Lateral classification system predicts the collapse of JIC type C1 nontraumatic osteonecrosis of the femoral head: a retrospective study.

PURPOSES: The aim of this study was to construct a lateral classification system for nontraumatic osteonecrosis of femoral head (NONFH) through three-dimensional reconstruction of the necrotic area to assist in evaluating the prognosis of patients with JIC type C1. METHODS: Retrospective analysis of patients with JIC type C1 NONFH from January 2018 to December 2020. All patients were followed up for more than 3.5 years. The patients were divided into collapse group and non-collapse group according to whether the femoral head collapsed during the follow-up.Lateral classification system for femoral head necrosis is constructed through three-dimensional reconstruction of the necrotic area.Comparison of lateral classification system,midsagittal necrosis angle(MNA)and general data between the two groups.Furthermore, ROC curve analysis and survival analysis were performed. RESULTS: 318 patients were included in this study.There was a significant difference between the two groups in the lateral classification system (P < 0.05). In addition, the MNA in the collapsed group was significantly greater than that in the non-collapse group(P < 0.05). As revealed by the results of ROC analysis, the cutoff point of MNA was 104.5° (P < 0.05).According to the survivorship analysis, the mean survival time of the hips of patients with MNA less than 104.5°was greater than that of patients with MNA over 104.5° (P < 0.05). The survival rates of 3.5 years femoral head were 45.8%, 33.7%, 14.8%, 93.0%, and 100% for lateral classification system 1, 2, 3, 4, and 5, respectively. CONCLUSION: Necrosis involving the anterior aspect of the femoral head is an important risk factor for collapse. The Lateral classification system can effectively predict the femoral head collapse in JIC C1 type NONFH patients, supplementing the deficiency of JIC classification in evaluating the front of the femoral head.

Prior Intra-articular Corticosteroid Injection Within 3 Months May Increase the Risk of Deep Infection in Subsequent Joint Arthroplasty: A Meta-analysis.

BACKGROUND: Intra-articular injections containing a corticosteroid are used frequently, and periprosthetic joint infection is a serious complication after total joint arthroplasty. There is debate regarding whether intra-articular corticosteroid injections before arthroplasty increase periprosthetic joint infection after surgery. QUESTIONS/PURPOSES: (1) Does a previous intra-articular corticosteroid injection increase the odds of infection after subsequent hip or knee arthroplasty? (2) Does this risk vary based on how soon before the arthroplasty (such as less than 3 months before surgery) the injection is administered? METHODS: Using the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to July 2021, we searched for comparative studies in English on patients who received intra-articular corticosteroid injections before arthroplasty and that tracked the frequency of infection after arthroplasty. We extracted data on the risk of infection after subsequent joint arthroplasty. The keywords included "corticosteroid," "steroid," "arthroplasty," "knee replacement," and "hip replacement." Eleven retrospective, comparative studies from four countries were included, of which 10 reported the specific diagnosis criteria and one did not. These articles included data on 173,465 arthroplasties in the hip or knee, as well as of 73,049 injections and 100,416 control patients. The methodologic quality of the included studies was evaluated according to the Newcastle-Ottawa Quality Assessment Scale; the articles' scores ranged from 6 to 7 (the score itself spans 0 to 9, with higher scores representing better study quality). We found no evidence of publication bias based on the Egger test, and tests of heterogeneity generally found heterogeneity, so a random-effects model was used of our meta-analyses. A meta-analysis was performed with Review Manager 5.3 software and Stata version 12.0 software. RESULTS: Overall, there were no differences in the odds of periprosthetic joint infection between the injection group and the control group among patients who received any kind of injection (odds ratio 1.22 [95% CI 0.95 to 1.58]; p = 0.12). However, in a subgroup analysis, there was a higher OR for postoperative PJI in patients with an intra-articular corticosteroid injection in the knee or hip within 3 months (OR 1.39 [95% CI 1.04 to 1.87]; p = 0.03). There were no differences in the infection risk in patients who had injections between 3 and 6 months before arthroplasty (OR 1.19 [95% CI 0.95 to 1.48]; p = 0.13) or between 6 and 12 months before arthroplasty. CONCLUSION: The current evidence suggests ipsilateral intra-articular corticosteroid injections within 3 months before arthroplasty were associated with an increased risk of periprosthetic joint infection during subsequent joint arthroplasty. We recommend against performing total joint arthroplasty on a patient who has received an intra-articular corticosteroid injection within 3 months. Further high-quality studies on this topic from registries, national databases, or insurance company data are still required to confirm and extend our findings. LEVEL OF EVIDENCE: Level III, therapeutic study.

