Melatonin rescues the mitochondrial function of bone marrow-derived mesenchymal stem cells and improves the repair of osteoporotic bone defect in ovariectomized rats.

Osteoporotic bone defects, a severe complication of osteoporosis, are distinguished by a delayed bone healing process and poor repair quality. While bone marrow-derived mesenchymal stem cells (BMMSCs) are the primary origin of bone-forming osteoblasts, their mitochondrial function is impaired, leading to inadequate bone regeneration in osteoporotic patients. Melatonin is well-known for its antioxidant properties and regulation on bone metabolism. The present study postulated that melatonin has the potential to enhance the repair of osteoporotic bone defects by restoring the mitochondrial function of BMMSCs. In vitro administration of melatonin at varying concentrations (0.01, 1, and 100 µM) demonstrated a significant dose-dependent improvement in the mitochondrial function of BMMSCs obtained from ovariectomized rats (OVX-BMMSCs), as indicated by an elevation in mitochondrial membrane potential, adenosine triphosphate synthesis and expression of mitochondrial respiratory chain factors. Melatonin reduced the level of mitochondrial superoxide by activating the silent information regulator type 1 (SIRT1) and its downstream antioxidant enzymes, particularly superoxide dismutase 2 (SOD2). The protective effects of melatonin were found to be nullified upon silencing of Sirt1 or Sod2, underscoring the crucial role of the SIRT1-SOD2 axis in the melatonin-induced enhancement of mitochondrial energy metabolism in OVX-BMMSCs. To achieve a sustained and localized release of melatonin, silk fibroin scaffolds loaded with melatonin (SF@MT) were fabricated. The study involved the surgical creation of bilateral femur defects in OVX rats, followed by the implantation of SF@MT scaffolds. The results indicated that the application of melatonin partially restored the mitochondrial energy metabolism and osteogenic differentiation of OVX-BMMSCs by reinstating mitochondrial redox homeostasis. These findings suggest that the localized administration of melatonin through bone implants holds potential as a therapeutic approach for addressing osteoporotic bone defects.

Melatonin-loaded self-healing hydrogel targets mitochondrial energy metabolism and promotes annulus fibrosus regeneration.

Intervertebral disc (IVD) herniation is a major cause of chronic low back pain and disability. The current nucleus pulposus (NP) discectomy effectively relieves pain symptoms, but the annulus fibrosus (AF) defects are left unrepaired. Tissue engineering approaches show promise in treating AF injury and IVD degeneration; however, the presence of an inflammatory milieu at the injury site hinders the mitochondrial energy metabolism of AF cells, resulting in a lack of AF regeneration. In this study, we fabricated a dynamic self-healing hydrogel loaded with melatonin (an endocrine hormone well-known for its antioxidant and anti-inflammatory properties) and investigate whether melatonin-loaded hydrogel could promote AF defect repair by rescuing the matrix synthesis and energy metabolism of AF cells. The protective effects of melatonin on matrix components (e.g. type I and II collagen and aggrecan) in AF cells were observed in the presence of interleukin (IL)-1ß. Additionally, melatonin was found to activate the nuclear factor erythroid 2-related factor signaling pathway, thereby safeguarding the mitochondrial function of AF cells from IL-1ß, as evidenced by the increased level of adenosine triphosphate, mitochondrial membrane potential, and respiratory chain factor expression. The incorporation of melatonin into a self-healing hydrogel based on thiolated gelatin and ß-cyclodextrin was proposed as a means of promoting AF regeneration. The successful implantation of melatonin-loaded hydrogel has been shown to facilitate in situ regeneration of AF tissue, thereby impeding IVD degeneration by preserving the hydration of nucleus pulposus in a rat box-cut IVD defect model. These findings offer compelling evidence that the development of a melatonin-loaded dynamic self-healing hydrogel can promote the mitochondrial functions of AF cells and represents a promising strategy for IVD regeneration.

Effect of the intermediate pedicle screws and their insertion depth on sagittal balance and functional outcomes of lumbar fracture.

