Effect of alendronate sodium plus vitamin D3 tablets on knee joint structure and osteoarthritis pain: a multi-center, randomized, double-blind, placebo-controlled study protocol.

BACKGROUND: Osteoarthritis (OA) is a major cause of pain and disability worldwide. Despite the relatively high burden of the disease, the currently available non-surgical treatment options are directed towards symptomatic relief. Therefore, we propose the use of alendronate as a disease modifying agent to help slow and prevent OA. In addition, this study will utilize Whole-Organ Magnetic Resonance Imaging Score (WORMS) to evaluate the structural integrity of cartilage in the study population. High-quality evidence, limited to a few well-conducted randomized trials, highlights contradictory results on the effect of bisphosphonates on knee function and progression of OA. Therefore, a placebo-controlled, randomized trial is needed to evaluate the combined effect of alendronate and vit D on the structure of cartilage utilizing the WORMS score and its ability to treat knee pain in OA patients. METHODS: This multicenter, randomized, double-blinded, placebo-controlled study will evaluate the efficacy and safety of alendronate in early OA. Patients will undergo a 1:1 double-blinded randomization to receive a one-year course of either alendronate sodium vitamin D3 or placebo. The primary outcome is to compare WORMS score of knee joint at 6 and 12 months between both groups. Secondary endpoints will include WORMS score at 24 months, knee pain, radiographic progression of OA, severity of OA, quality of life, and serum inflammatory biomarkers at different assessment timepoints. To detect a 2.2% difference in cartilage loss between both groups with power of 80%, a sample size of 60 (30 per group) is proposed. DISCUSSION: This trial will give helpful and high-quality evidence regarding the potential therapeutic role of alendronate sodium vitamin D3, as compared to placebo, in the management of patients with knee OA regarding its role on cartilage loss, radiographic progression of OA, severity of OA, knee pain, quality of life, and inflammatory biomarkers. If proven effective, this intervention would be a great option for providing beneficial outcomes with a reduced cost in this patient population. TRIAL REGISTRATION: This trial was registered on clinicaltrials.gov (registration number: NCT04739592 ).

Reduction of Blood Loss by Intra-articular Injection of Tranexamic Acid Combined with Knee and Hip Flexion at 45° During Primary Total Knee Arthroplasty: A Randomized Controlled Trial.

OBJECTIVE: To explore the hemostatic effect of intra-articular administration of tranexamic acid (TXA) combined with knee flexion in total knee arthroplasty (TKA). METHODS: This randomized controlled trial was conducted at the Third Affiliated Hospital of Southern Medical University (Guangzhou, China) from January 2017 to February 2018. The patients were randomized 1:1 to the TXA group (TXA 500 mg into the joint after closure, knee, and hip flexed at 45° for 4 h) or the control group (physiological saline, with limb fully extended). The primary endpoint was postoperative hemoglobin reduction. The postoperative levels of hemoglobin were measured at four time points: 6 h after operation, and on the first, second, and third postoperative days. Calculated blood loss (CBL) at 3 days, transfusion rate, range of motion (ROM), VAS pain score, and knee circumference increment were the secondary endpoints. Ninety-four (47/group) patients were analyzed. RESULTS: Postoperatively, there were statistically significant differences between the TXA and control groups in CBL (791 ± 212 mL vs 1175 ± 273 mL, P < 0.05). Hemoglobin reduction was significantly lower in the TXA group (2.0 ± 0.9 g/dL vs 4.5 ± 0.7 g/dL, P < 0.05). Based on the transfusion criteria, 3 out of 47 (6.4%) patients in the TXA group and 13 out of 47 (27.6%) patients in the control group received blood transfusions (P = 0.006). ROM (90.8° ± 6.2° vs 87.6° ± 6.4°, P = 0.004), VAS pain score (4.1 ± 1.1 vs 4.8 ± 1.3, P = 0.004), and KCI (2.4 ± 0.9 cm vs 3.2 ± 1.0 cm, P = 0.01) were better in the TXA group compared with thecontrols. There was no deep venous thrombosis (DVT), wound infection or other adverse events in either group. In the control group, 2 patients had a fever after blood transfusion. CONCLUSION: Intra-articular injection of TXA combined with knee and hip flexion at 45° can effectively attenuate CBL and hemoglobin reduction during primary TKA, without an additional adverse event.

Polydatin prevents the induction of secondary brain injury after traumatic brain injury by protecting neuronal mitochondria.

