Search

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

Hui-Ming Peng,1 Zong-Ke Zhou,2 Fei Wang,3 Shi-Gui Yan,4 Peng Xu,5 Xi-Fu Shang,6 Jia Zheng,7 Qing-Sheng Zhu,8 Li Cao,9 Xi-Sheng Weng1 1Department of Orthopedics, Peking Union Medical College Hospital, CAMS & PUMC, Beijing, 100730, People’s Republic of China; 2Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People’s Republic of China; 3Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, Hebei Province, People’s Republic of China; 4Department of Orthopedic Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang Province, People’s Republic of China; 5Department of Adult Joint Reconstruction, Xi’ an Honghui Hospital, Xi’ An, 710054, Shaanxi Province, People’s Republic of China; 6Department of Orthopedic Surgery, First Affiliated Hospital of University of Science and Technology of China, Hefei, 230001, Anhui Province, People’s Republic of China; 7Department of Orthopedic Surgery, Henan Provincial People’s Hospital, Zhengzhou, 450003, Henan Province, People’s Republic of China; 8Department of Orthopedic Surgery, Xijing Hospital of Air Force Medical University, Xi’ An, 710032, Shanxi Province, People’s Republic of China; 9Department of Orthopedic Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, People’s Republic of ChinaCorrespondence: Xi-Sheng WengDepartment of Orthopedics, Peking Union Medical College Hospital, CAMS & PUMC, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel/Fax +86-10-69152710Email drweng_wxs1377@163.comBackground and Aim: Periprosthetic joint infection (PJI) is one of the most devastating complications after total joint arthroplasty (TJA). However, the antibiotic resistance of infecting pathogens can significantly vary in different parts of the country. In the current study, we analyzed the demographic and microbiological profiles of knee and hip PJI over three years and compared the microbiological differences between them.Methods: A multicenter retrospective study of PJI patients in 34 referral medical centers in mainland China from January 2015 to November 2017 was performed.Results: A total of 925 PJI patients were recruited, 452 were identified as knee PJIs, and 473 were hip PJIs. The most common causative pathogens were Staphylococcus aureus (26.5%) and coagulase-negative staphylococci (14.3%). Methicillin-resistant staphylococci were involved in 25.6% (237/925) of all PJI cases. Mycobacterium and fungus only accounted for 6.5% (61) of all cases. Enteric gram-negative bacilli, anaerobes, and polymicrobial pathogens were more common in hip joint prostheses than in knee PJI (P = 0.014; P = 0.006; P = 0.002, respectively).Conclusion: While the majority of causative pathogens in PJI cases are staphylococcal species, the prevalence of atypical organisms and resistant pathogens should also be given attention and warrant the need for empiric antibiotic treatment.Keywords: arthroplasty, hips, knees, microorganism, prosthetic joint infection

Summary Zoledronic acid (ZOL) is a therapy inhibiting bone resorption. In this study, generic ZOL (Yigu®) showed its clinical efficacy consistency with original ZOL (Aclasta®) in Chinese postmenopausal women with osteoporosis. This study provides a practical basis for the application of Yigu® in Chinese population. Introduction Yigu® has been approved its bioequivalence to Aclasta®. However, the clinical efficacy and safety of Yigu® have not been evaluated yet. Here, we compared the effectiveness and safety between Yigu® and Aclasta® in Chinese postmenopausal women with osteoporosis and assessed the efficacy of intravenous infusion of ZOL. Methods This was a randomized open-label, active-controlled study in postmenopausal women with osteoporosis of 14 clinical centers in China. Postmenopausal women with osteoporosis were recruited and randomized to receive a single infusion of 5 mg Yigu® or Aclasta®. The primary endpoint was the percentage change in bone mineral density (BMD) at lumbar spine after 12 months of treatment and was assessed for equivalence. The secondary endpoint was the percentage change in BMD at proximal femur after 12 months. Additional secondary endpoints were percentage changes in BMD at the above sites after 6 months of treatment and changes in bone turnover biomarkers during ZOL treatment. Safety was also evaluated and compared between two groups. Results A total of 458 postmenopausal women with osteoporosis were enrolled (n = 227, Yigu®; n = 231, Aclasta®). The mean percentage change in the BMD had no statistical difference at the lumbar spine (5.32% vs 5.18%), total hip (2.72% vs 2.83%), and femoral neck (2.37% vs 2.81%) between Yigu® and Aclasta® groups after 12 months of treatment. The mean difference of BMD change at the lumbar spine after 12 months between two groups was 0.15% (95% CI: − 0.71 to 1.00, equivalence margin: − 1.5%, 1.5%), demonstrating the treatments were equivalent. Meanwhile, the decreases in the P1NP and β-CTX showed no difference between two groups after 14 days and 6 and 12 months of treatment. As regards the whole sample, BMD significantly increased after 12 months of treatment. Also, serum C-terminal telopeptide of type 1 collagen (β-CTX) and procollagen 1 N-terminal peptide (P1NP) significantly decreased at each visit period. The overall adverse events were comparable and quite well between two groups. Conclusion Intravenous infusion of zoledronic acid achieved the potent anti-resorptive effects which led to significant increase in BMD of Chinese postmenopausal women with osteoporosis. Yigu® was equivalent to Aclasta® with respect to efficacy and safety.

Previous articles about MAKO robotic-assisted total hip replacement (THR) were mainly in patients with comparatively normal anatomy.From July 2020 to June 2021, we performed MAKO robotic-assisted THR in three hip-fused patients. We assessed the accuracy of prostheses implantation, collected clinical data, and discussed the value of this technique in this kind of patients.All three patients achieved good leg length and prostheses position. A patient got femoral artery injury during the surgery. Moreover, she developed a thrombus. All three patients got acceptable Visual Analogue Scale scores and function recovery 6 months later.MAKO robotic-assisted THR achieved excellent prosthesis position in hip fused patients. More cases are needed to confirm this advantage. The function recovery was acceptable. Caution should be paid to protect the surrounding abnormal arteries, especially in a limited surgical field.