Composite indices of femoral neck strength predicts the collapse of steroid-associated osteonecrosis of the femoral head: a retrospective study.

PURPOSES: The purpose of this study was to investigate the predictive effect exerted by composite indices of femoral neck strength (compressive strength index (CSI), bending strength index (BSI) and impact strength index (ISI) on the femoral head collapse in steroid-associated ONFH patients. METHODS: Nonoperative steroid-associated osteonecrosis of the femoral head (ONFH) patients from 2017 to 2019 were selected. The patients fell into the collapsed group and the non-collapsed group according to whether the femoral head collapsed. CSI, BSI and ISI were calculated. Moreover, bone turnover markers were measured. The statistical analysis was conducted on the predictive effects of composite indices of femoral neck strength and bone turnover index on ONFH collapse. RESULTS: A total of 62 patients were included. The mean CSI, BSI and ISI were significantly lower in the collapsed group than those in the non-collapsed group (P < 0.05). CSI, ISI,t-P1NP and ß-CTx were suggested as the protective risk factors for the femoral head collapse in ONFH patients. The ISI area under the curve values was 0. 878.The mean survival time of the hips of patients with ISI greater than 0.435 was greater (P < 0.05) than that of patients with ISI less than 0.435. CONCLUSION: The composite indices of femoral neck strength can predict steroid-associated ONFH femoral head collapse more effectively than the bone turnover markers. The ISI value of 0.435 is a potential cut-off value, lower than this value can predict the early collapse of steroid-associated ONFH.

What happens to the gluteus medius in young and middle-aged patients with hip dysplasia?

BACKGROUND: Much research has focused on quantifying the bony characteristics of patients with developmental dysplasia of the hip (DDH). Far less attention, however, has been paid to muscle abnormalities around the hip such as those in the gluteus medius (GM). METHODS: We retrospectively examined clinical and imaging data, such as the age of onset and computed tomography (CT) findings, in 108 consecutive hips. Subjects for the control group were selected from our radiology database. Two readers independently evaluated the length (LGM), cross-sectional area (CSA), width (WGM), and thickness (TGM) of the GM and arm of GM (AGM) and angle of the GM activation (AOA) and bony parameters including the acetabulum-head index (AHI), lateral central edge angle (LCEA), acetabular index (AI), femoral offset (FO), and height of the rotation centre of femoral head (HCFH) among all cases using the imaging data. RESULTS: The patient group included 108 hips. The AGM, LGM, CSA, and TGM were lower in the DDH patients, while AOA was higher. However, there was no significant difference in the WGM between the two groups. Multiple linear regression analysis showed that AGM and AOA were independent factors affecting LCEA. The following regression equation was used: Y(LCEA) = 5.377 * X1 (AGM) - 0.310 * X2 (AOA) - 11.331. The mechanical characteristics of the GM and many bony parameters were significantly correlated (the AGM and AHI, LCEA, AI, FO, but not HCFH; AOA and AHI, LCEA, AI, but not FO or HCFH). The CSA was positively correlated with only HCFH. The rest were not statistical significance linear correlation. The multivariate regression results showed that the age of onset was positively correlated with AGM (r = 0.467). The regression equation used was Y = 9.0 * X (age of onset) - 11.4. CONCLUSION: We found difference in the morphological and mechanical characteristics of the GM between hips with DDH and hips of normal morphology. Of note, the mechanical characteristics of the GM were influenced by bony parameters in patients with DDH.

Diagnostic value of necrotic lesion boundary in bone collapse of femoral head osteonecrosis.

