Effect of whole body vibration therapy in the rat model of steroid-induced osteonecrosis of the femoral head.

Background: Steroid-induced Osteonecrosis of the Femoral Head (SIONFH) is a skeletal disease with a high incidence and a poor prognosis. Whole body vibration therapy (WBVT), a new type of physical training, is known to promote bone formation. However, it remains unclear whether WBVT has a therapeutic effect on SIONFH. Materials and methods: Thirty adult male and female Sprague-Dawley (SD) rats were selected and randomly assigned to three experimental groups: the control group, the model group, and the mechanical vibration group, respectively. SIONFH induction was achieved through the combined administration of lipopolysaccharides (LPS) and methylprednisolone sodium succinate for injection (MPS). The femoral head samples underwent hematoxylin and eosin (H&E) staining to visualize tissue structures. Structural parameters of the region of interest (ROI) were compared using Micro-CT analysis. Immunohistochemistry was employed to assess the expression levels of Piezo1, BMP2, RUNX2, HIF-1, VEGF, CD31, while immunofluorescence was used to examine CD31 and Emcn expression levels. Results: The H&E staining results revealed a notable improvement in the ratio of empty lacuna in various groups following WBVT intervention. Immunohistochemical analysis showed that the expression levels of Piezo1, BMP2, RUNX2, HIF-1, VEGF, and CD31 in the WBVT group exhibited significant differences when compared to the Model group (p < 0.05). Additionally, immunofluorescence analysis demonstrated statistically significant differences in CD31 and Emcn expression levels between the WBVT group and the Model group (p < 0.05). Conclusion: WBVT upregulates Piezo1 to promote osteogenic differentiation, potentially by enhancing the HIF-1α/VEGF axis and regulating H-vessel angiogenesis through the activation of the Piezo1 ion channel. This mechanism may lead to improved blood flow supply and enhanced osteogenic differentiation within the femoral head.

Mechanical properties of trabeculae and osteocyte morphology change significantly in different areas of the necrotic femoral head.

Background: Osteonecrosis of the femoral head is a complex hip ailment. The precise changes in bone tissue during the disease's onset remain unclear. It is vital to assess both the quantity and quality of the trabecular state in a necrotic femoral head. Aim: This study aims to identify and compare the ultrastructural changes in osteocyte morphology and nanomechanical characteristics within various regions of necrotic femoral heads. Methods: Between December 2016 and May 2023, we gathered ten necrotic femoral heads from patients and five femoral heads from cadavers. The samples from the necrotic femoral heads were categorized into three areas: necrotic, sclerotic, and normal. Our assessment methods encompassed hematoxylin and eosin staining, sclerostin (SOST) immunohistochemistry, micro-computed tomography, nanoindentation, and acid-etched scanning electron microscopy. These techniques enabled us to examine the SOST expression, trabecular microstructure, micromechanical properties of trabeculae, and modifications in osteocyte morphology at the ultrastructural level. Results: The protein level of SOST was found to be lower in the sclerotic area. In the necrotic area, decreased values of bone volume fraction, trabecular thickness, and trabecular number and an increased value of trabecular separation were found. Conversely, in the sclerotic area, higher mean values of bone volume fraction, trabecular number, and trabecular thickness and lower trabecular separation indicated significant changes in the structural characteristics of trabeculae. Compared with the healthy area, the elastic modulus and hardness in the sclerotic area were significantly higher than those in the necrotic, normal, and control areas, while those in necrotic areas were significantly lower than those in the healthy area. The number of osteocytes tended to increase in the sclerotic area with more canalicular cells compared to the healthy area and control group. Conclusion: These results imply that the stress distribution within the sclerotic area could potentially lead to enhanced trabecular quality and quantity. This effect is also reflected in the increased count of osteocytes and their canaliculars. It is plausible that the sclerotic trabecular bone plays a pivotal role in the repair of necrotic femoral heads.

Incidence of periprosthetic joint infection after primary total hip arthroplasty is underestimated: a synthesis of meta-analysis and bibliometric analysis.