Polydatin is thought to protect mitochondria in different cell types in various diseases. Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury. To investigate the protective effect of polydatin after traumatic brain injury, a rat brain injury model of lateral fluid percussion was established to mimic traumatic brain injury insults. Rat models were intraperitoneally injected with polydatin (30 mg/kg) or the SIRT1 activator SRT1720 (20 mg/kg, as a positive control to polydatin). At 6 hours post-traumatic brain injury insults, western blot assay was used to detect the expression of SIRT1, endoplasmic reticulum stress related proteins and p38 phosphorylation in cerebral cortex on the injured side. Flow cytometry was used to analyze neuronal mitochondrial superoxide, mitochondrial membrane potential and mitochondrial permeability transition pore opened. Ultrastructural damage in neuronal mitochondria was measured by transmission electron microscopy. Our results showed that after treatment with polydatin, release of reactive oxygen species in neuronal mitochondria was markedly reduced; swelling of mitochondria was alleviated; mitochondrial membrane potential was maintained; mitochondrial permeability transition pore opened. Also endoplasmic reticulum stress related proteins were inhibited, including the activation of p-PERK, spliced XBP-1 and cleaved ATF6. SIRT1 expression and activity were increased; p38 phosphorylation and cleaved caspase-9/3 activation were inhibited. Neurological scores of treated rats were increased and the mortality was reduced compared with the rats only subjected to traumatic brain injury. These results indicated that polydatin protectrd rats from the consequences of traumatic brain injury and exerted a protective effect on neuronal mitochondria. The mechanisms may be linked to increased SIRT1 expression and activity, which inhibits the p38 phosphorylation-mediated mitochondrial apoptotic pathway. This study was approved by the Animal Care and Use Committee of the Southern Medical University, China (approval number: L2016113) on January 1, 2016.

Attenuated levels of ghrelin in synovial fluid is related to the disease severity of ankle post-traumatic osteoarthritis.

Post-traumatic osteoarthritis (PTOA) of ankle joints results in pain and reduced joint function. Ghrelin, a 28-amino-acid polypeptide, has been previously identified as the first cognate natural ligand that binds to the growth hormone secretagogue receptor. In the present study, ghrelin has been validated to exert cartilage-protective and anti-inflammatory effects. The current study was aimed at investigating the potential role of the levels of serum and synovial fluid (SF) ghrelin on the severity of disease in patients suffering from ankle PTOA. Ninety-seven patients with ankle osteoarthritis who received an arthroscopical examination and debridement or replacement of the ankle joint were included in the study cohort. Meanwhile, 95 healthy individuals (whose age and sex were matched) who received periodic body checkups were enrolled as healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the ghrelin levels in serum and SF. SF was also probed for cartilage degradation enzyme matrix metalloproteinases-3 (MMP-3) and tumor necrosis factor alpha (TNF-α), which is a known pro-inflammatory cytokine. The clinical evaluation was carried out using the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot rating scale and visual analogue scale (VAS). The radiographic severity was evaluated using the modified Kellgren-Lawrence (K-L) grading system. We scored for the modified Mankin's score to depict histopathological changes due to cartilage lesions. The diagnostic relevance of the ghrelin concentrations in the prediction of the radiographic grading (in comparison with MMP-3 and TNF-α) was evaluated by calculating the area under the curve of the receiver operating characteristic (ROC) curve. The serum abundance of ghrelin was not significantly altered between ankle PTOA patients and healthy controls. SF ghrelin was negatively correlated with radiographic progression determined by modified ankle K-L grades. In addition SF ghrelin concentrations were negatively related to VAS scores, and positively associated with AOFAS ankle-hindfoot rating. Moreover, SF ghrelin was inversely proportional to the expressions of MMP-3 and TNF-α. ROC analysis curve demonstrated that ghrelin serves as a favorable marker for the diagnosis of radiographic severity by modified ankle K-L grade. The ghrelin concentration in SF is negatively proportional to disease progression in patients suffering from ankle PTOA. Local administration of ghrelin may function as a decent adjuvant therapy to delay the progress of ankle PTOA. © 2019 BioFactors, 45(3):463-470, 2019.

B-cell-specific mammalian target of rapamycin complex 1 activation results in severe osteoarthritis in mice.

