Safranal inhibits estrogen-deficiency osteoporosis by targeting Sirt1 to interfere with NF-κB acetylation.

BACKGROUND: Osteoporosis is a prevalent bone metabolic disease in menopause, and long-term medication is accompanied by serious side effects. Estrogen deficiency-mediated hyperactivated osteoclasts is the initiating factor for bone loss, which is regulated by nuclear factor-κB (NF-κB) signaling. Safranal (Saf) is a monoterpene aldehyde produced from Saffron (Crocus sativus L.) and possesses multiple biological properties, particularly the anti-inflammatory property. However, Saf's role in osteoporosis remains unknown. PURPOSE: This study aims to validate the role of Saf in osteoporosis and explore the potential mechanism. STUDY DESIGN: The RANKL-exposed mouse BMM (bone marrow monocytes) and the castration-mediated osteoporosis model were applied to explore the effect and mechanism of Saf in vitro and in vivo. METHOD: The effect of Saf on osteoclast formation and function were assessed by TRAcP staining, bone-resorptive experiment, qPCR, immunoblotting and immunofluorescence, etc. Micro-CT, HE, TRAcP and immunohistochemical staining were performed to estimate the effects of Saf administration on OVX-mediated osteoporosis in mice at imaging and histological levels. RESULTS: Saf concentration-dependently inhibited RANKL-mediated osteoclast differentiation without affecting cellular viability. Meanwhile, Saf-mediated anti-osteolytic capacity and Sirt1 upregulation were also found in ovariectomized mice. Mechanistically, Saf interfered with NF-κB signaling by activating Sirt1 to increase p65 deacetylation and inactivating IKK to decrease IκBα degradation. CONCLUSION: Our results support the potential application of Saf as a therapeutic agent for osteoporosis.

Gamma-oryzanol alleviates intervertebral disc degeneration development by intercepting the IL-1ß/NLRP3 inflammasome positive cycle.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a highly prevalent musculoskeletal disorder characterized by a local inflammatory response associated with the IL-1ß/NLRP3 inflammasome positive feedback loop. Rice bran-derived gamma-oryzanol (Ory) as a sterol ferulate has attracted much attention due to its powerful anti-inflammatory, hypoglycemic and hypolipidemic health effects. As a clinical pharmaceutical for autonomic disorders, Ory's role in musculoskeletal degenerative disease remains unknown. PURPOSE: This study aims to validate the role of Ory in IVDD and explore the potential mechanism. STUDY DESIGN: Establishing the in vitro and in vivo IVDD models to detect the protective effect and molecular mechanism of Ory. METHOD: The anti-ECM degradation, antioxidant and anti-NLRP3 inflammasome activation effects of Ory on IL-1ß-stimulated nucleus pulposus (NP) cells were assessed by immunoblotting and immunofluorescence, etc. MRI, S-O staining and immunohistochemistry were performed to estimate the effects of Ory administration on acupuncture-mediated IVDD in rats at imaging and histological levels. RESULTS: Ory treatment inhibited IL-1ß-mediated ECM degradation, oxidative stress and NLRP3 inflammasome activation in NP cells. By interfering with NF-κB signaling and ROS overproduction, Ory interrupted IL-1ß/NLRP3-inflammasome positive cycle. In vivo experiments showed that Ory delayed acupuncture-mediated IVDD development. CONCLUSION: Our results support the potential application of Ory as a therapeutic compound for IVDD.

Comparison of the effects of general and local anesthesia in lumbar interlaminar endoscopic surgery.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) with an interlaminar approach is a technique used to treat lumbar disc hernia. It has not yet been established whether general or local anesthesia (LA) is preferable for lumbar interlaminar endoscopic surgery. METHODS: Between October, 2012 and June, 2016, 60 patients were recruited and randomly divided into 2 groups: the general anesthesia (GA) group and the LA group. The patients' basic clinical data, intraoperative patient experience, Oswestry disability index (ODI), visual analog scale (VAS) score, and the postoperative patient satisfaction rate were assessed. RESULTS: Statistically significant differences were found between the two groups in operative time and length of hospital stay. There were no significant differences in postoperative ODI or VAS scores between the two groups during follow-up at 3, 6, and 12 months. One patient in the GA group sustained a nerve root injury intraoperatively. Two patients in the LA group suffered adverse reactions, as did six patients in the GA group. However, 50% of the patients expressed fear about undergoing the surgery with LA, while all patients felt they could undergo the same surgery with GA. CONCLUSIONS: General and LA are both suitable for use in lumbar interlaminar endoscopic surgery. However, GA makes a positive intraoperative surgical experience more likely for the patient.

