OBJECTIVE: To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms. METHODS: Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH. RESULTS: Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent. CONCLUSION At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.
Humans ; Femur Head/pathology* ; Osteonecrosis/therapy* ; Macrophages/pathology* ; Inflammation ; Femur Head Necrosis/pathology*

The approach combining disease, syndrome, and symptom was employed to investigate the characteristic changes of blood stasis syndrome in a rat model of steroid-induced osteonecrosis of the femoral head(SONFH) during disease onset and progression. Seventy-two male SD rats were randomized into a healthy control group and a model group. The rat model of SONFH was established by injection of lipopolysaccharide(LPS) in the tail vein at a dose of 20 μg·kg~(-1)·d~(-1) on days 1 and 2 and gluteal intramuscular injection of methylprednisolone sodium succinate(MPS) at a dose of 40 mg·kg~(-1)·d~(-1) on days 3-5, while the healthy control group received an equal volume of saline. The mechanical pain test, tongue color RGB technique, gait detection, open field test, and inclined plane test were employed to assess hip pain, tongue color, limping, joint activity, and lower limb strength, respectively, at different time points within 21 weeks of modeling. At weeks 2, 4, 8, 12, 16, and 21 after modeling, histopathological changes of the femoral head were observed by hematoxylin-eosin(HE) staining and micro-CT scanning; four coagulation items were measured by rotational thromboelastometry; and enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of six blood lipids, vascular endothelial growth factor(VEGF), endothelin-1(ET-1), nitric oxide(NO), tissue-type plasminogen activator(t-PA), plasminogen activator inhibitor factor-1(PAI-1), bone gla protein(BGP), alkaline phosphatase(ALP), receptor activator of nuclear factor-κB(RANKL), osteoprotegerin(OPG), and tartrate-resistant acid phosphatase 5b(TRAP5b) in the serum, as well as the levels of 6-keto-prostaglandin 1α(6-keto-PGF1α) and thromboxane B2(TXB2) in the plasma. The results demonstrated that the pathological alterations in the SONFH rats were severer over time. The bone trabecular area ratio, adipocyte number, empty lacuna rate, bone mineral density(BMD), bone volume/tissue volume(BV/TV), trabecular thickness(Tb.Th), trabecular number(Tb.N), bone surface area/bone volume(BS/BV), and trabecular separation(Tb.Sp) all significantly increased or decreased over the modeling time after week 4. Compared with the healthy control group, the mechanical pain threshold, gait swing speed, stride, standing time, and walking cycle of SONFH rats changed significantly within 21 weeks after modeling, with the greatest difference observed 12 weeks after modeling. The time spent in the central zone, rearing score, and maximum tilt angle in the open field test of SONFH rats also changed significantly over the modeling time. Compared with the healthy control group, the R, G, and B values of the tongue color of the model rats decreased significantly, with the greatest difference observed 11 weeks after modeling. The levels of total cholesterol(TC), total triglycerides(TG), low-density lipoprotein-cholesterol(LDL-C), and apoprotein B(ApoB) in the SONFH rats changed significantly 4 and 8 weeks after modeling. The levels of VEGF, ET-1, NO, t-PA, PAI-1, 6-keto-PGF1α, TXB2, four coagulation items, and TXB2/6-keto-PGF1α ratio in the serum of SONFH rats changed significantly 4-16 weeks after modeling, with the greatest differences observed 12 weeks after modeling. The levels of BGP, TRAP5b, RANKL, OPG, and RANKL/OPG ratio in the serum of SONFH rats changed significantly 8-21 weeks after modeling. During the entire onset and progression of SONFH in rats, the blood stasis syndrome characteristics such as hyperalgesia, tongue color darkening, gait abnormalities, platelet, vascular, and coagulation dysfunctions were observed, which gradually worsened and then gradually alleviated in the disease course(2-21 weeks), with the most notable differences occurred around 12 weeks after modeling.
Rats ; Male ; Animals ; Femur Head/pathology* ; Plasminogen Activator Inhibitor 1/adverse effects* ; Vascular Endothelial Growth Factor A ; Femur Head Necrosis/pathology* ; Rats, Sprague-Dawley ; Steroids ; Pain ; Cholesterol

OBJECTIVETo compare the differences between computer aided identification and ultra-thin layer slicing in measuring the lesions of femoral head necrosis,and to confirm the accuracy and practicability of computer aided method.

METHODSFrom June 2012 to December 2013, the X-ray and MRI of 24 patients (24 hips on unilateral) were reviewed, who had avascular necrosis of the femoral head (ANFA) at late stage (stage III and IV) according to the ARCO international staging system. There were 15 males and 9 females, with an average age of (65.1 ± 8.8) years old, ranged 33 to 74 years old. Based on the software system with seeds point identification, the ragional adaptive search method with computer aid was used to calculate the volume of necrotic lesion in femoral on MRI. Then the pathological slices of those intraoperative femoral heads were made to measure the gross volume of necrotic lesion in femoral head,and the values were compared with the data in the computer.

