Objective To explore the impact of preoperative traction on the osteonecrosis of the femoral head (ONFH) in patients with femoral neck fractures. Methods Between February 2013 and May 2016, 120 patients with femoral neck fractures, who were treated with screw fixation, were collected. Sixty patients with fractures of Garden type Ⅰ and Ⅱ were non-displaced fracture group; 60 cases with fractures of Garden type Ⅲ and Ⅳ were displaced fracture group. The patients in 2 groups were randomly divided into traction and non-traction subgroups (n=30). There was no significant difference in gender, age, injury mechanism, damage side, the time from injury to operation, and fracture classification between 2 subgroups (P>0.05). Intracapsular pressure was recorded before operation. The quality of fracture reduction and the satisfaction ratio of screw implant were evaluated during operation. Visual analogue scale (VAS), Harris score, joint mobility, and the incidence of ONFH would be evaluated at 6 months, 1 year, and 2 years after operation. Results All incisions of 2 groups healed by first intention after operation. There was no infection or deep vein thrombosis of lower extremity. All patients were followed up 2 years. In displaced and non-displaced fracture groups, the intracapsular pressure of traction subgroups were higher than that of non-traction group (P<0.05); the differences of the quality of fracture reduction and the satisfaction ratio of screw implant were not significant (P>0.05) between 2 subgroups. At 6 months, 1 year, and 2 years after operation, VAS scores were higher in traction subgroup than in non-traction subgroup (P<0.05); and the joint mobility and Harris scores were lower in traction subgroup than in non-traction subgroup (P<0.05). X-ray films showed all fractures healed. Except for the non-displaced group at 6 months, the incidences of ONFH were higher in traction subgroup than in non-traction subgroup at other time points (P< 0.05). Conclusion Preoperative traction may increase the risk of ONFH, which can increase the intracapsular pressure and affect the blood supply of femoral head.
Extracorporeal shock wave (ESW), as a noninvasive, safe, and effective treatment, was applied to the treatment in osteonecrosis of femoral head (ONFH) since the end of last century. Although this therapy is more and more widely used, there are many traps and challenges. We recommend using the high-energy focus ESW to treat ONFH, rather than using the low energy radial pressure wave. Furthermore, for different types ONFH, scientific personalized treatment planning should be made first. There are demands of multicenter united researches for this unknown field of ONFH treated with ESW, and so to provide high-level evidence-based medicine evidence.
【Abstract】 Objective To explore the correlation between pain grading, stage of necrosis and bone marrow edema(BME) in nontraumatic osteonecrosis of femoral head (NONFH) so as to strengthen understandings about cl inical significance of BME in NONFH. Methods From October 2004 to October 2006, 97 patients (149 hips) with NONFH were treated. There were 68 males and 29 femals with an average age of 38.8 years (19-62 years). The disease course was from 20 days to 4 years. BME was identified grade 0 to grade 2 according to MRI. Based on grading scale of pain, pain grading were divided into no pain (grade 0), mild pain (grade 1) and moderate or severe pain (grade 2). According to Association Research Circulation Osseous staging system, NONFH were divided into I-IV stages. The incidence rate of BME in each pain grading and stages of necrosis was analyzed respectively. Contingency table analyses and rank sum tests were used to compare the difference of pain grading and stages of necrosis among these groups. Results The total incidence rate of BME was 73.15% (109/149), the incidence rateswere 84.38% in pain groups (108 /128) and 94.12% in the grade 2 (32/34). Pain grading correlated with BME rating (P lt; 0.001).The results of rank sum tests for several independent samples showed significant difference in BME among pain groups(P lt; 0.001). With the advance of pain scale, the mean rank of BME increased gradually(28.19 for grade 0, 78.94 for grade 1 and 96.12 for grade 2). BME was more commonly and clearly seen in stage Ⅱ（77.05%）and stage Ⅲ（82.81%）of NONFH. Stage I-III of NONFH correlated with BME rating (P lt; 0.001). The results of rank sum tests showed significant difference in BME rating among three stages (P lt; 0.001). With the advance of disease, the rank of BME rating increased gradually (39.07 for grade 0, 60.16 for grade 1 and 86.15 for grade 2 ). Conclusion BME is a sign that is accompanied with NONFH. The probabil ity and extent of BME correlated well with the pain and stage of NONFH．The condition of BME can be used as a index for the appraisal of advancement of disease and the judgment of treatment result.