Wear particle-induced periprosthetic osteolysis is mainly responsible for joint replacement failure and revision surgery. Curculigoside is reported to have bone-protective potential, but whether curculigoside attenuates wear particle-induced osteolysis remains unclear. In this study, titanium particles (Ti) were used to stimulate osteoblastic MC3T3-E1 cells in the presence or absence of curculigoside, to determine their effect on osteoblast differentiation. Rat osteoclastic bone marrow stromal cells (BMSCs) were cocultured with Ti in the presence or absence of curculigoside, to evaluate its effect on osteoclast formation in vitro. Ti was also used to stimulate mouse calvaria to induce an osteolysis model, and curculigoside was administrated to evaluate its effect in the osteolysis model by micro-CT imaging and histopathological analyses. As the results indicated, in MC3T3-E1 cells, curculigoside treatment attenuated the Ti-induced inhibition on cell differentiation and apoptosis, increased alkaline phosphatase activity (ALP) and cell mineralization, and inhibited TNF-α, IL-1β, and IL-6 production and ROS generation. In BMSCs, curculigoside treatment suppressed the Ti-induced cell formation and suppressed the TNF-α, IL-1β, and IL-6 production and F-actin ring formation. In vivo, curculigoside attenuated Ti-induced bone loss and histological damage in murine calvaria. Curculigoside treatment also reversed the RANK/RANKL/OPG and NF-κB signaling pathways, by suppressing the RANKL and NF-κB expression, while activating the OPG expression. Our study demonstrated that curculigoside treatment was able to attenuate wear particle-induced periprosthetic osteolysis in in vivo and in vitro experiments, promoted osteoblastic MC3T3-E1 cell differentiation, and inhibited osteoclast BMSC formation. It suggests that curculigoside may be a potential pharmaceutical agent for wear particle-stimulated osteolysis therapy.

Heterotopic ossification is the formation of pathological bone in non-skeletal tissues (including muscles, tendons or other soft tissues), and the pathogenesis is not completely clear. It is often caused by musculoskeletal trauma, postoperative bone and joint surgery, or damage of the nervous system, the clinical manifestations are joint swelling, pain, and movement disorders, which often occur around the hips, knees, and elbows. At present, the prevention of heterotopic ossification mainly includes drugs, radiotherapy, molecular biological mechanism intervention, and Chinese medicine-related measures. Among them, drugs and radiotherapy are more effective methods to prevent heterotopic ossification. The intervention of molecular biology mechanism to prevent heterotopic ossification has become a new research direction and focus of attention inrecent years, and is basically at the experimental research stage. The treatment of heterotopic ossification includes various methods such as drugs, physical therapy, and surgery. Among them, surgery is recognized as the most effective treatment, however there are still some controversies and disagreements about the choice of operation time and surgical methods.

ObjectivesTo evaluate the morphine-sparing effects of the sequential treatment versus placebo in subjects undergoing total knee arthroplasty (TKA), the effects on pain relief, inflammation control and functional rehabilitation after TKA and safety.DesignDouble-blind, pragmatic, randomised, placebo-controlled trial.SettingFour tertiary hospitals in China.Participants246 consecutive patients who underwent elective unilateral TKA because of osteoarthritis (OA).InterventionsPatients were randomised 1:1 to the parecoxib/celecoxib group or the control group. The patients in the parecoxib/celecoxib group were supplied sequential treatment with intravenous parecoxib 40 mg (every 12 hours) for the first 3 days after surgery, followed by oral celecoxib 200 mg (every 12 hours) for up to 6 weeks. The patients in the control group were supplied with the corresponding placebo under the same instructions.Primary and secondary outcome measuresThe primary endpoint was the cumulative opioid consumption at 2 weeks post operation (intention-to-treat analysis). Secondary endpoints included the Knee Society Score, patient-reported outcomes and the cumulative opioid consumption.ResultsThe cumulative opioid consumption at 2 weeks was significantly smaller in the parecoxib/celecoxib group than in the control group (median difference, 57.31 (95% CI 34.66 to 110.33)). The parecoxib/celecoxib group achieving superior Knee Society Scores and EQ-5D scores and greater Visual Analogue Scale score reduction during 6 weeks. Interleukin 6, erythrocyte sedation rate and C-reactive protein levels were reduced at 72 hours, 2 weeks and 4 weeks and prostaglandin E2 levels were reduced at 48 hours and 72 hours in the parecoxib/celecoxib group compared with the placebo group. The occurrence of adverse events (AEs) was significantly lower in the parecoxib/celecoxib group.ConclusionsThe sequential intravenous parecoxib followed by oral celecoxib regimen reduces morphine consumption, achieves better pain control and functional recovery and leads to less AEs than placebo after TKA for OA.Trial registration numberClinicalTrials.gov (ID:NCT02198924).

Cellular senescence plays both beneficial and detrimental roles in embryonic development and tissue regeneration, while the underlying mechanism remains elusive. Recent studies disclosed the emerging roles of heat‐shock proteins in regulating muscle regeneration and homeostasis. Here, we found that Hsp90β, but not Hsp90α isoform, was significantly upregulated during muscle regeneration. RNA‐seq analysis disclosed a transcriptional elevation of p21 in Hsp90β‐depleted myoblasts, which is due to the upregulation of p53. Moreover, knockdown of Hsp90β in myoblasts resulted in p53‐dependent cellular senescence. In contrast to the notion that Hsp90 interacts with and protects mutant p53 in cancer, Hsp90β preferentially bound to wild‐type p53 and modulated its degradation via a proteasome‐dependent manner. Moreover, Hsp90β interacted with MDM2, the chief E3 ligase of p53, to regulate the stability of p53. In line with these in vitro studies, the expression level of p53‐p21 axis was negatively correlated with Hsp90β in aged mice muscle. Consistently, administration of 17‐AAG, a Hsp90 inhibitor under clinical trial, impaired muscle regeneration by enhancing injury‐induced senescence in vivo. Taken together, our finding revealed a previously unappreciated role of Hsp90β in regulating p53 stability to suppress senescence both in vitro and in vivo.

