Steroid-induced osteonecrosis of femoral head (SONFH) is a disease characterized by femoral head collapse and local pain caused by excessive use of glucocorticoids. Peroxisome proliferator-activated receptor-γ (PPARγ) is mainly expressed in adipose tissue. Wnt/β-catenin, AMPK and other related signaling pathways play an important role in regulating adipocyte differentiation, fatty acid uptake and storage. Bone marrow mesenchymal cells (BMSCs) have the ability to differentiate into adipocytes or osteoblasts, and the use of hormones upregulates PPARγ expression, resulting in BMSCs biased towards adipogenic differentiation. The increase of adipocytes affects the blood supply and metabolism of the femoral head, and the decrease of osteoblasts leads to the loss of trabecular bone, which eventually leads to partial or total ischemic necrosis and collapse of the femoral head. MicroRNAs (miRNAs) are a class of short non-coding RNAs that regulate gene expression by inhibiting the transcription or translation of target genes, thereby affecting cell function and disease progression. Studies have shown that miRNAs affect the progression of SONFH by regulating PPARγ lipid metabolism-related signaling pathways. Therefore, it may be an accurate and feasible SONFH treatment strategy to regulate adipogenic-osteoblast differentiation in BMSCs by targeted intervention of miRNA differential expression to improve lipid metabolism. In this paper, the miRNA-mediated PPARγ-related signaling pathways were classified and summarized to clarify their effects on lipid metabolism in SONFH, providing a theoretical reference for miRNA targeted therapy of SONFH, and then providing scientific evidence for SONFH precision medicine.
MicroRNAs/physiology* ; PPAR gamma/metabolism* ; Femur Head Necrosis/metabolism* ; Humans ; Signal Transduction/physiology* ; Lipid Metabolism/physiology* ; Animals ; Cell Differentiation ; Mesenchymal Stem Cells/cytology* ; Glucocorticoids/adverse effects*

This study aims to investigate the pharmacological effects and mechanisms of Yougui Yin in treating glucocorticoid-induced osteonecrosis. A rat model of glucocorticoid-associated osteonecrosis of the femoral head(GA-ONFH) was established by intramuscular injection of dexamethasone at 20 mg·kg~(-1) every other day for 8 weeks. Rats were randomly allocated into control, model, and low-and high-dose(1.5 and 3.0 g·kg~(-1), respectively) Yougui Yin groups. After modeling, rats in Yougui Yin groups were administrated with Yougui Yin via gavage, which was followed by femoral specimen collection. Hematoxylin-eosin staining was employed to observe femoral head repair, and immunofluorescence was employed to assess adipogenic differentiation of bone marrow mesenchymal stem cells(BMSCs) within the femoral head. Cell experiments were carried out with dexamethasone(1 μmol·L~(-1))-treated BMSCs to evaluate the effects of Yougui Yin-medicated serum on adipogenic differentiation. Animal experiments demonstrated that compared with the model group, Yougui Yin at both high and low doses significantly improved bone mineral density(BMD), bone volume/total volume(BV/TV) ratio, and trabecular thickness(Tb.Th) in the femoral head. Additionally, Yougui Yin alleviated necrosis-like changes and adipocyte infiltration and significantly reduced the expression level of peroxisome proliferator-activated receptor γ(PPARγ) in the femoral head, thereby suppressing the adipogenic differentiation of BMSCs in GA-ONFH rats. The cell experiments revealed that Yougui Yin-medicated serum markedly inhibited dexamethasone-induced adipogenic differentiation of BMSCs and down-regulated the level of PPARγ. The overexpression of PPARγ attenuated the inhibitory effect of Yougui Yin-medicated serum on the adipogenic differentiation of BMSCs, indicating the critical role of PPARγ in Yougui Yin-mediated suppression of adipogenic differentiation of BMSCs. In conclusion, Yougui Yin exerts therapeutic effects on glucocorticoid-induced osteonecrosis by down-regulating PPARγ expression and inhibiting adipogenic differentiation of BMSCs.
Animals ; Mesenchymal Stem Cells/metabolism* ; PPAR gamma/genetics* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Glucocorticoids/adverse effects* ; Rats, Sprague-Dawley ; Adipogenesis/drug effects* ; Osteonecrosis/genetics* ; Cell Differentiation/drug effects* ; Bone Marrow Cells/metabolism* ; Femur Head Necrosis/chemically induced* ; Humans

