[Research progress on mechanism of traditional Chinese medicine intervention in angiogenesis in prevention and treatment of nontraumatic avascular necrosis of femoral head].

Nontraumatic avascular necrosis of the femoral head(NANFH) is a common and refractory femoral head disease that causes bone death due to interruption of blood supply. Early clinical symptoms are atypical, such as hip pain and limited joint function. In the late stage, severe pain, shortening of the affected limb, claudication, and other serious symptoms are common, which se-riously affects the quality of life of patients. Therefore, it is of great significance to actively improve the clinical symptoms of NANFH to enhance the quality of life of patients. The pathogenesis of NANFH is complex, such as traumatic vascular circulatory disorders, the use of hormones or other drugs, alcoholism, and diabetes mellitus. These factors directly or indirectly lead to femoral head vascular damage, thrombosis, and coagulation system disorders, which reduce the blood supply to the acetabulum and femoral head, thus causing ischaemic death of the femoral head or even femoral head collapse. NANFH is mainly categorized as "bone impotence" and "bone paralysis" in traditional Chinese medicine(TCM). The treatment of NANFH with TCM has the characteristics and advantages of a long history, stable and reliable therapeutic effect, fewer adverse reactions, good patient tolerance, and high acceptance. Previous studies have shown that the promotion of angiogenesis is a key initiative in the prevention and treatment of NANFH, and TCM can promote fe-moral head angiogenesis by interfering with the expression of angiogenesis-related factors, which in turn can help to restore the blood supply of the femoral head and thus improve clinical symptoms of NANFH and prevent and treat NANFH. This article described the roles of blood supply interruption and angiogenesis in NANFH and the accumulated knowledge and experience of TCM in NANFH and summarized the role of angiogenesis-related factors in NANFH and the research progress on TCM intervention, so as to provide an idea for the subsequent research and a new basis for the clinical application of TCM in the treatment of NANFH.

Core decompression with ß-tri-calcium phosphate grafts in combination with platelet-rich plasma for the treatment of avascular necrosis of femoral head.

BACKGROUND: This study was aimed to investigate whether the application of platelet-rich plasma (PRP) combined with ß-tri-calcium phosphate (ß-TCP) grafts after core decompression (CD) could improve the clinical outcomes of early stage of avascular necrosis of femoral head. METHODS: Forty-five (54 hips) patients with Ficat-Arlet classification stage I-II treated by CD with ß-TCP grafts with or without the application of PRP from July 2015 to October 2020 were reviewed. Group A (CD + ß-TCP grafts) included 24 patients (29 hips), while group B (CD + ß-TCP grafts + PRP) included 21 patients (25 hips). Visual analogue scale (VAS) score, Harris hip score (HHS), change in modified Kerboul angle and the hip joint survival were evaluated and compared between the groups. Patients had a mean follow-up period of 62.1 ± 17.2 months and 59.3 ± 14.8 months in group A and group B, respectively. RESULTS: The mean VAS scores in group A was significantly higher than group B at the 6 months (2.9 ± 0.7 vs 1.9 ± 0.6, p < 0.01) and final follow up postoperative (2.8 ± 1.2 vs 2.2 ± 0.7, p = 0.04). The mean HHS in group A was significantly lower than group B at the 6 months (80.5 ± 13.8 vs 89.8 ± 12.8, p = 0.02). However, at the final follow up, there is no significant difference between the groups (77.0 ± 12.4 vs 83.1 ± 9.3, p = 0.07). The mean change in modified Kerboul angle was -7.4 ± 10.6 in group A and -19.9 ± 13.9 in group B which is statistically significant (p < 0.01). Survivorship from total hip arthroplasty were 86.2%/84% (p = 0.86) at the final follow up, which was not statistically significant. No serious complications were found in both groups. CONCLUSIONS: A single dose of PRP combined with CD and ß-TCP grafts provided significant pain relief, better functional outcomes, and delayed progression in the short term compared to CD combined with ß-TCP grafts. However, the prognosis of the femoral head did not improve significantly in the long term. In the future, designing new implants to achieve multiple PRP injections may improve the hip preservation rate.