PURPOSE: Our research developed a novel approach to quantitatively evaluate the boundary of necrotic lesions in osteonecrosis of the femoral head (ONFH) and to explore its diagnostic value in predicting bone collapse of the femoral head. METHODS: A retrospective cross-sectional study was conducted in our institution, and 146 hips (121 cases) identified as ONFH were recruited. The anterior and lateral boundaries of each enrolled subject were measured in standard anteroposterior (AP) view and frog-leg (FL) view of plain radiographic images, the intact rate of which was then calculated and presented as the anteroposterior view intact ratio (APIR) and frog-leg view intact ratio (FLIR), respectively. Univariate and multivariate logistic regression analyses were performed to identify risk factors for collapse. A receiver operating characteristic (ROC) curve analysis was performed to determine the sensitivity, specificity and cutoff value of the APIR and FLIR. A Kaplan-Meier (K-M) analysis was applied to calculate the survival rate of the femoral head, and bone collapse of the femoral head was regarded as the endpoint. RESULTS: Femoral head collapse was observed in 61 hips during the follow-up period. Patients with or without femoral head collapse were categorized into the collapse group and non-collapse group, respectively. The mean follow-up time was 3.7 years (2-9) for the collapse group and 7.7 years (5-20) for the non-collapse group. Univariate and multivariate logistic regression analysis and ROC analysis showed that APIR (< 25.61%) and FLIR (< 24.43%) were significantly associated with femoral head collapse. The K-M survival curves indicated that the overall survival rate of APIR (≥ 25.61%) was 94.8% at 7.5 years and 76.6% at 10 years, while that of FLIR (≥ 24.43%) was 87.3% at 7.5 years and ten years. CONCLUSION: The present study demonstrates that APIR and FLIR are of high diagnostic value in the early and middle stages of ONFH. APIR and FLIR can be used to predict the occurrence of femoral head collapse in patients with JIC classification types B and C1. The measurement of these two parameters in plain radiography images may contribute to the selection of a proper hip preservation strategy.

Dracorhodin perchlorate inhibits osteoclastogenesis through repressing RANKL-stimulated NFATc1 activity.

Osteolytic skeletal disorders are caused by an imbalance in the osteoclast and osteoblast function. Suppressing the differentiation and resorptive function of osteoclast is a key strategy for treating osteolytic diseases. Dracorhodin perchlorate (D.P), an active component from dragon blood resin, has been used for facilitating wound healing and anti-cancer treatments. In this study, we determined the effect of D.P on osteoclast differentiation and function. We have found that D.P inhibited RANKL-induced osteoclast formation and resorbed pits of hydroxyapatite-coated plate in a dose-dependent manner. D.P also disrupted the formation of intact actin-rich podosome structures in mature osteoclasts and inhibited osteoclast-specific gene and protein expressions. Further, D.P was able to suppress RANKL-activated JNK, NF-κB and Ca2+ signalling pathways and reduces the expression level of NFATc1 as well as the nucleus translocation of NFATc1. Overall, these results indicated a potential therapeutic effect of D.P on osteoclast-related conditions.

Porous tantalum rod implantation is associated with low survival rates in patients with type C2 osteonecrosis of the femoral head but has no effect on the clinical outcome of conversion total hip arthroplasty: a retrospective study with an average 8-year follow-up.

BACKGROUND: Our study aimed to investigate the clinical outcomes and survival rates following porous tantalum rod surgery (PTRS) and conversion total hip arthroplasty (THA) subsequent to failed PTRS. METHODS: A total of 38 subjects (40 hips) with osteonecrosis of the femoral head (ONFH) were included in this retrospective study between January 2008 and December 2011. All subjects were evaluated before surgery by using the Association Research Circulation Osseous (ARCO) classification system, the Japan Investigation Committee (JIC) classification and the Harris hip score (HHS). The endpoint of this study was set as final follow-up (including the survival time of PTRS and conversion THA). The rates of radiological progression were also evaluated. Patients who received conversion THA were further followed and compared to a control group of 58 patients with ONFH who underwent primary THA. RESULTS: The mean follow-up time was 120.7 ± 9.2 (range, 104-143) months, and the overall survival rate was 75% at 96 months (ARCO stage II: 81.5%; stage III: 38.5%; JIC type C1: 83.3%; C2: 30%). The HHS before surgery was 59 (55-61), in contrast to 94 (91-96) at 96 months follow-up (P < 0.01). HHS in stage III show a significant poorer result compared to stage II at 24 months. HHS in Type C2 group show no significant difference compared to HHS before surgery at 24 and 60 months follow up (P = 0.91, P = 0.30). Twelve hips requiring secondary THA were followed for 66.9 ± 31.7 months, and control hips that underwent primary THA was followed for 75.4 ± 14.9 months. The HHS in the conversion group was 89 (86-93) and that in the primary THA group was 92 (79-95, P = 0.09) at the 5-year follow-up. CONCLUSION: In the mid-term follow-up, porous tantalum implants showed an encouraging survival rate in symptomatic patients in early stages (ARCO stage II) or with limited necrotic lesions (JIC type C1). In addition, our results did not demonstrated any difference between primary THA and conversion THA.