Objective To evaluate the correlation between pelvic incidence (PI) angle, hip deflection angle (HDA), combined deflection angle (CDA) and osteonecrosis of the femoral head (ONFH) after femoral neck fracture, in order to explore early predictive indicators for ONFH occurrence after femoral neck fracture. Methods A study was conducted on patients with femoral neck fractures who underwent cannulated screw internal fixation between December 2018 and December 2020. Among them, 208 patients met the selection criteria and were included in the study. According to the occurrence of ONFH, the patients were allocated into ONFH group and non-NOFH group. PI, HDA, and CDA were measured based on the anteroposterior X-ray films of pelvis and axial X-ray films of the affected hip joint before operation, and the differences between the two groups were compared. The receiver operating characteristic curve (ROC) was used to evaluate the value of the above imaging indicators in predicting the occurrence of ONFH. ResultsAmong the 208 patients included in the study, 84 patients experienced ONFH during follow-up (ONFH group) and 124 patients did not experience ONFH (non-ONFH group). In the non-ONFH group, there were 59 males and 65 females, the age was 18-86 years (mean, 53.9 years), and the follow-up time was 18-50 months (mean, 33.2 months). In the ONFH group, there were 37 males and 47 females, the age was 18-76 years (mean, 51.6 years), and the follow-up time was 8-45 months (mean, 22.1 months). The PI, HDA, and CDA were significantly larger in the ONFH group than in the non-ONFH group (P<0.05). ROC curve analysis showed that the critical value of PI was 19.82° (sensitivity of 40.5%, specificity of 86.3%, P<0.05); the critical value of HDA was 20.94° (sensitivity of 77.4%, specificity of 75.8%, P<0.05); and the critical value of CDA was 39.16° (sensitivity of 89.3%, specificity of 83.1%, P<0.05). Conclusion There is a correlation between PI, HDA, CDA and the occurrence of ONFH after femoral neck fracture, in which CDA can be used as an important reference indicator. Patients with CDA≥39.16° have a higher risk of ONFH after femoral neck fracture.
ObjectiveTo elucidate the role of interleukin-33 (IL-33) in glucocorticoid-induced osteonecrosis of the femoral head (ONFH) in mice, with particular emphasis on its effects on bone remodeling, inflammatory regulation, and fibrosis. Methods In vivo: Fifteen 9-week-old male C57BL/6J wild-type mice were randomly divided into a normal control group, an ONFH group, and an intervention group, with 5 mice in each group. A glucocorticoid-induced ONFH model was established in the ONFH group and intervention group using a combined administration of lipopolysaccharide and methylprednisolone. The intervention group received intraperitoneal injection of IL-33 for 4 consecutive days during the early stage of model establishment; the normal control group received saline injection at the same time points. General conditions of mice were observed during the experiment. Endogenous IL-33 and transmembrane ST2 (ST2 ligand, ST2L) expression in the femoral head was assessed via immunofluorescence, quantitative PCR (qPCR), and Western blot. Bone necrosis and fibrosis were evaluated using HE and Masson staining. Immunohistochemistry was performed to detect osteogenic markers [osteocalcin (OCN), osteopontin (OPN), Runt-related transcription factor 2 (Runx2)] and osteoclastic marker (receptor activator of nuclear factor-κB ligand, RANKL), while serum cytokine levels [tumor necrosis factor (TNF-α), IL-6, IL-1β, IL-4, IL-10] were quantified by ELISA. In vitro: Murine osteoblasts were divided into control group (DMEM+PBS), IL-33 group (DMEM+10 ng/mL IL-33), and IL-33+ST2L group (DMEM+10 ng/mL IL-33+1 μg/mL ST2L antibody). After corresponding treatment, cell proliferation was detected by EdU incorporation assay. Additional osteoblasts were subjected to osteogenic induction culture, and mineralization, and the expression of osteogenesis-related genes (Runx2, collagen type Ⅰ, OCN, and OPN) were assessed by using alkaline