The biofilm-induced “relatively immune-compromised zone” creates an immunosuppressive microenvironment that is a significant contributor to refractory infections in orthopedic endophytes. Consequently, the manipulation of immune cells to co-inhibit or co-activate signaling represents a crucial strategy for the management of biofilm. This study reports the incorporation of Mn2+ into mesoporous dopamine nanoparticles (Mnp) containing the stimulator of interferon genes (STING) pathway activator cGAMP (Mncp), and outer wrapping by M1-like macrophage cell membrane (m-Mncp). The cell membrane enhances the material's targeting ability for biofilm, allowing it to accumulate locally at the infectious focus. Furthermore, m-Mncp mechanically disrupts the biofilm through photothermal therapy and induces antigen exposure through photodynamic therapy-generated reactive oxygen species (ROS). Importantly, the modulation of immunosuppression and immune activation results in the augmentation of antigen-presenting cells (APCs) and the commencement of antigen presentation, thereby inducing biofilm-specific humoral immunity and memory responses. Additionally, this approach effectively suppresses the activation of myeloid-derived suppressor cells (MDSCs) while simultaneously boosting the activity of T cells. Our study showcases the efficacy of utilizing m-Mncp immunotherapy in conjunction with photothermal and photodynamic therapy to effectively mitigate residual and recurrent infections following the extraction of infected implants. As such, this research presents a viable alternative to traditional antibiotic treatments for biofilm that are challenging to manage.

Regenerating bone defects in diabetic rats presents a significant challenge due to the detrimental effects of reactive oxygen species and impaired autophagy on bone healing. To address these issues, a metformin-modified biomimetic silicified collagen scaffold is developed utilizing the principles of biomimetic silicification. In vitro and in vivo experiments demonstrated that the scaffold enhanced bone tissue regeneration within the diabetic microenvironment through the release of dual bio-factors. Further analysis reveals a potential therapeutic mechanism whereby these dual bio-factors synergistically promoted osteogenesis in areas of diabetic bone defects by improving mitochondrial autophagy and maintaining redox balance. The present study provides critical insights into the advancement of tissue engineering strategies aimed at bone regeneration in diabetic patients. The study also sheds light on the underlying biological mechanisms.

The incidence of large bone defects caused by traumatic injury is increasing worldwide, and the tissue regeneration process requires a long recovery time due to limited self-healing capability. Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration. Inspired by bioelectricity, electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix, thereby accelerating bone regeneration. With ongoing advances in biomaterials and energy-harvesting techniques, electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue. In this review, we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue. Next, we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering. Finally, we emphasize the significance of simulating the target tissue's electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.

ObjectiveVertebral augmentation techniques are widely used to treat osteoporotic vertebral compression fractures (OVCFs). Superior analgesic effects and shortened bed rest time means patients recover quickly, but prolonged unscheduled hospitalization can increase medical expenses and the risk of bed rest complications. The aim of this study was to investigate the reasons for prolonged hospitalization after vertebral augmentation surgery and to determine the relative risk factors.MethodsA single-center retrospective study was conducted to enroll patients with OVCFs and accepted vertebral augmentation surgery from January 2017 to December 2017. Clinical information was collected from the Hospital Information System (HIS). The criterion of delayed discharge was postoperative hospitalization more than 3 days. Telephone interviews and medical history evaluations were conducted to confirm the exact reason for retention. The risk factors were analyzed by multiple logistic regression.ResultsOverall, 1,442 patients were included, and 191 (13.2%) stayed in the hospital for more than 3 days postoperatively. The reasons for delayed discharge were psychological factors (37.2%), residual pain (32.5%), cardiopulmonary complications (15.7%), nonspecific symptoms (8.4%), incision abnormalities (2.6%), thrombosis (2.1%), and postanesthesia reactions (1.6%). The multiple logistic model was significant; age (OR 1.028; 95% CI 1.009–1.046), preoperative stay (OR 1.192; 95% CI 1.095–1.298), operation type (OR 1.494; 95% CI 1.019–2.189), and the number of surgical segments (OR 2.238; 95% CI 1.512–3.312) showed statistical significance. In contrast, gender (P > 0.1) and chronic comorbidities (P > 0.1) were not predictors in this model.ConclusionOverall, 13.2% of OVCF patients who underwent vertebral augmentation surgery were not discharged within 3 days postoperatively, and several predictors were found. Preoperative communication and comprehensive evaluations are calling for more attention; physicians should adopt an appropriate medical process to enhance rehabilitation in geriatric orthopedics.