Prognostic analysis of different morphology of the necrotic-viable interface in osteonecrosis of the femoral head.

PURPOSE: The purpose of this study was to investigate the collapse progression in different morphologies of the necrotic-viable interface in osteonecrosis of the femoral head (ONFH). METHODS: A total of 168 patients (202 hips) with Association Research Circulation Osseous (ARCO) stage II ONFH were included. Ending with the collapse of the femoral head, all patients received conservative treatment but without surgical intervention and were followed for three to 91 months. Bilateral hip-joint radiographs and magnetic resonance imaging (MRI) were examined, and the largest layer of necrosis within the coronal section of MRI images was selected together with its anteroposterior radiograph to observe the morphology of the necrotic-viable interface. The morphology was divided into four types: I, type transverse; II, type "V"; III, type zigzag; IV, type closed. The collapse rate and the time to collapse in different morphologies were assessed. RESULTS: A total of 120 hips collapsed in two years or less, 61 were type-I, 51 were type-II, and 8 were type-III. Non-collapse occurred in all 17 hips with type-IV ONFH during long-term follow-up. In 202 hips with ARCO stage-II ONFH, the collapse rate in type-I ONFH was significantly higher than that of type-II and type-III ONFH (P < 0.01 for both). The time to collapse was markedly shortened. CONCLUSIONS: The risk of ONFH-induced collapse is influenced by the morphology of the necrotic-viable interface. Effective mechanical support for preventing the collapse of the femoral head is necessary when the morphology of the necrotic-viable interface is type transverse.

Association of reduced sclerostin expression with collapse process in patients with osteonecrosis of the femoral head.

PURPOSE: Sclerostin is an osteocyte-derived protein that has a potent inhibitory effect on osteoblast activity. The osteocyte apoptosis induced by various causes of osteonecrosis of the femoral head (ONFH) plays a key role in the promotion of femoral head collapse. But the effect of altering sclerostin level on the collapse of ONFH has not been studied. Our aim was to assess the role of sclerostin level in the collapse of ONFH. METHODS: Between May 2016 and November 2016, 236 subjects were enrolled in the present study. The patients were classified according to the Association Research Circulation Osseous (ARCO) classification. The clinical bone histomorphology, the expression position, and level of sclerostin as well as the plasma sclerostin level were evaluated. RESULTS: The sclerostin level was significantly lower in the non-traumatic ONFH group than those in the healthy control group (P = 0.002). The sclerostin level was negatively associated with ARCO stages (r = - 0.239, P = 0.009) and significantly lower in the postcollapse group (P = 0.025). CONCLUSIONS: The reduced expression of sclerostin may play a key role in the collapse process of ONFH and be predictive of the disease progression of ONFH.

Serum serotonin concentration associated with bone mineral density in Chinese postmenopausal women.

Recent studies have shown that circulating serotonin plays a potential role in bone metabolism. However, conflicting results have been reported for the relationship between serum serotonin concentrations and bone mineral density (BMD). We investigated whether the serum serotonin concentrations related to BMD in Chinese postmenopausal women. Serum serotonin and bone turnover concentrations of 117 premenopausal women and 262 asymptomatic postmenopausal women were analyzed by enzyme-linked immunosorbent assay. BMD at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry. The relationship between serotonin and BMD was investigated. The postmenopausal women had lower mean serum serotonin concentrations compared to the premenopausal women. Serotonin concentrations were negatively associated with age, weight, BMI, fat mass, and ß-CTX concentrations in postmenopausal women. No significant correlations were found between serotonin and these parameters in premenopausal women. In postmenopausal women, age- and BMI-adjusted serotonin concentrations were positively correlated with BMD of the lumbar spine and femoral neck. Multiple regression analyses showed serum serotonin and ß-CTX were the predictors for lumbar spine BMD. Only serum serotonin was the determinant for femoral neck BMD. In conclusion, lower serum serotonin concentrations are linked to low lumbar spine and femoral neck BMD in postmenopausal women.

Serum osteopontin levels in relation to bone mineral density and bone turnover markers in postmenopausal women.