The American Musculoskeletal Society updated the diagnostic criteria for periprosthetic joint infection (PJI) in 2011 and 2018. However, the overall incidence of PJI since the introduction of these new standards has not been assessed. In order to fill this knowledge gap, a single-group meta-analysis was conducted using articles obtained from several databases, focusing on the incidence of PJI after primary total hip arthroplasty (THA). Our study revealed a significant difference in the incidence of PJI reported by different national or regional databases. Moreover, most cases of PJI were found to be underestimated. This highlights the crucial need for standardized diagnostic criteria and monitoring methods to accurately identify and track cases of PJI. Furthermore, a bibliometric analysis was conducted to provide a comprehensive overview of the current state of research on PJI after THA. This analysis explored the most productive countries, organizations, journals, and individuals in this research area. Additionally, it identified the research trends and hotspots of the last decade, highlighting the advancements and areas of focus in this field. By conducting these analyses, the study aims to contribute to the understanding of PJI after THA and provide valuable insights for clinicians, researchers, and policymakers involved in the management of this condition.

Bibliometric and visualized analysis of research relating to minimally invasive spine surgery reported over the period 2000-2022.

Background: Since entering the 21st century, there has been an increasing interest in minimally invasive surgery for spinal diseases, which has led to the continued development of minimally invasive spine surgery (MISS), with major breakthroughs in technology and technical skills. However, in recent years, there is little relevant research using bibliometrics to analyze the field of MISS research. The purpose of this study is to sort out the publication situation and topic trends of articles in the field of MISS research from the perspective of bibliometrics. Methods: The articles and reviews related to MISS from 2000 to 2022 were retrieved and downloaded from the Web of Science Core Collection (WOSCC). Visualization and knowledge mapping were performed using three bibliometric tools, including online bibliometric platform, CiteSpace and VOSviewer software. Curve fitting and correlation analysis were performed using Microsoft Excel software. The global research publication output, contributions of countries, institutions, authors, and journals, average citations per item (ACI), Hirsch index (H-index), research hot keywords, etc., in this field were analyzed. Results: A total of 2384 papers were retrieved, including 2135 original papers and 249 review papers. In the past 22 years, the number of annual publications of MISS research has shown a steady growth trend. China contributed the most papers, and the United States ranked second, but the United States had the highest total citations, and H-index value. The most prolific institutions were Soochow University, Capital Medical University and Wooridul Spine Hospital. In this field, Professors Lee SH, Ahn Y and Yang HL have made significant achievements. However, there is relatively little international collaboration between institutions or researchers. World Neurosurgery is the most published journal on MISS research. According to the keyword co-occurrence analysis, recent keywords mainly focus on researches on minimally invasive modalities, techniques and prognosis, while on the keyword analysis of the ongoing bursts, percutaneous transforaminal endoscopic discectomy, lumbar diskectomy, spinal stenosis, recompression, diskectomy, endoscopic spine surgery, laminectomy, transforaminal lumbar interbody fusion, etc., will likely continue to be a research hotspot in the near future. Conclusion: Looking at the temporal trend in the number of publications per year, the number of publications for the MISS study will increase in the near future. China has the highest number of publications, but the US has the highest quality publications. International cooperation needs to be further strengthened. Our findings can provide useful information for the academic community and identify possible research fronts and hotspots in the coming years.

Application of protective weight-bearing in osteonecrosis of the femoral head: A systematic review and meta-analysis of randomized controlled trials and observational studies.