OBJECTIVE The objective of this study was to describe and evaluate a new surgical procedure for the correction of coronal imbalance (CI) in adult spinal deformity patients, called the "kickstand rod" technique. METHODS The authors analyzed the records of 24 consecutive patients with pediatric and adult spinal deformity and CI treated between July 2015 and October 2017 with a long-segment fusion and a kickstand rod. For the kickstand rod technique, an iliac screw was placed on the ipsilateral side of the trunk shift and connected proximally through a side-by-side domino link to the thoracolumbar junction; this rod was distracted to promote coronal plane balancing. Distraction occurred with the rod on the contralateral side locked in order to preserve sagittal correction. Radiographic and clinical analyses were conducted to evaluate the outcomes and possible complications of the kickstand rod technique. RESULTS The mean age of the patients was 55 years (range 14-73 years). Eighteen of the 24 patients were female. CI preoperatively was a mean of 63 mm, and the mean measurement at the final follow-up (mean duration 1.4 years) was 47 mm. There were no neurological, vascular, or implant-related complications in any of the patients. One patient developed wound dehiscence that was successfully treated without implant removal, and one developed proximal junctional kyphosis requiring extension of the construct proximally. One patient also returned to the operating room for excision of a spinous process. There were no complaints about screw prominence, kickstand construct failure, or significant worsening of CI after surgery. CONCLUSIONS The kickstand rod technique is safe and effective for the correction of CI in spinal deformity patients. This technique was found to provide marked coronal correction and additional strength to the overall construct without significant adverse consequences.

Pelvic incidence (PI) is assumed to be fixed, yet studies have reported PI changes after long fusions to the pelvis. In a cohort of ASD patients undergoing surgery with S2-alar-iliac (S2AI) screws, we sought to: (1) report the magnitude of PI changes, and (2) evaluate subsequent pelvic parameter changes. A retrospective case series of ASD patients undergoing surgical correction with S2AI screw placement and sagittal cantilever correction maneuvers was conducted. Patients were categorized based on preoperative PI: High-PI (H-PI) (PI ≥ 60°); Normal-PI (N-PI) (60° > PI > 40°); Low-PI (L-PI) (PI ≤ 40°). PI was measured preoperatively and immediately postoperatively. A significant PI change was established a priori at ≥ 6.0. PI, pelvic tilt (PT), lumbar lordosis (LL), and PI-LL mismatch were analyzed. In 68 patients (82.3% female, ages 22–75 years), the average change in PI was 4.6° ± 3.1, and 25 (36.8%) had a PI change ≥ 6.0° with breakdown as follows: H-PI 12 (66.7%) patients, 9 (25.87%) patients, and 4 (33.3%) patients. Of 25 patients with PI changes, 10 (14.7%) had a PI increase and 15 (22.1%) had a PI decrease. Significant improvements were seen in PT, LL, PI-LL mismatch in all patients with a PI change ≥ 6.0°, in addition to both subgroups with an increase or decrease in PI. PI changes of ≥ 6.0° occurred in 36.8% of patients, and H-PI patients most commonly experienced PI changes. Despite PI alterations, pelvic parameters significantly improved postoperatively. These results may be explained by sacroiliac joint laxity, S2AI screw placement, or aggressive sagittal cantilever techniques.