Osteopontin (OPN) is an extracellular matrix protein that is expressed in bone cells such as osteoblast and osteocytes and associated with bone turnover and bone mineral density (BMD) in postmenopausal women. Here, we aimed to investigate the relationship between circulating OPN levels and BMD in postmenopausal women in Southern China. A total of 362 postmenopausal women were consecutively recruited into this study from 2011-2013. Serum levels of OPN, receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL), and bone turnover markers were analyzed. BMD was measured by dual energy X-ray absorptiometry. Osteoporosis and osteopenia were diagnosed according to the World Health Organization criteria. Serum OPN levels were remarkably higher in the osteoporotic group than those in the osteopenic and normal groups (all p < 0.001). The cut-off value of OPN for diagnosing postmenopausal osteoporosis was 10.1 ng/mL, which had a sensitivity of 89.5%, a specificity of 70.8%, and an area under curve of 0.953. Serum OPN was negatively correlated with parathyroid hormone (PTH), lumbar spine BMD, and femoral neck BMD (r = -0.25, p = 0.004; r = -0.66, p < 0.001; r = -0.28, p = 0.001; respectively) and positively associated with type I procollagen amino-terminal propeptide (PINP), carboxy-terminal cross-linking telopeptide of type I collagen (CTX), and RANKL (r = 0.20, p = 0.020; r = 0.17, p = 0.036; r = 0.19, p = 0.028, respectively) in the osteoporotic group. In multiple regression analyses, lumbar spine BMD, PTH and RANKL were the predictors for serum OPN levels. In conclusion, OPN serum levels are negatively related to BMD and positively correlated with bone turnover levels in this group of Chinese postmenopausal women.

The Preserved Thickness Ratio of the Femoral Head Contributes to the Collapse Predictor of Osteonecrosis.

OBJECTIVES: The collapse of femoral head is a serious symptom of osteonecrosis of the femoral head (ONFH), resulting in hip pain and deformity. However, it is hardly possible to reestablish the femoral head nonoperatively once the collapse happens. Predicting femoral head collapse is of great value for the prognosis of ONFH. This study aimed to develop a new method to quantify the preserved thickness of femoral head and to assess its diagnostic contribution in predicting femoral head collapse on plain radiographs. METHODS: This was a single-center retrospective study. A total of 101 hips (85 patients) with ARCO stage II from January 2008 to December 2016 were included in this study. The preserved thickness was measured on standard anteroposterior (AP) and frog-leg (FL) radiographs. The anteroposterior view's preserved thickness ratio (APTR) and the frog-leg view's preserved thickness ratio (FPTR) were calculated to show the preserved thickness ratio of the femoral head anteriorly and laterally. Univariate and multivariate logistic regression was performed to determine the risk factors for collapse. Sensitivity, specificity, and cut-off values for APTR and FPTR were determined by the receiver operating characteristic (ROC) curve analysis. Kaplan-Meier (K-M) analysis was applied to determine femoral head survival in ONFH patients. RESULTS: The mean age of the 27 females and 58 males was 38.93 years old. The mean follow-up time was 74.62 (36-124) months in the non-collapse group and 18.66 (3-82) months in the collapse group. Femoral head collapse was observed in 62 hips during the follow-up period. Logistic regression analysis and ROC results showed that APTR <24.79% and FPTR <10.62% were significantly correlated with femoral head collapse. The Kaplan-Meier survival curve suggested that the overall survival rate of APTR ≥24.79% was 68.2% at 5 and 10 years and FPTR ≥10.62% was 71.63% at 5 and 10 years. At the last follow-up, 26 hips had collapse on the anterior side of the femoral head, 12 hips occurred on the lateral side, and 24 hips happened to collapse on both anterior and lateral sides. CONCLUSION: Femoral head collapse predominantly occurred anteriorly rather than laterally in ONFH patients. The measurements of APTR and FPTR have noticeable implications for the prediction of femoral head collapse, and contribute to the selection of treatment options for ONFH patients with types B and C1 according to the JIC classification.

Therapeutic potential of a prominent dihydroxyflavanone pinocembrin for osteolytic bone disease: In vitro and in vivo evidence.