RESULTSFor 24 hips, by the calculation of computer, the necrotic volume was (20.00 ± 3.04) cm (ranged, 18.72 to 21.29 cm³). Under the pathological section, the necrotic volume of the femoral head was (19.89 ± 3.17) cm³ (ranged, 18.55 to 21.23 cm³). In computer and pathology two kinds of measurement, the two entire femoral head volume had no significant difference using these two measurements (t = -1.227, P = 0.232).

CONCLUSIONComputer aided identification for necrotic area of femoral head adaptive can demonstrate the morphology of femoral head necrosis accurately and reliably, which will help surgeon better understand the morphology and orientation in femoral head.

Adult ; Aged ; Diagnosis, Computer-Assisted ; Female ; Femur Head Necrosis ; pathology ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged

PURPOSE: To explore the value of transplanting peripheral blood-derived mesenchymal stem cells from allogenic rabbits (rPBMSCs) to treat osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: rPBMSCs were separated/cultured from peripheral blood after granulocyte colony-stimulating factor mobilization. Afterwards, mobilized rPBMSCs from a second passage labeled with PKH26 were transplanted into rabbit ONFH models, which were established by liquid nitrogen freezing, to observe the effect of rPBMSCs on ONFH repair. Then, the mRNA expressions of BMP-2 and PPAR-γ in the femoral head were assessed by RT-PCR. RESULTS: After mobilization, the cultured rPBMSCs expressed mesenchymal markers of CD90, CD44, CD29, and CD105, but failed to express CD45, CD14, and CD34. The colony forming efficiency of mobilized rPBMSCs ranged from 2.8 to 10.8 per million peripheral mononuclear cells. After local transplantation, survival of the engrafted cells reached at least 8 weeks. Therein, BMP-2 was up-regulated, while PPAR-γ mRNA was down-regulated. Additionally, bone density and bone trabeculae tended to increase gradually. CONCLUSION: We confirmed that local transplantation of rPBMSCs benefits ONFH treatment and that the beneficial effects are related to the up-regulation of BMP-2 expression and the down-regulation of PPAR-γ expression.
Animals ; Blood Cells/*cytology ; Bone Morphogenetic Protein 2/genetics ; *Cell- and Tissue-Based Therapy ; Femur Head Necrosis/metabolism/*pathology/*therapy ; Gene Expression Regulation ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/*cytology ; Osteonecrosis/*pathology/*therapy ; PPAR gamma/genetics ; Rabbits ; Transplantation, Homologous

OBJECTIVETo explore the preventive effect of Yougui drink on femoral head necrosis in rats under micro CT.

METHODSTwenty-five SD rats were divided into steroid hormone group (group A, 10 rats ), Yougui drink group (group B,10 rats) and normal group (group C,5 rats)with random number table. Endotoxin were injected into abdominal cavity of rats in group A and B for 2 days, methylprednisolone sodium succinate were injected by gluteus for twice a week continued for 6 weeks; group B were gavaged by Yougui drink (veryday for 8 weeks; group C did not do any processing. All rats were killed on the 10th weeks,m icro CT were used to scan femoral head in vitro and preventive effect of Yougui drink (n femoral head necrosis in rats.

RESULTSThere was statistical significance in BMD, BV/TV, Tb.N, Tb, Th, Thb, Sp, BS/TV and DA but no significance in SMI between group A and B. Comparison between A and C, there was significant meaning in BMD, BV/TV, Tb.N, Tb, Th, Tb, Sp, BS/TV, DA and SMI.

CONCLUSIONYougui drink on femoral head necrosis in rats under micro CT has preventive effect from BMD BV/TV, Tb.N, Tb, Th, Tb, Sp, BS/TV and DA.

Animals ; Apoptosis ; Bone Density ; Drugs, Chinese Herbal ; therapeutic use ; Femur Head Necrosis ; diagnostic imaging ; pathology ; prevention & control ; Rats ; Rats, Sprague-Dawley ; X-Ray Microtomography ; methods

OBJECTIVETo observe the changes of proximal femoral geometry after femoral neck fracture treated with THA, analyze the existent of differences and their manifestation.

METHODSAll patients of femoral neck fracture (FNF) and osteonecrosis of femoral head (ONFH) were treated with THA by the same operating team from January to December of 2014, including 22 patients with FNF (11 males and 11 females,with age from 44 to 83 years old (means 66.18 ± 11.47) and 23 patients with ONFH (12 males and 11 females, with age from 19 to 68 years old (means 51.91 ± 11.76). After THA, height of femorals, offsets, osteotomy position and adjusting modes were measured and the statistic analysis was done.