phosphatase (ALP) staining, Alizarin red staining, and qPCR, respectively. Results In vivo: All animals survived until the completion of the experiment. Mice in the intervention group and ONFH group showed restricted mobility. Compared with the normal control group, the expressions of IL-33 and ST2L significantly upregulated at both mRNA and protein levels (P<0.05). Exogenous IL-33 administration exacerbated, rather than ameliorated, trabecular destruction and fibrosis, with the intervention group showing significantly increased fibrosis area percentage and empty lacunae rate compared with the other two groups (P<0.05). Furthermore, IL-33 treatment further suppressed the expressions of osteogenic markers (Runx2, OCN, OPN) while significantly enhancing the expression of the osteoclastic marker (RANKL) (P<0.05). ELISA results showed that compared with the ONFH group, serum levels of pro-inflammatory cytokines (IL-4, IL-6, IL-1β) were significantly lower in the intervention group (P<0.05). In vitro: Compared with control group, IL-33 significantly impaired osteoblast proliferation and differentiation, as evidenced by reduced cell proliferation rate, decreased ALP activity, and reduced calcium nodule formation (P<0.05). The expression of osteogenesis-related genes was also suppressed, with significant differences between groups (P<0.05). ST2L blockade effectively reversed these IL-33-mediated suppressive effects, leading to significant recovery of osteoblast proliferation and differentiation (P<0.05). Notably, the mRNA expression levels of collagen typeⅠand OCN were restored to normal (P>0.05). ConclusionIL-33 exacerbates ONFH by impairing osteoblast viability and function and inhibiting bone regeneration. Targeting the IL-33/ST2L signaling axis may represent a promising novel therapeutic strategy for ONFH.
【Abstract】 Objective To investigate both incidence and mechanism attributing to steroid-associated osteonecrosisof femoral head(ONFH) using an experimental protocol with a single low-dose l i popolysaccharide (LPS) injection andsubsequently three injections of high-dose methylprednisolone (MPS). Methods Twenty-five New Zealand white rabbits with body weight of (3.0 ± 0.3) kg were divided randomly into 2 groups. In treatment group, 19 rabbits received one intravenous injection of LPS (10 μg/kg); 24 hours later, three injections of 20 mg/kg of MPS were given intramuscularly at an interval of 24 hours. Additional 6 rabbits which received normal sal ine injection at the same time point were used as controls(control group). The blood samples were collected for hematological examinations before and after LPS injection, MRI was performed on bilateral hip six weeks after last MPS injection, meanwhile, bone marrow was aspirated from femoral head region to evaluate stem cell’s activity. Bilateral femoral heads were harvested to make histopathology examination. Results All animals survived throughout the experiment period except one death on the second day after LPS injection. In the histopathological examinationfor the femoral head, ONFH+ was observed in 16 rabbits (88.9%), and the lesions were mainly in the metaphysis. In ONFH+ rabbits, micro vessels fibrous thrombosis and extravascular marrow fat cell size increasing were found around necrotic bone; The femoral heads of control group had no changes. MRI accurate ratio was 93.8% (15/16). Compared to basel ine, a significant decrease in ratio of tissue plasminogen activator/plasminogen activator inhibitor 1 and activated partial thromboplatin time, and a significant increase in ratio of low-density l ipoprotein/high-density l ipoprotein were only found in ONFH+ rabbits (P lt; 0.05). Meanwhile there was a significant decrease in the number of CFU-F (8.50 ± 9.63) compared with the control (70.17 ± 7.78, P lt; 0.05). Conclusion A single low-dose LPS injection and subsequent three injections of high-dose MPS is effective on building steroid-associated ONFH model, coagulation and l ipometabol ism abnormal ity, activity degeneration of stem cell may be the key factors of ONFH.