Background/objective: As the pivotal cellular mediators of bone resorption and pathological bone remodeling, osteoclasts have emerged as a prominent target for anti-resorptive interventions. Pinocembrin (PIN), a predominant flavonoid found in damiana, honey, fingerroot, and propolis, has been recognized for its potential therapeutic effects in osteolysis. The purpose of our project is to investigate the potential of PIN to prevent bone resorption in ovariectomized (OVX) mice by suppressing osteoclast production through its underlying mechanisms. Methods: The study commenced by employing protein-ligand molecular docking to ascertain the specific interaction between PIN and nuclear factor-κB (NF-κB) ligand (RANKL). Subsequently, PIN was introduced to bone marrow macrophages (BMMs) under the stimulation of RANKL. The impact of PIN on osteoclastic activity was assessed through the utilization of a positive TRAcP staining kit and a hydroxyapatite resorption assay. Furthermore, the study investigated the generation of reactive oxygen species (ROS) in osteoclasts induced by RANKL using H2DCFDA. To delve deeper into the underlying mechanisms, molecular cascades triggered by RANKL, including NF-κB, ROS, calcium oscillations, and NFATc1-mediated signaling pathways, were explored using Luciferase gene report, western blot analysis, and quantitative real-time polymerase chain reaction. Moreover, an estrogen-deficient osteoporosis murine model was established to evaluate the therapeutic effects of PIN in vivo. Results: In this study, we elucidated the profound inhibitory effects of PIN on osteoclastogenesis and bone resorption, achieved through repression of NF-κB and NFATc1-mediated signaling pathways. Notably, PIN also exhibited potent anti-oxidative properties by mitigating RANKL-induced ROS generation and augmenting activities of ROS-scavenging enzymes, ultimately leading to a reduction in intracellular ROS levels. Moreover, PIN effectively abrogated the expression of osteoclast-specific marker genes (Acp5, Cathepsin K, Atp6v0d2, Nfatc1, c-fos, and Mmp9), further underscoring its inhibitory impact on osteoclast differentiation and function. Additionally, employing an in vivo mouse model, we demonstrated that PIN effectively prevented osteoclast-induced bone loss resultant from estrogen deficiency. Conclusion: Our findings highlight the potent inhibitory effects of PIN on osteoclastogenesis, bone resorption, and RANKL-induced signaling pathways, thereby establishing PIN as a promising therapeutic candidate for the prevention and management of osteolytic bone diseases. The translational potential of this article: PIN serves as a promising therapeutic agent for the prevention and management of osteolytic bone diseases and holds promise for future clinical applications in addressing conditions characterized by excessive bone resorption. PIN is a natural compound found in various sources, including damiana, honey, fingerroot, and propolis. Its widespread availability and potential for therapeutic use make it an attractive candidate for further investigation and development as a clinical intervention.

[Study of model establishment of unicompartmental knee athroplasty based on three-dimensional parametric modeling method].

The model of knee OA (KOA) was established in our laboratory with three-dimensional (3D) reconstruction technique based on the CT data. We then designed the unicompartmental prosthesis matching KOA model with parametric software Pro/e 5. 0. Finally, the models were used to mimic the operation of knee unicompantment replacement and the model of unicompartmental knee athroplasty (UKA) was analyzed using 3D finite element method. The results indicates that the approach for designing the model by 3D parametric is effective and meets the need of automation and efficacy to design unicompartmental prosthesis. The results proves that the model is vivid and precise, and the 3D parameteric modeling method can provide biomechanical research of unicompantment replacement with model foundation and new experimental method. It can be widely utilized in the clinics and research.

Fibula allograft with cannulated screw fixation versus ordinary cannulated screw fixation for femoral neck fractures: a 10-year retrospective comparative study.

BACKGROUND: For femoral neck fractures in young and middle-aged patients, both fibula allograft with cannulated screw fixation and ordinary cannulated screw fixation are clinically effective treatments. However, for unstable femoral neck fractures, ordinary cannulated screw fixation is characterized by a high risk of postoperative complications and a high rate of mechanical failure after internal fixation. For this study, we systematically compared the long-term efficacy and postoperative complications of these two procedures. METHODS: A total of 156 subjects diagnosed as femoral neck fractures participated in our study. Subjects in the combination group underwent fibula allograft with cannulated screw fixation (n = 76), and those in the control group were treated with ordinary cannulated screw fixation (n = 80). Baseline characteristics, perioperative outcomes, Harris hip score (HHS) and EuroQoL five-dimension questionnaire (EQ-5D); and the incidence of postoperative and bone healing complications in the two groups were recorded and compared. RESULTS: The average follow-up time was more than 10 years. Intra-operative blood loss significantly increased in the combination group compared with the control group (P < 0.05). There were significantly improved performances in healing time, the time course of recovery of full-weight-bearing stepping, HHS and EQ-5D scores in the combination group compared with the control group (P < 0.05). Besides, the incidence rates of femoral head necrosis, nonunion, femoral neck shortening and total hip replacement were significantly lower in the combination group than those in the control group (P < 0.05). CONCLUSION: Fibula allograft with cannulated screw fixation shows a better long-term therapeutic effect than ordinary cannulated screw fixation for femoral neck fractures in young and middle-aged patients. Patients receiving the combination strategy have faster and high-quality functional recovery after femoral neck fractures and a lower incidence rate of postoperative complications.

