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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

To explore the intermediate outcomes of third-generation alumina-on-alumina total hip arthroplasty (THA).A consecutive series of 165 primary alumina-on-alumina total hip arthroplasties were performed in 135 patients. Three patients died and 13 patients lost follow-up so that a total of 119 patients (146 hips) were available for study. The mean patient age was 53.4 ± 11.0 years old (range: 26 - 79). Hydroxyapatite. (HA)-coated press-fit acetabular cups were used in all cases. At femoral side, 123 cases were implanted with HA-coated uncemented stems and 23 cases implanted with high polished double taped cemented stems. All patients were evaluated clinically and radiographically after a minimal follow-up duration of 60 months.The preoperative mean Harris hip score of 49.6 ± 7.9 points improved to 91.7 ± 3.0 points at the last follow-up (P0.05). The 5-year survival for any reason lead to revision was 96.6%. Five hips were under revision, 1 for acetabular shell loosening and migration, 1 for Vancouver B2 periprosthetic fracture, 1 for fracture of pure alumina liner and 2 for infections. All other prostheses demonstrated no radiographic evidence of loosening. No periprosthetic osteolysis was found. There were 2 cases of dislocations and 2 patients presented postoperatively with "squeaking-like" hips.The clinical and radiographic outcomes after primary THA with third-generation ceramic-on-ceramic bearing surfaces are favorable after a minimal follow-up duration of 5 years. The modified alumina-on-alumina bearing implants offer a better option for younger and active patients.

Over the past three decades, alumina ceramic, now in its third/fourth generation, has been markedly improved in terms of its mechanical properties, including purity, grain microstructure, and burst strength. In the clinic, it is particularly suitable for young and for very active patients. This paper discusses the development and characteristics of different kinds of ceramics. In addition, ceramics in the third/fourth generation which are used in total hip arthroplasty clinically are reviewed in detail.

Isolated patellofemoral osteoarthritis is not uncommon. Surgical treatment of isolated patellofemoral arthritis remains controversial and poses a challenging treatment dilemma. The present study aimed to evaluate the short-term results of patellofemoral arthroplasty for patients with isolated patellofemoral osteoarthritis.We analyzed 11 patellofemoral arthroplasties performed from March 2006 to September 2009 in 11 patients with isolated patellofemoral arthritis. The patients comprised 2 males and 9 females with an average age of 53.7 years (range, 46 - 74 years). Standard weightbearing radiographs were taken in the anteroposterior, lateral, and 45° axial views. The knee pain and functional status were evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scales and American Knee Society (AKS) scores. For comparison, 23 total knee arthroplasties in 23 patients with primary tibiofemoral osteoarthritis were matched according to age, gender, bilaterality and body mass index. The duration of follow-up was 23.7 months (range, 12 - 47 months).The majority of the 11 patients experienced improvement in their patellofemoral symptoms after patellofemoral arthroplasty. The WOMAC scores improved considerably by 7.4 points with respect to pain and by 5.2 points with respect to function. The AKS scores also improved considerably by 23.9 points with respect to pain and 44.3 points with respect to function. Although the clinical outcomes after patellofemoral arthroplasty were not better than those after total knee arthroplasty, patellofemoral arthroplasty exhibited advantages in the shorter operation time, lower blood loss and increased postoperative range of motion. At the latest follow-up, there was no clinical or radiographic evidence of patellofemoral maltracking, loosening or wear.On the basis of our experience in this relatively small series of patients with a short-term follow-up, patellofemoral arthroplasty is an effective treatment alternative to total knee arthroplasty in isolated patellofemoral arthritis. MRI and arthroscopy may contribute to define those patients with isolated patellofemoral degeneration.