Background: The aim of this systematic review and meta-analysis was to estimate the efficacy and prognostic value of protective weight-bearing for ONFH. Methods: The authors searched the PubMed, EMBASE and Cochrane Library databases, up to February 25, 2022. RCTs and observational studies on conservative treatment, including the use of crutches, for skeletally mature patients with ONFH and written in English were included. Outcomes were the total hip arthroplasty (THA) rate, collapse rate, Hip Harris score (HHS) and visual analog scale (VAS) score. Cochrane Review Manager Software 5.4 and Stata 15.1 were used to perform the statistical analyses. Results: A total of 14 studies involving 813 patients (1,025 hips) were included in this meta-analysis. The results showed that the THA rate, collapse rate, HHS and VAS scores in the protective weight-bearing group were not significantly different from those in the surgical group. In the protective weight-bearing group, the results showed that the THA rate was 40%, 8% in ARCO stage II, 37% in ARCO stage III, and the collapse rate was 46%. The mean HHS and VAS score was 80.86 and 1.00, respectively. The HHS score at the 3-, 6-, 12-, and 24-month follow-up was 79.93, 83.94, 85.94, and 96.09 points, respectively, whereas the VAS score at the 6- and 12-month follow-up was 2.20 and 1.29, respectively. Conclusion: Protective weight bearing could achieve satisfactory results in terms of THA rate, collapse rate, HHS and VAS scores. Protective weight-bearing allows most precollapse patients to preserve the hip but also allows postcollapse patients to delay THA or hip-preserving surgery. The effects and prognosis of protective weight-bearing in the short or mid-term are noninferior to surgical hip preservation and are a viable alternative option for osteonecrosis of the femoral head.

Combining frog-leg lateral view may serve as a more sensitive X-ray position in monitoring collapse in osteonecrosis of the femoral head.

Load-bearing capacity of the bone structures of anterolateral weight-bearing area plays an important role in the progressive collapse in osteonecrosis of the femoral head (ONFH). The purpose of this study is to assess the efficacy of combined evaluation of anteroposterior (AP) and frog-leg lateral (FLL) view in diagnosing collapse. Between December 2016 and August 2018, a total of 478 hips from 372 patients with ONFH (268 male, 104 female; mean age 37.9 ± 11.4 years) were retrospectively evaluated. All patients received standard AP and FLL views of hip joints. Japanese Investigation Committee (JIC) classification system was used to classify necrotic lesion in AP view. Anterior necrotic lesion was evaluated by FLL view. All patients with pre-collapse ONFH underwent non-operative hip-preserving therapy. The collapse rates were calculated and compared with Kaplan-Meier survival analysis with radiological collapse as endpoints. Forty-four (44/478, 9.2%) hips were classified as type A, 65 (65/478, 13.6%) as type B, 232 (232/478, 48.5%) as type C1 and 137 (137/478, 28.7%) as type C2. Three hundred cases (300/478, 62.5%) were collapsed at the initial time point. Two hundred and twenty six (226/300, 75.3%) hips and 298 (298/300, 99.3%) hips collapse were identified with AP view and FLL view, respectively. An average follow-up of 37.0 ± 32.0 months was conducted to evaluate the occurrence of collapse in 178 pre-collapse hips. Collapses occurred in 89 hips (50.0%). Seventy-seven (77/89, 86.5%) hips were determined with AP view alone and 85 (85/89, 95.5%) hips were determined with the combination of AP and FLL views. The collapse rates at five years were reported as 0% and 0%, 16.2% and 24.3%, 58.3% and 68.1% and 100% and 100% according to AP view alone or combination of AP and FLL views for types A, B, C1 and C2, respectively. The collapse can be diagnosed more accurately by combination of AP and FLL views. Besides, JIC type A and type B ONFH can be treated with conservative hip preservation, but pre-collapse type C2 ONFH should be treated with joint-preserving surgery. Type C1 needs further study to determine which subtype has potential risk of collapse.

Corrigendum: The Therapeutic Effect of Huo Xue Tong Luo Capsules in Association Research Circulation Osseous (ARCO) Stage II Osteonecrosis of the Femoral Head: A Clinical Study With an Average Follow-up Period of 7.95 Years.

[This corrects the article DOI: 10.3389/fphar.2021.773758.].

Predicting Collapse in Osteonecrosis of the Femoral Head Using a New Method: Preserved Angles of Anterior and Lateral Femoral Head.