The outcomes of total hip replacement in osteonecrosis versus osteoarthritis: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to compare the outcomes of THA in patients with osteonecrosis (ON) and those with osteoarthritis (OA). METHODS: Four databases were searched from inception till December 2022 for original studies that compared the outcomes of THA in ON and OA. The primary outcome was the revision rate; the secondary outcomes were dislocation and Harris hip score. This review was conducted in line with PRISMA guidelines, and the risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: A total of 14 observational studies with 2,111,102 hips were included, with a mean age of 50.83 ± 9.32 and 55.51 ± 8.95 for ON and OA groups, respectively. The average follow-up was 7.25 ± 4.6 years. There was a statistically significant difference in revision rate between ON and OA patients in favour of OA (OR: 1.576; 95%CI: 1.24-2.00; p-value: 0.0015). However, dislocation rate (OR: 1.5004; 95%CI: 0.92-2.43; p-value: 0.0916) and Haris hip score (HHS) (SMD: - 0.0486; 95%CI: - 0.35-0.25; p-value: 0.6987) were comparable across both groups. Further sub-analysis adjusting for registry data also showed similar results between both groups. CONCLUSION: A higher revision rate, periprosthetic fracture and periprosthetic joint infection following total hip arthroplasty were associated with osteonecrosis of the femoral head compared with osteoarthritis. However, both groups had similar dislocation rates and functional outcome measures. This finding should be applied in context due to potential confounding factors, including patient's age and activity level.

Survival of total hip arthroplasty (THA) in sickle cell disease.

BACKGROUND: The objective of this study was to evaluate the outcome of THA done in patients with sickle cell disease at a single center, and compare with rest of the world before we could recommend routine THA in SCD patients. METHODS: In 92 patients, 117 THAs were performed in sickle cell patients. Seventy-six (76) patients had homozygous hemoglobin (Hgb SS) disease, whereas sixteen had sickle cell trait (Hgb AS). Patients with Grade III Ficat and above avascular necrosis of the head of femur (ANFH) with cementless porous-coated proximal femur fixation were included in this analysis. Harris hip score was modified (MHHS) and used for assessment of improvement and visual analog scale score (VAS), for pain assessment. RESULT: VAS improved from average pre-operative mean of 7 (7-9) to 2.5 (1-5). The average pre-operative MHHS was 44 (32-63), and it improved to 79 (71-88) in the final mean follow-up of 12.4 (4-18) years. Nine patients (9.7%) had complications and revision surgery was required in seven (5.9%) for aseptic loosening. CONCLUSION: Our analysis shows that THA in sickle cell disease is safe with average 12 years of follow-up, indicating that surgery in these young patients (≤ 25 years) is safe and should not be delayed.

Essential role of reliable reduction quality in internal fixation of femoral neck fractures in the non-elderly patients-a propensity score matching analysis.

BACKGROUND: The rate of failure of internal fixation for femoral neck fractures has remained largely unchanged over the past 30 years. The current study attempted to identify the controllable variables influencing the failure of internal fixation of femoral neck fractures. METHODS: The study included 190 patients aged from 20 to 65 with femoral neck fracture caused by low energy violent injuries (fall from standing height), who were treated with multiple cannulated screws over the period 2005-2019 at a single centre. Kaplan-Meier (KM) survival analysis was firstly utilized to evaluate the potential interaction between each variable and cumulative rates of reoperation. If P < 0.1 in KM survival analysis, the variables would be included in subsequent Cox survival analysis to explore the influencing need for reoperation of a femoral neck fracture. Next, all of the 190 patients were divided into perfect reduction group (Garden Alignment Index I) and imperfect reduction group (Garden Alignment Index II, III, IV). Propensity score matching (PSM) analysis resulted in 39 pairs. After the baseline variables were balanced between the two groups, cox survival analysis was utilized again to explore the variables influencing the need of reoperation of a femoral neck fracture. Finally, KM survival analysis was utilized to compare the cumulative rate of reoperation between perfect reduction (Group PR) and imperfect reduction (Group IR) as a subgroup analysis. RESULTS: Before PSM analysis, the mean age was 49.96 ± 12.02 years and the total reoperation rate was 17.40%. Cox survival analysis showed that only reduction quality was interrelated with the need for reoperation before PSM analysis and after PSM analysis. Kaplan-Meier cumulative reoperation rate was higher in Group IR than in Group PR after PSM analysis. CONCLUSION: To prolong the service life of the original femoral head, it is essential to achieve a completely anatomical reduction and maintain the reduction quality until the patient fully recovers.

