ObjectiveTo explore the feasibility of establishment of a artificial joint aseptic loosening mouse model by cobalt-chromium particles stimulation.MethodsTwenty-four 8-week-old male severe combined immunodeficient (SCID) mice were divided into experimental group (n=12) and control group (n=12). The titanium nail was inserted into the tibial medullary cavity of mouse in the two groups to simulate artificial joint prosthesis replacement. And the cobalt-chromium particles were injected into the tibial medullary cavity of mouse in experimental group. The survival of the mouse was observed after operation; the position of the titanium nail and the bone mineral density of proximal femur were observed by X-ray film, CT, and Micro-CT bone scanning; and the degree of dissolution of the bone tissue around the tibia was detected by biomechanical test and histological staining.ResultsTwo mice in experimental group died, and the rest of the mice survived until the experiment was completed. Postoperative imaging examination showed that there was no obvious displacement of titanium nails in control group, and there were new callus around the titanium nails. In experimental group, there was obvious osteolysis around the titanium nails. The bone mineral density of the proximal tibia was 91.25%±0.67%, and the maximum shear force at the tibial nail-bone interface was (5.93±0.85) N in experimental group, which were significantly lower than those in control group [102.07%±1.87% and (16.76±3.09) N] (t=5.462, P=0.041; t=3.760, P=0.046). Histological observation showed that a large number of inflammatory cells could be seen around the titanium nails in experimental group, while there was no inflammatory cells, and obvious bone tissue formation was observed in control group.ConclusionThe artificial joint aseptic loosening mouse model can be successfully established by cobalt-chromium particles stimulation.
Objective To observe the human mononuclear cell releasing TNF-α and the activation of Caspase-3 during apoptosis after stimulated by Co2+ and Cr3+, to discuss the mechanism of artificial joint wear production metal ion on aseptic loosening. Methods CoCl2 powder and CrCl3 powder were dissolved by asepsis inject water, preparing solution for10 mg/L and 500 mg/L, respectively. Mononuclear cells were acquired from peripheral blood, 4 × 106/culture dish. According to the difference of culture solution, the cells were divided into 3 groups. Group A: mononuclear cell was culture with normal sal ine as control; group B: mononuclear cell was cultured with CoCl2 solution; group C: mononuclear cell was cultured with CrCl3 solution. The production of TNF-α was assessed by ELISA, the activation of Caspase-3 was measured by colorimetric assay and the apoptotic cell was detected by TUNEL assays at 12, 24 and 48 hours after co-cultured respectively. Results The concentration of TNF-α and the expression of Caspase-3 in groups B and C were higher than those in group A (P lt; 0.05), and reached the peak level at 24, 48 hours, respetively. The TUNEL positive cells were detected in the all groups, nucleus was pyknotic and darker-staining, cell body was crinkle and cell membrane was integrity. There were significant differences in the apoptosis rate between groups B, C and group A (P lt; 0.05). And the activation of Caspase-3 increased and had the positive correlation with the apoptosis rate (r=0.765). Conclusion Co2+ and Cr3+ ions can stimulate human mononuclear cell to release TNF-α and induce human mononuclear cell apoptosis, which result in periprosethetic osteolysis and related to activation of Caspase-3.
ObjectiveTo investigate the expression changes of the receptor activator of nuclear factor-κB ligand (RANKL) in the peripheral blood of patients with aseptic loosening of the implant after total hip arthroplasty (THA) by comparing with that of patients with femoral neck fracture and to analyze the correlation between RANKL expression and aseptic loosening. MethodsBetween January 2008 and January 2013,the peripheral blood were harvested from 58 patients with aseptic loosening of the implant after THA (trial group) and 63 patients with femoral neck fracture (control group).The 2 groups were well matched,with no significant differences in age and gender (P>0.05).The expressions of the RANKL mRNA and RANKL protein were evaluated by quantitative real-time PCR and Western blot respectively.At the same time,the concentration of RANKL was also measured by ELISA. ResultsThe expression of the RANKL mRNA in the trial group was 18.30±1.09,which was significantly higher than that of control group (1.00±0.05)(t=125.390,P=0.000).The relative RANKL protein expression values in trial group and control group were 0.856±0.254 and 0.404±0.102 respectively,showing significant difference (t=13.032,P=0.000).The results of ELISA showed that the concentration of RANKL in trial group [(3.553 5±0.129 7) ng/mL] was significantly higher than that of control group [(1.912 3±0.126 2) ng/mL] (t=18.124,P=0.000). ConclusionThe high RANKL expression in peripheral blood is probably correlated with aseptic loosening of the implant in patients undergoing THA,which possibly is the prognostic factor of aseptic loosening of the implant.
