within the IVD and participates in its maintenance and repair; however, excessive ECM turn over drives IVD degeneration and its progression. Periostin influences IVD degeneration through mechanical stress and inflammatory pathways, and serum periostin levels are elevated in patients with severe IVD degeneration. A recent study demonstrated strong corrrelation between serum periostin concentration and the Pfirmann grading system. The Oswestry disability index is a validated scale that measures functional disability in patients with spinal pain, and the EQ-5D is a breif questionnaire used to assess health related quality of life. Because serum periostin levels reflect the severity of IVDD, periostin may also influence patient's functional disability and quality of life. However, whether serum periostin concentration correlates with functional disability and quality of life has not yet been studied.