To study clinical effects of double plating through different approaches for communicated and obvious osteoporosis periprosthetic femoral fracture following total knee arthroplasty(TKA).From July 2010 to June 2017, 21 patients with periprosthetic femoral fracture following TKA were divided into two groups according to operative approach. Fifteen patients in medial and lateral double approaches group, including 5 males and 10 females aged from 63 to 79 years old with an average of (67.2±5.9) years old; 11 patients were type 33-A2 and 4 patients were type 33-A3 according to AO-OTA classification; 12 patients injured by falling down and 3 patients by traffic accident; treated with double plating. Six patients in medial parapatellar approach group, including 3 males and 3 females, aged from 61 to 74 years old with an average of (64.6±6.0) years old; 3 patients were type 33-A2 and 3 patients were type 33-A3 according to AO-OTA classification; 5 patients injured by falling down and 1 patient by traffic accident; treated with double plating. Operative time, blood loss, postoperative drainage, fracture healing time were compared between two groups; HSS score and radiology at 3 and 12 months were compared between two groups.All patients were followed up, and the follow-up time of bilateral approaches group ranged from 12 to 18 months with an average of (14.2±2.6 ) months, while the follow-up time of single approach group ranged from 12 to 16 months with an average of (12.6±2.5) months, and there was no statistical difference between two groups. The operative time and postoperative drainage in bilateral approaches group were (107.2±10.4) min and (213.9±30.4) ml, while in sigle approach group was (95.4±12.8) min and (256.8±34.2) ml, and the differences were significant(Double plating technique for communicated and obvious osteoporosis periprosthetic femoral fracture following TKA could obtain good function of knee joint. The medial parapatellar approach has shorter operative time, while the bilateral approaches had less drainage.

The regenerative process of injured muscle is dependent on the fusion and differentiation of myoblasts derived from muscle stem cells. Hsp70 is important for maintaining skeletal muscle homeostasis and regeneration, but the precise cellular mechanism remains elusive. In this study, we found that Hsp70 was upregulated during myoblast differentiation. Depletion or inhibition of Hsp70/Hsc70 impaired myoblast differentiation. Importantly, overexpression of p38 mitogen-activated protein kinase α (p38MAPKα) but not AKT1 rescued the impairment of myogenic differentiation in Hsp70- or Hsc70-depleted myoblasts. Moreover, Hsp70 interacted with MK2, a substrate of p38MAPK, to regulate the stability of p38MAPK. Knockdown of Hsp70 also led to downregulation of both MK2 and p38MAPK in intact muscles and during cardiotoxin-induced muscle regeneration. Hsp70 bound MK2 to regulate MK2-p38MAPK interaction in myoblasts. We subsequently identified the essential regions required for Hsp70-MK2 interaction. Functional analyses showed that MK2 is essential for both myoblast differentiation and skeletal muscle regeneration. Taken together, our findings reveal a novel role of Hsp70 in regulating myoblast differentiation by interacting with MK2 to stabilize p38MAPK.

To investigate clinical efficacy and experience of total knee arthroplasty in treating knee osteoarthritis patients with Parkinson's disease.From January 2011 to January 2014, 19 knee osteoarthritis patients with Parkinson's disease treated with total knee arthroplasty were collected. Among them, including 9 males and 10 females aged from 61 to 83 years old with an average of 71.3 years old. Radiology results were checked before and after operation. VAS score and KSS score were applied to evaluate clinical effects. Patients were classified according to HoehnYahr grade, 3 cases in grade 1, 4 cases in grade 1.5, 2 cases in grade 2, 4 cases in grade 2.5, 2 cases in grade 3 and 1 case in grade 4.Nineteen patients were followed up from 3 to 7 years with an average of 4.3 years. The pain of patients was significantly reduced or disappeared. All incisions were healed at stage I. At the latest follow-up, 3 patients had knee pain, and mild pain in 1 patient, moderate in 1 patient without severe pain. VAS score was reduced from preoperative 8.4±1.3 to the latest follow-up 3.1±1.2, the difference was statistically significant (Total knee arthroplasty is a safe and effective method for the treatment of Parkinson's disease and has satisfactory mid-term clinical effect.

To explore clinical efficacy of hip replacement for hip-joint diseases with Parkinson disease.From December 2011 to December 2016, 18 patients with hip-joint diseases with Parkinson disease treated by hip replacement, including 8 males and 10 females aged from 59 to 87 years old with an average of 71 years old. Among them, 3 cases were developmental dysplasia of hip, 3 cases were femoral head necrosis and 12 cases were femoral neck fracture. All patients manifested with obvious pain and limitation of stepping ability. Postoperative complications were observed and Harris score were used to compare hip joint function after operation.The incision were healed well, and pain were alleviated or disappeared, and hip joint function were improved. Eighteen patients were followed up from 1 to 3 years with an average of 2.3 years. At the latest follow up, 14 cases recovered freedom-walk, 2 cases could walk with walking stick, 1 case could walk with walking aid and 1 case was died. Among 18 patients, 2 cases were occurred dislocation, and 1 case were died for cardiac disease at 3 months after operation. Four patients were occurred slight pain. There were significant differences in Harris scores among preoperative (41.7±1.4), 6 months after operation(80.1±5.4) and the final follow-up (83.4±2.1), and 10 cases got excellent result, 4 good, 1 fair and 2 poor.Application of hip replacement for hip-joint diseases with Parkinson disease is a safe and effective clinical therapy, and has advantages of less complications and rapid recovery of hip joint function.