Pyogenic hip arthritis occurs most often in young patients. Delayed treatment causes significant anatomical deformation of bony and soft tissue structures leading to premature onset of secondary osteoarthritis. Total hip arthroplasty (THA) in patients who had osteoarthritis secondary to hip pyogenic infection has been associated with high complication rates.We analyzed 19 THAs performed from April 2003 to July 2008 in adults with osteoarthritis secondary to hip pyogenic infection (average age 40.7 years; range 34-52 years). There were 7 males and 12 females, the average age of infection was 10.6 years (range 7-13 years) and the average quiescent period of infection was 29.5 years (range 22-41 years). The count of white blood cell (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were examined routinely before surgery. The duration of followup was 34 months (range 6-52 months).There was no evidence of infection according to laboratory values, intraoperative exploration and bacterial culture of joint fluids and synovial tissues. Split fracture above the lesser trochanter occurred in two hips and healed without adverse sequelae after fixation with wires. One patient with sciatic nerve palsy was successfully treated by positioning the hip in extension and the knee in flexion with complete resolution of motor symptoms one month later. There were no cases of dislocation, deep vein thrombosis, or postoperative reinfection. The symptoms and hip joint activities were significantly improved. The median Harris hip score improved from 47.3 preoperatively to 89.7 and the median range of motion from 53 degrees to 125 degrees.It is safe and efficient to perform THA in patients who had osteoarthritis secondary to pyogenic hip arthritis when the infection is quiescent. The key points of successful surgery are exclusion of active infection preoperatively, quiescent period of infection more than ten years and adequate intraoperative soft tissue releases.

Periprosthetic femoral fractures following total hip arthroplasty are getting more prevalent. The aim of this study was to evaluate the clinical results of combined use of uncemented extensively porous coated femoral components with onlay cortical strut allografts in revision of Vancouver type B2 and B3 periprosthetic femoral fractures.Thirteen hips after total hip arthroplasty in 13 patients who suffered a Vancouver B2 or B3 periprosthetic fracture were treated with an uncemented extensively porous coated femoral component combined with onlay cortical strut allografts. Each patient was assigned a Harris hip score, and a visual analog scale (VAS) score for pain and satisfaction. Radiographs were examined for component stability, fracture site and allograft-host union and allograft reconstruction.At an average of 5.3-year follow-up, no patient required repeat revision. The average Harris hip score was (71.8 +/- 6.3) points, the pain VAS score was (16.6 +/- 4.3) points, and the patient satisfaction VAS score was (81.5 +/- 5.7) points. Radiographic examination showed no detectable loosening of the prostheses, and 12 cases were presented fixation by osseointegration and the other one was stable fibrous ingrown fixation. All fractures united for (5.2 +/- 1.4) months in average. And all onlay strut allografts united to host bone for about (11.5 +/- 2.6) months.Combined use of uncemented, long stemmed, extensively porous coated implant with cortical onlay strut allografts can achieve good clinic results and high rate of union for both fracture site and allograft-host bone junction. This technique could be used routinely to augment fixation and healing of Vancouver B2 and B3 periprosthetic fractures.

