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*

Humans ; Femoral Fractures, Distal ; Fracture Fixation, Internal ; Femoral Fractures/surgery* ; Femur/surgery* ; Bone Plates ; Retrospective Studies

Humans ; Aged ; Femoral Neck Fractures/surgery* ; Fracture Fixation, Internal/adverse effects* ; Osteonecrosis/surgery* ; Femur Head Necrosis/surgery*

This study aimed to investigate the protective effect and underlying mechanism of Mailuo Shutong Pills(MLST) on posterior limb swelling caused by femur fracture in rats. The rats were randomly divided into a sham operation group, a model group, a low-dose MLST group(1.8 g·kg~(-1)·d~(-1)), a high-dose MLST group(3.6 g·kg~(-1)·d~(-1)), and a positive drug group(60 mg·kg~(-1)·d~(-1) Maizhiling Tablets). The femur in the sham operation group was exposed and the wound was sutured, while the other four groups underwent mechanical damage to cause femur fracture. The rats were treated with corresponding drugs by gavage 7 days before modeling and 5 days after modeling, while those in the sham operation group and the model group were given an equivalent dose of distilled water by gavage. Hematoxylin-eosin(HE) staining was used to detect the pathological injury of the posterior limb muscle tissues in rats, and the degree of hind limb swelling was measured. The enzyme-linked immunosorbent assay(ELISA) kit was used to detect the expression levels of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in the serum of rats in each group. The activity of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and glutathione peroxidase(GSH-Px) in rat serum was also measured. Western blot was used to detect the protein expression levels of heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), and nuclear transcription factor E2-related factor 2(Nrf2) in rat posterior limb muscle tissues. The changes in the intestinal flora and intestinal metabolites in rats were detected by 16S rDNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), respectively, to explore the underlying mechanism of MLST in treating posterior limb swelling caused by femur fracture in rats. Compared with the model group, MLST significantly improved the degree of posterior limb swelling in rats, reduced the levels of serum inflammatory factors, and alleviated oxidative stress injury. The HE staining results showed that the inflammatory infiltration in the posterior limb muscle tissues of rats in the MLST groups was significantly improved. Western blot results showed that MLST significantly increased the protein expression of HO-1, NQO1, and Nrf2 in rat posterior limb muscle tissues compared with the model group. The 16S rDNA sequencing results showed that MLST improved the disorder of intestinal flora in rats after femur fracture. The UPLC-MS/MS results showed that MLST significantly affected the bile acid biosynthesis and metabolism pathway in the intestine after femur fracture, and the Spearman analysis confirmed that the metabolite deoxycholic acid involved in bile acid biosynthesis was positively correlated with the abundance of Turicibacter. The metabolite cholic acid was positively correlated with the abundance of Papilibacter, Staphylococcus, and Intestinimonas. The metabolite lithocholic acid was positively correlated with Papilibacter and Intestinimonas. The above results indicated that MLST could protect against the posterior limb swelling caused by femur fracture in rats. This protective effect may be achieved by improving the pathological injury of the posterior limb muscle, reducing the expression levels of inflammatory and oxidative stress-related factors in serum, reducing the oxidative injury of the posterior limb muscle, improving intestinal flora, and balancing the biosynthesis of bile acids in the intestine.
Rats ; Animals ; NF-E2-Related Factor 2/metabolism* ; Gastrointestinal Microbiome ; Chromatography, Liquid ; Multilocus Sequence Typing ; Tandem Mass Spectrometry ; Oxidative Stress ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Femur ; Bile Acids and Salts ; DNA, Ribosomal ; Superoxide Dismutase/metabolism*

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

Reconstructing three-dimensional (3D) models from two-dimensional (2D) images is necessary for preoperative planning and the customization of joint prostheses. However, the traditional statistical modeling reconstruction shows a low accuracy due to limited 3D characteristics and information loss. In this study, we proposed a new method to reconstruct the 3D models of femoral images by combining a statistical shape model with Laplacian surface deformation, which greatly improved the accuracy of the reconstruction. In this method, a Laplace operator was introduced to represent the 3D model derived from the statistical shape model. By coordinate transformations in the Laplacian system, novel skeletal features were established and the model was accurately aligned with its 2D image. Finally, 50 femoral models were utilized to verify the effectiveness of this method. The results indicated that the precision of the method was improved by 16.8%-25.9% compared with the traditional statistical shape model reconstruction. Therefore, the method we proposed allows a more accurate 3D bone reconstruction, which facilitates the development of personalized prosthesis design, precise positioning, and quick biomechanical analysis.
Imaging, Three-Dimensional/methods* ; Tomography, X-Ray Computed/methods* ; Femur/surgery* ; Models, Statistical ; Lower Extremity