Since 1985, on the basis of anatomical observation of 50 fresh adult specimens, we designed the transposition oF vascularized capitate bone carrying the dorsal branche of the anteriot interosses artery to replace the damaged lunate bone from avascular necrosis. The operation had been done in 6 patients and the follow-up observation (from 6 months to 4 years) showed that the operation was satisfactory. The anatomic basis, the advantages and disadvantages, and the surgical indications were discussed.
Objective Aseptic loosening of prosthesis is associated with peri prosthetical osteolysis caused by osteoclast activation. Receptor activator of nuclear factor kappa B (NF-κB) l igand (RANKL)/receptor activator of NF-κB (RANK) signalpathway is fundamental in osteoclast activation. To determine whether RANKL antibody can inhibit inflammatory osteolysis in a osteolysis model of mouse. Methods Sixty female BALB/c mice (aged 8-10 weeks, weighing 18-20 g) were selected. The skull bone piece was harvested from 20 mice as the donor of bone graft; the subcutaneous air pouches (2 cm × 2 cm) models were established on the back of the other 40 mice and the skull bone piece was inserted into the air pouches. The 40 mice were equally divided into groups A (negative control group), B (positive control group), C (low-dose RANKL antibody group), and D (high-dose RANKL antibody group). At 1 day after bone graft, 0.5 mL PBS was injected into the pouch of group A, 0.5 mL PBS containing titanium particle into groups B, C, and D. At 2 days before the titanium particle was injected, RANKL antibody (0.1 mL) were injected into the pouch of group C (50 μg/mL) and group D (500 μg/mL), respectively every day for 2 days, and 0.1 mL PBS into groups A and B. At 14 days after bone implantation, the pouchmembranes containing implanted bone were harvested for gross observation and histological analyse. Results All mice survived to the end of experiment, and incisions healed well. The gross observation showed that inflammatory responses, exudation, and vascular proliferation were obvious in group B, and were inconspicuous in groups A, C, and D. The histological analysis showed that significantly more infiltration of inflammatory cells, more obvious bone resorption, more bone collagen loss, and more positive staining area were observed in group B than in groups A, C, and D. There were significant differences in inflammatory cell number, pouch membrane thickness, bone collagen loss, and osteoclast content between group B and groups A, C, and D (P lt; 0.05). Conclusion RANKL antibody can directly blockRANKL/RANK signal pathway, which is an efficient therapy to inhibit bone absorption associated with implant wearing particles.
Objective To introduce the occurrence mechanisms, prevention, and treatment measures of prosthetic aseptic loosening. Methods The recent original articles about prosthetic aseptic loosening were extensively reviewed and analyzed. Results Prosthetic aseptic loosening was a very complex process involving many mechanical and biological aspects. The main mechanical factors included prosthetic materials, shapes and sizes, implant fixation methods (including surfacetreatments), cl inical installation, interface micromotion, stress shielding, implant wear, interface integrity, and peri prosthetic high hydraulic pressure, etc.; the main biological factors included the types and sizes of wear particles, cell-activated responses, cytokine release, enzyme activation and allergic reactions to wear particles, etc.. Many measures should be adopted to effectively prevent and treat it, including improving materials and designs of prostheses, fixation techniques, surgical techniques, and drug treatments. Conclusion Prosthetic aseptic loosening is still a troublesome compl ication after joint replacements in orthopaedics, and more attention should be paid for its effective prevention and treatment.