Objective To evaluate the effects and the molecular mechanism of Liuwei dihuang pills in preventing steroid-induced osteonecrosis of the femoral head (ONFH) so as to provide an expremental basis for preventing ONFH cl inically. Methods Thirty-six adult Kunming mice (weighing 40-50 g, 46 g on average) were randomly divided into three groups (n=12): group A (control group), group B (model group) and group C (prevention group). In groups B and C, ONFHmice models were produced by intraperitoneal injection of horse serum at first (10 mL/kg) and a second injection of horse serum intraperitoneally (5 mL/kg) and prednisolone intramuscularly [45 mL/(kg?day), for 5 days] 2 weeks later. At the same time, the mice in group C were given Liuwei dihuang pills intragastrically [2 g/(kg?day)] and were given normal sal ine [10 mL/(kg?day)] in group B. In group A, mice were given normal sal ine intramuscularly and intragastrically as controls. The animals were sacrificed 2, 4, and 8 weeks after first treatment with prednisone, and femoral heads and l ivers were harvested to do histopathology analysis and apoptosis assay. Results Other mice survived throughout the experiment period except two death at 7 and 11 days after second injection of horse serum intraperitoneally in group B and one death at 24 hours after second injection of horse serum intraperitoneally in group C. The appearance and shape of the femoral head and the surface of cartilages were all normal. The histological observation showed: normal structures of l iver and femoral head were seen in group A at each time point; swell ing l iver cells with small fat vacuole, unclear structure of hepatic cords and narrower sinus hepaticus were seen, the bone trabeculae of femoral head was thin, sparse and collapsed in some regions and the changes became more obvious with time in group B; group C had similar results to group A. The percentage of empty osteocyte lacunae was significantly higher in group B than in groups A and C (P lt; 0.01). The osteoprotegrin expression significantly decreased and the osteoprotegrin l igand expressionsignificantly increased in group B when compared with groups A and C (P lt; 0.01). Apoptosis analysis showed that the apoptosis index in group B was significantly higher than that in groups A and C (P lt; 0.01). Conclusion Liuwei dihuang pills can prevent steroid-induced ONFH by improving l ipid metabol ism, releiving bone lesion, and protecting against cell death.
ObjectiveTo explore the effect of icariin on early steroid-induced osteonecrosis of the femoral head in rabbits.MethodsFifty mature New Zealand rabbits (weighing, 2.5-3.0 kg) were randomly divided into control group (n=10), model group (n=20), and experimental group (n=20). The rabbits of model and experimental groups were injected with lipopolysaccharide and methylprednisolone to establish the animal model of early steroid-induced osteonecrosis of the femoral head. The rabbits of experimental group were feeded with icariin solution once a day for 6 weeks since the first injection of methylprednisolone, whereas the rabbits of control and model groups were given normal saline at the same time points. The left femoral heads were removed after 6 weeks and gross morphological features were evaluated. Micro-CT scan was performed to analyze the trabecular microstructure with the following parameters: trabecular bone volume to total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Tn), and trabecular separation (Tb.Sp). The Micro-CT scan was also converted to three-dimensional reconstruction images for observation. HE staining was applied to observe the trabecular structure and morphological changes of osteocytes and marrow adipocytes. It was also used to determine whether the samples of femoral heads occurred osteonecrosis based on the criteria for pathological diagnosis, and calculate the rate of empty lacunae.ResultsSeven rabbits died during the study, and 9, 16, and 18 rabbits in the control, model, and experimental groups, respectively, enrolled the final analysis. Compared with control group, the femoral head collapse and trabecular breaks were more obvious, and the trabeculae were sparse with irregular arrangement in the model group according to the results of gross observation, Micro-CT scan, and three-dimensional reconstruction images. But in the experimental group, the surface of femoral head was slight shrinking without obvious collapse, and the degeneration of trabecular structure was mild. According to bone microstructures analysis, the Tb.N, Tb.Tn, and BV/TV of femoral head in model and experimental groups were lower than those in control group, while the Tb.Sp in the model and experimental groups were significantly higher. The Tb.N, Tb.Tn, and BV/TV of femoral head in experimental group were higher than those in model group, while the Tb.Sp in the experimental group was significantly lower. The differences between groups were all significant (P<0.05). In the model group, HE staining showed that the number of osteocytes reduced, the number of empty lacunae increased, and the marrow adipocytes piled up in the space between femoral trabeculae, some even mashed together like a cyst. In the experimental group, the trabecular structure was still relatively complete compared with model group, no obvious apoptosis of osteocytes was observed, the size and number of adipocytes were basically normal. None of the animals in control group occurred osteonecrosis of the femoral head based on the criteria for pathological diagnosis, and the incidence of osteonecrosis were 81.3% (13/16) in the model group and 66.7% (12/18) in the experimental group, and the difference was not significant (P=0.448). The rate of empty lacunae of osteonecrotic femoral heads in the model group was 33.1%±1.4%, which was higher than that in experimental group (18.9%±0.8%) and in control group (12.7%±1.5%), and the differences between groups were significant (P<0.05).ConclusionThe icariin has a protective effect on the early steroid-induced osteonecrosis of the femoral head in rabbits, which can decrease osteocytes apoptosis, improve the bone microstructure, and delay such disease processes.