Osteogenic differentiation is great significance for improving the bone regeneration. Present study evaluates the osteogenic ability of lanthanum (La3+) and silicate (SiO44-) substituted hydroxyapatite (MHAP) - polymeric composite coated surface treated titanium (Ti) implant. The bio-ceramic MHAP was synthesized by hydrothermal process with assistance of calcium alginate template. For enhance the hydrophilicity, the polymer poly (vinyl pyrrolidone) (PVP) was included in the composite by ultra-sonication method. The negative zeta potential value -9.97 mV of Ca-alg/ La, Si-HAP was observed after the incorporation of PVP in the matrix. Incorporation of minerals and PVP polymer was confirmed and analyzed by Energy Dispersive X-ray analysis (EDX), Fourier Transform Infra-Red spectroscopy (FT-IR) and Electron Microscopy techniques. A compact coating of the composite with the thickness of 448 nm on Ti surface was achieved by Electrophoretic deposition (EPD) method. The in-vitro MTT assay method and alkaline phosphate ALP activity (94% and 0.94 a.u respectively for the optimized composite) were utilized to determine the cell viability and differentiation on human Bone Marrow-Derived Stem Cells (hBMSCs). The osteogenic ability of bio-composite coated Ti in hBMSCs and in-vivo rat model has strongly suggests the fabricated Ti plate with bio-composite coatings can act as promising biomaterial for orthopedics.

Abstract Background Oligodendrocytes (OLs) death after spinal cord injury (SCI) contributes to demyelination, even leading to a permanent neurological deficit. Besides apoptosis, our previous study demonstrated that OLs underwent receptor-interacting serine-threonine kinase 3(RIP3)/mixed lineage kinase domain-like protein (MLKL)-mediated necroptosis. Considering that necroptosis is always accompanied with pro-inflammatory response and quercetin has long been used as anti-inflammatory agent, in the present study we investigated whether quercetin could inhibit necroptosis of OLs and suppress the M1 macrophages/microglia-mediated immune response after SCI as well as the possible mechanism. Methods In this study, we applied quercetin, an important flavonoid component of various herbs, to treat rats with SCI and rats injected with saline were employed as the control group. Locomotor functional recovery was evaluated using Basso-Beattie-Bresnahan (BBB) scoring and rump-height Index (RHI) assay. In vivo, the necroptosis, apoptosis, and regeneration of OLs were detected by immunohistochemistry, 5′-bromo-2′-deoxyuridine (BrdU) incorporation. The loss of myelin and axons after SCI were evaluated by Luxol fast blue (LFB) staining, immunohistochemistry, and electron microscopic study. The polarization of macrophages/microglia after SCI and the underlying mechanisms were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. In vitro, the ATP and reactive oxygen species (ROS) level examination, propidium iodide (PI) labeling, and Western blotting were used to analyze the necroptosis of cultured OLs, while the signaling pathways-mediated polarization of cultured macrophages/microglia was detected by qRT-PCR and Western blotting. Results We demonstrated that quercetin treatment improved functional recovery in rats after SCI. We then found that quercetin significantly reduced necroptosis of OLs after SCI without influencing apoptosis and regeneration of OLs. Meanwhile, myelin loss and axon loss were also significantly reduced in quercetin-treated rats, as compared to SCI + saline control. Further, we revealed that quercetin could suppress macrophages/microglia polarized to M1 phenotype through inhibition of STAT1 and NF-κB pathway in vivo and in vitro, which contributes to the decreased necroptosis of OLs. Conclusions Quercetin treatment alleviated necroptosis of OLs partially by inhibiting M1 macrophages/microglia polarization after SCI. Our findings suggest that necroptosis of OLs may be a potential therapeutic target for clinical SCI.