RESULTSAfter THA, all patients were measured. Decreased femoral height, offsets and lower osteotomy positions were found in patients with FNF than those with ONFH, and 3 kinds of adjustments because of lower-positional osteotomy were found.

CONCLUSIONAfter THA, lower-positional osteotomy and decreased femoral offsets may occur on patients with FNF. The adjustments caused by lower-positional osteotomy may lead to negative results.

Adult ; Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip ; methods ; Female ; Femoral Neck Fractures ; pathology ; surgery ; Femur ; pathology ; Femur Head Necrosis ; pathology ; surgery ; Humans ; Male ; Middle Aged

OBJECTIVETo discuss the management of vascular crisis of free flaps after reconstruction of head and neck defects caused by tumor resection.

METHODSA total of 259 cases of free flap reconstruction performed in the Cancer Hospital of Chinese Academy of Medical Sciences from 2010 to 2013 were retrospectively analyzed, including 89 cases of anterolateral thigh flaps, 48 cases of radial forearm flaps, 46 free fibula flaps, 5 cases of inferior epigastric artery perforator flaps, 5 cases of free latissimus dorsi flaps, one case of lateral arm flap, and one case of medial femoral flap. The surveillance frequency of free flaps was q1h on post-operative day (POD) 1, q2h on POD 2 and 3, and q4h after POD 3. Vascular crises were reviewed for analysis.

RESULTSThe incidence rate of vascular crisis was 8.1% (21/259), with 15 males and 6 females. The average age was 54.8 years old (17-68), and the average time of vascular crisis was 100.8 h post-operation (3-432). There were 7 cases of free jejunum flaps and 14 dermal free flaps. Seven of these 21 cases with vascular crisis were rescued by surgery. The success rate of salvage surgery within 72 hours from the primary operation was 54.5% (6/11), significantly higher than that of salvage surgery performed later than 72 hours from primary operation (10.0%, 1/10, P=0.043). There were 14 cases of flap necrosis, two of which died of local infection.

CONCLUSIONEarly detection of vascular crisis can effectively improve the success rate of salvage, so as to avoid the serious consequences caused by free flap necrosis.

Adolescent ; Adult ; Aged ; Female ; Femur ; Free Tissue Flaps ; blood supply ; pathology ; surgery ; Head and Neck Neoplasms ; surgery ; Humans ; Jejunum ; Male ; Middle Aged ; Necrosis ; Postoperative Period ; Reconstructive Surgical Procedures ; Retrospective Studies ; Salvage Therapy ; Time Factors ; Treatment Outcome

BACKGROUNDStudies have reported that patients with human immunodeficiency virus (HIV) have a high incidence of osteonecrosis of the femoral head (ONFH). Total hip arthroplasty (THA) is an effective management of ONFH. However, little data exist regarding the use of THA for the HIV patients with ONFH in China. This study reviewed the outcomes of HIV-positive patients who underwent THA for ONFH, compared with HIV-negative individuals.

METHODSThe patients who underwent THA for ONFH from September 2012 to September 2014 in Beijing Ditan Hospital, Capital Medical University were retrospectively studied. Twenty-eight HIV-positive patients and 35 HIV-negative patients underwent 48 THAs and 45 THAs with cementless components, respectively. Medical records and follow-up data were reviewed. Harris Hip Score (HHS) was applied to evaluate the pain and function of the hips before and after THA. Complications such as wound healing, surgical site infection, deep venous thrombosis, pulmonary embolism, sepsis, mortality, and complications from the prosthesis were reviewed. The operation time, blood loss, and hospital stay were compared between the two groups.

RESULTSThe mean follow-up period was 19.5 ± 5.8 months (ranging from 6 to 30 months). The mean age of the HIV-positive patients with osteonecrosis at the time of surgery was 35 years old, which was significantly lower than that of the HIV-negative group (42 years old) (P < 0.05). The HIV-positive patients underwent surgery a mean of 2.5 years after their original symptoms, which was significantly shorter than the HIV-negatives' (mean 4 years) (P < 0.05). Among HIV-positive patients, the prevalence of being male and rate of bilateral procedures were significantly higher than those in the HIV-negative group (P < 0.05). The operation time in HIV-positive patients was significantly longer than that in HIV-negative patients (P < 0.05). There were no significant differences in blood loss or hospital stay between the two groups (P > 0.05). The HHSs of two groups significantly improved after THAs (P < 0.05), without significant difference between two groups. No wound complication, sepsis, mortality, prosthesis complication, and occupational exposure occurred, except for two cases of heterotopic ossification and one case of humeral head necrosis.