BACKGROUND: Femoral head collapse (FHC) is associated with a poor prognosis in osteonecrosis of the femoral head (ONFH). Preserved angles (PAs), including the lateral preserved angle (LPA), the anterior preserved angle (APA) and the combined preserved angle (CPA), can be used to quantify the extent of femoral head necrosis and predict the risk of femoral head collapse. The purpose of this retrospective cohort study was to assess the efficacy of these preserved angles in the prediction of femoral head collapse using plain radiographs. METHODS: Patients with ONFH treated conservatively between January 2010 and January 2019 were analyzed retrospectively to assess the risk of FHC. A logistic regression model was used to evaluate the independent prognostic factors associated with FHC, including age, sex, etiology, onset of symptom, The Japanese Investigation Committee classification, and PAs (LPA, APA, and CPA). RESULTS: A total of 137 patients, with 180 hips, had follow-up of at least two years and were included. During the follow-up period, FHC occurred in 89 hips (49.44%) after the initial diagnosis. Multivariable analysis indicated that CPA (odds ratio [OR] = 0.95; 95%CI = 0.93-0.97; P < 0.01) was a stronger predictor of femoral head collapse compared with the Japanese Investigation Committee classification (OR = 2.40, 95%CI = 0.92-6.25; P > 0.01). The receiver operating characteristic and survival curve analyses revealed that the predictive cutoff point for the CPA was 118.7° (sensitivity = 96.70%, specificity = 79.78%, log-rank test: P < 0.01). CONCLUSIONS: Assessment of preserved angles on plain radiographs is a simple method to quantify the extent of lateral and anterior necrosis of the femoral head. Specifically, CPA has a potential value in predicting femoral head collapse.

Global research trends and hotspots in calcaneal fracture: A bibliometric analysis (2000-2021).

Background: Calcaneal fracture is common and carries high morbidity and disability. Its treatment is therefore of vital concern. Many topics concerning calcaneal fracture remain controversial, and the subject has not yet been well-researched. We aim to analyze and illustrate the trends in development, overall knowledge structure, "hotspots," and research frontiers on the topic of calcaneal fracture. Methods: Literature relating to calcaneal fracture published between 2000 and 2021 was retrieved from Science Citation Index Expanded (SCIE) database of the Web of Science. Three bibliometric tools (Bibliometrix, CiteSpace, and VOSviewer software) were used for analysis and the generation of knowledge maps. Annual trends in publication counts and the relative contributions of different countries, regions, institutions, authors, and journals, as well as keyword clusters, "hot topics," and research frontiers, were analyzed. Results: A total of 1,687 publications were included in the analysis. The number of calcaneal fracture articles published worldwide each year was highest in 2019, with a total of 128 articles. The United States has made the greatest contribution to the field, with the largest number of publications and the highest H-index. Foot & Ankle International was the most productive journal, publishing a total of 167 articles on calcaneal fracture during the study period. Hebei Medical University of China and the University of California, San Francisco were the most prolific institutions. Professors T. Schepers, S. Rammelt, H. Zwipp, and Y. Z. Zhang have made remarkable contributions to the field. However, the degree of collaboration between researchers and among institutions was relatively low, and took place mainly in Europe and the Americas. All relevant keywords could be categorized into three clusters: studies of internal fixation, studies of fractures, and studies of osteoporosis. A trend of balanced and diversified development could be seen within these clusters. Keywords with ongoing "citation bursts," such as sinus tarsi approach, wound complications, minimally invasive technique, extensile lateral approach, surgical treatment, and plate, may continue to be research "hotspots" in the near future. Conclusion: Based on current global trends, the number of publications on calcaneal fracture will continue to increase. Topics such as minimally invasive techniques and complications have become important hotspots of research. We recommend enhancing international communication and collaboration for future research in this field.

The Therapeutic Effect of Huo Xue Tong Luo Capsules in Association Research Circulation Osseous (ARCO) Stage II Osteonecrosis of the Femoral Head: A Clinical Study With an Average Follow-up Period of 7.95 Years.