OBJECTIVE: To explore effectiveness of positive support reduction and internal fixation in the treatment of femoral neck fractures. METHODS: A clinical data of 74 patients with femoral neck fractures treated with hollow screw internal fixation between September 2017 and September 2021 was retrospectively analyzed. Based on the quality of fracture reduction, they were divided into positive support reduction group (group A, n=25), negative support reduction group (group B, n=21), and anatomical reduction group (group C, n=28). There was no significant difference in baseline data such as gender, age, cause of injury, disease duration, fracture side, Garden classification, and fracture line position classification between groups (P>0.05). The occurrence of complications such as early fixation failure, femoral neck shortening, non-union of fractures, and femoral head necrosis in three groups, as well as the Harris score of the hip joint were recorded and compared. RESULTS: All patients had primary healing of incisions after operation and were followed up more than 12 months. The follow-up time for groups A, B, and C was (21.1±5.7), (22.6±4.3), and (21.9±4.1) months, respectively; there was no significant difference between groups (P>0.05). There was no significant difference in the incidences of non-union of fractures, early internal fixation failure, and the femoral head necrosis between groups (P>0.05). The incidence and length of femoral neck shortening, and the hip Harris score at last follow-up in groups A and C were all superior to those in the group B, with significant difference (P<0.05). There was no significant difference in the above indicators between groups A and C (P>0.05). CONCLUSION Positive support reduction can provide a good biomechanical environment for the healing of femoral neck fractures, thereby achieving a higher fracture healing rate, reducing the occurrence of femoral neck shortening, minimizing the function of hip joint, and achieving effectiveness similar to anatomical reduction.
Humans ; Femur Head Necrosis ; Retrospective Studies ; Femoral Neck Fractures/surgery* ; Femur Neck ; Plastic Surgery Procedures

OBJECTIVE: To explore the design points of a three-dimensional (3D) printed customized cementless intercalary endoprosthesis with an intra-neck curved stem and to evaluate the key points and mid-term effectiveness of its application in the reconstruction of ultrashort bone segments in the proximal femur. METHODS: Between October 2015 and January 2021, 17 patients underwent reconstruction with a 3D printed-customized cementless intercalary endoprosthesis with an intra-neck curved stem. There were 11 males and 6 females, the age ranged from 10 to 76 years, with an average of 30.1 years. There were 9 cases of osteosarcoma, 4 cases of Ewing sarcoma, 2 cases of chondrosarcoma, 1 case of liposarcoma, and 1 case of myofibroblastoma. The disease duration was 5-14 months, with an average of 9.5 months. Enneking staging included 16 cases of stage ⅡB and 1 case of stage ⅢB. The distances from the center of the femoral head to the body midline and the acetabular apex were measured preoperatively on X-ray images. Additionally, the distances from the tip of the intra-neck curved stem to the body midline and the acetabular apex were measured at immediate postoperatively and last follow-up. The neck-shaft angle was also measured preoperatively, at immediate postoperatively, and at last follow-up. The status of osseointegration at the bone-prosthesis interface and bone growth into the prosthesis surface were assessed by X-ray films, CT, and Tomosynthesis-Shimadzu metal artefact reduction technology (T-SMART). The survival status of the patients, presence of local recurrence or distant metastasis, and occurrence of postoperative complications were assessed. The recovery of lower limb function was evaluated pre- and post-operatively using the Musculoskeletal Tumor Society (MSTS) scoring system, and pain relief was evaluated using the visual analogue scale (VAS) scores. RESULTS: The patient's femoral resection length was (163.1±57.5) mm, the remaining proximal femoral length was (69.6±9.3) mm, and the percentage of femoral resection length/total femoral length was 38.7%±14.6%. All 17 patients were followed up 25-86 months with an average of 58.1 months. During the follow-up, 1 patient died of lung metastasis at 46 months postoperatively, and the remaining 16 patients survived tumor-free. There was no complication such as periprosthetic infection, delayed incision healing, aseptic loosening, prosthesis fracture, or periprosthetic fracture. No evidence of micromotion or wear around the implanted stem of the prosthesis was detected in X-ray and T-SMART evaluations. There was no significant radiolucent lines, and radiographic evidence of bone ingrowth into the bone-prosthesis interface was observed in all stems. There was no significant difference in the distance from the tip of the curved stem to the body midline and the apex of the acetabulum at immediate postoperatively and last follow-up compared with the distance from the center of the femoral head to the body midline and the apex of the acetabulum before operation, respectively (P>0.05), and there was no significant difference in the above indexes between immediate postoperatively and last follow-up (P>0.05). The differences in the neck-shaft angle at various time points before and after operation were also not significant (P>0.05). At last follow-up, the MSTS score was 26.1±1.2 and the VAS score was 0.1±0.5, which were significantly improved when compared with those before operation [19.4±2.1 and 5.7±1.0, respectively] (t=14.735, P<0.001; t=21.301, P<0.001). At last follow-up, none of the patients walked with the aid of crutches or other walkers. CONCLUSION The 3D printed customized cementless intercalary endoprosthesis with an intra-neck curved stem is an effective method for reconstructing ultrashort bone segments in the proximal femur following malignant tumor resection. The operation is reliable, the postoperative lower limb function is satisfactory, and the incidence of complications is low.
Female ; Male ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Femur/surgery* ; Lower Extremity ; Bone-Implant Interface ; Femur Head ; Artificial Limbs