Minimally invasive surgery for degenerative spondylolisthesis: transforaminal or oblique lumbar interbody fusion.

Aim: To compare the outcomes of minimally invasive surgery (MIS) for degenerative spondylolisthesis transforaminal lumbar interbody fusion (TLIF) and oblique lumbar interbody fusion (OLIF). Materials & methods: The clinical and surgical characteristics and outcomes of 38 patients with MIS-OLIF and 55 with MIS-TLIF were retrospectively evaluated. Results: Procedures and hospital stay were shorter and blood loss was less, with MIS-OLIF than with MIS-OLIF. The clinical and radiographic outcomes were similar. Postoperative changes in disk height and foraminal dimension were greater and patient satisfaction was better with MIS-OLIF than with MIS-TLIF. Conclusion: The clinical findings associated with the two procedures were similar; but patients preferred MIS-OLIF, which is less invasive, to MIS-TLIF. Clinical trial registration number: ChiCTR1800019443.

Design and Application of Individualized, 3-Dimensional-Printed Navigation Template for Placing Cortical Bone Trajectory Screws in Middle-Upper Thoracic Spine: Cadaver Research Study.

OBJECTIVE: To evaluate the safety and accuracy of use of a 3-dimensional printed navigation template in the placement of a cortical bone trajectory (CBT) screw in the middle-upper thoracic spine. METHODS: Ten human cadavers were included in the study. Sixty CBT screws were placed on 1 side, using the free-hand technique, and 60 CBT screws were placed on the other side, using the navigation template that was designed and printed using data from 10 cadavers. The safety and accuracy of use of the CBT screws were directly evaluated by radiography and computed tomography. RESULTS: Computed tomography revealed that 2 and 3 of 60 screws, placed using the navigation template, were broken in the medial or lateral areas and in the superior or inferior pedicle wall, respectively. Furthermore, 8 screws were broken in the medial or lateral areas and 11 screws were broken in the superior or inferior pedicle wall when the free-hand technique was used. Radiography revealed that 3 screws in zone I, 55 screws in zone II, and 2 screws in zone III were placed using the navigation template. Furthermore, 7 screws in zone I, 45 screws in zone II, and 8 screws in zone III were placed using the free-hand technique. CONCLUSIONS: In this cadaver study, insertion of the CBT screws in the middle-upper thoracic spine with the assistance of the navigation template was safe and convenient.

Optimal medial transforaminal lumbar interbody fusion approach with five extensive options: A simulated study on three-dimensional digital reconstructed images.