Identification of key non-coding RNAs and transcription factors regulators and their potential drugs for steroid-induced femoral head necrosis.

Steroid-induced necrosis of femoral head (SINFH) is a femoral head necrotic disease caused by prolonged use of hormones. The detailed pathogenesis has not been fully demonstrated. In this study, we employed the bioinformatics approach to probe the roles of SINFH inhibitors. Core dysfunction modules related to SINFH was obtained. Meanwhile, GO and KEGG analysis of genes in dysfunction modules are carried out. Furthermore, the pivot prediction analysis of dysfunction modules related to ncRNA and transcription factor (TF) has been performed. The functions of the enriched modules were focused on multiple perspectives, including circulation, gland development, bone development and reconstruction, calcium production, and fatty acid metabolism regulation. The ncRNAs and TFs analysis showed that miR-322-5p, miR-124-3p, miR-125a-3p, and Ctnnb1 were important members of SINFH dysfunction. Drug targets suggested that Zinc and adenosine monophosphate may have an impact on SINFH dysfunction. SINFH was closely related to bone development and reconstruction.

[Effect of Jianpi Huogu Formula on function damage of vascular endothelial cells induced by glucocorticoid].

This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 µg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 µg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 µg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 µg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.

Total hip arthroplasty for osteonecrosis of the femoral head in sickle cell disease: a case series from our African experience.

Sickle cell disease causes osteonecrosis (20% to 50% of patients) and collapse of the femoral head that result in secondary osteoarthritis. Total hip arthroplasty (THA) is a valid alternative for these patients. We define the difficulties that can be encountered when undertaking THA in sickle cell disease patients and give advice on how to deal with these technically demanding procedures. We undertook total hip arthroplasty procedures on 12 patients (4 females and 8 males) with osteonecrosis of the femoral head. Two bilateral prostheses were performed. We had only one type of stem, only one type of acetabular cup and only 28 mm cobalt chrome heads. The procedures were performed through either an anterior or a direct lateral approach. The average size of the Cup was 46 (Versafit, Medacta), the average size of the femoral stem was 0 (Amistem, Medacta), the most used size of the modular head was a S. Standard stem that was used in nine patients, while three patients received a lateralizing stem. Three patients had periprosthetic fracture, treated by cerclage. Total hip replacement is an excellent alternative for patients with osteonecrosis from sickle cell disease. The preparation of the acetabulum and the femur is difficult and requires attention, time and appropriate equipment.

Variables influencing the pelvic radiological evaluation in children with developmental dysplasia of the hip managed by closed reduction: a multicentre investigation.

PURPOSE: This study aims to evaluate (1) the probability to achieve normal pelvic radiographs in children with developmental dysplasia of the hip (DDH) treated by closed reduction and (2) the amount of time needed to achieve normal pelvic radiographs and to assess what factors influence both probability and time to achieve normal radiographic parameters following CR and spica cast immobilization for DDH. METHODS: We retrospectively reviewed 436 patients (393 girls, 43 boys; 507 hips) with DDH treated by closed reduction (CR). Tönnis grade, AVN, acetabular index (AI), centre-edge angle (CEA), and Severin radiographic grade were evaluated on plain radiographs. Criteria to rate pelvis radiographs as normal were established. Cox regression was used to evaluate the factors influencing the probability and the time to achieve normal radiographs. RESULTS: According to our criteria, 167 hips (32.9%) achieved normal radiographic parameters during follow-up. The overall amount of time to achieve normal pelvis radiographs was 36.1 ± 15.5 months. Patients older than 24 months of age at the time of CR needed longer time to achieve normal radiographic parameters (55.2 ± 28 months) compared with other age groups. Cox regression analysis suggested the overall cumulative probability of recovery increased by 46% at five years following CR, then it tended to plateau with an annual increase less than 5%. Age older than 24 months, bilateral dislocation, pre-operative AI greater than 40°, and AVN were risk factors for reduced probability of achieving normal radiographic parameters. CONCLUSIONS: The cumulative probability of achieving normal pelvis radiographs increases linearly during the first five years following CR, then it tends to plateau. Age older than 24 months and Tönnis grade III and IV are associated with longer time to achieve normal radiographic parameters. Age older than 24 months, bilateral dislocation, pre-operative AI greater than 40°, and AVN are risk factors for reduced probability of achieving normal radiographic parameters in children with DDH treated by closed means.