This study aims to investigate the effect of enriched plasma cells on the production of inflammatory cytokines and development of osteoarthritis (OA) in mice with B-cell-specific conditional deletion of the tuberous sclerosis 1 gene (TSC1). OA was induced by destabilization of the medial meniscus (DMM) in mice with TSC1 disruption in B cells (CD19-TSC1) and in littermate control mice (CON). The effects of DMM and incidence of OA were evaluated histologically, mRNA levels of inflammatory cytokines were detected by polymerase chain reaction, and serum cytokine levels were detected by enzyme-linked immunosorbent assay. Deletion of TSC1 caused constitutive activation of mechanistic target of rapamycin complex 1 mTORC1 in B cells. CON mice subjected to DMM exhibited a severe OA phenotype with increased inflammatory cytokines in B cells, serum, and the synovial membrane. Importantly, inflammatory cytokine production was also increased in B cells from the spleen of CD19-TSC1 conditional KO mice, but the OA phenotype was significantly elevated in conditional KO mice after DMM surgery compared with CON mice, as indicated by more severe articular cartilage destruction, increased protein expression of matrix metalloproteinase-13 and mRNA of type X collagen in the articular cartilage, decreased mRNA expression of type II collagen in the articular cartilage, and increased inflammatory cytokines in serum and the synovial membrane. The results demonstrate that inflammatory cytokine synthesis by B cells was enriched in CD19-TSC1 conditional KO mice, and this enhanced synthesis of inflammatory cytokines accelerated the incidence of OA.

Inhibition of osteoclastogenesis for periprosthetic osteolysis therapy through the suppression of p38 signaling by fraxetin.

Periprosthetic osteolysis belongs to osteolytic diseases, which often occur due to an imbalance between osteoclast and osteoblast number or activity. Fraxetin, a natural plant extract, inhibits osteoblast apoptosis and has therapeutic potential for treating osteolytic diseases. However, data pertaining to the effects of fraxetin on osteoclasts are limited. In the present study, it was demonstrated that the inhibition of osteoclastogenesis by fraxetin had an important role on the therapy of titanium particle­induced osteolysis in vivo. In addition, fraxetin was demonstrated to suppress receptor activator of nuclear factor­κB ligand (RANKL)­mediated osteoclast differentiation and bone resorption in vitro in a dose­dependent manner. Fraxetin inhibited osteoclast differentiation and function through the suppression of p38 signaling and subsequently, the suppression of osteoclast­specific gene expression, including tartrate­resistant acid phosphatase, nuclear factor of activated T­cells, cytoplasmic 1, and cathepsin K. In conclusion, fraxetin administration may have potential as a treatment method for periprosthetic osteolysis and other osteolytic diseases.

Intraperitoneal injection of thalidomide alleviates early osteoarthritis development by suppressing vascular endothelial growth factor expression in mice.

Vascular endothelial growth factor (VEGF) is expressed in articular cartilage and increases in expression levels have been associated with the progression of osteoarthritis (OA). Thalidomide is a drug that has been reported to inhibit angiogenesis and reduce VEGF production by downregulating VEGF expression. The objective of the present study was to determine whether intraperitoneal administration of thalidomide may attenuate early OA development in mice. Male C57BL/6 mice (10­weeks­old) were randomly assigned into the destabilization of the medial meniscus (Dmm) with thalidomide treatment (Dmm+Th), Dmm and Sham groups equally. An OA model was induced surgically in Dmm+Th and Dmm groups, and mice of the Dmm+Th group were subsequently treated with an intraperitoneal injection of thalidomide (200 mg/kg/day). At 2 and 4 weeks following surgery, the pathological alterations in cartilage samples were assessed qualitatively by hematoxylin and eosin staining and Safranin O/Fast green staining, and quantitatively by the Osteoarthritis Research Society International scoring system. The mRNA expression levels of matrix metalloproteinase­13 (MMP­13) and VEGF were measured by reverse transcription­quantitative polymerase chain reaction. The protein expression levels of MMP­13 and VEGF were detected by immunofluorescence and immunohistochemistry, respectively. The production of VEGF in serum was evaluated via an ELISA assay. Pathological scores were significantly higher in the Dmm and the Dmm+Th groups than those in the Sham group; however, the Dmm+Th group exhibited markedly less severe pathological changes compared with the Dmm group. Compared with the Sham group, the mRNA and protein expression levels of VEGF and MMP­13 in the Dmm and the Dmm+Th groups were significantly increased. The Dmm+Th group exhibited significantly decreased expression levels of VEGF and MMP­13, as well as significantly decreased serum VEGF concentration compared with the Dmm group. Thus, the results of the present study demonstrated that intraperitoneal administration of thalidomide may alleviate the development of early OA by suppressing VEGF expression in mice and may have potential as a novel therapy for the treatment of OA.