Dear Editor, We read with great interest the article by Sener et al. [1] and would like to bring four issues to your attention. First, the authors analysed the difference in the bacterial density between four groups with repetitive Mann-Whitney U test. Unavoidably, type I error (α) would be magnified [2]. It would be appropriate to calibrate the P value as: [2]. Thus, we made a second statistical analysis (Table 1). The data showed, however, no difference was found between group 2 and group 3 nor between group 3 and group 4. Combined with the inferior performance of group 3 in both radiological findings and macroscopic findings, antibiotic-loaded bone cement did not show superiority over other treatment modalities. Table 1 Statistical results of subgroup comparison in microbiological evaluation Second, the results showed that teicoplanin-loaded bone graft could not help, and could even interfere, with the infection control. Apart from the mechanisms discussed by the authors, other interpretations may be considered (Fig. 1). For example, local subacute inflammation was assumed two weeks after the bacterial inoculation. Less encapsulation of granulation tissue and bone callus, more osteolysis and exudation, and greater hyperemia were anticipated compared with chronic osteomyelitis [3]. Also, teicoplanin releasing systems were placed at the fracture site, a more open space than the medullary cavity. As a result, the adopted model of implant-related infection might present greater dilution, absorption, distribution, and elimination of teicoplanin than that of chronic osteomyelitis [4]. Some hidden or distant bacteria might be spared from the locally compromised teicoplanin level and account for recurrence of infection. Moreover, it was reported that the length of time during which the local antibiotic level exceeded minimal inhibition concentration (T>MIC) highly predicted antimicrobial potency of glycopeptide releasing systems [4]. Applying morselised cancellous bone, lengthening the duration of immersion in antibiotic solution, and the technique of iontophoresis would facilitate the teicoplanin impregnation into bone and prolong the T>MIC [5]. The authors simply immersed the corticocancellous grafts in teicoplanin solution for only one hour. The adsorption was possibly far below the saturation threshold, which may underestimate the antimicrobial efficacy of teicoplanin-loaded bone grafts. To our disappointment, no in vivo investigation was attempted on the kinetics of antibiotic release from bone. Also, implant removal is a prerequisite for thorough debridement; however, the authors retained the infected implant, where bacteria colonised and biofilm probably developed (Fig. 1). It was difficult to reach effective antibiofilm concentrations of teicoplanin around the implant. Fig. 1 Schematic diagram of osteomyelitis models of subacute infection (a) and chronic infection (b). In comparison with the model of chronic osteomyelitis (b), the subacute animal model (a) had less encapsulation of granulation tissue and bone callus, more ... Third, substantial details concerning the fabrication of teicoplanin-loaded bone grafts and acrylic beads [5], such as the concentration and pH of teicoplanin solution, the surface area, the bulk volume and the weight of bone grafts and acrylic beads, were not mentioned, which made comparison on antimicrobial efficacy impossible. Fourth and finally, the authors indicated that use of antibiotic-loaded beads was superior to debridement and systematic antibiotic treatment while antibiotic-loaded autogenous bone was not. This did not seem reasonable. In fact, debridement and systematic teicoplanin treatment were also offered in groups 3 and 4. What differed from group 2 was additional teicoplanin-loaded beads and teicoplanin-loaded autogenous bone in groups 3 and 4, respectively. It seems more appropriate to conclude that the inhibition by both antibiotic delivery systems was inferior to their aggravation of infection.

Total knee arthroplasties (TKR) combined with the concept of reduced trauma to tissue has been performed by many doctors. The aim of this study was to retrospectively assess the early results of a group of TKR with a mid-vastus approach, which was characterized as no patellar eversion, no disruption of suprapatellar pouch and extensor mechanism, and to compare the outcome with conventional operative techniques.A total of 59 patients (67 knees) were followed. All patients received the same prosthesis of Genesis II posterior-stabilized total knees. Of them, 29 consecutive patients (34 knees) had a mid-vastus approach and were operated on with less invasive instruments and techniques. The mean follow-up duration was 11.6 months. Clinical evaluations were performed according to the Hospital for Special Surgery scores; radiographic assessment followed the guidelines of the Knee Society. Postoperative recovery of quadriceps strength and the extensor mechanism was also evaluated.No prosthetic loosening or anterior knee pain was found at the latest follow-up; 1 patient had a superficial infection and postoperative stiffness of the knee who undertook a debridement and manipulation several months later. The angulations of tibial osteotomy were within normal range. The average preoperative and postoperative Hospital for Special Surgery scores were 57.9 points and 86.1 points respectively. The mean postoperative range of motion was 113.5 degrees . Most patients regained their quadriceps strength at the third or fourth month postoperatively.The overall early results from using the mid-vastus approach were comparable with that of using a standard approach, and the exposure did not affect the accuracy of the tibial cut. The muscle maximal contraction strength recovered gradually after operation. The approach was safe and patients of this group obtained satisfactory outcomes.