Transcervical superior wedge resection (osteotomy) and fixation with contoured plate for the non- union of femoral neck fractures.

Study was conducted to determine the healing rate of non-union femoral neck fractures following a new transcervical superior based wedge resection and fixation with contoured plate. This study is based on a concept, that the presence of a residual part of the femoral neck on the trochanteric side of the non-union and removal of a wedge with a superior base not only converts shearing forces into compression forces but also provides fresh bone with an osteogenic potential. This is a descriptive case series 'one group pre-test post-test design', conducted from 2010 to 2016 with a sample size of 18, convenience sampling technique with a minimum follow up of 12 months. Eighteen patients with a mean age of 32.44±8.8 years were operated with transcervical wedge resection and fixation. However, only 14 completed a minimum follow up of twelve months. Thirteen (93%) patients achieved union while, one had stable fibrous union which later on developed avascular necrosis and underwent a total hip replacement. There was a mean shortening of 2.05±0.4 cm. Seven (50%) had post-operative Lurch and 4 (28.6%) required shoe raise while 1 had low grade infection.

Rheumatological complications of beta-thalassaemia: an overview.

Beta-thalassaemia, an autosomal recessive haemoglobinopathy, ranks among the most frequent monogenetic diseases globally. The severe form of the disease, beta-thalassaemia major, is accompanied by progressive involvement of multiple organ systems as a result of the disease pathophysiology as well as iron overload from blood transfusions on a regular basis. Some of the manifestations might also be caused by medications used to manage iron overload. The purpose of this review is to highlight the rheumatological complications of beta-thalassaemia, which include musculoskeletal manifestations, such as arthritis and arthropathies, joint effusions, osteoporosis, bone fractures and myalgias, in addition to CTDs, such as pseudoxanthoma elasticum. Rheumatologists are strongly encouraged to take part in a multidisciplinary approach to the management of this debilitating disease.

High incidence of aseptic hip necrosis in Hodgkin lymphoma patients treated with escalated BEACOPP receiving methylprednisolone.

BACKGROUND: Escalated BEACOPP (eBEACOPP) is an effective but fairly toxic regimen for the treatment of Hodgkin lymphoma (HL). Avascular necrosis (AVN) of femoral head was previously reported to increase in patients treated with eBEACOPP, but so far, no systematic analysis of its frequency has been published. AIMS: To analyse the frequency and identify possible risk factors for AVN development in patients treated with eBEACOPP. METHODS: We identified 26 patients treated with eBEACOPP for newly diagnosed high-risk advanced-stage HL, 25 of whom were alive at the time of study. All patients were invited to participate in a cross-sectional study; 17 patients responded and were evaluated by magnetic resonance imaging and orthopaedic examination. RESULTS: Six patients (35.3%) were diagnosed with AVN after receiving eBEACOPP treatment. AVN was not correlated with age, gender, number of received eBEACOPP cycles, irradiation therapy or cumulative dose of steroids administered. There were significantly more cases of AVN in patients receiving methylprednisolone than prednisone (P = 0.01). CONCLUSION: The use of methylprednisolone was shown to be a risk factor for the development of AVN in patients treated with eBEACOPP and should not be the corticosteroid of choice in the treatment of patients with HL.

Hip osteonecroses treated with calcium sulfate-calcium phosphate bone graft substitute have different results according to the cause of osteonecrosis: alcohol abuse or corticosteroid-induced.