[Application of 3D printing and computer-assisted surgical simulation in preoperative planning for acetabular fracture].

OBJECTIVE: To evaluate the feasibility and effectiveness of using 3D printing and computer-assisted surgical simulation in preoperative planning for acetabular fractures. METHODS: A retrospective analysis was performed in 53 patients with pelvic fracture, who underwent surgical treatment between September, 2013 and December, 2015 with complete follow-up data. Among them, 19 patients were treated with CT three-dimensional reconstruction, computer-assisted virtual reset internal fixation, 3D model printing, and personalized surgery simulation before surgery (3D group), and 34 patients underwent routine preoperative examination (conventional group). The intraoperative blood loss, transfusion volume, times of intraoperative X-ray, operation time, Matta score and Merle D' Aubigne & Postel score were recorded in the 2 groups. Preoperative planning and postoperative outcomes in the two groups were compared. RESULTS: All the operations were completed successfully. In 3D group, significantly less intraoperative blood loss, transfusion volume, fewer times of X-ray, and shortened operation time were recorded compared with those in the conventional group (P<0.05). According to the Matta scores, excellent or good fracture reduction was achieved in 94.7% (18/19) of the patients in 3D group and in 82.4% (28/34) of the patients in conventional group; the rates of excellent and good hip function at the final follow-up were 89.5% (17/19) in the 3D group and 85.3% (29/34) in the conventional group (P>0.05). In the 3D group, the actual internal fixation well matched the preoperative design. CONCLUSIONS: 3D printing and computer-assisted surgical simulation for preoperative planning is feasible and accurate for management of acetabular fracture and can effectively improve the operation efficiency.

Effects of the 1, 4-dihydropyridine L-type calcium channel blocker benidipine on bone marrow stromal cells.

Osteoporosis (OP) often increases the risk of bone fracture and other complications and is a major clinical problem. Previous studies have found that high blood pressure is associated with bone formation abnormalities, resulting in increased calcium loss. We have investigated the effect of the antihypertensive drug benidipine on bone marrow stromal cell (BMSC) differentiation into osteoblasts and bone formation under osteoporotic conditions. We used a combination of in vitro and in vivo approaches to test the hypothesis that benidipine promotes murine BMSC differentiation into osteoblasts. Alkaline phosphatase (ALP), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), ß-catenin, and low-density lipoprotein receptor-related protein 5 (LRP5) protein expression was evaluated in primary femoral BMSCs from C57/BL6 mice cultured under osteogenic conditions for 2 weeks to examine the effects of benidipine. An ovariectomized (OVX) mouse model was used to investigate the effect of benidipine treatment for 3 months in vivo. We found that ALP, OCN, and RUNX2 expression was up-regulated and WNT/ß-catenin signaling was enhanced in vitro and in vivo. In OVX mice that were intragastrically administered benidipine, bone parameters (trabecular thickness, bone mineral density, and trabecular number) in the distal femoral metaphysis were significantly increased compared with control OVX mice. Consistently, benidipine promoted BMSC differentiation into osteoblasts and protected against bone loss in OVX mice. Therefore, benidipine might be a suitable candidate for the treatment of patients with postmenopausal osteoporosis and hypertension.

Comparative serum proteome expression of the steroid-induced femoral head osteonecrosis in adults.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a disabling, aseptic and ischemic disease that develops following steroid therapy. The pathogenesis of SONFH is unclear, so the early diagnosis and treatment for this disease is yet to be established. The purpose of the present study was to identify potential biomarkers for SONFH. The differential expression of serum proteins from patients with SONFH and healthy volunteers was analyzed by the proteomics method. The protein samples were labeled and subjected to isoelectric focusing and two-dimensional gel electrophoresis. The resultant protein spots were matched and quantified by an imaging analysis system. The differentially-expressed protein spots were subjected to in-gel trypsin digestion followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Significantly lower levels of complement component 3 (C3), C4, inter-α-trypsin inhibitor heavy chain H4 and α-2-macroglobulin were found in the serum of patients with SONFH. These proteins are reported to be actively involved in intravascular coagulation, apoptosis and reactive oxygen species imbalance, indicating that multiple pathological reactions occur in SONFH and these proteins may serve as potential biomarkers for the diagnosis of SONFH.

[Expression of lipoprotein related genes in subchondral bone of early experimental osteoarthritis].

