Endoplasmic reticulum (ER) stress and its adaptive mechanism, the unfolded protein response (UPR), are triggered by the accumulation of unfolded and misfolded proteins. During osteoclastogenesis, a large number of active proteins are synthesized. When an imbalance in the protein folding process occurs, it causes osteoclasts to trigger the UPR. This close association has led to the role of the UPR in osteoclastogenesis being increasingly explored. In recent years, several studies have reported the role of ER stress and UPR in osteoclastogenesis and bone resorption. Here, we reviewed the relevant literature and discussed the UPR signaling cascade response, osteoclastogenesis-related signaling pathways, and the role of UPR in osteoclastogenesis and bone resorption in detail. It was found that the UPR signal (PERK, CHOP, and IRE1-XBP1) promoted the expression of the receptor activator of the nuclear factor-kappa B ligand (RANKL) in osteoblasts and indirectly enhanced osteoclastogenesis. IRE1 promoted osteoclastogenesis via promoting NF-κB, MAPK signaling, or the release of pro-inflammatory factors (IL-6, IL-1β, and TNFα). CREBH promoted osteoclast differentiation by promoting NFATc1 expression. The PERK signaling pathway also promoted osteoclastogenesis through NF-κB and MAPK signaling pathways, autophagy, and RANKL secretion from osteoblasts. However, salubrinal (an inhibitor of eIF2α dephosphorylation that upregulated p-eIF2α expression) directly inhibited osteoclastogenesis by suppressing NFATc1 expression and indirectly promoted osteoclastogenesis by promoting RANKL secretion from osteoblasts. Therefore, the specific effects and mechanisms of p-PERK and its downstream signaling on osteoclastogenesis still need further experiments to confirm. In addition, the exact role of ATF6 and BiP in osteoclastogenesis also required further exploration. In conclusion, our detailed and systematic review provides some references for the next step to fully elucidate the relationship between UPR and osteoclastogenesis, intending to provide new insights for the treatment of diseases caused by osteoclast over-differentiation, such as osteoporosis.

Nanozymes, a category of nanomaterials with enzyme-like activity, have garnered growing interest in various biomedical contexts. Notably, nanozymes that are capable of regulating reactive oxygen species levels by emulating antioxidant or prooxidant enzymes within cells hold significant therapeutic potential for a range of disorders. Herein, we overview the catalytic mechanisms of four exemplary nanozymes within the orthopedic domain. Subsequently, we emphasize recent groundbreaking advancements in nanozyme applications in orthopaedics, encompassing osteoarthritis, osteoporosis, intervertebral disc degeneration, bone defects, spinal cord injury, gout, rheumatoid arthritis, osteosarcoma and bone infection. Furthermore, we discuss the emerging area's future prospects and several noteworthy challenges in biomedical application. This review not only fosters the ongoing development of nanozyme research but also fosters the emergence of more potent nanozymes for the treatment of orthopaedical diseases in the future.

Objective: To investigate the independent influencing factors of bone cement displacement following percutaneous vertebral augmentation (PVA) in patients with stage I and stage II Kümmell’s disease. Methods: We retrospectively reviewed the records of 824 patients with stage Ⅰ and stage Ⅱ Kümmell’s disease treated with percutaneous vertebroplasty (PVP) or percutaneous vertebroplasty (PKP) from January 2016 to June 2022. Patients were divided into the postoperative bone cement displacement group (n = 150) and the bone cement non-displacement group (n = 674) according to the radiographic inspection results. The following data were collected: age, gender, body mass index (BMI), underlying disease, bone mineral density (BMD), involved vertebral segment, Kümmell’s disease staging, anterior height, local Cobb angle, the integrity of anterior vertebral cortex, the integrity of endplate in surgical vertebrae, surgical method, surgical approach, the volume of cement, distribution of cement, the viscosity of cement, cement leakage, and postoperative anti-osteoporosis treatment. Binary logistic regression analysis was performed to determine the independent influencing factors of bone cement displacement. The discrimination ability was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC). Results: The results of logistic regression analysis revealed that thoracolumbar junction (odds ratio (OR) = 3.23, 95% confidence interval (CI) 2.12–4.50, p = 0.011), Kümmell’s disease staging (OR = 2.23, 95% CI 1.81–3.41, p < 0.001), anterior cortex defect (OR = 5.34, 95% CI 3.53–7.21, p < 0.001), vertebral endplates defect (OR = 0.54, 95% CI 0.35–0.71, p < 0.001), cement distribution (OR = 2.86, 95% CI 2.03–3.52, p = 0.002), cement leakage (OR = 4.59, 95% CI 3.85–5.72, p < 0.001), restoration of local Cobb angle (OR = 3.17, 95% CI 2.40–5.73, p = 0.024), and postoperative anti-osteoporosis treatment (OR = 0.48, 95% CI 0.18–0.72, p = 0.025) were independently associated with the bone cement displacement. The results of the ROC curve analysis showed that the AUC was 0.816 (95% CI 0.747–0.885), the sensitivity was 0.717, and the specificity was 0.793. Conclusion: Thoracolumbar fracture, stage Ⅱ Kümmell’s disease, anterior cortex defect, uneven cement distribution, cement leakage, and high restoration of the local Cobb angle were risk factors for cement displacement after PVA in Kümmell’s disease, while vertebral endplates defect and postoperative anti-osteoporosis treatment are protective factors.

Background: In the treatment of spinal metastases, stereotactic body radiotherapy (SBRT) delivers precise, high‐dose radiation to the target region while sparing the spinal cord. A range of doses and fractions had been reported; however, the optimal prescribed scheme remains unclear.Methods: Two reviewers performed independent literature searches of the PubMed, EMBASE, Cochrane Database, and Web of Science databases. Articles were divided into one to five fractions groups. The Methodological Index for Non‐randomized Studies (MINORS) was used to assess the quality of studies. Local control (LC) and overall survival (OS) were presented for the included studies and a pooled value was calculated by the weighted average.Results: The 38 included studies comprised 3,754 patients with 4,731 lesions. The average 1‐year LCs for the one to five fractions were 92.7%, 84.6%, 86.8%, 82.6%, and 80.6%, respectively. The average 1‐year OS for the one to five fractions were 53.0%, 70.4%, 60.1%, 48%, and 80%, respectively. The 24 Gy/single fraction scheme had a higher 1‐year LC (98.1%) than those of 24 Gy/two fractions (85.4%), 27 Gy/three fractions (84.9%), and 24 Gy/three fractions (89.0%). The incidence of vertebral compression fracture was 10.3%, with 10.7% in the single‐fraction group and 10.1% in the multi‐fraction group. The incidence of radiation‐induced myelopathy was 0.19%; three and two patients were treated with single‐fraction and multi‐fraction SBRT, respectively. The incidence of radiculopathy was 0.30% and all but one patient were treated with multi‐fraction SBRT.Conclusions: SBRT provided satisfactory efficacy and acceptable safety for spinal metastases. Single‐fraction SBRT demonstrated a higher local control rate than those of the other factions, especially the 24 Gy dose. The risk of vertebral compression fracture (VCF) was slightly higher in single‐fraction SBRT and more patients developed radiculopathy after multi‐fraction SBRT.