Dislocation is the second most common complication of hip replacement surgery, and impact of the prosthesis is believed to be the fundamental reason. The present study employed Solidworks 2003 and MSC-Nastran software to analyze the three dimensional variables in order to investigate how to prevent dislocation following hip replacement surgery.Computed tomography (CT) imaging was used to collect femoral outline data and Solidworks 2003 software was used to construct the cup model with variabilities. Nastran software was used to evaluate dislocation at different prosthesis positions and different geometrical shapes. Three dimensional movement and results from finite element method were analyzed and the values of dislocation resistance index (DRI), range of motion to impingement (ROM-I), range of motion to dislocation (ROM-D) and peak resisting moment (PRM) were determined. Computer simulation was used to evaluate the range of motion of the hip joint at different prosthesis positions.Finite element analysis showed: (1) Increasing the ratio of head/neck increased the ROM-I values and moderately increased ROM-D and PRM values. Increasing the head size significantly increased PRM and to some extent ROM-I and ROM-D values, which suggested that there would be a greater likelihood of dislocation. (2) Increasing the anteversion angle increased the ROM-I, ROM-D, PRM, energy required for dislocation (ENERGY-D) and DRI values, which would increase the stability of the joint. (3) As the chamber angle was increased, ROM-I, ROM-D, PRM, Energy-D and DRI values were increased, resulting in improved joint stability. Chamber angles exceeding 55 degrees resulted in increases in ROM-I and ROM-D values, but decreases in PRM, Energy-D, and DRI values, which, in turn, increased the likelihood of dislocation. (4) The cup, which was reduced posteriorly, reduced ROM-I values (2.1 -- 5.3 degrees ) and increased the DRI value (0.073). This suggested that the posterior high side had the effect of 10 degrees anteversion angle.Increasing the head/neck ratio increases joint stability. Posterior high side reduced the range of motion of the joint but increased joint stability; Increasing the anteversion angle increases DRI values and thus improve joint stability; Increasing the chamber angle increases DRI values and improves joint stability. However, at angles exceeding 55 degrees , further increases in the chamber angle result in decreased DRI values and reduce the stability of the joint.

Spinal cord injury (SCI)-induced bone loss represents the most severe osteoporosis with no effective treatment. Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae, and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography (µCT), micro-finite element, histology, and serum biochemical analyses. At trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI.

To evaluate the clinical and radiographic results of extensively porous-coated femoral stem in revision of total hip arthroplasty (THA).From January 1999 to December 2003, fifteen hips of fifteen cases received revision of THA with extensively porous-coated femoral stem. There were six males and nine females. The average age was 66 years (ranging 58-82 years). The reason for the revision was aseptic loosening in 10 cases, septic loosening in 2, femoral shaft fracture around loose implant in 2, and femoral revision for malposition of the femoral component in 1. All the patients were clinically evaluated using Harris hip score and radiographically evaluated both preoperatively and postoperatively at regular follow-up intervals.No patients were lost for follow-up. The average length of follow-up was 2.3 years (range, 1-5 years). The average preoperative Harris hip score was 42 points, which was improved to 89 points at latest follow-up. The latest follow-up showed that bone in-growth occurred in fourteen stems and solid fibrous fixation in one. Complications consisted of femoral shaft fracture in two cases (1 undisplaced distal femur fracture and 1 cortical perforation at the tip of the prosthesis), and postoperative dislocation in one. There was no mechanical failure of the stem in this study.Satisfactory results of short-term clinical and radiographic follow-up have been achieved in using extensively porous-coated femoral stem for revision of THA. It should be noticed that the straight, 203 mm stem should be used with caution in short people.

To evaluate the results of total knee arthroplasty (TKA) in patients with posttraumatic degenerative arthritis due to a previous fracture around the knee.We analyzed the results of 15 TKAs, performed from 1997 to 2003, in 15 patients with post-traumatic degenerative arthritis due to a previous fracture around knee. There were 3 women and 12 men with an average age of 58 years (range, 31-76 years). The time from fracture to arthroplasty averaged 8.2 years (range, 2-27 years). Internal fixation had previously been performed in 8 patients resulting in retained hardware. At the time of arthroplasty a femoral fracture malunion was present in two knees. Lateral retinacular release (4 knees), extensor mechanism realignment (1 knee) or medial collateral ligament reconstruction (1 knee) were needed at the time of arthroplasty.Follow-up averaged 35 months (range, 12-73 months). No patient was lost for follow-up. According to the Knee Society Score scale, the mean preoperative knee score was 37 (range, 10-70) and functional score was 41 (range, 0-60). They were improved significantly to a mean of 84 (range, 10-100) and 76 (range, 20-100) points, respectively at the latest follow-up. The mean knee arc of motion were improved from 84 degree preoperation to 94 degree at the latest follow-up. Postoperative manipulation under anesthesia for poor motion was carried out in 4 knees. No knee had aseptic loosening that required subsequent revision. Two knees developed superficial infection and were treated with debridement. It subsequently recovered with the retention of components.Significant improvement in function and relief of pain has been achieved in patients with previous fractures undergoing subsequent TKA. However, this procedure is technically demanding and patients are at increased risk for restricted motion and need more care following TKA. This study suggests that the outcome of TKA may be improved further by making special efforts to restore limb alignment, to ensure correct component positioning, and to manage soft tissue balance.