Background: Huo Xue Tong Luo (HXTL) capsules are an oral preparation that could relieve pain and ameliorate osteonecrosis in patients with asymptomatic osteonecrosis of femoral head (ONFH). We wanted to verify whether it could be a treatment option for ARCO stage II ONFH. Methods: A total of 44 patients (66 hips) with ARCO stage II ONFH were recruited from June 1996 to October 2013 (clinical trial registry number: ChiCTR-RPC-15006,290). HXTL capsules were given under a specific protocol, and the endpoint was set as femoral head collapse. The clinical indicators [including visual analog scale (VAS) and Harris Hip Score (HHS)] and radiological indicators [including Tonnis classification, ARCO stage, Japanese Investigation Committee (JIC) classification, lateral preserved angle (LPA), anterior preserved angle (APA), and combined preserved angle (CPA)] before and after treatment were compared. Kaplan-Meier survival analysis and Cox regression analysis were used to identify the risk factors associated with femoral head collapse. Result: Twenty-six males and 18 females with an average age of 38.3 ± 2.8 were followed for an average of 7.95 years. Forty-six of the 66 (69.7%) hips had no progression in pain or collapse, and patients exhibited a higher HHS (p < 0.05) after therapy. Twenty of the 66 (30.3%) hips progressed in Tonnis classification and ARCO stage, but only one of the 66 (1.5%) hips required total hip arthroplasty (THA). The Kaplan-Meier survivorship curve suggested that the survival rates were 96.97% at 5 years, 69.15% at 10 years, and 40.33% at 15 years. Patients with type A necrotic lesions on anteroposterior (AP) and frog-leg lateral (FLL) radiographs revealed 100% survival rates. Multivariate Cox regression analysis revealed that patients with an LPA ≤ 60.9 exhibited a 3.87 times higher risk of collapse of the femoral head [95% confidence interval (CI), 1.241-5.673] than did those patients with an LPA>60.9. Conclusion: HXTL capsules could be a treatment option for ARCO stage II ONFH, resulting in improved hip function and delayed progression to femoral head collapse, especially when the anterior and lateral portions of the femoral head were not affected. However, an LPA of less than 60.9° may be a risk factor for collapse of the femoral head. Clinical Trial Registration: [http://www.chictr.org.cn/showproj.aspx?projZ10829].

Arthroplasty vs proximal femoral nails for unstable intertrochanteric femoral fractures in elderly patients: A systematic review and meta-analysis.

BACKGROUND: Proximal femoral nails (PFNs) are the most common method for the treatment of unstable intertrochanteric femoral fractures (IFFs), but postoperative bed rest is required. There is a large amount of blood loss during the operation. Osteoporosis in elderly patients may cause nonunion of fractures and other complications. Arthroplasty can give patients early weight bearing and reduce financial burden, but whether it can replace PFNs remains controversial. AIM: To compare the clinical outcomes of arthroplasty and PFNs in the treatment of unstable IFFs in elderly patients. METHODS: A search was conducted in the PubMed, Embase, and Cochrane Library databases and included relevant articles comparing arthroplasty and PFN. The search time was limited from January 1, 2005 to November 1, 2020. Two investigators independently screened studies, extracted data and evaluated the quality according to the inclusion and exclusion criteria. According to the research results, the fixed effect model or random effect model were selected for analysis. The following outcomes were analyzed: Harris Hip score, mortality, complications, operation time, blood loos, hospital stay, weight-bearing time, fracture classification and type of anesthesia. RESULTS: We analyzed four randomized controlled trials that met the requirements. A total of 298 patients were included in these studies. According to the AO/OTA classification, there are 20 A1 types, 136 A2 types, 42 A3 types and 100 unrecorded types. Primary outcome: The Harris Hip Score at the final follow-up of the PFN group was higher [mean difference (MD): 9.01, 95% confidence interval (CI): 16.57 to 1.45), P = 0.02]. There was no significant difference between the two groups in the rate of overall mortality [risk ratio (RR): 1.44, P = 0.44] or the number of complications (RR: 0.77, P = 0.05). Secondary outcomes: blood loss of the arthroplasty group was higher (MD: 241.01, 95% CI: 43.06-438.96, P = 0.02); the operation time of the PFN group was shorter (MD: 23.12, 95%CI: 10.46-35.77, P = 0.0003); and the length of hospital stay of the arthroplasty group was shorter [MD: 0.97, 95% CI: 1.29 to 0.66), P < 0.00001]. There was no difference between the two groups in the type of anesthesia (RR: 0.99). There were only two studies recording the weight-bearing time, and the time of full weight bearing in the arthroplasty group was significantly earlier. CONCLUSION: Compared with PFN, arthroplasty can achieve weight bearing earlier and shorten hospital stay, but it cannot achieve a better clinical outcome. Arthroplasty cannot replace PFNs in the treatment of unstable IFFs in elderly individuals.

