Intervertebral disc degeneration (IDD) is a common degenerative musculoskeletal disorder and is recognized as a major contributor to discogenic lower back pain. However, the molecular mechanisms underlying IDD remain unclear, and therapeutic strategies for IDD are currently limited. Oxidative stress plays pivotal roles in the pathogenesis and progression of many age-related diseases in humans, including IDD. Nuclear factor E2-related factor 2 (Nrf2) is a master antioxidant transcription factor that protects cells against oxidative stress damage. Nrf2 is negatively modulated by Kelch-like ECH-associated protein 1 (Keap1) and exerts important effects on IDD progression. Accumulating evidence has revealed that Nrf2 can facilitate the transcription of downstream antioxidant genes in disc cells by binding to antioxidant response elements (AREs) in promoter regions, including heme oxygenase-1 (HO-1), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and NADPH quinone dehydrogenase 1 (NQO1). The Nrf2 antioxidant defense system regulates cell apoptosis, senescence, extracellular matrix (ECM) metabolism, the inflammatory response of the nucleus pulposus (NP), and calcification of the cartilaginous endplates (EP) in IDD. In this review, we aim to discuss the current knowledge on the roles of Nrf2 in IDD systematically.

OBJECTIVE: The authors investigated the relation between Hounsfield unit (HU) values measured on CT and the risk of pedicle screw loosening in patients who underwent lumbar pedicle screw fixation for degenerative lumbar spine disease.METHODS: Patients who were treated with lumbar pedicle screw fixation between July 2011 and December 2015 at the authors’ department were reviewed. Age, sex, BMI, smoking and diabetes histories, range of fixation, and fusion method were recorded as the basic patient information. The HU values for lumbar bone mineral density (BMD) for the L1, L2, L3, and L4 vertebra were measured on CT scans. Logistic regression analysis was used to identify the independent influencing factors of pedicle screw loosening.RESULTS: A total of 503 patients were included in the final analysis. The pedicle screw loosening rate at the 12-month follow-up was 30.0% (151 of 503 patients). There were no significant differences in sex, BMI, or histories of smoking and diabetes between the patients with (loosening group) and those without (nonloosening group) screw loosening (p > 0.05). The mean HU value of L1–4 was lower in the loosening group than the nonloosening group (106.3 ± 33.9 vs 132.6 ± 42.9, p < 0.001). In logistic regression analysis, being male (OR 2.065; 95% CI 1.242–3.433), HU value (OR 0.977; 95% CI 0.970–0.985), length of fixation (OR 3.616; 95% CI 2.617–4.996), and fixation to S1 (OR 1.699; 95% CI 1.039–2.777) were the independent influencing factors for screw loosening.CONCLUSIONS: HU value measured on CT was an independent predictor for pedicle screw loosening, and lower HU value was significantly correlated with higher risk of screw loosening.

OBJECTIVE: The authors aimed to compare the efficacy of lumbar vertebral body Hounsfield units (HUs) and pedicle HUs at predicting pedicle screw loosening. METHODS: The authors retrospectively assessed 143 patients with L3–5 instrumentation. The patients were classified into one of two groups based on the status of their L3 screws (a screw loosening group or a control group). The pedicle HUs and vertebral HUs of L3 were measured using preoperative lumbar CT scans, and the pedicle HUs were measured in two ways: by excluding or by including cortical bone. RESULTS: The screw loosening rate was 20.3% (n = 29/143) at the 12-month follow-up. The vertebral body HUs and pedicle HUs in the screw loosening group were lower than those in the control group (vertebral body group: 98.6 HUs vs 121.4 HUs, p < 0.001; pedicle excluding cortical bone: 208.9 HUs vs 290.5 HUs, p = 0.002; pedicle including cortical bone: 249.4 HUs vs 337.5 HUs, p < 0.001). The pedicle HUs tended to have a higher area under the receiver operating characteristic curve value in predicting screw loosening, compared with that of vertebral body HUs, but the difference was not statistically significant (p > 0.05). Among patients with low vertebral body HUs of ≤ 130, the loosening rate was much lower in patients with pedicle HUs of ≤ 340 than in those with pedicle HUs of > 340 (31.0% vs 13.0%, respectively; p < 0.05). CONCLUSIONS: Vertebral body HUs alone are insufficient to accurately evaluate the risk of pedicle screw loosening. Therefore, it is important to collect both the pedicle HU and vertebral body HU measurements for surgical planning.

Metallic scaffolds have shown promise in regenerating critical bone defects. However, limitations persist in achieving a modulus below 100 MPa due to insufficient strength. Consequently, the osteogenic impact of lower modulus and greater bone tissue strain ( > 1%) remains unclear. Here, we introduce a metamaterial scaffold that decouples strength and modulus through two-stage deformation. The scaffold facilitates an effective modulus of only 13 MPa, ensuring adaptability during bone regeneration. Followed by a stiff stage, it provides the necessary strength for load-bearing requirements. In vivo, the scaffold induces > 2% callus strain, upregulating calcium channels and HIF-1α to enhance osteogenesis and angiogenesis. 4-week histomorphology reveals a 44% and 498% increase in new bone fraction versus classic scaffolds with 500 MPa and 13 MPa modulus, respectively. This design transcends traditional modulus-matching paradigms, prioritizing bone tissue strain requirements. Its tunable mechanical properties also present promising implications for advancing osteogenesis mechanisms and addressing clinical challenges.