Objective To observe the expressions of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase 9 (MMP-9) around the prosthesis, and to study the relationship between the expressions of EMMPRIN and MMP-9 and osteolysis around prosthesis. Methods Interface tissues were obtained at three Delee-Charnley acetabular sections and seven Gruen femur sections from 8 cases (8 hips) undergoing revision after total hip arthroplasty between February 2010 and January 2012, and were divided into osteolysis group and non-osteolysis group based on preoperative X-ray film and intraoperative observation; the tissues from another 8 patients with osteoarthritis undergoing total hip arthroplasty as the control group. The immunohistochemical staining and RT-PCR assays were used to determine the expressions of EMMPRIN and MMP- 9. The correlation between the positive cells and the severity of osteolysis were analyzed and compared. Results Histological examination showed that many macrophages, multinucleated giant cells assembled in the membrane of osteolysis zone, but many fibroblasts and synovial cells in non-osteolysis zones. EMMPRIN and MMP- 9 positive cells and gene expressions were observed in every group. The percentage of positive cells and gene expression of EMMPRIN and MMP-9 in osteolysis group were significantly higher than those in non-osteolysis and control groups (P lt; 0.05), but no significant difference was found between non-osteolysis group and control group (P gt; 0.05). The percentage of positive cells of EMMPRIN in zone III of acetabular was higher than that in zone I and zone II of revision hip (P lt; 0.05), but no significant difference between zone I and zone II (P gt; 0.05). The percentage of positive cells of MMP-9 in zone I and zone III was significantly higher than that in zone II of revision hip (P lt; 0.05), but no significant difference between zone I and zone III (P gt; 0.05). The expression of EMMPRIN from high to low in order was zones 1, 7, 4, 2, 3, 5, and 6 at femur; the values of zones 1, 7, and 4 were significantly higher than those of zones 2, 3, 5, and 6 (P lt; 0.05), but no significant difference among zones 1, 7, and 4, and among zones 2, 3, 5, and 6 (P gt; 0.05). The expression of MMP-9 from high to low in order was zones 1, 7, 4, 2, 3, 6, and 5 at femur; the values of zones 1 and 7 were significantly higher than those of zones 4, 2, 3, 6, and 5 (P lt; 0.05), and the values of zones 4 and 2 were significantly higher than those of zones 3, 6, and 5 (P lt; 0.05), but no significant difference between zone 1 and zone 7, between zone 4 and zone 2, and among zones 3, 5, and 6 (P gt; 0.05). Conclusion The expressions of EMMPRIN and MMP-9 have certain coherence. The over-expressions of EMMPRIN and MMP-9 may be one of the key points of inhibiting bone reconstruction and bone resorption at bone-implant interface under the stimulation of wear debris．
Objective To review the recent advances in treatment of aseptic femoral shaft nonunion. Methods The clinical studies about the treatments of aseptic femoral shaft nonunion in recent years were widely reviewed and analyzed. Results There are several surgical methods for aseptic femoral shaft nonunion. Due to uncertain clinical outcome, dynamization of nail should be carefully selected. The exchange nailing is suitable for the hypertrophic nonunion of the isthmal femoral shaft fracture. The exchange lateral plating is suitable for nonunion with obvious malformation. However, wave plate or dual plate should be chosen when the bone nonuinon is combined with the medial defect. The augmentation plating improves the success rate of nailing for femoral shaft nonunion, but it should be carefully selected for patients with obvious deformity or bone defect. Ilizarov technique is suitable for various bone nonunion, especially with complicated or large segmental bone defects. Induced membrane technique is also an important method for the treatment of bone nonunion with large bone defects. The clinical efficacy of the blocking screw remains to be supported by further evidence. Biological stimulants are mainly used for atrophic nonunion, and the clinical efficacy of them alone are still controversial. Conclusion Due to lack of comparative studies between different surgical methods, the orthopedist should choose the appropriate treatment according to the individual situations of the patient and the types of bone nonunion.