INTRODUCTION: The aim of the study was to assess the factors influencing the final results of treatment of the femoral head osteonecrosis (ONFH) with core decompression and bone substitute grafting. The special interest was focused on comparison between alcohol- and steroid-induced ONFHs. MATERIAL AND METHODS: In this prospective study, a total of 53 patients (58 hips) in the mean age of 35.5 years were included: 29 had a history of alcohol use (32 hips) and 24 of steroid use (26 hips). The mean follow-up was 4.2 years (minimum 3 years). RESULTS: At last follow-up, significant improvements were noted in the Harris Hip Score (HHS) (mean 44.0 vs 55.9 points, p < 0.00002) and VAS scores (mean 7.0 vs 5.8 points, p < 0.0002) for the whole ONFH cohort, comparing to pre-operative status. The degree of improvement did not differ between Ficat and Arlet grade II and grade III (mean 14.9 vs 6.2 points, respectively, p = 0.1). No change was found between the final and initial results in this group in the steroid group (HHS mean 42.2 vs 45.5 points, p = 0.5 and VAS mean 6.8 vs 6.5 points, p = 0.5), but the improvement was noted in the alcohol group (HHS mean 45.5 vs 64.4 points, p < 0.0001; VAS mean 7.1 vs 5.2 points, p < 0.0001) comparing to pre-operative status. CONCLUSIONS: Presented treatment of ONFH significantly improves hip function, offers pain reduction, and gives similar functional improvement for hips scoring grade II and III on the Ficat and Arlet scale. A good response to operative treatment is seen in patients with alcohol-induced ONFH, but not in those with steroid-induced ONFH.

Regenerative therapies increase survivorship of avascular necrosis of the femoral head: a systematic review and meta-analysis.

PURPOSE: The aim of this study was to document the available evidence on the use of regenerative techniques for the treatment of femoral head osteonecrosis (or avascular necrosis of femoral head, AVN) and to understand their benefit compared to core decompression (CD) alone in avoiding failure and the need for total hip replacement (THR). METHODS: The search was conducted on three medical electronic databases according to PRISMA guidelines. The studies reporting number and timing of failures were included in a meta-analysis calculating cumulative survivorship with a Kaplan-Mayer curve. Moreover, the results on failures in treatment groups reported in RCT were compared with those documented in control groups, in order to understand the benefit of biological therapies compared to CD for the treatment of AVN. RESULTS: Forty-eight studies were included in this systematic review, reporting results of different types of regenerative techniques: mesenchymal stem cell implantation in the osteonecrotic area, intra-arterial infiltration with mesenchymal stem cells, implantation of bioactive molecules, or platelet-rich plasma. Overall, reported results were good, with a cumulative survivorship of 80% after ten year follow-up, and better results when regenerative treatments were combined to CD compared to CD alone (89.9% vs 70.6%, p < 0.0001). CONCLUSION: Regenerative therapies offer good clinical results for the treatment of AVN. The combination of CD with regenerative techniques provides a significant improvement in terms of survivorship over time compared with CD alone. Further studies are needed to identify the best procedure and the most suitable patients to benefit from regenerative treatments for AVN.

Acetabular index is the best predictor of late residual acetabular dysplasia after closed reduction in developmental dysplasia of the hip.