OBJECTIVE: To evaluate precise assessment methods for predicting the optimal acetabular cup size in total hip arthroplasty (THA). METHODS: A clinical data of 73 patients (80 hips) who underwent primary THA between December 2022 and July 2024 and met the inclusion criteria was analyzed. There were 39 males and 34 females with an average age of 66.3 years (range, 56-78 years). Among them, 66 cases were unilateral THA and 7 were bilateral THAs. There were 29 patients (34 hips) of osteoarthritis, 35 patients (35 hips) of femoral neck fractures, and 9 patients (11 hips) of osteonecrosis of the femoral head. Based on anteroposterior pelvic X-ray films, three methods were employed to predict acetabular cup size, including preoperative template planning, radiographic femoral head diameter (FHD) measurement, and intraoperative FHD measurement. The predicted acetabular cup sizes from these methods were compared with the actual implanted sizes. RESULTS: The predicted acetabular cup sizes using the preoperative template planning, radiographic FHD measurement, and intraoperative FHD measurement were (51.25±2.81), (49.72±3.11), and (49.90±2.74) mm, respectively, compared to the actual implanted cup size of (50.57±2.74) mm, with no significant difference ( P>0.05). Regarding agreement with the actual implanted cup size, the preoperative template planning achieved exact matches in 35 hips (43.75%), one-size deviation in 41 hips (51.25%), and two-size deviations in 4 hips (5%); the radiographic FHD measurement achieved exact matches in 12 hips (15%), one-size deviation in 57 hips (71.25%), and two-size deviations in 11 hips (13.75%); and the intraoperative FHD measurement achieved exact matches in 26 hips (32.5%), one-size deviation in 52 hips (65%), and two-size deviations in 2 hips (2.5%). There were significant differences in agreement distributions between the three methods and the actual implanted cup sizes ( H=18.579, P<0.001). CONCLUSION The intraoperative FHD measurement, as a simple, cost-effective, and accurate method, effectively guides acetabular cup selection, reduces the risk of prosthesis wear, enhances postoperative joint stability.
Humans ; Arthroplasty, Replacement, Hip/instrumentation* ; Male ; Female ; Middle Aged ; Acetabulum/diagnostic imaging* ; Aged ; Hip Prosthesis ; Prosthesis Design ; Femur Head/surgery* ; Osteoarthritis, Hip/surgery* ; Radiography ; Femoral Neck Fractures/surgery* ; Femur Head Necrosis/surgery*

OBJECTIVE: To compare the effects of double-channel core decompression (CD) combined with medullary cavity irrigation with those of simple CD on progression of collapse and clinical outcomes in non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: A retrospective analysis was conducted on the clinical data of 19 patients (30 hips) with non-traumatic ONFH who underwent double-channel CD combined with medullary cavity irrigation and admitted between January 2024 and October 2024 (CD+irrigation group). According to a 1: 2 ratio, 54 patients (60 hips) who underwent simple CD and were matched in terms of age, gender, and body mass index (BMI) were included as the control (CD group). There was no significant difference in baseline data such as age, gender, BMI, affected side, ONFH type, preoperative Association Research Circulation Osseous (ARCO) stage, bone marrow edema stage, visual analogue scale (VAS) score for pain, and Harris score between the two groups ( P>0.05). The postoperative discharge time and occurrence of complications were recorded for both groups. The VAS scores before operation and at discharge after operation were compared, and the differences between pre- and post-operation (change values) were calculated for intergroup comparison. The Harris scores before operation and at discharge and 3 months after operation were also compared. During follow-up, X-ray film, CT, and MRI were performed for reexamination. The ARCO stage and bone marrow edema stage were evaluated at 3 months after operation and compared with those before operation to determine whether there was radiological progression or relief. RESULTS: All incisions in both groups healed by first intention after operation, with no infection, femoral neck fracture, or other operation-related complications. All patients were followed up, and the follow-up time of the CD+irrigation group was (146.8±27.7) days, and that of the CD group was (164.3±48.2) days; there was no significant difference between the two groups ( t=1.840, P=0.069). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). At discharge after operation, the VAS score of the CD+irrigation group was significantly lower than that of the CD group ( P<0.05), and the change value was significantly higher than that of the CD group ( P<0.05). The Harris scores at discharge and 3 months after operation in the CD+irrigation group were significantly higher than those in the CD group ( P<0.05). The Harris score gradually increased with time, and the differences between different time points were significant ( P<0.05). Radiological reexamination showed that there was no significant difference in the ARCO stage and the incidence of radiological progression between the two groups at 3 months after operation ( P>0.05); however, the bone marrow edema stage and the degree of bone marrow edema relief in the CD+irrigation group were better than those in the CD group, with significant differences ( P<0.05). CONCLUSION Double-channel CD combined with medullary cavity irrigation can significantly alleviate hip joint pain and improve joint function in patients with non-traumatic ONFH, reduce the degree of bone marrow edema in the femoral head, and delay the progression of ONFH.
Humans ; Femur Head Necrosis/therapy* ; Retrospective Studies ; Male ; Female ; Decompression, Surgical/methods* ; Therapeutic Irrigation/methods* ; Adult ; Treatment Outcome ; Middle Aged ; Femur Head/surgery*