CONCLUSIONSONFH is more likely to occur bilaterally in younger HIV-positive males. The development of osteonecrosis seems faster in HIV-positive patients than in HIV-negative patients. This should be cautionary for asymptomatic HIV-positive patients with low viral RNA level and in the primary HIV stage. Despite longer operation times in the HIV-positive patients than in the HIV-negative patients, THA is still a safe and efficient approach to treat ONFH in HIV-positive patients. The incidence of complications is much lower than previously reported. However, the long-term follow-up is needed.

Adult ; Arthroplasty, Replacement, Hip ; methods ; China ; Female ; Femur Head Necrosis ; pathology ; surgery ; HIV Infections ; surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo observe the distribution law and study the factors related to the femoral neck anteversion angle among the patients with developmental dysplasia of the hip of Hartofilakidis type I.

METHODSAmong the patients with hip dysplasia of Hartofilakidis type I who was admitted to Department of Orthopaedic Surgery, the First Affiliated Hospital of People's Liberation Army General Hospital from June 2010 to June 2013, a total of 340 hips (25 male and 161 female) were included in the study. The average age was 28.3 years, ranging from 13.5 to 49.9 years. The observation index included: femoral neck anteversion angle, lateral center-edge angle, acetabular index angle, lateral displacement of the femoral head, superior displacement of the femoral head, continuity of Shenton's line and Calve's line. The correlation between different factors was analyzed, and the factor closest to femoral neck anteversion angle was analyzed further by regression analysis.

RESULTSAmong the patients of developmental dysplasia of the hip of Hartofilakidis type I, the femoral neck anteversion angle increased, with an average of 28°±13°. Correlation and regression analysis showed significant negative correlation with treatment age (r=-0.158, P=0.003; t=-6.892, P=0.000); positive correlation with gender (r=0.332, P=0.000; t=-4.376, P=0.000); significant positive correlation with lateral displacement of the femoral head (r=0.092, P=0.000; t=3.766, P=0.000); significant negative correlation with central-edge angle (r=-0.122, P=0.024; t=2.031, P=0.043). The femoral neck anteversion angle showed correlation with acetabular index angle, continuity of Calve's line and superior displacement of the femoral head in correlation analysis, not in regression analysis, however, it did not show correlation with side and continuity of Shenton's line.

CONCLUSIONAmong the patients of developmental dysplasia of the hip of Hartofilakidis type I, the increasing of the femoral neck anteversion angle may not only lead to early onset and therefore early treatment of pain in the hip joint but also the lateral displacement of the femoral head that requires immediate medical attention.

Acetabulum ; Adolescent ; Adult ; Female ; Femur Head ; Femur Neck ; pathology ; Hip Dislocation, Congenital ; pathology ; surgery ; Hip Joint ; Humans ; Hyperplasia ; Male ; Middle Aged ; Orthopedic Procedures ; Orthopedics ; Regression Analysis ; Tomography, X-Ray Computed ; Young Adult

OBJECTIVE: To investigate the usefulness of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion MRI for the evaluation of femoral head ischemia. MATERIALS AND METHODS: Unilateral femoral head ischemia was induced by selective embolization of the medial circumflex femoral artery in 10 piglets. All MRIs were performed immediately (1 hour) and after embolization (1, 2, and 4 weeks). Apparent diffusion coefficients (ADCs) were calculated for the femoral head. The estimated pharmacokinetic parameters (Kep and Ve from two-compartment model) and semi-quantitative parameters including peak enhancement, time-to-peak (TTP), and contrast washout were evaluated. RESULTS: The epiphyseal ADC values of the ischemic hip decreased immediately (1 hour) after embolization. However, they increased rapidly at 1 week after embolization and remained elevated until 4 weeks after embolization. Perfusion MRI of ischemic hips showed decreased epiphyseal perfusion with decreased Kep immediately after embolization. Signal intensity-time curves showed delayed TTP with limited contrast washout immediately post-embolization. At 1-2 weeks after embolization, spontaneous reperfusion was observed in ischemic epiphyses. The change of ADC (p = 0.043) and Kep (p = 0.043) were significantly different between immediate (1 hour) after embolization and 1 week post-embolization. CONCLUSION: Diffusion MRI and pharmacokinetic model obtained from the DCE-MRI are useful in depicting early changes of perfusion and tissue damage using the model of femoral head ischemia in skeletally immature piglets.
Animals ; Arteries/physiopathology ; Diffusion Magnetic Resonance Imaging/*methods ; Disease Models, Animal ; Embolism/complications ; Epiphyses/*blood supply/*pathology ; Femur Head/*blood supply/*pathology ; Male ; Osteonecrosis/pathology ; Pelvic Bones/blood supply/pathology ; Reperfusion Injury/complications/*diagnosis ; Swine