To determine the variation in femoral stress after insertion of Elite cemented femoral prosthesis.Three-dimentional finite element models of the normal human femur and Elite femoral prosthesis were developed through CT scan. With the application of hip joint loading, quantitatively measure stress changes of an intact femur with corresponding femur inserted with Elite implants were measured.Compared with intact femur, insertion of Elite implants into the femoral canal decreased the proximal femoral stresses level, especially in calcar femoral, femur wall and tuberositas. However, the stress in the prosthesis distal end.Insertion of Elite implants induced significant stress shielding in the proximal femur, especially at calcar femoral, femur wall and tuberositas. However, stress concentrates in the prosthesis distal end.

To evaluate the outcome of total hip arthroplasty (THA) with cementless cups and femoral head autografts for patients with hip dysplasia and osteoarthritis.Between 1995 and 2002, we implanted 23 cementless cups and femoral head autografts in 20 patients with hip dysplasia and osteoarthritis. In this study, a retrospective study was made on 21 hips in 20 patients (18 females and 2 males, aged 50 years on an average) with developmental hip dysplasia treated by THA with a cementless cup and femoral head autograft. The acetabular cup was placed at the level of the true acetabulum and all the patients required autogenous femoral head grafts due to acetabular deficiency. The average rate of the acetabular cup covered by the femoral head autograft was 31% (ranging from 10% to 45%). Eight hips had less than 25% cup coverage and thirteen between 25% and 50%. The average follow-up period was 4.7 years (range, 1-8 years). The replacing outcome was evaluated by modified Harris hip score. Preoperative and follow-up radiographs were made.All the autografts were united to the host bones. No autograft was collapsed or no component from the hip was loosed in all the patients. According to the modified Harris hip score, the average hip score increased from 46 before operation to 89 at the final review. Before operation, the leg-length discrepancy was greater than 2 cm in all the patients except one with bilateral hip dysplasia. After operation, only 2 out of 20 patients had a leg-length discrepancy greater than 1 cm. Three hips showed minor bone resorption in the lateral portion of the graft, which did not support the cup. Three hips developed Grade 1 Brooker heterotopic ossification and one developed Grade 2.THA with a cementless cup and a femoral head autograft for patients with osteoarthritis resulted from hip dysplasia can result in favorable outcomes. This method can provide reliable acetabular fixation and restore the acetabular bone stock in patients with developmental hip dysplasia when the cementless cup covered by the graft does not exceed 50%.

To evaluate the results of reconstructive intramedullary interlocking nail in the treatment of ipsilateral hip and femoral shaft fractures.From August 1997 to November 2001, 13 patients were treated with the reconstructive intramedullary interlocking nail. Nine patients were associated with ipsilateral femoral neck fractures, three with ipsilateral intertrochanteric fractures, and one with subtrochanteric fracture.The follow-up time was from 6 to 38 months with an average of 14 months. All the femoral shaft and hip fractures healed up well. There was no nonunion of the femoral neck, and only one varus malunion. No patient had avascular necrosis of the femoral head. The average healing time for femoral neck fracture was 4.6 months and for shaft fracture 5.8 months. The joint movement and other functions were fairly resumed.The reconstructive intramedullary interlocking nail, with less trauma, reliable fixation, and high rate of fracture healing, is an ideal method of choice in the treatment of ipsilateral hip and femoral shaft fractures.