ObjectiveTo evaluate the effectiveness of locking compress plate (LCP) for the treatment of aseptic diaphyseal humeral nonunions. MethodsBetween January 2006 and January 2012, 23 patients with aseptic diaphyseal humeral nonuninons were treated with LCP and autologous iliac crest bone graft, and the clinical data were retrospectively analyzed. There were 15 males and 8 females with the average age of 42.5 years (range, 28-60 years). The fracture located at left side in 11 cases and right side in 12 cases. The mechanism of the injury was traffic accident in 15 patients, and falling from height in 8 patients. Fracture was treated by internal fixation in 20 cases and external fixation in 3 cases. And 6 patients had open fractures and other 17 had close fractures. Based on the Weber-Cech classification, 6 cases were rated as atrophic nonunions, and 17 cases as hypertrophic nonuninons. Shoulder function was evaluated by Constant-Murley score and elbow function was evaluated by Mayo score. ResultsAfter operation, 2 patients had transient radial nerve symptoms of numbness and 1 patient had superficial infection. Primary healing of incision was obtained in the other patients. All patients were followed up 22.22 months on average (range, 16-30 months). Normal range of motion of the shoulder was found in 11 cases; and limited movements of abduction, elevation, and posterior extension were observed in 12 cases. And osseous union was observed clinically and radiographically in all patients. The average union time was 16.95 weeks (range, 12-24 weeks). The average Constant-Murley score was 81.87 (range, 50-98); and shoulder function was excellent in 14 cases, good in 6, and fair in 3. And the average Mayo score was 87.78 (range, 70-96); and the result was excellent in 14 cases, good in 7, and fair in 2. ConclusionAseptic diaphyseal humeral nonunions can be successfully treated with LCP, coupled with the use of autologous iliac crest bone graft.
Objective To evaluate the mechanisms of p42/p44 kinase phosphorylation in cell models and to investigate the effect of simvastatin on the prevention and treatment of aseptic loosening of prosthesis by observing the influence of simvastatin on the levels of tumor necrosis factor α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) of human peri pheral blood mononuclear cell (PBMC) challenged with titanium particles. Methods PBMC from 45 mL peripheral blood of healthy adult voluntary donators, were separated and cultured, and divided into 5 groups according to different culturemedium: group A, PBMC and titanium particles; group B, PBMC and titanium particles with 1 × 10-5 mol/L simvastatin; group C, PBMC and titanium particles with 1 × 10-6 mol/L simvastatin; group D, PBMC and titanium particles with 1 × 10-7 mol/L simvastatin; and group E, PBMC and titanium particles with the extracellular signal-regulated kinase (ERK1/2) inhibitor U0126. The contents of TNF-α and MCP-1 were tested by ELISA after 24 hours of culture. PBMC were pretreated with different medium grouping as groups A, B, C, D, and E for 60 minutes, and were challenged with titanium particles for 30 minutes and 60 minutes, then the level of ERK1/2 expression was tested by Western blot. Results In groups A, B, C, D, and E, the absorbance (A) values of TNF-α were 1.115 5 ± 0.243 6, 0.693 6 ± 0.354 3, 0.695 7 ± 0.387 3, 0.716 4 ± 0.478 9, and 0.263 5 ± 0.101 6, respectively; and the A values of MCP-1 were 1.421 0 ± 0.105 3, 0.915 1 ± 0.411 3, 1.003 5 ± 0.464 2, 1.102 0 ± 0.353 9, and 0.271 3 ± 0.145 1, respectively. The levels of TNF-α and MCP-1 in group A were significantly higher than others, showing significant differences (P lt; 0.05). There were significant differences between group E and groups B, C, and D (P lt; 0.05), between group B and groups C, D (P lt; 0.05); no significant difference between group C and group D (P gt; 0.05). Western blot results showed the expression of ERK1/2 in all groups at 30 minutes and 60 minutes of culture. The levels of ERK1/2 expression were 1.612 1 ± 0.068 2, 1.078 1 ± 0.072 8, 1.268 7 ± 0.223 1, 1.439 7 ± 0.180 1, and 0.732 0 ± 0.110 4 in groups A, B, C, D, and E, respectively; showing significant differences between groups (P lt; 0.05). Conclusion ERK1/2 is a phosphorylated protein after stimulated by wear particles; it is also one of the most important cell signal ing activation of macrophage. Simvastatin can inhibit the expression of bone absorptive factors induced by wear particles and may be used in the prevention and treatment of aseptic loosening of prosthesis.