OBJECTIVE: To study the expression of lipoprotein related genes in subchondral bone of early experimental os-teoarthritis, which may play an important role in the pathogenesis of osteoarthritis. METHODS: Animals are equally divided into two groups: experimental group and control group, both of which contain fifteen rats of similar weight. The right knee joints of experimental group underwent surgery,which involved in both medial collateral ligament(MCL) transaction and medial meniscectomy, while the control group was only carried out with a sham operation. Rats were killed at 1, 2 and 4 weeks postsurgery to obtain the right knee joints. Total RNA of the subchondral bone was extracted,and then hybridized to Agilent Whole Rat Genome Microarray. Differentially expressed genes analysis was used to study the chemokine signaling pathway. RESULTS: Apoa5 expression was down-regulated at 1, 2 weeks post-surgery, Apoc2 expression was up-regulated at 1 week after surgery, Apol3 expression was up-regulated at 1 and down-regulated at 4 weeks post-surgery, Lrp1 expression was down-regulated at 1, 2 weeks after surgery. Lrp5 was down-regulated at 2 weeks after surgery. Gpihbp1, Lpl, Tfpi and Vldlr were up-regulated at 1 weeks after surgery. Lrpap1 and RGD1309808 were down-regulated at 4 weeks after surgery. CONCLUSION: Dysregulation of lipoprotein related genes plays an important role in pathogenesis of early experimental osteoarthritis.

Simultaneous bilateral patellar tendon rupture without predisposing systemic disease or steroid use: a case report.

There is a dearth of case reports describing simultaneous bilateral patellar tendon ruptures in the medical literature. These ruptures are often associated with systemic disorders such as lupus erythematosus or chronic steroid use. The author describes a case of a 24-year-old man who sustained traumatic bilateral patellar tendon ruptures without any history of systemic disease or steroidal medication. We repaired and reattached the ruptured tendons to the patella and augmented our procedure with allogeneic tendon followed by wire loop reinforcement. One year after operation, the patient regained a satisfactory range of motion of both knees with good quadriceps strength and no extensor lag. The recurrent microtrauma from a history of intense sports activity and a high body mass index may have played an important role in this trauma event.

Whole meniscus regeneration using polymer scaffolds loaded with fibrochondrocytes.

OBJECTIVE: To study the feasibility of regenerating a whole menisci using poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) scaffolds loaded with meniscal cells in rabbits undergoing total meniscectomy, and to explore its protective effect on cartilage degeneration. METHODS: A solvent casting and particulate leaching technique was employed to fabricate biodegradable PHBV scaffolds into a meniscal shape. The proliferated meniscal cells were seeded onto the polymer scaffolds, transplanted into rabbit knee joints whose lateral menisci had been removed. Eight to 18 weeks after transplantation, the rege- nerated neomenisci were evaluated by gross and histological observations. Cartilage degeneration was assessed by Mankin score. RESULTS: Eighteen weeks after transplantation, the implants formed neomenisci. Hematoxylin and eosin (HE) staining of the neomenisci sections revealed regeneration of fibrocartilage. Type I collagen in the neomenisci was also proved similar to normal meniscal tissue by immunohistochemical analysis and Sirius scarlet trinitrophenol staining. Articular cartilage degeneration was observed 8 weeks after implantation. It was less severe as compared with that in total meniscectomy controls and no further degeneration was observed at 18 weeks. At that time, the regenerated neomenisci strongly resembled normal meniscal fibrocartilage in gross and histological appearance, and its mechanical property was also close to that of normal meniscus. CONCLUSIONS: The present study demonstrates the feasibility of tissue-engineering a whole meniscal structure in total meniscectomy rabbit models using biodegradable PHBV scaffolds together with cultured allogeneic meniscal cells. Cartilage degeneration is decreased. But long-term in vivo investigations on the histological structure and cartilage degeneration of the neomenisci regenerated by this method are still necessary to determine the clinical potential of this tissue engineering avenue.

[Treatment of tibial avulsion fracture of the posterior cruciate ligament with open reduction and steel-wire internal fixation].