The present study was undertaken to explore the therapeutic potential of hydrogen sulfide against bone loss induced by modeled microgravity. Hindlimb suspension (HLS) and rotary wall vessel bioreactor were applied to model microgravity in vivo and in vitro, respectively. Treatment of rats with GYY4137 (a water soluble donor of hydrogen sulfide, 25 mg/kg per day, i.p.) attenuated HLS-induced reduction of bone mineral density in tibiae, and preserved bone structure in tibiae and mechanical strength in femurs. In HLS group, GYY4137 treatment significantly increased levels of osteocalcin in sera. Interestingly, treatment of HLS rats with GYY4137 enhanced osteoblast surface, but had no significant effect on osteoclast surface of proximal tibiae. In MC3T3-E1 cells exposed to modeled microgravity, GYY4137 stimulated transcriptional levels of runt-related transcription factor 2 and enhanced osteoblastic differentiation, as evidenced by increased mRNA expression and activity of alkaline phosphatase. HLS in rats led to enhanced levels of interleukin 6 in sera, skeletal muscle, and tibiae, which could be attenuated by GYY4137 treatment. Our study showed that GYY4137 preserved bone structure in rats exposed to HLS and promoted osteoblastic differentiation in MC3T3-E1 cells under modeled microgravity.

BACKGROUND:Cervical spinal cord injury (SCI) is a devastating condition with very few treatment options. It remains unclear if early surgery correlated with conversion of American Spinal Injury Association Impairment Scale (AIS) grade A injuries to higher grades.OBJECTIVE:To determine the optimal time to surgery after cervical SCI through retrospective analysis.METHODS:We collected data from 48 patients with cervical SCI. Based on the time from Emergency Department (ED) presentation to surgical decompression, we grouped patients into ultra-early (decompression within 12 h of presentation), early (within 12-24 h), and late groups (>24 h). We compared the improvement in AIS grade from admission to discharge, controlling for confounding factors such as AIS grade on admission, injury severity, and age. The mean time from injury to ED for this group of patients was 17 min.RESULTS:Patients who received surgery within 12 h after presentation had a relative improvement in AIS grade from admission to discharge: the ultra-early group improved on average 1.3. AIS grades compared to 0.5 in the early group (P = .02). In addition, 88.8% of patients with an AIS grade A converted to a higher grade (AIS B or better) in the ultra-early group, compared to 38.4% in the early and late groups (P = .054).CONCLUSION:These data suggest that surgical decompression after SCI that takes place within 12 h may lead to a relative improved neurological recovery compared to surgery that takes place after 12 h.

To investigate the clinical efficacy of surgical treatment for thoracic spinal tuberculosis with kyphosis deformity via posterolateral debridement, fusion, posterior instrumentation and local continuous chemotherapy. A total of 25 patients with thoracic tuberculosis received surgery by posterolateral decompression, fusion, posterior instrumentation, and postural drainage with local continuous chemotherapy between June 2009 and October 2011. The clinical outcomes was evaluated using statistical analysis about deformity correction, bone fusion, neurologic status, and the visual analog score (VAS) and erythrocyte sedimentation rate (ESR). All of 25 patients were followed up for 39.0 +/- 10.7 months (range, 24-60 months) postoperatively. There was no recurrence of tuberculosis, breakage and looseness of internal fixation. Bony fusion was achieved in all cases with 6.7 +/- 1.9 months. The values of ESR recovered to normal within 6 months postoperatively. All patients with neurological deficit had significant improvement at the final follow-up. The average preoperative Cobb angles were significantly decreased to 12.2 +/- 2.9 (range, 8-17) postoperatively, and at final follow-up were 12.9 +/- 2.7. Our results showed that single-stage posterolateral debridement fusion, posterior instrumentation and local continuous chemotherapy can be expected to yield satisfactory clinical and radiographic outcomes in patients with thoracic spinal tuberculosis.