Finite element modeling of proximal femur with quantifiable weight-bearing area in standing position.

BACKGROUND: The positional distribution and size of the weight-bearing area of the femoral head in the standing position as well as the direct active surface of joint force can directly affect the result of finite element (FE) stress analysis. However, the division of this area was vague, imprecise, and un-individualized in most studies related to separate FE models of the femur. The purpose of this study was to quantify the positional distribution and size of the weight-bearing area of the femoral head in standing position by a set of simple methods, to realize individualized reconstruction of the proximal femur FE model. METHODS: Five adult volunteers were recruited for an X-ray and CT examination in the same simulated bipedal standing position with a specialized patented device. We extracted these image data, calculated the 2D weight-bearing area on the X-ray image, reconstructed the 3D model of the proximal femur based on CT data, and registered them to realize the 2D weight-bearing area to 3D transformation as the quantified weight-bearing surface. One of the 3D models of the proximal femur was randomly selected for finite element analysis (FEA), and we defined three different loading surfaces and compared their FEA results. RESULTS: A total of 10 weight-bearing surfaces in 5 volunteers were constructed, and they were mainly distributed on the dome and anterolateral of the femoral head with a crescent shape, in the range of 1218.63-1,871.06 mm2. The results of FEA showed that stress magnitude and distribution in proximal femur FE models among three different loading conditions had significant differences, and the loading case with the quantized weight-bearing area was more in accordance with the physical phenomenon of the hip. CONCLUSION: This study confirmed an effective FE modeling method of the proximal femur, which can quantify the weight-bearing area to define a more reasonable load surface setting without increasing the actual modeling difficulty.

Osteoclastic activity was associated with the development of steroid-induced osteonecrosis of femoral head.

This study is focussed on evaluating and comparing two mediators of osteoclast, osteoprotegerin (OPG) and nuclear factor-κB ligand (RANKL), in plasma and tissue levels in patients with steroid-induced osteonecrosis of femoral head (SIONFH). Subjects were included in this cross-sectional case-control study in 2016. Bone histomorphology, immunohistochemistry, Western blotting, OPG and RANKL plasma levels, post-hoc statistical power and receiver-operating characteristic (ROC) curves were evaluated. Eighty-six patients diagnosed with SIONFH and 51 healthy subjects were included. OPG expression levels in bone samples increased with ARCO stage, and RANKL expression levels decreased with ARCO stages. Plasma OPG and RANKL levels were significantly higher in the SIONFH group compared with the healthy control group. The plasma OPG level and ratio of OPG and RANKL were positively associated with ARCO stages and significantly higher in stages III and IV. Plasma RANKL levels were negatively associated with ARCO stage and were significantly higher in ARCO stages II and III. Plasma OPG and RANKL may represent potential biomarkers during SIONFH at different stages. Higher plasma OPG levels indicated late-stage SIONFH, and higher plasma RANKL levels indicated early stage. Our findings may provide a clue for the development of diagnostic tools and therapies for SIONFH.

Polydatin improves osteogenic differentiation of human bone mesenchymal stem cells by stimulating TAZ expression via BMP2-Wnt/ß-catenin signaling pathway.