OBJECTIVE: To study the curative effects of the treatment of tibial avulsion fracture of the posterior cruciate ligament with open reduction and steel-wire internal fixation. METHODS: From January 2003 to June 2009, 28 patients of tibial avulsion fracture of the posterior cruciate ligament were treated with open reduction and steel-wire internal fixation through posteromedial inverted "L" approach. There were 19 males and 9 females with an average age of 35.3 years old ranging from 16 to 55 years. The X-ray examination showed that there were II degree displaced in 10 cases and III degree in 18 patients. The affected lower extremity was put in a controlled hinge knee brace after operation. The patients were asked to do passive extension and flexion of the knee joint with the assistance of a CPM 2 weeks after operation,and allowed to be partial weight-bearing as tolerated with the hinged brace locked in extension if concomitant injuries allowed 4 weeks postoperatively. The brace were removed 6 weeks later. RESULTS: Among them, 25 patients were followed up for 6 to 24 months with an average of 15 months. The X-ray examination showed satisfactory reduction, and bony union was obtained in all the patients. The Lachman test was negative in all patients. No complications such as malunion or joint stiffness were found. The extension of affected knee was normal and its flexion were (136 +/- 12) degrees. According to Lysholm knee score system,it was preoperatively (41.80 +/- 6.16) and (94.10 +/- 8.26) six months after surgery respectively. Twenty-two cases were excellent, 2 cases good and 1 fair. CONCLUSION: Treatment of tibial avulsion fracture of the posterior cruciate ligament with open reduction and internal fixation with wires through posteromedial inverted "L" approach is a safe, effective method, due to its stable fixation and relatively low expense. It is believed as an ideal choice for tibial avulsion fracture of the posterior cruciate ligament.

[Arthroscopic diagnosis and treatment of posttraumatic chronic ankle pain].

OBJECTIVE: To evaluate the arthroscopic diagnosis and treatment of the chronic ankle pain after injury. METHODS: From April 1999 to June 2008, 39 patients with posttraumatic chronic ankle pain were treated. The mean duration between the initial injury and treatment was 18 months (2 months to 11 years). There were 15 males and 24 females with a mean age of 32 years (15 to 58 years). All the patients were treated with arthroscopic debridement. The preoperative and postoperative ankle functions were evaluated by the AOFAS (the American Orthopaedic Foot and Ankle Society) Clinical Rating System for the ankle-hindfoot. RESULTS: Twenty-six patients had osteochondral lesions. Impingement syndrome in ankle was observed in 21 patients. The impingement tissue included synovial hypertrophy in 3 patients, ligament injury in 10 patients (7 patients had anterior talofibular ligament injury and 3 patients had anteroinferior tibiofibular ligament injury), meniscoid tissue in 6 patients, pathological labrum in 3 patients. All the patients were followed up with an average of (14.2+/-8.4) months (ranged from 5 to 36 months). The AOFAS scores increased significantly from pre-operative (59.7+/-16.9) to post-operative (68.8+/-21.2), and it was obvious in relieving pain, which was pre-operative (22.8+/-10.0) and post-operative (29.5+/-12.1). CONCLUSION: Arthroscopy can be used to diagnose the cause of chronic ankle pain after injury. Furthermore, arthroscopic debridement was useful to relieve the pain and improve the joint function, and it is appropriate for patients who had no fractures and dislocations.

[Additional screws fixation on fractured vertebrae versus only short-segment posterior instrumentation for thoracolumbar A3 fracture without neurologic deficit].

OBJECTIVE: To compare the clinical results of additional screws fixation on fractured vertebrae versus only short-segment posterior transpedicular instrumentation for A3 thoracolumbar fracture without neurologic deficit. METHODS: Clinical data of 52 cases of thoracolumbar burst fracture without neurologic deficit were retrospectively analyzed. All patients were divided into 2 groups due to different instrumentation and all fractures were classified as type A3 according to AO Classification.From January 2005 to December 2006, 23 cases in group A were treated by short-segment posterior instrumentation combined with additional screws fixation on fractured vertebrae. There were 18 male and 5 female with a mean age of (35.3+/-8.3) years. The fracture segment included 1 in T11, 9 in T12, 11 in L1 and 2 in L2. From January 1999 to December 2004, 29 cases in group B were treated only by conventional short-segment posterior transpedicular instrumentation. There were 20 male and 9 female with a mean age of (37.3+/-6.8) years. The fracture segment included 1 in T11, 7 in T12, 20 in L1 and 1 in L2. The clinical effect and radiographic measurements were respectively compared preoperatively, immediate and 2 years postoperatively. RESULTS: All patients were followed up and the mean follow-up time was (37.4+/-10.9) months (from 24 to 48 months). There was no statistic difference of mean JOA and VAS score between 2 groups preoperatively, immediate and 2 years postoperatively (P>0.05). The average immediate postoperative correction of Cobb's angle was 13.7 degrees+/-7.7 degrees in group A, which was statistically significantly higher than that of 8.8 degrees+/-5.0 degrees in group B (P<0.01). The mean kyphosis correction loss of 2.9 degrees+/-1.5 degrees in group A was statistically significantly lower than that of 5.0 degrees+/-2.9 degrees in group B 2 years postoperatively (P<0.01). The average restoration of anterior height of fractured vertebral body immediate postoperatively was (29.4+/-6.0)% and (21.7+/-6.9)% respectively. The mean correction loss of anterior height 2 years postoperatively was (3.1+/-0.8)% and (6.6+/-3.0)% respectively. The average restoration of posterior height of fractured vertebral body immediate postoperatively was (8.5+/-3.2)% and (6.1+/-1.8)% respectively. The mean correction loss of posterior height 2 years postoperatively was (2.0+/-0.8)% and (3.4+/-1.0)% respectively. There were significant differences in average restoration of anterior/posterior height immediate postoperatively and correction loss of anterior/posterior height 2 years postoperatively between the 2 groups (P<0.01). According to fracture fragments protruded into the spinal canal on immediate postoperative CT image, there were complete reduction in 11 cases (47.8%) and partial reduction in 12 cases (52.2%) in group A, which was statistically significantly better than those in group B (P<0.01). There was no severe neurologic complications and no other complications related to additional screws fixation postoperatively. Pedicle screw breakage occurred in 2 cases in group B and none in group A. CONCLUSIONS: Better initial kyphosis correction and less loss of correction 2 years after operation can be obtained by using additional screws fixation on fractured vertebra for thoracolumbar A3 fracture without neurologic deficit.