Objective To summarize the characteristics and clinical significance of irreducible Pipkin type Ⅰ and Ⅱ femoral head fracture-dislocations. Methods The clinical data of 4 patients with irreducible Pipkin type Ⅰ and Ⅱ femoral head fracture-dislocations between January 2010 and December 2019 were collected. There were 2 males and 2 females and the age ranged from 24 to 41 years, with an average age of 33.5 years. The cause of injury included traffic accident in 3 cases and falling in 1 case. Pipkin classification was 2 cases of type Ⅰ and 2 cases of type Ⅱ. The time from injury to operation was 1-2 days. The clinical features were that the hip joint of the affected limb was in a locked position, and the passive range of motion was poor. The affected limb was slightly flexed at the hip joint and shortened, in a state of neutral position or slight adduction and internal rotation. The imaging data suggested that the femoral head dislocated backward and upward, and the hard cortex of the posterior edge of the acetabulum was embedded in the cancellous bone of the femoral head, and the two were compressed and incarcerated. Patients of cases 1-3 underwent closed reduction of hip dislocation 1-2 times at 3, 1, and 3 hours after injury respectively, and femoral neck fracture occurred. The injury types changed to Pipkin type Ⅲ, and open reduction and internal fixation were performed. Patient of case 4 did not undergo closed reduction, but underwent open reduction and internal fixation directly. Results Patients of cases 1-3 were followed up 14, 17, and 12 months, respectively. They developed osteonecrosis of the femoral head at 9, 5, and 10 months after operation respectively, and all underwent total hip arthroplasty. Patient of case 4 was followed up 24 months and had no hip pain and limited mobility; the imaging data indicated that the internal fixator position was good and the fracture healed; no collapse or deformation of the femoral head was seen, and no osteonecrosis of the femoral head occurred. Conclusion Clinicians need to improve their understanding of the unique clinical features and imaging findings of irreducible Pipkin type Ⅰ and Ⅱ femoral head fracture-dislocations. It is suggested that open reduction and simultaneous fixation of femoral head fracture should be directly used to reduce the incidence of osteonecrosis of the femoral head.
Objective To explore the significance of osteocyte apoptosis in steroidinduced osteonecrosis of the femoral head. Methods SixtyNew Zealand rabbits were divided into experimental group and control group(n=30). The experimental group was given 10 ml/kg of horse serum intravenously 2 times at 2 weeks intervals and an intraperitoneal injection of 45 ml/kg·d of methylprednisolone acetate for 3 days；the control group was given equal isotonic Na chloride. Osteocyteapoptosis was observe by means of TUNEL. Results The number of apoptosis in the experimental group(112.33‰±26.12‰) was significantly higher than that in the control(47.01‰±22.95‰) (Plt;0.01)in the 4th week. With time, osteocytes apoptosis progressively increased. In the 6thand 8th weeks, the percentage of empty osteocyte lacunae in the experimental group (17.23%±3.44%, 28.56%±3.45%) was significantly higher than that in the control group (11.29%±2.89%,11.26%±2.75%，Ｐlt;0.05). The transmission electron microscope showed that the characteristics of osteocyte apoptosisincluded intact nuclear membrane,comdensed chromatin and increased electron dense. Conclusion Osteocytes apoptosis may play a key role in the process of steroidinduced early osteonecrosis of the femoral head.