BACKGROUND AND PURPOSE: Aseptic prosthesis loosening, caused by wear particles, is one of the most common causes of arthroplasty failure. Extensive and over‐activated osteoclast formation and physiological functioning are regarded as the mechanism of prosthesis loosening. Therapeutic modalities based on inhibiting osteoclast formation and bone resorption have been confirmed to be an effective way of preventing aseptic prosthesis loosening. In this study, we have investigated the effects of sophocarpine (SPC, derived from Sophora flavescens) on preventing implant loosening and further explored the underlying mechanisms. EXPERIMENTAL APPROACH: The effects of SPC in inhibiting osteoclastogenesis and bone resorption were evaluated in osteoclast formation, induced in vitro by the receptor activator of NF‐κB ligand (RANKL). A rat femoral particle‐induced peri‐implant osteolysis model was established. Subsequently, micro‐CT, histology, mechanical testing and bone turnover were used to assess the effects of SPC in preventing implant loosening. KEY RESULTS: In vitro, we found that SPC suppressed osteoclast formation, bone resorption, F‐actin ring formation and osteoclast‐associated gene expression by inhibiting NF‐κB signalling, specifically by targeting IκB kinases. Our in vivo study showed that SPC prevented particle‐induced prosthesis loosening by inhibiting osteoclast formation, resulting in reduced periprosthetic bone loss, diminished pseudomembrane formation, improved bone‐implant contact, reduced bone resorption‐related turnover and enhanced stability of implants. Inhibition of NF‐κB signalling by SPC was confirmed in vivo. CONCLUSION AND IMPLICATIONS: SPC can prevent implant loosening through inhibiting osteoclast formation and bone resorption. Thus, SPC might be a novel therapeutic agent to prevent prosthesis loosening and for osteolytic diseases.

To retrospective analysis the mid-term follow-up effect of hip joint replacement in elderly patients with failure of intertrochanteric fractures of the hip joint internal fixation.From December 2008 to December 2011, 32 elderly patients underwent arthroplasty after intertrochanteric fracture fixation failure, of which, 4 death cases were excluded from the study, and the remaining 28 cases were in the study group. The age of patients ranged from 69 to 83 years old with a mean of 75 years old. The time from the internal fixation to the hip replacement were 8 to 72 months. Among them, 6 patients were Evans I type, 11 patients were Evans II type, 9 patients were Evans III type, and 2 patients were Evans IV type. Nine cases showed fracture of the lateral plate before operation, while 15 cases were femoral head screw cut-out and 4 cases were screw loosening. Harris score was used to compare the changes of hip function before operation with the final follow-up. Imaging results(X-ray) and erythrocyte sedimentation rate(ESR) were performed during the follow-up.All patients were followed up from 4 to 7 years with an average of 5.3 years. Pain was significantly reduced or disappeared in patients compared with pre-operation. And hip function was significantly improved. Two cases had moderate pain after the physical activity and 4 cases had mild pain after the physical activity. At the final follow-up, 19 patients resumed free walking, 8 patients required walking with walking sticks, and 1 patient needed walking aid. The Harris scores improved from preoperative 34.9±2.4 to 83.4±5.7 at the final follow-up, among them, 15 cases were classified as excellent, 10 as good, 2 as fair, and 1 as poor. X-ray examination showed no prosthesis loosening and sinking fracture.Salvage THA surgery could improve the hip function and the quality of life for old patients with intertrochanteric fracture fixation failure, and the middle-term follow-up results support that.

We studied the effect of molecular polyethylene particles on local heterotopic ossification. A total of 36 healthy Sprague-Dawley rats were randomly divided into the control group (n=18) and the observation group (n=18). High molecular polyethylene particles were injected to rupture Achilles tendon position in the observation group, and normal saline was injected in the control group. X-ray examinations were conducted on Achilles tendon in the 4th, 8th and 12th week after operation. The incidence rate of heterotopic ossification was evaluated, and bone trabecula morphological structure was studied under optical microscope after hematoxylin and eosin staining. Bone morphogenetic protein 2 (BMP-2), transforming growth factor-β (TGF-β), interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), runt-related transcription factor 2 (Runx2) and matrix metalloproteinase-9 (MMP-9) expression levels were also measured. Our results showed that heterotopic ossification incidence in the observation group was significantly lower than that in the control group. Achilles tendon structure in the control group increased in volume, and its texture was harder and cartilage-like. In the observation group, trabecular bone volume, thickness and quantity were more than those observed in the control group. BMP-2, TGF-β, IL-1, TNF-α, Runx2 and MMP-9 levels in the observation group were significantly lower than those in the control group. We concluded that, high molecular polyethylene particles had a significant inhibiting effect on local heterotopic ossification.

To investigate the stability of internal fixation for femoral neck fracture(FNF) using two or three cannulated screws directed to different fracture lines, and to provide a theoretical basis for the clinical decision making.Fifteen fresh frozen human femur samples were selected and the FNF model was established with Pauwels angle of 30°, 50° and 70° respectively. The models were fixed with three or two cannulated screws, and their differences at tensile strength, subsidence, shear strength and composite displacement, gap distance, torsional angle and stiffness values of four types of femur were evaluated to identify their biomechanical stability.With Pauwels angle of 30° and 50°, no statistical differences at the referenced outcomes were observed between two and three cannulated screw fixation for FNF(With Pauwels angle of 30° and 50°, two cannulated screws fixation was similarly stable as using three cannulated screws for FNF. Three cannulated screws fixation were obviously superior to two cannulated screws fixation when Pauwels angle was 70°, but the application of three cannulated screws could still be insufficiently stable when only such routine fixations were utilized. Therefore, Angle Stabilizing System or anti-sliding screws were needed to enhance the stability of FNF fixation.

The osteonecrosis of femoral head (ONFH) has been a common disorder in clinical orthopaedic practice. ONFH is the relative contraindication of hip arthroplasty for the young and active patients since they suffer a high rate of revision and inferior function postoperatively. The primary importance in therapy is to prevent the progression of the disease and the collapse of the articular surface in order to keep away from hip arthroplasty. Low-intensity pulsed ultrasound (LIPUS) has been indicated to enhance the osteogenic differentiation of mesenchymal stem cells, stimulate the differentiation and the proliferation of osteoblasts, inhibit osteoclasts, improve the local blood perfusion and the angiogenesis, and accelerate the healing process of the stress fracture. We present a hypothesis that LIPUS may be an appropriate non-invasive modality for bone repair in the early stage of ONFH so that the progressive collapse of the articular surface and the subsequent arthroplasty would be avoided.