OBJECTIVES: Polydatin (PD), extracted from Polygonum cuspidatum, has shown potential therapeutic applications due to its antiosteoporotic and anti-inflammatory activities. Our previous study suggested that PD promotes the osteogenesis of human bone marrow stromal cells (hBMSCs) via the BMP2-Wnt/ß-catenin pathway. The aim of our present study was to further explore the role of PD-mediated regulation of Tafazzin (TAZ), a transcriptional coactivator with a PDZ-binding motif, in osteogenesis. MATERIALS AND METHODS: hBMSCs were isolated and treated with PD at various concentrations. Alizarin red staining and RT-qPCR were performed to identify calcium complex deposition in hBMSCs as well as the expression of specific osteoblast-related markers, respectively, in each group. Next, TAZ-silenced hBMSCs were generated by lentivirus-produced TAZ shRNA. After treatment with PD, the osteogenic abilities of the TAZ-silenced and control hBMSCs were estimated by ALP activity assay, and expression of the TAZ protein was detected by Western blot analysis and immunofluorescence staining. In vitro, an ovariectomized (OVX) mouse model was established and used to evaluate the effect of PD on bone destruction by micro-CT, immunohistochemistry, and ELISA. RESULTS: In vitro, 30 µM PD significantly improved the proliferation and calcium deposition of hBMSCs and markedly stimulated the expression of the mRNAs RUNX2, Osteopontin, DLX5, ß-catenin, TAZ, and Osteocalcin (OCN). Osteogenic differentiation induced by PD was blocked by lentivirus-mediated TAZ shRNA. Furthermore, Noggin (a regulator of bone morphogenic protein 2 (BMP2)) and DKK1 (an inhibitor of the Wnt/ß-catenin pathway) were found to inhibit the increase in TAZ expression induced by PD. In vivo, PD prevented estrogen deficiency-induced bone loss in the OVX mouse model. CONCLUSION: Taken together, our findings suggest that PD improved the osteogenic differentiation of hBMSCs and maintained the bone matrix in the OVX mouse model through the activation of TAZ, a potential target gene of the BMP2-Wnt/ß-catenin pathway.

The survival of non-traumatic osteonecrosis of femoral head at ARCO II with ring-shaped sclerotic zone: a mid-term follow-up retrospective study.

The sclerotic zone in the osteonecrosis of femoral head (ONFH), containing condensed trabecular bone and abundant neovascularization, is the transition area between osteonecrosis and normal tissue. Due to the prominent feature in ONFH, the characteristics of the sclerotic zone might indicate the femoral head survival of the disease. Thirty ONFH patients (41 hips) with ring-shaped sclerotic zone at Association Research Circulation Osseous-II were recruited during 1996 to 2019, and the corresponding radiographic images in their follow-up are reviewed retrospectively. Two subtypes (type A and B) are defined to discriminate different locations of ring-shaped sclerotic zone in the femoral head (center or subchondral bone plate) in accordance with the radiographic images. The natural history of the enrolled subjects was followed up for average 9 years to record and compare their collapse incidences as well as the progress of hip symptoms. Chi-square test shows that the occurrence rates of symptomatic hip of type A are significantly lower than that of type B and differences between these two groups were significant (P < 0.05). Kaplan Meier survival curve analysis shows that the mean survival time of type A is 247.600 M (95% CI: 203.072 ∼ 292.128 M) and type B is 88.795 M (95% CI: 72.607 ∼ 104.984 M). The survival rate of femoral head of type A is significantly higher than that of type B (P < 0.005). This study demonstrates that type A shows a more satisfactory clinical outcomes and lower femoral head collapse rate in a mid-term follow-up.

Huo Xue Tong Luo capsule, a vasoactive herbal formula prevents progression of asymptomatic osteonecrosis of femoral head: A prospective study.

BACKGROUND/OBJECTIVE: A prospective cohort study aimed to evaluate the clinical efficacy of a specific vasoactive herbal formula, Huo Xue Tong Luo capsule (HXTL capsule), for the treatment of patients with asymptomatic osteonecrosis of femoral head (ONFH). METHODS: We evaluated a clinical trial of 55 patients (59 hips) with asymptomatic ONFH (no joint collapse) evaluated by Steinberg staging system and necrosis range classification criteria. Then, they were given HXTL capsule under specific protocol. Among them, 39 males and 16 females with an average age of 36.4 ± 10.1 years were followed up for an average of 4.38 years during treatment. The aggravation of clinical and imaging results was assessed by initial pain and joint collapse. The clinical and imaging outcomes of these patients were compared with those of a historical control group from the literature under critical inclusion criteria. RESULTS: At the latest follow-up, initial pain occurred in five of 59 (8.5%) hips of patients taking HXTL capsule compared with 31 of 81 (38.3%) controls (p < 0.001), and joint collapse occurred in 13 of 59 (22.0%) hips of patients taking HXTL capsule compared with 26 of 81 (32.1%) controls (p < 0.001). There was no association between joint collapse and multiple key factors of ONFH. Only the location of type C2 necrotic lesions (hazard ratio, 4.12; 95% confidence interval, 2.64-18.91) and the extent of large necrotic lesions (hazard ratio, 3.39; 95% confidence interval, 1.43-16.21) predicted joint collapse. CONCLUSION: As an agent formulated by vasoactive herbals, HXTL capsule with specific protocol is an effective medicine for relieving hip pain and preventing joint collapse in patients with asymptomatic ONFH. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The translation potential of this prospective cohort study is that the initially officially approved clinical indication for HXTL capsule for treatment of ONFH is due to its possible effect of revascularization on angiogenesis of necrosis. It is has been now proven to be effective for a new clinical application.