OBJECTIVE: To explore the related factors of femoral stem anteversion (FSA) after total hip arthroplasty (THA), so as to provide reference for clinical design of FSA before operation and reduce the risk of hip dislocation after arthroplasty. METHODS: Ninty-three patients (103 hips) who underwent THA between October 2021 and September 2022 and met the selection criteria were selected as the study subjects. Among them, there were 48 males and 45 females with an average age of 58.5 years (range, 25-88 years). Body mass index was 18.00-37.84 kg/m ², with an average of 24.92 kg/m ². There were 51 cases (57 hips) of osteonecrosis of femoral head, 35 cases (39 hips) of hip osteoarthritis, and 7 cases (7 hips) of congenital hip dysplasia. Based on CT images, the following indicators were measured: preoperative femoral neck anteversion (FNA), preoperative femoral rotation angle (FRA), preoperative acetabular anteversion (AA), and preoperative combined anteversion (CA; the sum of preoperative FNA and AA); postoperative FSA and the change in femoral anteversion angle (the difference between postoperative FSA and preoperative FNA). Based on preoperative X-ray films, the following indicators were measured: femoral cortical thickness index (CTI) and canal flare index (CFI), the proximal femoral medullary cavity was classified according to Noble classification (champagne cup type, normal type, chimney type), neck-shaft angle (NSA), and femoral offset (FO). Pearson correlation analysis, one-way ANOVA, and Point-biserial correlation analysis were used to investigate the correlation between postoperative FSA, postoperative change in femoral anteversion angle, and patient diagnosis, proximal femoral medullary cavity anatomy type, gender, age, as well as preoperative FNA, FRA, AA, CA, NSA, FO, CTI, and CFI. FSA was used as the dependent variable and the independent variables that may be related to it were included for multiple linear regression analysis. RESULTS: Based on CT image measurement, preoperative FNA was (15.96±10.01)°, FRA (3.36±10.87)°, AA (12.94±8.83)°, CA (28.9±12.6)°, postoperative FSA (16.18±11.01)°, and postoperative change in femoral anteversion angle was (0.22±9.98)°. Based on preoperative X-ray films measurements, the CTI was 0.586±0.081; the CFI was 4.135±1.125, with 23 hips classified as champagne cup type, 68 hips as normal type, and 12 hips as chimney type in the proximal femoral medullary cavity anatomy; NSA was (132.87±7.83)°; FO was (40.53±10.11) mm. There was no significant difference between preoperative FNA and postoperative FSA ( t=-0.227, P=0.821). Pearson correlation analysis showed that postoperative FSA was positively correlated with preoperative FNA, preoperative CA, postoperative change in femoral anteversion angle, and age ( P<0.05), while negatively correlated with preoperative FRA ( P<0.05). The postoperative change in femoral anteversion angle were positively correlated with preoperative FRA and postoperative FSA ( P<0.05), and negatively correlated with preoperative CA and FNA ( P<0.05). One-way ANOVA analysis showed that the above two indicators were not correlated with diagnosis and the proximal femoral medullary cavity anatomy type ( P>0.05). Multiple linear regression analysis showed a linear correlation between FSA and FNA, CA, age, and FRA ( F=10.998, P<0.001), and the best fit model was FSA=0.48×FNA-2.551. CONCLUSION The factors related to FSA after THA include patient's age, preoperative FNA, CA, FRA and postoperative femoral anteversion, of which preoperative FNA is the most closely related. When designing a surgical plan before surgery, attention should be paid to the patient's preoperative FNA, and if necessary, CT around the hip joint should be scanned to gain a detailed understanding of the proximal femoral anatomical structure.
Female ; Male ; Humans ; Middle Aged ; Arthroplasty, Replacement, Hip ; Femur/diagnostic imaging* ; Femur Neck ; Femur Head ; Hip Joint