Objective: This study aimed to examine the effect of the intermediate pedicle screws and their insertion depth on sagittal balance and functional outcomes of lumbar fracture. Methods: This study reviewed 1,123 patients with lumbar fractures between January 2015 and June 2019, and 97 patients were ultimately enrolled in this study: Group A: 32 patients in the four-pedicle screws fixation group; Group B: 28 patients in the six-pedicle screws fixation with long intermediate pedicle screws group; Group C: 37 patients in the six-pedicle screws fixation with short intermediate pedicle screws group. The radiographic outcomes were assessed with lumbar lordosis (LL), segmental lordosis (SL), fractured vertebral lordosis (FL), sacral slope (SS), pelvic incidence (PI), and pelvic tilt (PT). The visual analog scale (VAS) and the Oswestry disability index (ODI) scores were used for assessing functional outcomes. Results: The PI, PT, and SS showed no significant differences between the three groups (P > 0.05). Compared with Group A, Groups B and C showed better FL, SL, and LL 1 month after operation (5.96 ± 1.67/4.81 ± 1.49 vs. 8.78 ± 2.90, 24.39 ± 3.80/23.70 ± 4.10 vs. 20.09 ± 3.33, 39.07 ± 3.61/39.51 ± 3.23 vs. 36.41 ± 3.11, P < 0.05) and at final follow-up (8.75 ± 1.40/6.78 ± 1.70 vs. 11.31 ± 2.61, 22.11 ± 3.39/23.70 ± 4.10 vs. 17.66 ± 2.60, 38.04 ± 3.49/39.51 ± 3.23 vs. 35.41 ± 3.11, P < 0.05). The FL of Group C were significantly better than those of Group B 1 month after operation (4.81 ± 1.49 vs. 5.96 ± 1.67, P < 0.05) and at final follow-up (6.78 ± 1.70 vs. 8.75 ± 1.40, P < 0.05). No significant differences in VAS and ODI were found between Group A and Group B (P > 0.05). There were also no significant differences in VAS and ODI between Group A and Group C (P > 0.05). However, The VAS and ODI of Group C showed better than Group B 1 month after operation (3.05 ± 0.70 vs. 3.54 ± 0.79, 17.65 ± 3.41 vs. 19.71 ± 2.35, P < 0.05) and at final follow-up (2.19 ± 0.46 vs. 2.57 ± 0.57, 13.81 ± 2.20 vs. 15.57 ± 1.73, P < 0.05). Conclusions: Both four-pedicle screw fixation and six-pedicle screw fixation were effective in treating lumbar fracture. However, six-pedicle screw fixation with short intermediate pedicle screws showed better radiographic and functional outcomes after surgery. Therefore, we recommend six-pedicle screws fixation with short intermediate pedicle screws for the long-term recovery of sagittal balance and function.

Comparison of Efficacy of Percutaneous Vertebroplasty versus Percutaneous Kyphoplasty in the Treatment of Osteoporotic Vertebral Asymmetric Compression Fracture.

BACKGROUND: This study aims to compare the clinical efficacy of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral asymmetric compression fracture (OVACF). METHODS: This study retrospectively reviewed the patients who were diagnosed with OVACF between September 2015 and July 2019. Forty-one patients received PVP surgery (group A), and 44 patients received PKP surgery (group B). The visual analog scale, Oswestry Disability Index, scoliosis angle (SA), height of long side, height of short side (HS), and lateral height difference (LHD) before operation and 3 days and 1 year after operation were compared between both groups. The operation time, fluoroscopic time, hospital stay, cement volume, and complications were also compared between both groups. RESULTS: The visual analog scale and Oswestry Disability Index differed significantly between the groups 1 year after operation (P < 0.05). Compared with the preoperative results, there were significant differences in SA, height of long side, HS, and LHD 3 days and 1 year after operation (P < 0.05). Compared with group A, group B showed significantly better in SA, HS, and LHD in group B 3 days and 1 year after operation (P < 0.05). More patients in group A suffered cement leakage and scoliosis than group B after operation (P < 0.05). CONCLUSIONS: In our study, PVP and PKP are both effective in the treatment of OVACF, but PKP surgery had better long-term clinical efficacy.

Comparison of 3-level anterior cervical discectomy and fusion and open-door laminoplasty in cervical sagittal balance: A retrospective study.

Objective: To compare the clinical efficacy and radiological outcomes of 3-level anterior cervical discectomy and fusion (ACDF) and open-door laminoplasty (LP). Methods: A total of 74 patients from January 2017 to January 2020 were enrolled in this retrospective study. There were two groups. Group A (30 cases) received 3-level ACDF, while Group B (44 cases) received open-door LP. Clinical evaluation included perioperative parameters, Neck Disability Index (NDI), and Japanese Orthopaedic Association (JOA) scores. Radiological evaluation included cervical curve depth (CCD), C2-7 angle, C2-7 sagittal vertical axis (cSVA), C7 slope (C7S), and T1 slope (T1S). Results: Perioperative parameters such as blood loss, drainage volume after surgery, and hospital stay of patients in Group A were significantly less than those in Group B (P < .001). NDI scores decreased and JOA scores increased significantly after surgery in both groups (P < .05). There was a significant difference in both scores postoperatively and at 1 month after surgery between the two groups (P < .05). CCD and C2-7 angle of Group A increased significantly postoperatively at 1 month after surgery and at final follow-up (FFU) (P < .05). There was a significant difference in CCD and the C2-7 angle between the two groups postoperatively at 1 month after surgery and at FFU (P < .05). T1S increased significantly in Group A postoperatively and at 1 month after surgery (P < .05). Conclusion: 3-level ACDF and open-door LP achieved favorable clinical outcomes and ACDF benefited patients in the early stage of rehabilitation. Compared with open-door LP, 3-level ACDF had advantages of reconstructing cervical lordosis with increased CCD and C2-7 angle.