Osteonecrosis of the femoral head (ONFH) is a devastating disease that can result in a femoral head collapse. By proteomics analysis, we identified 1,967 proteins with two or more unique peptides from ONFH and from control bones with a false discovery rate of 4.8%. Using spectral counting, we identified 141 overexpressed and 56 underexpressed proteins comparing ONFH bones to the controls. GSEA (gene set enrichment analysis) revealed that proteins overexpressed in ONFH are enriched for gene sets related to multiple myeloma and adult T-cell lymphoma (ATL), and to JAK2-dependent genes. We confirmed the underexpression of CHST2 (isoform 1 of carbohydrate sulfotransferase 2), a key protein involved in biosynthesis of chondroitin sulfate proteoglycans, and the underexpression of GPCR26 (G-protein coupled receptor 26), a protein that mediates intracellular calcium mobilization, in ONFH bones compared to controls. Taken together, our data suggest that biosynthesis of chondroitin sulfate proteoglycans and cation transport and mobilization may be a key process involved in the pathogenesis of ONFH. Our analysis sheds new light on the understanding of the pathogenesis of ONFH.

Rhizoma drynariae is used commonly in the treatment of osteoporosis and bone nonunion in traditional Chinese medicine. Modern pharmacological research indicates that naringin is the main effective component of rhizoma drynariae, which can induce the expression of the osteogenic marker in the osteoblast cell line. However, no former study has described its effect on bone mesenchymal stem cells (BMSCs). In our experiment, we co-cultured human BMSCs with different concentrations of naringin solution, then the osteogenic differentiation markers and proliferation ability were analyzed. The results indicated that a certain concentration (1–100 μg/ml) of the naringin solution may enhance the proliferation and osteogenic differentiation of human BMSCs. Also, our research explains excellently the anti-osteoporotic and bone nonunion treatment mechanism of rhizoma drynariae, thus contributing to the exploration of osteogenic differentiation agents from Chinese herbs.

In this cross-sectional study, we examined whether hyperuricemia is associated with hypertension and the association exists in a Chinese population at a high risk of hypertension. The study population included 813 consecutively clinical patients with suspected cardiovascular disease, including the subjects with the current use of antihypertensive medications and self-reported diagnosis of hypertension. The subjects underwent three measures of blood pressure and were divided into two groups: 502 non-hypertensive subjects and 311 hypertensive subjects. Clinical and biochemical variables were measured. Results showed that uric acid level, fasting glucose, low-density lipoprotein (LDL)-cholesterol, total cholesterol and urea nitrogen were significantly higher (all p0.05) in hypertension subjects than in non-hypertension subjects. The risk of hypertension was significantly higher in the group with higher uric acid (400 micromol/l), compared with that with lower uric acid (200 micromol/l) (odds ratio: 2.09, 95% CI 1.13-3.88). The odds ratio was 1.73, 95% CI 1.05-2.85 in the higher uric acid (200-400 micromol/l) group, compared with that with lower uric acid. In addition, age, gender, weight, fasting glucose, triglycerides and total cholesterol were also significantly associated with the incidence of hypertension. In age-adjusted logistic regression analysis, the effect of uric acid concentration on hypertension was attenuated. In conclusion, hyperuricemia is associated with hypertension in a Chinese population at a high risk of hypertension.

In the present investigation, four titanium (Ti) surfaces of dental implants were compared through in vitro systems. The surface roughness of Ti was measured by TR240 mobile surface roughmeter. The Ti implants were seeded with human periodontal ligament cells (hPLDCs) and maintained for a period of 0-7 days. The adhesion, proliferation, and differentiation of hPLDCs were observed by using Cell morphology, cell counting and Osteocalcin (OC) immunofluorescent staining. Results suggest that surface roughness of titanium favors hPDLCs behavior and improves cell adhesion, proliferation, and differentiation.

To evaluate the effectiveness of the cell-material in situ on joint resurfacing, a woven fabric polyglycolic acid (PGA) treated with fresh chondrocytes was used for repairing cartilage defects. Full-thickness defects were created in the weight-bearing surfaces of the femoral intercondylar fossa in a rabbit model. The defect was filled with and without PGA under surgical condition. Before implantation, chondrocytes were co-cultured with PGA for one day. The animals were sacrificed at eight weeks after implantation and evaluated grossly and histological score. Morphological examination showed that for PGA/chondrocytes group, the repaired tissue appeared similar in color and texture to the surrounding articular surface. While for the untreated control, no cartilage-like tissue was observed at all defects, but connective fibrous tissue. Histological analysis revealed neochondrogenesis and clusters of cartilage matrix with specific safranin-O staining for the PGA/cell group. The Gross and histological evaluation indicated a significantly higher score for PGA/cell group than for PGA and control group. These results suggest that the woven fabric PGA may facilitate the formation of cartilage tissues by providing a biodegradable and good-handle vehicle for the delivery to and retention of organized cell matrix constructs in vivo site. It might therefore enhance neochondrogenesis because of the superior biodegradable and biocompatible of PGA scaffold sheet, while the more suitable biological environment might sustain cell growth and in situ cell function, suggesting a promising candidate for functional tissue engineering of clinical environment.

To study the bone state with ultimate stress by examining biomechanical distribution of upper femur in Chinese, in order to accumulate more experiences for clinical work.Totally 60 Chinese femurs from fresh cadavers were randomly divided into two groups. All the femurs were cleaned, and the body age ranged from 36 to 72 years old, averaged 56.4 years, including 41 from males, and 19 from females. These two groups underwent mechanical stress and bending stress tests. Special mechanical laboratory and machines were used to get the information. Results about the loading value at each testing point under stress were collected.The four faces of the upper femur suffered different stress under external forces. The bone on upper femur can tolerate more mechanical stress than bending stress. Medial and lateral region of the femur neck and the rear side of the small tuberosity section were themain position enduring the vertical stress. The rear position of the base femur neck and the small tuberosity section were the main regions enduring the bending stress. Those main positions had strong cancellous bones. The intertrochanteric fracture fixation and artificial femoral stems were designed depending on this biomechanical basis.According to our experiment result, doctors need to chose more effective fixations for upper femur fracture, and femoral stems for the patients. More information should be collected by further researches.