OBJECTIVE: The objective of this study is to use 3D digital lumbar models to investigate and simulate the optimal posterior operative approach for safe decompression and insertion of an interbody cage. METHODS: Thirty lumbar spine (L3-S1) computed tomography data are collected for 3D reconstruction. We cut medial half part of the superior facet and define the distance between the margin of the operative side of the spinous process and the medial margin of the cut superior facet as "medial distance (MD)". Then, we cut the total superior facet and define the distance between the margin of the operative side of the spinous process and the lateral side of the junction of the pedicle and the vertebral body as "extend distance (ED)". The feasible insertion of the current standard width size (10 mm and 12 mm) interbody cages was assessed by the two aforementioned MD and ED approaches. Besides the ED, we also simulate four other extensive options of lateral upper, lateral lower, vertical upper and lower and transmedian contralateral decompression on 3D digital lumbar model. RESULTS: The MD increased from 13.48 ± 1.28 mm at L3/4 to 18.05 ± 1.43 mm at L5/S1, and the ED increased from 16.64 ± 1.34 mm at L3/4 to 21.12 ± 1.62 mm at L5/S1. To insert a 10-mm-wide cage, 16.7% (left) and 13.3% (right) of MD for L3/4 is not enough, 60.0% (left) and 46.7% (right) of MD for L3/4 is subsafe, 13.3% (left) and 16.7% (right) of MD for L4/5 is subsafe and all others are safe. To insert a 12-mm-wide cage, 76.7% (left) and 60.0% (right) of MD for L3/4 is not enough, 20.0% (left) and 30.0% (right) of MD for L3/4 is subsafe, 13.3%% (left) and 16.7% (right) of MD for L4/5 is not enough, 63.3% (left) and 56.7% (right) of MD for L4/5 is subsafe and 6.7% (left) and 10.0% (right) of MD for L5/S1 is subsafe, whereas 33.3%% (left) and 30.0% (right) of ED for L3/4 is subsafe, 3.3% (left) and 3.3% (right) of ED for L4/5 is subsafe and all others are safe. Besides the ED, on 3D models, four other extensive options could be simulated too and may need to be performed for different special individuals. CONCLUSION: Our 3D digital image study provides a feasible optimal medial transforaminal lumbar interbody fusion approach with five extensive options on lower lumbar region. It can provide safe lumbar decompression and interbody fusion in most population. In addition, surgeons can choose the different extensive options for special individual conditions. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Transforminal lumbar interbody fusion is very common used for lumbar degenerative diseases. The optimal medial transforminal lumbar interbody fusion with five options provide a safe and precise approach for surgeons in treatment of lumbar degenerative diseases.

Risk Factor of Failed Reduction of Posterior Ligamentatoxis Reduction Instrumentation in Managing Thoracolumbar Burst Fractures: A Retrospective Study.

OBJECTIVE: To determine whether radiographic findings associated with thoracolumbar burst fractures could be predictors of failure of short-segment posterior instrumentation with insertion screw at the fracture level (SSPI-f). METHODS: Seventy-five patients with thoracolumbar burst fracture surgically treated by SSPI-f were enrolled in the study and divided into 2 groups: a reduction group (n = 46) and a failed-reduction group (n = 29). Radiographic data including local kyphosis, Cobb angle, anterior vertebral height, posterior vertebral height (PVH), anterior/posterior vertebral height ratio, interpedicle distance (IPD), bony compress area, bony fracture area, and compress-fracture area of the fractured vertebra and clinical data including age and neurologic function were also analyzed. t test, Pearson χ2 test, and binary logistic regression were performed to compare the values. RESULTS: The PVH in the failed-reduction group was smaller than that of the reduction group (83.5% ± 7.2% and 89.1% ± 5.4%, respectively) (P = 0.001). The IPD differed between the reduction and failed-reduction group (18.0% ± 4.1% and 25.8% ± 7.1%, respectively) (P < 0.001). There was a statistical difference between the 2 groups in delayed time before surgery (P = 0.008). There was a significant difference of bony fracture area and compress-fracture area of the fractured vertebra between the failed-reduction and reduction group (both P < 0.001). Binary logistic regression showed that IPD was a risk factor of reduction failure of SSPI-f (P = 0.001). CONCLUSIONS: These results showed that increased IPD was a risk factor of failed-reduction of SSPI-f in managing thoracolumbar burst fractures, particularly for patients with neurologic deficit, whereas local kyphosis, Cobb angle, anterior vertebral height, PVH, anterior/posterior vertebral height ratio, bony compress area, bony fracture area, and compress-fracture area of the fractured vertebra were not.

A Novel Technique for Cervical Facet Joint Hyperplasia-Spondylotic Radiculopathy by Laminar and Lateral Mass Screw Cofixations.