PURPOSE: Our objective was to find the best predictor of late residual acetabular dysplasia in developmental dysplasia of the hip (DDH) after closed reduction (CR) and discuss the indications for secondary surgery. METHODS: We retrospectively reviewed the records of 89 patients with DDH (mean age 16.1 ± 4.6 months; 99 hips) who were treated by CR. Hips were divided into three groups according to final outcomes: satisfactory, unsatisfactory and operation. The changes in the acetabular index (AI), centre-edge angle of Wiberg (CEA), Reimer's index (RI) and centre-head distance discrepancy (CHDD) over time among groups were compared. The power of predictors for late residual acetabular dysplasia of AI, CEA, RI and CHDD at different time points was analysed by logistic regression analysis. Receiver operating characteristics (ROC) curve analysis was used to determine cutoff values and corresponding sensitivity, specificity and diagnostic accuracy for these parameters. RESULTS: Both AI and CEA improved in all groups of patients following CR. In the satisfactory group, AI progressively decreased until seven to eight years, while CEA increased until nine to ten years (P < 0.05). In the unsatisfactory group, AI and CEA ceased to improve three and two years after CR, respectively (P < 0.05). CEA and RI were significantly better in the satisfactory group compared with the unsatisfactory group at all time points (P < 0.05). Following CR, both RI and CHDD remained stable over time in all groups. Final outcome following CR could be predicted by AI, CEA and RI at all time points (P < 0.01). Cutoff values of AI, CEA and RI were 28.4°, 13.9° and 34.5%, respectively, at one year and 25°, 20° and 27%, respectively, at two to four years post-CR. A total of 80-88% of hips had an unsatisfactory outcome if AI > 28.4° and >25 at one and two to four years following CR, respectively. However, if CEA was less than or RI was larger than the cutoff values at each time point, only 40-60% of hips had an unsatisfactory outcome. Mean sensitivity (0.889), specificity (0.933) and diagnostic accuracy (92.1%) of AI to predict an unsatisfactory outcome were significantly better compared with CEA (0.731; 0.904; 78.2%) and RI (0.8; 0.655; 70.8%) (P < 0.05). CONCLUSIONS: Satisfactory and unsatisfactory hips show different patterns of acetabular development after reduction. AI, CEA and RI are all predictors of final radiographic outcomes in DDH treated by CR, although AI showed the best results. AI continues to improve until seven years after CR in hips with satisfactory outcomes, while it ceases to improve three to four years after CR in hips with unsatisfactory outcomes. According to our results, surgery is indicated if AI >28° 1 year following CR or AI >25° two to four years after CR. CEA and RI should be used as a secondary index to aid in the selection of patients requiring surgery.

The Multiplicity of Infection-Dependent Effects of Recombinant Adenovirus Carrying HGF Gene on the Proliferation and Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells.

Absence of effective therapeutic methods for avascular necrosis of femoral head (ANFH) is still perplexing the world's medical community. Bone marrow mesenchymal stem cells (BMSCs) adoptive cell therapy combined with core decompression is a promising modality, which is highly dependent on the cellular activities of BMSCs. Hepatocyte growth factor (HGF) is a survival factor for BMSCs, yet the underlying mechanism is not fully elucidated. In this study, the effects of multiplicity of infections (MOIs) of recombinant adenovirus carrying HGF gene (rAd-HGF) on human BMSC proliferation and osteogenic differentiation were systemically examined. Infection of rAd-HGF produced secretory HGF and promoted hBMSC proliferation in a MOI-dependent manner, while the osteogenesis was also strengthened as indicated by enhanced calcium nodule formation with the strongest effects achieved at MOI = 250. Blocking the activities of c-MET or its downstream signaling pathways, WNT, ERK1/2, and PI3K/AKT led to differential consequents. Specifically, blockage of the WNT pathway significantly promoted osteogenic differentiation, which also showed additive effects when combined application with rAd-HGF. Our data demonstrated the pro-osteogenic effects of optimized MOIs of rAd-HGF, while inhibition of WNT pathway or activation of PI3K/AKT pathway may act as candidate adjuvant modalities for promoting osteogenic differentiation in rAd-HGF-modified hBMSC treatment on ANFH.

Hyperbaric oxygen therapy modulates serum OPG/RANKL in femoral head necrosis patients.

Hyperbaric oxygen therapy (HBOT) has beneficial effects on avascular necrosis of femoral head (ANFH), but its mechanism of action is still unclear. We investigated if HBOT upregulates serum osteoprotegerin (OPG) and/or inhibits osteoclast activation. 23 patients with unilateral ANFH at stage I, II and III consented to the study: the patients received standard HBOT. Serum OPG levels were obtained at the beginning of HBOT (T0), after 15 sessions (T1), 30 sessions (T2), after a 30-day break (T3), and after 60 sessions (T4). Magnetic resonance imaging (MRI) was obtained at T0 and about one year from the end of HBO treatments. Lesion size was compared between pre- and post-HBOT. 19 patients completed the study. HBOT reduced pain symptoms in all patients. HBOT significantly reduced lesion size in all stage I and II patients and in 2 of 11 stage III patients. HBOT increased serum OPG levels but receptor activator of nuclear factor kappa-B ligand (RANKL) levels did not change.