[Correlations of extrocellular matrix metalloproteinase inducer and microvessel density to invasiveness of ameloblastoma].

BACKGROUND & OBJECTIVE: Matrix metalloproteinases (MMPs) are involved in local invasion of ameloblastomas. This study was to evaluate the role of matrix metalloproteinase inducer (EMMPRIN) in angiogenesis in ameloblastomas by analyzing EMMPRIN expression and microvessel density (MVD) in ameloblastomas and odontogenic cysts. METHODS: EMMPRIN expression and MVD in 41 specimens of ameloblastoma and 40 specimens of odontogenic cyst were examined by SP immuno-histochemistry. RESULTS: EMMPRIN was detected in all specimens of ameloblastomas and odontogenic cysts. The strong positive rate of EMMPRIN was significantly higher in ameloblastomas than in odontogenic cysts (85.4% vs. 62.5%, P<0.05). MDV was positively correlated to EMMPRIN expression to some extent (r=0.677, P<0.01). CONCLUSION: EMMPRIN may play an important role during the progression of ameloblastoma via controlling angiogenesis and degradation of extracellular MMPs.

Spinal surgeons' learning curve for lumbar microendoscopic discectomy: a prospective study of our first 50 and latest 10 cases.

BACKGROUND: Microendoscopic discectomy (MED) is a minimally invasive operation that allows rapid recovery from surgery for lumbar disc herniation, but has replaced traditional open surgery in few hospitals because most surgeons avoid its long learning curve. We evaluated the effectiveness and safety of lumbar MED at stages of spinal surgeons' learning curve. METHODS: Fifty patients receiving MED from June 2002 to February 2003 were divided into chronological groups of ten each: A - E. The control group F was ten MED patients treated later by the same medical team (September - October 2006). All operations were performed by the same team of spinal surgeons with no MED experience before June 2002. We compared groups by operation time, blood loss, complications and need for open surgery after MED failure. RESULTS: Operation times by group were: A, (107 +/- 14) minutes; B, (85 +/- 13) minutes; C, (55 +/- 19) minutes; D, (52 +/- 12) minutes; E, (51 +/- 13) minutes; and F, (49+/- 15) minutes. Blood loss were: A, (131 +/- 73) ml; B, (75 +/- 20) ml; C, (48 +/- 16) ml; D, (44 +/- 17) ml; E, (45 +/- 18) ml; and F, (45 +/- 16) ml. Both operation time and blood loss in groups C, D, E and F were smaller and more stable compared with groups A and B. Japanese Orthopedic Association assessment (JOA) score of each group in improvement rate immediately and one year after operation were as follows (in percentage): A, (79.8 +/- 8.8)/(89.8 +/- 7.7); B, (78.6 +/- 8.5)/(88.5 +/- 7.8); C, (80.8 +/- 11.3)/(90.8 +/- 6.7); D, (77.7 +/- 11.4)/(88.9 +/- 9.3); E, (84.0 +/- 8.7)/(89.6 +/- 9.0); and F, (77.8 +/- 11.6)/(86.9 +/- 8.4). Groups showed no statistical difference in improvement rates. Complications developed in three patients in group A, two in group B, and none in the other groups. CONCLUSIONS: Spinal surgeons performing MED become proficient after 10 - 20 operations, when their skill becomes fairly sophisticated. Patients' improvement rate is the same regardless of surgeons' phase of learning curve.