OBJECTIVE: We sought to describe the novel technique and report the outcomes of cervical spondylotic radiculopathy caused by facet joint hyperplasia treated with minimally invasive surgery by laminar and lateral mass screw cofixations. METHOD: In this retrospective study, patients with spondylotic radiculopathy caused by facet joint hyperplasia underwent this technique in our unit between January 2010 and June 2015. Hospital charts, magnetic resonance imaging studies, and follow-up records for all the patients were reviewed. Outcomes were assessed on the basis of neurologic status, magnetic resonance imaging, and visual analog scale for neck and radicular pain and by the short form-36 health survey questionnaire. RESULTS: Thirteen men and 5 women, aged 47-73 years (mean, 61.8 years), were included in this study. The follow-up time ranged from 19-50 months (mean, 32.4 months). The mean visual analog scale scores for radicular pain and neck pain, as well as the scores for all 8 domains of the short form-36 health survey questionnaire, showed significant improvements (P < 0.05). Cervical lordosis showed bending, whereas the height of the targeted disk segment showed no change (P > 0.05). Complications included 2 cases of neck pain that lasted for 3 months. CONCLUSION: Minimally invasive surgery by lamina and lateral mass screw cofixation is safe and effective for the treatment of cervical spondylotic radiculopathy caused by facet joint hyperplasia. In addition to sufficient decompression, this technique provides relative stability to the cervical spine.

An ultrastructural study of chondroptosis: programmed cell death in degenerative intervertebral discs in vivo.

Apoptosis has been regarded to mediate intervertebral disc degeneration (IDD); however, the basic question of how the apoptotic bodies are cleared in the avascular intervertebral disc without phagocytes, which are essential to apoptosis, remains to be elucidated. Our goals were to investigate the ultrastructure of nucleus pulposus (NP) cells undergoing chondroptosis, a variant of apoptotic cell death, in a rabbit annular needle-puncture model of IDD. Experimental IDD was induced by puncturing discs with a 16-G needle in New Zealand rabbits. At 4 and 12 weeks after puncture, progressive degeneration was demonstrated by X-ray, magnetic resonance imaging and histological staining. TUNEL staining suggested a significant increase in the apoptosis index in the degenerated NP. However, the percentage of apoptotic cells with the classic ultrastructure morphology was much less than that with chondroptotic ultrastructure morphology under transmission electron microscopy (TEM). The chondroptotic cells from the early to late stage were visualized under TEM. In addition, the percentage of chondroptotic cells was significantly enhanced in the degenerated NP. Furthermore, 'paralyzed' cells were found in the herniated tissue. Western blotting revealed an increase in caspase3 expression in the degenerated NP. The expression of the Golgi protein (58K) was increased by the fourth week after puncture but decreased later. These findings indicate that chondroptosis is a major type of programmed cell death in the degenerated rabbit NP that may be related to the progressive development of IDD.

Pterostilbene inhibits inflammation and ROS production in chondrocytes by activating Nrf2 pathway.

Pterostilbene has been reported as a potential drug to inhibit oxidative stress and inflammation. However, the effect of pterostilbene on chondrocytes and osteoarthritis remains to be elucidated. We sought to investigate whether pterostilbene could protect chondrocytes from inflammation and ROS production through factor erythroid 2-related factor 2 (Nrf2) activation. The pterostilbene toxicity on chondrocytes collected from cartilages of Sprague-Dawley rats was assessed by CCK-8 test. Immunofluorescence and Western blotting explored the nuclear translocation of Nrf2. Nrf2 expression was silenced by siRNA to evaluate the involvement of Nrf2 in the effect of pterostilbene on chondrocytes. Finally, osteoarthritis model was established by the transection of anterior cruciate ligament and partial medial meniscectomy in rats, and then these rats received pterostilbene 30 mg/kg, daily, p.o. for 8 weeks. Histology and immunohistochemistry were used to assess histopathological change and Nrf2 expression in cartilage. Nuclear translocation of Nrf2 was stimulated by pterostilbene without cellular toxicity. Pterostilbene inhibited the level of COX-2, iNOS, PGE2, and NO, as well as the mitochondrial and total intracellular ROS production induced by IL-1ß in chondrocytes, partially reversed by the Nrf2 silencing. Pterostilbene prevented cartilage degeneration and promoted the nuclear translocation of Nrf2 in cartilage. These results suggest that pterostilbene could inhibit the IL-1ß-induced inflammation and ROS production in chondrocytes by stimulating the nuclear translocation of Nrf2.