OBJECTIVE: To investigate the long-term effectiveness of uncemented allograft-prosthesis composite (APC) for reconstruction of bone defects after proximal femur tumor resection. METHODS: Between June 2007 and March 2014, 21 patients who underwent uncemented APC reconstruction of proximal femur after tumor resection were retrospectively evaluated. There were 9 males and 12 females with an average age of 33.2 years (range, 19-54 years). There were 9 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 4 cases of osteoblastic osteosarcoma, 2 cases of chondrosarcoma, and 1 case of undifferentiated pleomorphic sarcoma. Thirteen cases of benign bone tumors were all classified as stage 3 by Enneking staging; and 8 cases of malignant bone tumors were classified as grade ⅡB in 7 cases and grade ⅡA in 1 case according to the American Joint Committee on Cancer (AJCC) staging system. Among them, 7 patients underwent reoperation after recurrence, and the rest were primary operations; 8 patients presented with pathological fractures. The preoperative Harris hip score (HHS) and American Musculoskeletal Tumor Society (MSTS) score was 40 (30, 49) and 9.1±3.5, respectively. The length of osteotomy was 80-154 mm, with an average of 110 mm. At 1 year after operation and last follow-up, HHS and MSTS scores were utilized to evaluate the function of hip joint; the gluteus medius strength score was used to evaluation of the hip abduction function. Image examinations were taken at 1, 3, 6, 9, and 12 months after operation and every year thereafter to assess the union of allograft-host bone interfaces. Intra- and post-operative complications were also recorded. RESULTS: All patients were followed up 84-163 months (mean, 123.5 months). At 1 year after operation and last follow-up, the HHS and MSTS scores significantly improved when compared with the preoperative scores ( P<0.05). However, there was no significant difference in the HHS score, MSTS score, and gluteus medius strength score between the two time points after operation ( P>0.05). Image examination showed that all allograft-host bone interfaces achieved union after 5-10 months (mean, 7.6 months). At last follow-up, all patients had bone resorption, including 11 severe cases, 4 moderate cases, and 6 mild cases; the bone resorption sites included Gruen 1, 2, and 7 regions. Complications included 10 fractures and 1 prosthetic fracture. Local recurrence occurred in 3 patients and pulmonary metastasis in 3 patients. CONCLUSION Uncemented APC is a reliable method for the reconstruction of bone defects after proximal femur tumor resection. It has the good long-term effectiveness and possesses obvious advantages in the union at the bone-bone surface.
Adult ; Female ; Humans ; Male ; Allografts/pathology* ; Bone Neoplasms/surgery* ; Bone Resorption/pathology* ; Bone Transplantation/methods* ; Femur/surgery* ; Osteosarcoma/pathology* ; Prostheses and Implants ; Retrospective Studies ; Treatment Outcome ; Young Adult ; Middle Aged