CircHIPK3 promotes bone microvascular endothelial cell proliferation, migration and angiogenesis by targeting miR-7 and KLF4/VEGF signaling in steroid-induced osteonecrosis of the femoral head.

BACKGROUND: Circular RNA homeodomain interacting protein kinase 3 (circHIPK3) has been implicated in facilitating angiogenesis in various conditions. However, its role in steroid-induced osteonecrosis of the femoral head (ONFH) remains unclear. OBJECTIVES: To investigate whether circHIPK3 promotes bone microvascular activity and angiogenesis by targeting miR-7 and Krüppel-like factor 4 (KLF4)/vascular endothelial growth factor (VEGF) signaling in ONFH. MATERIAL AND METHODS: Fifty patients with steroid-induced ONFH undergoing hip-preserving surgery or total hip arthroplasty were included in this study. The expression of circHIPK3, miR-7 and KLF4 was evaluated using reverse transcription polymerase chain reaction (RT-PCR) in necrotic and healthy samples of the femoral head. Bone microvascular endothelial cells (BMECs) were extracted and cultured with 0.1 mg/mL hydrocortisone to create a hormonally deficient cell model. These BMECs were then transfected with either circHIPK3 overexpressing or silencing plasmids with or without miR-7 mimics. The MTT assays were used to detect cell proliferation. Scratch assays were used to assess the migration ability of the BMECs. The tube formation was carried out using an in vitro Matrigel angiogenesis assay. Annexin V-FITC/PI and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used to assess the degree of apoptosis. Western blot assays were carried out to discern KLF4 and VEGF expression. The interactions of circHIPK3, miR-7 and KLF4 were confirmed using luciferase, RNA-binding protein immunoprecipitation (RIP), RNA pull-down, and fluorescence in situ hybridization (FISH) assays. RESULTS: The circHIPK3 and KLF4 expression was decreased, whereas miR-7 expression was increased in necrotic tissues compared to non-necrotic samples. Both circHIPK3 and KLF4 expression correlated negatively with miR-7. The overexpression of circHIPK3 promoted the proliferative, migratory and angiogenic capabilities of the BMECs, while adding an miR-7 mimic reversed these effects. At the same time, the overexpression of circHIPK3 reduced the apoptosis rate of the BMECs and increased KLF4 and VEGF protein expression, but adding an miR-7 mimic reversed these effects. The FISH, RNA pull-down, RIP, and luciferase assays revealed an interaction between circHIPK3, miR-7 and KLF4. CONCLUSIONS: The circHIPK3 promotes BMEC proliferation, migration and angiogenesis by targeting miR-7 and KLF4/VEGF signaling.

Dihydrotanshinone I attenuates estrogen-deficiency bone loss through RANKL-stimulated NF-κB, ERK and NFATc1 signaling pathways.

Postmenopausal osteoporosis, a chronic condition that predominantly affects postmenopausal women, presents a significant impediment to their overall well-being. The condition arises from estrogen deficiency, leading to enhanced osteoclast activity. Salvia miltiorrhiza, a well-established Chinese herbal medicine with a history of clinical use for osteoporosis treatment, contains diverse active constituents that have shown inhibitory effects on osteoclast formation and bone loss. Dihydrotanshinone I (DTI), a phenanthrenonequinone compound derived from the root of Salvia miltiorrhiza, has been identified as a potential therapeutic agent, although its mechanism of action on osteoclasts remains elusive. In this study, we aimed to elucidate the inhibitory potential of DTI on RANKL-induced osteoclastogenesis. We observed the ability of DTI to effectively impede the expression of key osteoclast-specific genes and proteins, as assessed by Real-time PCR and Western Blotting analyses. Mechanistically, DTI exerted its inhibitory effects on osteoclast formation by modulating critical signaling pathways including NF-κB, ERK, and calcium ion signaling. Notably, DTI intervention disrupted the nuclear translocation and subsequent transcriptional activity of the NFATc1, thus providing mechanistic insights into its inhibitory role in osteoclastogenesis. To further assess the therapeutic potential of DTI, we employed an ovariectomized osteoporosis animal model to examine its impact on bone loss. Encouragingly, DTI demonstrated efficacy in mitigating bone loss induced by estrogen deficiency. In conclusion, our investigation elucidates the ability of DTI to regulate multiple signaling pathways activated by RANKL, leading to the inhibition of osteoclast formation and prevention of estrogen-deficiency osteoporosis. Consequently, DTI emerges as a promising candidate for the treatment of osteoporosis.