Long fusion correction of degenerative adult spinal deformity and the selection of the upper or lower thoracic region as the site of proximal instrumentation: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to compare outcomes when the upper and lower thoracic regions were used as the site of proximal instrumentation to treat adult spinal deformity. METHODS: MEDLINE, Embase and Cochrane library searches were performed to identify studies that compared outcome measures when the upper and lower thoracic vertebrae (UTV and LTV, respectively) were used as the site of proximal instrumentation. The weighted mean difference (WMD) was calculated for continuous outcomes, and the relative risk (RR) was calculated for dichotomous outcomes. RESULTS: Seven articles (n=554 patients) met the final inclusion criteria, and we compared the outcome measures of a long fusion extending to the upper and lower thoracic regions. The pooled analysis revealed that extending fixation into the upper thoracic region decreased the risk of proximal junctional kyphosis (PJK) revision surgery (RR: 0.36, 95% CI 0.14 to 0.90, p<0.05). The operation time (WMD: 0.93, 95% CI 0.48 to 1.39, p<0.05) and estimated blood loss (WMD: 0.59, 95% CI 0.33 to 0.85, p<0.05) were significantly greater in the UTV group than in the LTV group. No significant differences were found in the Scoliosis Research Society pain, self-image, function, mental health, subtotal, satisfaction or total scores; the total number of complications or the total number of revision surgeries. CONCLUSIONS: Long posterior fixation extending into the upper thoracic region reduces the incidence of revision surgery related to PJK; however, it increased the operative level resulting in a longer operative time and greater estimated blood loss. This initial analysis indicates that extending fixation to the upper thoracic region is appropriate for patients who are likely to develop PJK following initial scoliosis correction.

Cortical bone trajectory screws for the middle-upper thorax: An anatomico-radiological study.

To quantify the reference data concerning the morphometrics of the middle-upper thorax to guide the placement of cortical bone trajectory (CBT) screws.Eighty patients were studied on computed tomography (CT) scans. The reference anatomical parameters were measured. Next, 20 cadaveric specimens were implanted with CBT screws based on CT measurements. These specimens were then judged directly from the cadaveric vertebrae and X-ray.The maximum length of the trajectory, the maximum diameter, and the cephaled angle exhibited a slight increase trend while the transverse and sagittal angles of the pedicle tended to decrease from T3 to T8. We recommend that the width of CBT screw for middle-upper thoracic spine is 5.0 mm, the length is 25 to 35 mm. The cadaveric anatomical study revealed that 5/240 screws penetrated in the medial or lateral areas, 5/240 screws penetrated in the superior or inferior pedicle wall, and 2/240 screws did not fit into the superior endplate of the pedicle.The CBT screws are safe for the middle-upper thorax. This study provides a theoretical basis for clinical surgery.

Risk factors of kyphosis recurrence after implant removal in thoracolumbar burst fractures following posterior short-segment fixation.

PURPOSE: Our aim was to evaluate the results of short-segment pedicle instrumentation with screw insertion in the fracture level and find factors predicting kyphosis recurrence in thoracolumbar burst fractures. METHODS: We retrospectively analysed 122 patients with thoracolumbar burst fracture who were divided into two groups: kyphosis recurrence and no kyphosis recurrence. Pre-operative radiographic data comprising Cobb angle (CA), regional angle, anterior vertebra height (AVH), upper intervertebral angle, vertebral wedge angle (VWA), pre-anteroposterior A/P approach, superior endplate fracture, load-sharing classification (LSC) score and clinical data including age, visual analogue scale (VAS) score, thoracolumbar injury classification and severity score were compared between groups. T test, Pearson's chi-square and multivariate logistic regression were calculated for variables. RESULTS: CA, VWA and AVH were significantly corrected after surgery. CA changed from 23.7 to 3.0 (p <0.001), VWA from 38.7 to 9.6 (p <0.001) and AVH from 48.8 % to 91.2 % (p <0.001). These parameters were well maintained during the follow-up period with a mild, tolerant loss of correction. Neurological function and pain were significantly improved without deterioration. Age, pre-A/P and pre-AVH < 50 % influenced kyphosis recurrence (p = 0.032, 0.026, 0.011, respectively). CONCLUSIONS: Short-segment pedicle instrumentation including the fractured vertebra was effective in treating thoracolumbar burst fractures. The loss of correction at follow-up after implant removal was associated with age, A/P ratio and anterior vertebral height < 50 %.