This retrospective cohort study aimed to evaluate the clinical outcomes of posterior surgical treatment of ankylosing spondylitis (AS) with spinal tuberculosis (STB). This was a retrospective study including 12 patients treated between January 2004 and April 2014 for AS with STB at our department. All patients underwent 1-stage posterior internal fixation, debridement, and bone fusion. The patients were evaluated based on the American Spinal Injury Association (ASIA), kyphotic Cobb angle, and the visual analog score (VAS). All patients were followed up for an average of 42.7 +/- 13.2 months after surgery and bone fusion was achieved 6.8 +/- 1.3 months. According to ASIA, 2 cases were rated as Grade D, 10 cases were Grade E at last follow-up. The average preoperative Cobb angle was 26.7 +/- 7.6 degrees (range 15-36) and the average postoperative Cobb angle was 7.8 +/- 1.2 degrees (range 6-9). The mean latest follow-up Cobb angle was 9.1 +/- 1.0 degrees (range 6-10). Compared with the average preoperative Cobb angle, there were significant differences regarding the kyphotic Cobb angle measured postoperatively and at final follow-up (P<.05). The VAS significantly was considerably improved between the preoperative and the last clinical visits. These positive results demonstrate that 1-stage surgical treatment for AS with STB by posterior debridement, fusion, and instrumentation can be an effective and feasible treatment method for this specific condition. It should be noted that it is necessary to carry out antiosteoporosis treatment and perform long-segmental instrumentation in order to obtain spinal stabilization.

The study aims to evaluate the clinical efficacy of bilateral costotransverse debridement, transpedicular fixation, fusion, and local continuous chemotherapy in 20 patients of contiguous multisegmental thoracic spinal tuberculosis (CMTSTB). We analyzed 20 patients with contiguous thoracic spinal tuberculosis (TB) who underwent surgery via bilateral costotransverse debridement, fusion, posterior instrumentation, and postural drainage with local continuous chemotherapy. The clinical outcomes were evaluated in terms of kyphotic angle, bone fusion, neurologic status, erythrocyte sedimentation rate (ESR), and intraoperative and postoperative complications. All of the patients (8M/12F), averaged 45.8 +/- 15.6 years old. The mean duration of postoperative follow-up was 30.7 +/- 4.0 months. There was no recurrent TB infection. The values of ESR returned to normal levels at final follow-up. All patients got bony fusion within 8.1 +/- 2.3 months after surgery. The average preoperative Cobb angle was 39.9 degrees +/- 8.6 degrees, correcting to 9.8 degrees +/- 2.3 degrees postoperatively and 10.8 degrees +/- 2.3 degrees at the last follow-up. All patients with neurological deficit had dramatic improvement at the final follow-up. Our results showed that bilateral costotransverse surgery and local continuous chemotherapy are feasible and effective procedures in the treatment of CMTSTB. The approach can provide radical debridement, rebuild spinal stability, and cure TB.

OBJECTIVES:To compare the efficacy and safety of novel percutaneous minimally invasive pedicle screw fixation and traditional open surgery for thoracolumbar fractures without neurological deficit. METHODS:Sixty adult patients with single thoracolumbar fracture between June 2014 and June 2016 were recruited in this study, randomly divided into open fixation group (group A) or minimally invasive percutaneous fixation group (group B). Clinical and surgical evaluation including surgery time, blood losses, radiation times, hospital stay, and complication were performed. The two groups of patients with pre-operative and last follow-up anterior height ratio of fracture vertebral, Cobb angle of fracture vertebral, and VAS score of back pain were compared. RESULTS:All patients completed valid follow-ups, with an average time period of 15.4 months (12-26 months). Group B achieved much better results in time of operation, intra-operative blood loss, and length of stay than group A (P < 0.05). Group A was significantly better than group B in the times of radiation (P < 0.05). The VAS score was significantly lower in group B than in group A at three days after the operation (P < 0.05). There were no significant differences between the two groups in the anterior height ratio of fracture vertebral, Cobb angle, and VAS score in the last follow-up (P > 0.05). No injured nerve or other severe complications occurred in both groups; one of the patients from group A had back and loin pain lasting for about one month, which resolved after analgesia and functional training. There was no significant difference between the two groups in incidence of complications. CONCLUSIONS:Novel percutaneous pedicle screws with angle reset function can achieve the same effect as traditional open pedicle screw fixation in the treatment of thoracolumbar fractures without nerve injuries. Percutaneous minimally invasive pedicle screw fixation has the characteristics of shorter operative time, less bleeding, and less pain, but it needs more radiation times.