Kyphoplasty for thoracic and lumbar fractures with an intravertebral vacuum phenomenon in ankylosing spondylitis patients.

Background: Intravertebral vacuum phenomenon (IVP) is a special sign after vertebral fractures, which is common in patients with ankylosing spondylitis (AS) and may indicate pseudarthrosis and bone nonunion that lead to spinal instability. The objective of this study is to evaluate the efficacy and safety of kyphoplasty (KP) in treating such types of vertebral fractures with AS. Methods: Sixteen patients with AS suffering from thoracic or lumbar fractures with IVP received KP from 2015 to 2020 and were monitored for more than 1 year. The visual analog scale (VAS) score was used to evaluate back pain relief. The Oswestry Disability Index (ODI) questionnaire was used to assess the improvement of the patients' living quality. The anterior and middle vertebral height restoration ratio (AVH, MVH) and the kyphotic angle (KA) were used to evaluate the radiographic results. Results: The mean follow-up period was 20.8 months (12-28 months). The VAS and ODI significantly reduced at 3 days, 3 months after surgery, and at the last follow-up compared with the preoperative outcomes (p < 0.05). The AVH and MVH were significantly increased compared with the preoperative outcomes (p < 0.05). There was a significant correction in the KA between pre- and postoperative assessments (p < 0.05). Asymptomatic intradiscal polymethylmethacrylate (PMMA) cement leakage was found in two patients. Conclusions: For thoracic or lumbar fractures with IVP in AS patients, KP may be safe and effective, which achieves pain relief and satisfying functional improvement, restores the anterior and middle height, and corrects the kyphotic angle of the fractured vertebra.

Influence of Different Surgical Timing after Percutaneous Kyphoplasty for Osteoporotic Vertebral Compression Fractures: A Retrospective Study.

Background: A large number of people suffer from osteoporotic vertebral compression fractures (OVCFs) worldwide. Percutaneous kyphoplasty (PKP), considered a minimally invasive surgery, has been widely used to treat OVCFs and achieves satisfactory outcomes. However, the surgical timing of PKP is still under discussion. Methods: A total of 149 patients were enrolled in the study and were divided into 3 groups according to different surgical timing. Group A (n = 52) included patients who required emergency surgery. Group B (n = 50) included patients who required surgery around a week after injury. Group C (n = 47) included patients who required surgery a month or more after injury. Characteristics of patients and radiological images were recorded. The Visual Analog Scale (VAS) scores and the Oswestry Disability Index (ODI) scores were analyzed before, 1 day, 1 month, and 6 months after surgery. In addition, compression rates of anterior vertebral height (AVH) were calculated and the kyphosis Cobb angle was measured before and after surgery. Results: There was a significant difference in the VAS and ODI scores between the three groups at 1 day, 1 month, and 6 months after PKP. The VAS and ODI scores of Group C were higher than those of Groups A and B. The AVH compression rates of Group C were significantly higher than those of Groups A and B postoperatively 1 day, 1 month, and 6 months. The kyphosis Cobb angles in Group C was significantly larger than those in Groups A and B at 1 day and 1 month after PKP. Conclusions: Emergency PKP showed more advantages in both clinical and radiological outcomes. We recommend early PKP for the treatment of OVCFs.

Effects of distribution of bone cement on clinical efficacy and secondary fracture after percutaneous kyphoplasty for osteoporotic vertebral compression fractures.

Objective: To investigate the effect of bilateral bone cement distribution on the clinical efficacy of percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fracture (OVCF). Methods: According to strict inclusion and exclusion criteria, 109 cases of OVCF patients treated with bipedicular PKP were included in this study from August 2018 to July 2020. According to the distribution morphology of bilateral bone cement in vertebral body, patients were divided into 3 groups, including Group A (n = 44): bilateral diffuse type; Group B (n = 31): bilateral dense type; Group C (n = 34): mixed type. To assess the clinical and radiographic efficacy of the surgery, the visual analogue scale (VAS) score, Oswestry disability index (ODI) score, anterior vertebral height (AVH), anterior vertebral height ratio (AVHR) and local kyphotic angle (LKA) were recorded at preoperatively, 2 days after surgery and 1 year after surgery. Results: Compared with the preoperative recorded value, the VAS score, ODI score, AVH, AVHR and LKA of the three groups were significantly improved at 2 days after surgery and 1 year after surgery (p < 0.05). At 1 year after surgery, the VAS score of Group A was better than that of groups B and C (p < 0.05), and there were significantly differences in ODI score, AVH, and LKA between Group A and Group B (p < 0.05). Compared with other bone cement distribution patterns, the incidence of recompression in bilateral diffuse bone cement distribution pattern was lower (p < 0.05). Conclusion: In the mid-term follow-up of patients undergoing bipedicular PKP, diffuse and symmetrical distribution of bone cement can obtain better clinical improvement and lower the incidence of secondary compression.