Comparison of Cervical Spine Anatomy in Calves, Pigs and Humans.

BACKGROUND CONTEXT: Animals are commonly used to model the human spine for in vitro and in vivo experiments. Many studies have investigated similarities and differences between animals and humans in the lumbar and thoracic vertebrae. However, a quantitative anatomic comparison of calf, pig, and human cervical spines has not been reported. PURPOSE: To compare fundamental structural similarities and differences in vertebral bodies from the cervical spines of commonly used experimental animal models and humans. STUDY DESIGN: Anatomical morphometric analysis was performed on cervical vertebra specimens harvested from humans and two common large animals (i.e., calves and pigs). METHODS: Multiple morphometric parameters were directly measured from cervical spine specimens of twelve pigs, twelve calves and twelve human adult cadavers. The following anatomical parameters were measured: vertebral body width (VBW), vertebral body depth (VBD), vertebral body height (VBH), spinal canal width (SCW), spinal canal depth (SCD), pedicle width (PW), pedicle depth (PD), pedicle inclination (PI), dens width (DW), dens depth (DD), total vertebral width (TVW), and total vertebral depth (TVD). RESULTS: The atlantoaxial (C1-2) joint in pigs is similar to that in humans and could serve as a human substitute. The pig cervical spine is highly similar to the human cervical spine, except for two large transverse processes in the anterior regions ofC4-C6. The width and depth of the calf odontoid process were larger than those in humans. VBW and VBD of calf cervical vertebrae were larger than those in humans, but the spinal canal was smaller. Calf C7 was relatively similar to human C7, thus, it may be a good substitute. CONCLUSION: Pig cervical vertebrae were more suitable human substitutions than calf cervical vertebrae, especially with respect to C1, C2, and C7. The biomechanical properties of nerve vascular anatomy and various segment functions in pig and calf cervical vertebrae must be considered when selecting an animal model for research on the spine.

Anatomy of large animal spines and its comparison to the human spine: a systematic review.

Animal models have been commonly used for in vivo and in vitro spinal research. However, the extent to which animal models resemble the human spine has not been well known. We conducted a systematic review to compare the morphometric features of vertebrae between human and animal species, so as to give some suggestions on how to choose an appropriate animal model in spine research. A literature search of all English language peer-reviewed publications was conducted using PubMed, OVID, Springer and Elsevier (Science Direct) for the years 1980-2008. Two reviewers extracted data on the anatomy of large animal spines from the identified articles. Each anatomical study of animals had to include at least three vertebral levels. The anatomical data from all animal studies were compared with the existing data of the human spine in the literature. Of the papers retrieved, seven were included in the review. The animals in the studies involved baboon, sheep, porcine, calf and deer. Distinct anatomical differences of vertebrae were found between the human and each large animal spine. In cervical region, spines of the baboon and human are more similar as compared to other animals. In thoracic and lumbar regions, the mean pedicle height of all animals was greater than the human pedicles. There was similar mean pedicle width between animal and the human specimens, except in thoracic segments of sheep. The human spinal canal was wider and deeper in the anteroposterior plane than any of the animals. The mean human vertebral body width and depth were greater than that of the animals except in upper thoracic segments of the deer. However, the mean vertebral body height was lower than that of all animals. This paper provides a comprehensive review to compare vertebrae geometries of experimental animal models to the human vertebrae, and will help for choosing animal model in vivo and in vitro spine research. When the animal selected for spine research, the structural similarities and differences found in the animal studies must be kept in mind.