Osteonecrosis of femoral head (ONFH) is a common joint disease with high morbidity in mainland China. We performed a retrospective case investigation based on the widest range of patients ever to reveal the demographic and clinical characteristics of ONFH in mainland China. We collected data from hospitalized patients of nine large tertiary hospitals in China, focusing on the aetiology of ONFH. Medical records and self-design questionnaires were used to collect data. We determined the patients’ aetiology according to established guidelines and categorized patients into different subgroups. We further analysed the underlying illness of the steroid-induced osteonecrosis of femoral head. A total of 6,395 patients with complete medical records were included in the study. The age (mean ± SD) of the patients was 46.45 ± 13.80 years. Males dominate with 70.1 % of all ONFH patients. In all the ONFH patients, 24.1 % are steroid induced, 30.7 % are alcoholic, 16.4 % are traumatic and 28.8 % are idiopathic. Among steroid-induced osteonecrosis of femoral head patients, 546 patients have autoimmune disorder (46.63 %), which is the most common underling illness, among these, the most common disease is systemic lupus erythematosus (SLE). The most common age when ONFH occurs is between 40 and 50 years old. Male patients developed ONFH 3.4 years earlier than female patients. The number of the male patients is greater than the female, reaching the overall gender proportion of 7:3. Autoimmune disease is the primary cause of steroid-induced ONFH, among which SLE is the most common disease.

Monotropein, the primary iridoid glycoside isolated from Morindacitrifolia, has been previously reported to possess potent antioxidant and antiosteoporotic properties. However, there is no direct evidence correlating the antiosteoporotic effect of monotropein with its observed antioxidant capacity, and the molecular mechanisms involved in mediating these processes remain unclear. Therefore, the aim of the present study was to investigate the protective effects of monotropein against oxidative stress in osteoblasts and the mechanisms involved in mediating this process. Osteoblast viability was evaluated using the MTT assay. The mitochondrial membrane potential and reactive oxygen species were detected by flow cytometry analyses. Western blotting and enzyme‑linked immunosorbent assays were performed to detect protein expression levels. A significant reduction in osteoblast viability was observed at 24 h following exposure to various concentrations (100‑1,000 µM) of H2O2 compared with untreated osteoblasts. The cytotoxic effect of H2O2 was notably reversed when osteoblasts were pretreated with 1‑10 µg/ml monotropein. Pretreatment with 1-10 µg/ml monotropein increased the mitochondrial membrane potential and reduced the generation of reactive oxygen species in osteoblasts following exposure to H2O2. In addition, the H2O2‑induced increase in apoptotic markers (caspase-3 and caspase-9) and H2O2-induced reduction in sirtuin 1 levels were significantly reversed following pretreatment of cells with monotropein. Furthermore, monotropein significantly reduced H2O2‑induced stimulation of NF‑κB expression, in addition to the expression of a number of proinflammatory mediators. These results indicate that monotropein suppresses apoptosis and the inflammatory response in H2O2‑induced osteoblasts through the activation of the mitochondrial apoptotic signaling pathway and inhibition of the NF‑κB signaling pathway.

According to the information obtained from the revision of total hip arthroplasty, the situations of the artificial femoral stem under physiological stress were analyzed preliminarily. In order to accumulate clinical experience, the discussions about how to enlongate the life of artifical joints were performed.Fifty-three patients required revision operations were selected, including 28 males and 25 females,with an average age of 74.66 years old (61 to 84 years old). The average life of artificial joints was 18.24 years (3 to 27 years). The initial weightbearing was started 11 days (5 to 16 days) after the first operation. The main reasons for the revision were the spontaneous loosening and trauma. Based on imaging and surgical findings, as well as the histological pathology, the situations of the stems in human bodies were determined.Femoral prosthesis would sink under physiological stress. The design of femoral stems, motion of patients', and bone growth determined the secondary stability. Straight stems were helpful for physiological subsidence of prosthesis, achieving the stability with close bone-implant contact by bone growth,which allowed the patient to do early landing exercise. The collared prosthesis and prosthesis combined with internal fixation limited the subsidence of femoral stems. Their stability depends on the time of initial placement and the bone growth for supporting. Delaying the inital weightbearing was suggested for patients with these protheses.According to the actual situation of the patients, the appropriate chosen of femoral stems and time to perform the weightbearing can extend the life of the femoral prosthesis.

Stimulation of bone healing through local application of growth factors from implants may improve the clinical outcome in fracture treatments. However, the growth factors in reconstructive application require supraphysiologic dosing and considerable expense while hampering their clinical application. Genetic modification of mesenchymal stem cells (MSCs) to both produce and respond to osteogenic factors may have potential for use in enhancing bone healing. In this study, MSCs were genetically modified by a recombinant adenoviral containing the gene for human bone morphogenetic protein 2 (hBMP-2). The gene-transduced cells were incorporated with a porous beta-tricalcium phosphate (TCP) as a novel complex. We investigated osteogeneic potential of gene-transduced MSCs/ceramic and the ability of the complex on facilitating bone formation in a radius segmental defect of rabbits. In vitro results showed that there were apparent hBMP2 gene expression and protein synthesis in MSCs with hBMP2 stably transfection, whereas negative expression of hBMP2 in controls. Histological studies demonstrated that gene-transfected MSCs/ceramic composite appeared an ability of heterotopic osteogenesis. In the segmental bone defects, endochondrial ossification at fracture sites was found in both transfected and untransfected MSCs-ceramic composites. While the composite with hBMP2 transfection showed the earliest and the most effective healing of the segmental bone defects both radiographically and morphologically. Our results show that genetically modified MSCs/ceramics had enhanced osteogeneic capacity relative to unmodified MSCs or only ceramic implants. This study suggests that use of cell-and gene-activated bioceramics may offer promise for molecular design of implants to induce osteogenesis and enhance bone regeneration.

Though it is well accepted that low-intensity pulsed ultrasound (LIPUS) can accelerate the healing process of a fracture with very good results, we should still pay attention to its side effects and further improve its application in detail, such as the appropriate time and point for the application. In the early phase of a bone fracture, there are millions of oxygen radicals released by neutrophils in the injured area. This article focuses on whether the increased permeability of normal cell membranes by LIPUS makes the concentration of oxygen radicals increase to such a high degree that damage occurs to healthy tissue cells. It is proposed that it may be better not to use LIPUS in the acute phase of a fracture (i.e. within 1week after injury) but instead delay its application until after any inflammatory reaction has weakened to yield better results.