BACKGROUND CONTEXT: Atlantoaxial fixation with C1 lateral mass-C2 translaminar bicortical (C1LM-C2TB) screws has been reported to afford good stability with the least risk of injury to vertebral artery. However, no comparative in vitro studies have been conducted to evaluate the biomechanical stability of this method. PURPOSE: This study aimed to compare in vitro biomechanics of fixation with C1LM-C2TB with fixation with C1 lateral mass-C2 translaminar unicortical screws (C1LM-C2TU) and with C1 lateral mass-C2 pedicle screws (C1LM-C2PS). STUDY DESIGN: This is an in vitro biomechanical study. METHODS: Fifteen fresh-frozen human cadaveric cervical spines (C1-C3) were tested after destabilization by transverse-alar-apical ligament disruption. Instrumentation was performed with three fixation constructs: C1LM-C2PS, C1LM-C2TU, and C1LM-C2TB. Flexion, extension, lateral bending, and axial rotation were tested. Range of motion and neutral zone pre-fatigue and post-fatigue values were measured. RESULTS: No significant differences were observed in flexion-extension among the three groups. However, C1LM-C2TB fixation was superior to C1LM-C2TU fixation in lateral bending and axial rotation. CONCLUSION: C2 translaminar bicortical screws are biomechanically superior to C2TU screws for fixation of the atlantoaxial complex, and it is equivalent to C2PS fixation. C2 translaminar bicortical screws or C2PS should be preferred over C2TU screws. (C) 2017 Elsevier Inc. All rights reserved.

Diabetic neuropathic pain (DNP) plays a major role in decreased life quality of diabetes patients, however, the neural mechanisms underlying DNP remain unclear. Endomorphins are the endogenous ligands for mu-opioid receptor. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neuropathic pain. In this study, using a streptozotocin induced diabetic rat model that displayed obvious mechanical allodynia, it was found that the expression of spinal EM2 was significantly decreased in DNP rats. While intrathecal administration of exogenous EM2 attenuated mechanical allodynia in DNP rats, the mu-opioid receptor antagonist β-funaltrexamine facilitated these events. It was found that the reduction in spinal EM2 was mediated by increased activity of dipeptidylpeptidase IV, possibly as a consequence of diabetes-induced oxidative stress. Taken together, our results provide the first evidence that the reduction in the level of an endogenous opioid in primary afferents was significantly associated with DNP. This indicates that the chronic pain associated with DNP might be due to the loss of an inhibitory effect on pain signal transmission.

BACKGROUND:With the improved survival for patients with bone sarcomas, there is a trend to reconstruct intercalary femur defects using biologic techniques. This study examined whether the results of a frozen femur autograft with vascularised fibula are comparable to other reconstructive options in terms of the functional outcomes and the complications. MATERIALS AND METHODS:Between 2008 and 2012, eight patients with bony sarcoma of the femur were subjected to reconstruction with a recycled frozen autograft combined with a vascularised fibula flap inside. The oncologic and functional results were analysed retrospectively. RESULTS:The mean follow-up was 48.7 months (37-71). The oncologic results were continuously disease free in five patients; there was no evidence of disease in one, one patient was alive with disease and another died of the disease. The average length of defect was 13.6 cm (9-21). Bone union was achieved in all cases. The mean time to bone union was 7.9 months (5-19) and to full weight bearing was 7.8 months (6-11). There was no infection or construct fracture in this series. Two complications were observed. One tumour recurrence in soft tissue was treated with reresection. One tibia fracture was successfully managed with cast immobilisation. The average Musculoskeletal Tumor Society functional score was 95% (27-30). The construct was intact in all patients. CONCLUSIONS:Vascularised fibular flap combined with frozen autografts is a dependable and durable option for the reconstruction of large bony defects after femoral sarcoma resection. It had the merits of reliable bone union and low complications, which compare well with other biological reconstructions. Evidence Rating Scale for Therapeutic Studies Level IV, therapeutic study.