Polydatin promotes the osteogenic differentiation of human bone mesenchymal stem cells by activating the BMP2-Wnt/ß-catenin signaling pathway.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory disease induced by glucocorticoids. Marrow mesenchymal stem cells (MSCs) differentiate into multiple bone matrix cells and have been used as cell-based therapies to treat ONFH. However, the osteogenesis of MSCs isolated from patients with SONFH is significantly decreased. Polydatin has been widely used in traditional Chinese remedies due to its multiple pharmacological actions. As shown in our previous study, Polydatin protects from oxidative stress and promotes BMSC migration. However, little is known about its role in BMSC (Bone marrow mesenchymal stem cells) osteogenesis; therefore, we further investigated the effect and mechanism of Polydatin in hBMSC osteogenesis. The ability of Polydatin to promote the proliferation and osteogenic differentiation of hBMSCs was determined using the MTT assay, ALP staining and the ALP activity assay. Next, qPCR and western blotting were performed to measure the levels of genes and proteins related to the osteogenesis of hBMSCs. Then, the effect of Polydatin on the nuclear translocation of ß-catenin was determined using immunofluorescence staining. Polydatin (30 µM) markedly enhanced the proliferation of hBMSCs and alkaline phosphatase (ALP) activity. Additionally, it also significantly upregulated the expression of osteogenic genes (Runx2, osteopontin, DLX5, osteocalcin, collagen type I and BMP2) and components of the Wnt signaling pathway (ß-catenin, Lef1, TCF7, c-jun, c-myc and cyclin D). These osteogenesis-potentiating effects of Polydatin were blocked by Noggin, an inhibitor of the BMP pathway, and DKK1, an inhibitor of the Wnt/ß-catenin pathway. However, DKK1 did not affect Polydatin-induced BMP2 expression. Based on our results, Polydatin promotes the proliferation and osteogenic differentiation of hBMSCs through the BMP2-Wnt/ß-catenin signaling pathway.

Plasma C-terminal cross-linking telopeptide of type II collagen as a biomarker in advanced stages of femoral head osteonecrosis.

AIM: The aim of this study is to investigate the potential role of C-terminal cross-linking telopeptide of type II collagen (CTX-II) in the development of femoral head osteonecrosis (FHN).Materials and methodsOne hundred and thirty-two patients diagnosed with FHN and 66 age- and sex-matched healthy subjects were included in this cross-sectional case-control study between May 2016 and November 2016. Bone histomorphology, cartilaginous immunohistochemistry, Western blotting, and level of plasma CTX-II, as well as the receiver operating characteristic (ROC) curve, were evaluated. ResultsImmunohistochemistry and Western blotting showed that CTX-II was abundantly detected in the cartilage of FHN samples in stages III & IV. Plasma CTX-II levels were significantly higher in FHN patients in the advanced stages (III & IV) than was the level in the control group (164.81% and 198.15% higher in stages III & IV, respectively). However, the levels of CTX-II did not differ significantly among the FHN patients with different etiology or other clinical data. ConclusionOur result suggests that the degeneration of cartilage has already begun in stage III, even though a relatively normal articular gap can be found in the X-ray. Plasma CTX-II level may be a biomarker of the development of FHN.