To evaluate the clinical efficiency of selective cyclo-oxygenase-2 (COX-2) inhibitor compared to traditional nonselective NSAIDs for the prevention of heterotopic ossification (HO) after total hip arthroplasty (THA).By searching Medline, Embase, CENTRAL (Cochrane Central Register of Controlled Trials) and Science Citation Index et al, only randomised controlled studies of selective COX-2 inhibitors VS nonselective COX-1 and COX-2 inhibitors for the prevention of HO after THA were included. The quality assessment of included studies was evaluated according to the standard of the Cochrane Collaboration, and the data were analysised by statistic software Stata 10.0. The HO incidence of both groups in different degrees was compared.Four eligible randomised controlled trials of totally 808 patients were included. Meta-analysis results showed that no statistically significant difference was found in overall incidence of HO (RR = 1.08, 95% CI: 0.71-1.64,P = 0.73), incidence of moderate severe HO (Brooker II and III) (RR = 0.83, 95% CI: 0.48-1.42, P = 0.49) and any grade of Brooker classification between two groups. In all included studies, 16 patients receiving nonselective COX inhibitor (4.4%) discontinued treatment because of gastrointestinal toxicity,whereas 10 patients in the selective COX-2 inhibitor group (2.7%) discontinued for gastrointestinal side effects.The selective COX-2 inhibitors are as equally effective as nonselective NSAIDs for the prevention of HO after THA. Considering the side effects of nonselective NSAIDs, selective COX-2 inhibitors were recommend for the prevention of HO after THA.

OBJECTIVE: The purpose of this study was to systematically review published reports that compare the outcomes of single‐row and double‐row suture anchor fixation in arthroscopic rotator cuff repair. METHODS: Combined data regarding relevant patient characteristics, rotator cuff pathology, surgical techniques, postoperative rehabilitation regimens, University of California at Los Angeles (UCLA) Scores, Constant scores, American Shoulder and Elbow Society (ASES) scores, tendon healing, incidence of recurrent rotator cuff defects, shoulder muscle strength, range of motion, surgical time and patient satisfaction were assessed. RESULTS: Seven eligible randomized controlled studies and four prospective cohort studies were identified. There were no significant differences between the single‐row and double‐row groups in terms of Constant or ASES scores. However, UCLA scores, tendon healing, abduction shoulder strength index (SSI), external rotation SSI and internal rotation SSI were significantly better for double‐row technique than for single‐row technique. A statistically significant advantage for double‐row repair according to UCLA score and external rotation SSI was found in the subgroup with tears greater than 3 cm. CONCLUSION: No definite conclusion could be drawn about differences in overall outcomes of double‐ and single‐row techniques for repairing for small to medium (3 cm) rotator cuff tears, even though some measures of clinical outcome showed significant differences between these two techniques.

To retrospectively study medium-term follow-up outcomes of total hip arthroplasty (THA) for patients with ankylosing spondylitis (AS).From January 2000 to December 2008, 67 patients (88 hip joints) with AS were treated with all ceramic interface THA. And 55 patients (74 hips) were finally followed up. Among them, there were 30 males and 25 females, with an average age of 32.6 (ranged 19 to 58) years old. Sixty-one hips were treated with biological prosthesis and 13 hips were treated with hybrid prosthesis. Fifty-five patients were followed up at least 5 years, with an average of (75.2 +/- 8.6) months. Clinical symptoms and radiography information were evaluated after follow-up.Harris hip score were significantly improved from 30.8 +/- 7.0 preoperatively to 85.2 +/- 5.5 at the last follow-up (P0.01). The hip movement range increased from (21.2 +/- 8.5) degrees preoperatively to (142.0 +/- 10.2) degrees postoperatively (P0.01). The 5-year survival of prosthesis was 95.9%. One patient were renovated because of internal wall broken caused by injury, 1 was renovated for infection, 1 was renovated for fracture arround femoral stem prostheses, and 1 was treated with conservative treatment by dislocation. Three cases with abnormal sound were cured with non-operation. 7 cases with heterotopic ossification were not treated, 2 cases with thigh pain received conservative treatment. Bone dissolve around prosthesis, loose and sink of femur and acetabulum prosthesis were occurred in other cases.THA for the treatment of AS is a reliable method, which has a satisfied medium-term follow-up outcomes.

OBJECTIVE: To investigate the effect of overexpression of cartilage oligomeric matrix protein (COMP) on bone morphogenetic protein‐2 (BMP‐2) induced osteogenic and chondrogenic differentiation of mesenchymal stem cells (MSCs). In this study, we used liposomes to transfect MSCs with plasmid encoding COMP and then induced the transfected MSCs to differentiate in osteogenic and chondrogenic differentiation media containing BMP‐2. METHODS: MSCs transfected with plasmid DNA encoding recombinant human COMP were induced to differentiate into osteocytes and chondrocytes by BMP‐2. Real‐time polymerase chain reaction (PCR) assays of osteogenesis‐related markers (collagen type I alpha 1, runt‐related transcription factor 2, osteopontin, bone gla protein) and chondrogenesis‐related markers (collagen type II alpha 1, sry‐related high‐mobility group box 9, Aggrecan) was performed to evaluate the process of cell differentiation. Cell differentiation was evaluated by alkaline phosphatase (ALP) and Alizarin red S stains for osteogenic differentiation and alcian blue staining for chondrogenic differentiation. RESULTS: Real‐time PCR assay showed significantly greater COMP expression by MSCs when COMP gene had been transfected into the cells (P < 0.01). Overexpression of COMP down‐regulated expression of osteogenesis‐related markers and up‐regulated expression of chondrogenesis‐related markers. ALP staining and Alizarin red S staining were weakened, whereas alcian blue staining was enhanced. CONCLUSION: Overexpression of COMP inhibits BMP‐2‐induced osteogenic differentiation and promotes BMP‐2‐induced chondrogenic differentiation. These findings may provide new insights for cartilage tissue engineering. The experiments in the present study were all in vitro, which has potential limitations. Further in vivo studies to investigate the effects of COMP in animal models are necessary, which will be the next step in our research.