Concurrent arthroscopic bicruciate ligament reconstruction using Achilles tendon-bone allografts: experience with 15 cases.

OBJECTIVE: To evaluate the clinical outcome of arthroscopically assisted combined anterior and posterior cruciate ligament (ACL/PCL) reconstructions using Achilles tendon-bone allografts. METHODS: Associated meniscus injuries were treated according to established methods prior to ligament reconstructions during arthroscopic surgery. Thirty Achilles tendon-bone allografts were used to reconstruct torn ACL and PCL in 15 knees. At postoperative follow-up, all knees were graded using the modified IKDC and the Lysholm scoring systems just as done preoperatively. RESULTS: were analyzed compared with the contralateral healthy knees. Results: Eleven men and 4 women with a minimum of 3-year follow-up (mean 38 months) were included in the study. Preoperatively, the group ratings by the modified IKDC standards were all severely abnormal. Twelve bicruciate reconstructions were performed in subacute or chronic stage (larger than 3-8 weeks), 3 for acute ligamentous deficiencies (less than or equal to 3 weeks). The noticeable early complication was transitory local fever combined with joint effusion in one case. At postoperative follow-up, 9 knees were normal, 5 nearly normal and 1 abnormal. On Lysholm score the difference was statistically significant (t- test, P less than 0.001) before and after operation. CONCLUSIONS: Achilles tendon-bone allograft offers an alternative for simultaneous arthroscopic ACL/PCL reconstructions. However, further investigation is needed to eradicate its potential immunogenicity for better use.

Biodegradable chitosan scaffolds containing microspheres as carriers for controlled transforming growth factor-beta1 delivery for cartilage tissue engineering.

BACKGROUND: Natural articular cartilage has a limited capacity for spontaneous regeneration. Controlled release of transforming growth factor-beta1 (TGF-beta1) to cartilage defects can enhance chondrogenesis. In this study, we assessed the feasibility of using biodegradable chitosan microspheres as carriers for controlled TGF-beta1 delivery and the effect of released TGF-beta1 on the chondrogenic potential of chondrocytes. METHODS: Chitosan scaffolds and chitosan microspheres loaded with TGF-beta1 were prepared by the freeze-drying and the emulsion-crosslinking method respectively. In vitro drug release kinetics, as measured by enzyme-linked immunosorbent assay, was monitored for 7 days. Lysozyme degradation was performed for 4 weeks to detect in vitro degradability of the scaffolds and the microspheres. Rabbit chondrocytes were seeded on the scaffolds containing TGF-beta1 microspheres and incubated in vitro for 3 weeks. Histological examination and type II collagen immunohistochemical staining was performed to evaluate the effects of released TGF-beta1 on cell adhesivity, proliferation and synthesis of the extracellular matrix. RESULTS: TGF-beta1 was encapsulated into chitosan microspheres and the encapsulation efficiency of TGF-beta1 was high (90.1%). During 4 weeks of incubation in lysozyme solution for in vitro degradation, the mass of both the scaffolds and the microspheres decreased continuously and significant morphological changes was noticed. From the release experiments, it was found that TGF-beta1 could be released from the microspheres in a multiphasic fashion including an initial burst phase, a slow linear release phase and a plateau phase. The release amount of TGF-beta1 was 37.4%, 50.7%, 61.3%, and 63.5% for 1, 3, 5, and 7 days respectively. At 21 days after cultivation, type II collagen immunohistochemical staining was performed. The mean percentage of positive cells for collagen type II in control group (32.7% +/- 10.4%) was significantly lower than that in the controlled TGF-beta1 release group (92.4% +/- 4.8%, P < 0.05). Both the proliferation rate and production of collagen type II in the transforming growth factor-beta1 microsphere incorporated scaffolds were significantly higher than those in the scaffolds without microspheres, indicating that the activity of TGF-beta1 was retained during microsphere fabrication and after growth factor release. CONCLUSION: Chitosan microspheres can serve as delivery vehicles for controlled release of TGF-beta1, and the released growth factor can augment chondrocytes proliferation and synthesis of extracellular matrix. Chitosan scaffolds incorporated with chitosan microspheres loaded with TGF-beta1 possess a promising potential to be applied for controlled cytokine delivery and cartilage tissue engineering.