Impaired osteogenic differentiation associated with connexin43/microRNA-206 in steroid-induced avascular necrosis of the femoral head.

Connexin(Cx)43 and microRNA(miR)-206 play an important role in osteogenesis. However, their role in steroid-induced femoral head osteonecrosis (SANFH) is still ambiguous. The present study aimed to establish a rabbit model and investigate osteogenesis in steroid-induced femoral head osteonecrosis occurring via Cx43/miR-206 and the changes of Wnt/ß-catenin signal pathway-related proteins. A total of 72 adult New Zealand white rabbits were divided randomly into a model group (Group A) and a control group (Group B) of 36 rabbits each. Group A was injected intravenously with lipopolysaccharide (10µg/kg body weight, once per day). After 48h, three injections of methylprednisolone (MPS; 20mg/kg body weight) were administered intramuscularly at 24-hour intervals. Group B were fed and housed under identical conditions but received saline injections. All animals were sacrificed at two, four, and eight weeks from the first MPS injection. Typical early osteonecrosis symptoms were observed in Group A. The expression of miR-206 in Group A was significantly higher than that of Group B. The mRNA and protein levels of Cx43, ß-catenin, runt-related transcription factor 2, and alkaline phosphatase gradually decreased while Dickkopf-1 (Dkk-1) gradually increased in Group A compared with Group B. These findings indicated that Cx43/miR-206 is involved in the pathogenesis of early stage SANFH and may be associate with Wnt/ß-catenin signal pathway.

Pulsed electromagnetic fields protect the balance between adipogenesis and osteogenesis on steroid-induced osteonecrosis of femoral head at the pre-collapse stage in rats.

This study was designed to investigate the effects of pulsed electromagnetic fields (PEMF) on the balance of adipogenesis and osteogenesis on steroid-induced osteonecrosis of the femoral head (OFH) in rats. Forty-two rats were divided into three groups: Steroid group (S, n = 16); Steroid + PEMF group (S + P, n = 16); and Control group (C, n = 10). For groups S and S + P, all rats were first intravenously given 10 µg/kg lipopolysaccharide on day 1, and then intramuscularly injected with 20 mg/kg methylprednisolone acetate on days 2, 3, and 4, with an interval of 24 h. After 4 weeks, the S + P group was treated with PEMF (4.5-ms square pulse, repeated at 15 Hz, with a peak of 1.2 mT) for 4 h a day for the next 8 weeks. Group S was not exposed to PEMF. Group C was chosen as the control group, without steroid use and exposure to PEMF. After 8 weeks of treatment, the histological changes, and mRNA and protein expressions of PPAR-γ2 and Runx2 were measured and analyzed. Compared with the S group, lower incidence of osteonecrosis (31% vs. 69%, P < 0.05) and empty osteocyte lacuna rate (36.16 ± 15.34 vs. 59.55 ± 21.70, P < 0.01) was observed in the S + P group. Furthermore, PEMF suppressed the expressions of PPAR-γ2 and improved the expressions of Runx2 in the femoral head (P < 0.05). All data suggest that PEMF is an effective physiotherapy in the treatment of steroid-induced ONFH, and the possible underlying mechanisms include protecting the balance between adipogenesis and osteogenesis.

Outcome of total hip arthroplasty for avascular necrosis of the femoral head in systemic lupus erythematosus.

This study evaluated the result of total hip arthroplasty (THA) for avascular necrosis of the femur head (AVNFH) in systemic lupus erythematosus (SLE) patients. Nineteen THAs were performed on 13 patients with SLE. The results of these patients were compared with the results of the control group (19 patients) who had THR due to AVNFH with none-SLE conditions. The Harris hip score increased from a preoperative average of 65.3 points to 94.9 at the most recent follow-up. In the control group, the mean HHS was 67.2 preoperatively and 96.1 postoperatively at the last follow-up. No significant difference was found between SLE patients and non-SLE patients who underwent hip arthroplasty. In conclusion, THA is an acceptable treatment for achieving functional improvement in patients who had SLE and AVNFH.