To develop the techniques of total hip arthroplasty(THA) for Crowe type IV developmental dysplasia of the hip (DDH) with S-ROM prosthesis,and to assess its clinical results.From October 2000 to October 2011,30 patients (36 hips) with Crowe type IV DDH underwent THA,including 6 patients with bilateral hip involved and 24 patients with unilateral. S-ROM prosthesis was adopted together with subtrochanteric transverse osteotomy. All the cementless acetabular cups were placed at the original anatomic location. The threaded cups were put in or near the level of the true acetabulum in all patients. Full coating stems were used in femoral side. All the patients were evaluated by using the Modified Harris Hip Score. Radiographic evaluations were made preoperatively and during follow-up.Two patients lost of follow-up. Twenty-seven patients with 32 hips were followed up,and the average duration was 48 months (ranging from 7 to 84 months). There was 1 patient with bilateral THA died from hemorrhagic shock. Two patients could walk freely with the visible fracture lines at 12th and 18th months postoperatively. There were no complications such as infection or nerve injuries. Modified Harris Hip Score improved from preoperative 41.7+/-3.7 to postoperative 89.1+/-2.9. There was no acetabular or femoral component revision because of mal-position or loosening of the prostheses in all patients. Postoperative X-ray showed that all the prostheses in place,good integration between acetabular cups,femoral prosthesis and host bone without loosening. All bone grafts were integrated. All the hips acquired union of osteotomy and bone in-growth. None of the patients had radiographic evidence of aseptic loosening of prosthesis.For the complex DDH, follow methods should be used to improve therapeutic effects:good exposure of the true acetabulum,deepen acetabulum, femoral shortening, oblique osteotomy, using the S-ROM prosthesis.

Ceramic bearing surfaces have been introduced to prevent osteolysis after total hip arthroplasty (THA), but little is known about the difference in clinical and radiological results between pure alumina and sandwich alumina bearings. The purpose of this study was to analyze the results obtained with third-generation alumina-on-alumina THA with two different designs both in liner and femoral stem fixation after a minimum follow-up of 4.2 years.The results of 195 primary alumina-on-alumina THAs in 167 patients were evaluated. The procedures were performed between January 1998 and October 2006. Three patients died and 11 patients were lost to follow-up, leaving a total of 153 patients (181 hips) available for study. In the 88 group A patients, 107 hips were implanted using pure alumina bearings with cementless femoral stems. These patients were followed for (6.84 ± 1.49) years. In the 65 group B patients, 74 hips were implanted using sandwich alumina ceramic bearings with cemented femoral stems. These patients had a follow-up period of (7.73 ± 1.60) years. Patients in both groups were evaluated clinically and radiographically.One ceramic liner fracture occurred in group A and five took place in group B (P0.05), four of them revised for liner fracture. In each group, one acetabular shell migration happened without liner breakage and two hips developed deep infections, and all these six hips received revisions. Nine femoral components loosened in group B, with seven undergoing revisions. Kaplan-Meier survivorship at 5 years for revision of any component for any reason in group A was 96.26% compared to 90.54% in group B (P0.05). Better function was determined in group A (average Harris hip scores: 92.13 ± 2.85) than in group B (average Harris hip scores: 86.03 ± 4.21) and the difference was significant (P0.05). Squeaking was not recorded in either group.The sandwich design of the acetabular bearings can not reduce the migration rate in ceramic bearings but increase the liner fracture rate compared to pure ceramic liners. The high loosening rate in fluted and taped designed cemented stems with sandwich liners warrant caution to their use.

It is well accepted that the minimally invasive surgery (MIS) for total hip arthroplasty (THA) should combine with less or no muscle damage and is different from mini-incision technique and MIS should have better outcomes than mini-incision surgery. The aim of current analysis was to apply an explicitly defined sub-group analysis to confirm whether this hypothesis is true.A computerized literature search was applied to find any data concerning MIS or mini-incision THAs. A multistage screening was then performed to identify randomized studies fulfilling the inclusive criteria for the analysis. The data were extracted, and sub-group analyses of MIS or mini-incision surgery for different kinds of outcomes were carried out. The P(sub) value for difference between MIS sub-group and mini-incision sub-group was also calculated.Eleven studies that fulfilling the inclusion criteria were included, with 472 cases in the study group (MIS or mini-incision) and 492 cases in the conventional group. The overall analysis showed the study group would achieve less surgical duration (P = 0.037), intraoperative blood (P0.001) and incision length (P0.001) than conventional group. The difference between sub-groups showed, the MIS would achieve shorter incision length (P(sub)0.05) and bigger cup abduction angle (P(sub)0.05), and cause more blood loss (P (sub)0.05) than mini-incision technique. Other indexes were comparable between the two sub-groups.Though further high quality studies are still needed, the result of current analysis offered an initial conclusion that MIS THA failed to achieve a better clinical outcome than mini-incision technique. The exact definition of MIS still needs to be improved.

This work was carried out to evaluate the clinical efficacy and the complications of S-ROM modular hip arthroplasty combined with transverse subtrochanteric shortening for Crowe type IV congenital dislocation of the hip (CDH).A total of 28 consecutive patients with Crowe type IV CDH received treatment using this surgical technique from June 2003 to June 2010. The follow-up was conducted at 3 days, 1, 6, and 12 months after the operation and later annually at the outpatient of our hospital. Sequential pelvic plain film and normotopia film of the affected hip joint were taken. The limp and the Trendelenburg sign were also assessed, the ischiadic nerve injury was also evaluated by electromyogram, and Harris hip scores were recorded.After operation, both the alignment and the position of the transverse osteotomies were good. None of the patients had presented complications of joint infection, prosthesis loosening, joint dislocation, or nerve injury.S-ROM modular hip arthroplasty combined with transverse subtrochanteric shortening was a satisfactory and safe technique for the Crowe type IV congenital hip dislocation within a mean follow up of 53 months. Transverse subtrochanteric shortening could effectively prevent the distraction injury of sciatic nerve.