This work aimed to investigate the therapeutic effect of curcumin on sublesional bone loss induced by spinal cord injury (SCI) in rats. SCI model in this work was generated in rats by surgical transaction of the cord at the T10-12 level. After the surgery, animals were treated with curcumin (110 mg/kg body mass/day, via oral gavages) for 2 weeks. Treatment of SCI rats with curcumin prevented the reduction of bone mass in tibiae and femurs, preserved bone microstructure including trabecular bone volume fraction, trabecular number, and trabecular thickness in proximal tibiae, and preserved mechanical properties of femoral midshaft. Treatment of SCI rats with curcumin increased osteoblast surface and reduced osteoclast surface in proximal tibiae. Treatment of SCI rats with curcumin increased osteocalcin mRNA expression and reduced mRNA levels of tartrate-resistant acid phosphatase and mRNA ratio of receptor activator of NF-κB ligand/osteoprotegerin in distal femurs. Treatment of SCI rats with curcumin reduced serum and femoral levels of thiobarbituric acid reactive substances. Treatment of SCI rats with curcumin had no significant effect on serum 25(OH)D, but enhanced mRNA and protein expression of vitamin D receptor (VDR) in distal femurs. Treatment of SCI rats with curcumin enhanced mRNA levels of Wnt3a, Lrp5, and ctnnb1 and upregulated protein expression of β-catenin in distal femurs. In conclusions, treatment with curcumin abated oxidative stress, activated VDR, and enhanced Wnt/β-catenin pathway, which might explain its beneficial effect against sublesional bone loss following SCI in rats, at least in part.

BACKGROUND:It is a challenge to perform a joint-preserving resection for young patients with juxta-articular bone sarcomas. We determined whether osteotomy under image-guided navigation make joint-saving resection possible for juxta-articular lesions while adhering oncological principles.METHODS:Between June 2008 and July 2010, joint-preserving limb salvage surgeries were performed on 9 patients with juxta-articular bone sarcomas under navigation guidance. Computed tomography/magnetic resonance imaging fusion images were used for real-time navigation. Eight lesions located around the knee and 1 in hip. Six tumors extend to and 3 beyond the epiphyseal line. Planned osteotomy under image-guided navigation was employed for achieving clear surgical margin while maximizing host tissue preservation. All tumors were en bloc removed and intercalary defect were reconstructed by combination of allograft with vascularized fibula graft. All specimens were examined for resection margin. Patients were followed up for an average of 25.2 months for evaluating of functional and oncology outcomes.RESULTS:Entire joint were preserved in 6 patients and part of joint were saved in another 3 patients. The mean registration error for navigation was 0.40 mm (range, 0.31 to 0.62 mm). Clear surgical margin was obtained in all specimens. The average closest distance between the osteotomy line and tumor edge was 9.6 mm (range, 6 to 14 mm). Entire joint cartilage was preserved in 6 patients and portion of joint were saved in 3 patients (2 in proximal tibia, 1 in distal femur). No patient experienced local recurrence. Two patients developed lung metastasis. One died of disease and the other underwent metastasectomy and had no evidence of disease at the most recent follow-up. All reconstruction was in situ with the Musculoskeletal Tumor Society average score of 26.7 at final follow-up.CONCLUSIONS:With careful patient selection, image navigation-assisted surgery made it possible to resect the bone exactly as planned in length and orientation in the magnetic resonance imaging image, yielding a clear margin and preserving the entire or part of the articular cartilage in joint-sparing limb salvage procedures for treating skeletally immature patients with juxta-articular bone sarcomas.LEVEL OF EVIDENCE:Level IV--therapeutic study.