A novel Glycyrrhiza glabra extract liquiritin targeting NFATc1 activity and ROS levels to counteract ovariectomy-induced osteoporosis and bone loss in murine model.

Osteoporosis, a prevalent osteolytic condition worldwide, necessitates effective strategies to inhibit excessive bone resorption by curbing osteoclast hyperactivation. Liquiritin (LIQ), an flavanone derivative employed in acute lung injury and rheumatoid arthritis treatment, possesses an unclear role in addressing excessive bone resorption. In this investigation, we found that LIQ demonstrates the ability to inhibit osteoclast formation and the bone-resorbing activity induced by RANKL. At a specific concentration, LIQ significantly attenuated NF-κB-Luc activity induced by RANKL and curtailed NF-κB activation in RANKL-stimulated RAW264.7 cells, resulting in reduced IκB-α breakdown and diminished nuclear NF-κB levels. Furthermore, LIQ markedly inhibited RANKL-induced NFATc1 activation, as evidenced by diminished NFATc1 luciferase activity, reduced NFATc1 mRNA levels, and decreased nuclear NFATc1 protein levels. Subsequent experiments demonstrated that LIQ effectively restrained the RANKL-induced elevation of intracellular calcium as well as reactive oxygen species. Additionally, LIQ exhibited a downregulating effect on the expression of osteoclast-specific genes, which include Acp5, Cathepsin K, Atp6v0d2, Nfatc1, c-Fos, and Mmp9. Notably, our findings revealed the potential of LIQ to counteract decreased bone density in mice that underwent ovariectomy. Collectively, the data indicate that LIQ impedes osteoclast formation triggered by RANKL and the subsequent reduction in bone mass by mitigating ROS levels and suppressing the Ca2+/MAPK-NFATc1 signaling pathway, suggesting its promising candidacy as a therapeutic agent for RANKL-mediated osteoporosis.

Dragon blood resin ameliorates steroid-induced osteonecrosis of femoral head through osteoclastic pathways.

Objective: Dragon's Blood resin (DBR) is a traditional medicinal substance renowned for its diverse pharmacological effects, which consists of potent anti-inflammatory, antioxidant and angiogenic properties. This study aimed to elucidate its therapeutic mechanism in alleviating steroid-induced osteonecrosis of the femoral head (SIONFH). Methods: Techniques such as SPR and LC-MS were employed to identify and analyze the target proteins of DBR in bone marrow macrophages (BMMs). In vitro, BMMs were treated with RANKL and DBR, and TRAcP staining and actin belt staining were utilized to assess osteoclast activity. The inhibitory effects and underlying mechanisms of DBR on osteoclastogenesis and reactive oxygen species (ROS) generation were determined using real-time PCR, western blotting and immunofluorescence staining. An in vivo SIONFH rat model was set up to assess the curative impacts of DBR using micro-CT scanning and pathological staining. Results: Bioinformatic tools revealed a pivotal role of osteoclast differentiation in SIONFH. Proteomic analysis identified 164 proteins binding in BMMs. In vitro assessments demonstrated that DBR hindered osteoclastogenesis by modulating the expression of specific genes and proteins, along with antioxidant proteins including TRX1 and Glutathione Reductase. Notably, the resin effectively inhibited the expression of crucial proteins, such as the phosphorylation of JNK and the nuclear localization of p65 within the TRAF6/JNK and NFκB signaling pathways. In vivo experiments further confirmed that DBR mitigated the onset of SIONFH in rats by curbing osteoclast and ROS activities. Conclusion: These findings underscore the potential of Dragon's Blood as an effective administration for early-stage SIONFH, shedding light on its therapeutic influence on ROS-mediated osteoclastic signaling pathways.