OBJECTIVE: To explore the therapeutic effect of polygonum cuspidatum glycoside on steroid-induced osteonecrosis of the femoral head(SONFH) in rats and its potential mechanism of protecting bone tissue by regulating the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway(JAK2/STAT3). METHODS: Fifty male SD rats were randomly divided into control group, model group, low-dose polygonum cuspidatum glycoside group (polygonum cuspidatum glycoside-L), high-dose polygonum cuspidatum glycoside group (polygonum cuspidatum glycoside-H), and polygonum cuspidatum glycoside-H+Colivelin (JAK2/STAT3 pathway activator) group. SONFH model was induced by lipopolysaccharide and dexamethasone. The treatment groups were given polygonum cuspidatum glycoside orally(polygonum cuspidatum glycoside-L 10 mg·kg^-1, polygonum cuspidatum glycoside-H 20 mg·kg^-1, and the polygonum cuspidatum glycoside-H+Colivelin group was injected with Colivelin (1 mg·kg^-1) intraperitoneally once a day, while the control and model groups were given an equal volume of saline for 6 weeks. The observed indicators included serum calcium(Ca), serum phosphorus (P), alkaline phosphatase, and transforming growth factor β1(TGF-β1) levels, micro-CT scanning, hematoxylin-eosin staining, and Western blot detection of JAK2/STAT3 signaling pathway and osteogenic differentiation marker genes, including Runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (BMP2), and osteopontin (OPN) protein expression. RESULTS: Compared with the model group, the trabecular bone area percentage in the polygonum cuspidatum glycoside-L and polygonum cuspidatum glycoside-H groups was significantly increased, and the empty lacunar rate was significantly decreased (P<0.05). Micro-CT analysis showed that the bone volume fraction, trabecular number, and thickness increased, and the trabecular separation decreased in the polygonum cuspidatum glycoside-treated groups(P<0.05). Serum biochemical tests found that the serum Ca and P concentrations in the polygonum cuspidatum glycoside-L and polygonum cuspidatum glycoside-H groups were restored, the alkaline phosphatase levels decreased, and the transforming growth factor β1 levels increased (P<0.05). Western blot analysis showed that polygonum cuspidatum glycoside significantly inhibited the activation of the JAK2/STAT3 signaling pathway in the model group and promoted the expression of osteogenic differentiation marker genes such as Runx2, BMP2, and OPN (P<0.05). Compared with the polygonum cuspidatum glycoside-H group, the improvements in the polygonum cuspidatum glycoside-H+Colivelin group were somewhat weakened, indicating the importance of the JAK2/STAT3 signaling pathway in the action of polygonum cuspidatum glycoside. CONCLUSION polygonum cuspidatum glycoside promotes osteogenic differentiation, improves bone microstructure, and has significant therapeutic effects on rat SONFH by regulating the JAK2/STAT3 signaling pathway.
Animals ; Male ; Janus Kinase 2/physiology* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Glucosides/pharmacology* ; STAT3 Transcription Factor/genetics* ; Femur Head Necrosis/chemically induced* ; Stilbenes/pharmacology*

OBJECTIVE: To assess the mid-term clinical efficacy of the direct anterior approach for window decompression and bone grafting surgery in the treatment of early to mid-stage osteonecrosis of the femoral head (ONFH). METHODS: A retrospective analysis was performed on 40 patients (40 hips) diagnosed with osteonecrosis of the femoral head (ONFH), classified as types L1 and L2 according to the China-Japan Friendship Hospital (CJFH) classification system, and at stagesⅡ, ⅢA, and ⅢB based on the Association Research Circulation Osseous (ARCO) staging system. All patients underwent head-neck junction fenestration decompression and bone grafting via the direct anterior approach between January 2015 and May 2022, with complete follow-up data available for a minimum of three years. The ages of the patients ranged from 35 to 69 years old, with a mean of (49.13±6.14 ) years old;their body mass index (BMI) ranged from 20.02 to 27.94 kg·m^-2, with a mean of (23.65±1.69) kg·m^-1;the duration of the disease ranged from 13 to 36 months, with a mean of (24.55±4.14) months. Preoperative and 3-year postoperative X-ray parameters were collected, including the anterior preserved angle(APA), lateral preserved angle (LPA), and combined preserved angle (CPA). Additionally, hip joint disability and osteoarthritis outcome scores (HOOS) and Harris hip scores (HHS) were recorded. RESULTS: Forty patients were followed up for a period ranging from 36 to 59 months, with a mean duration of (47.18±6.18) months. At 3 years postoperative, none of the patients underwent hip replacement surgery. The APA (73.15±19.35)°, LPA (75.35 ±21.48)°, and CPA (136.25±26.78)° at the 3-year postoperative significantly improved compared to preoperative measurements (61.93±20.54)°, (59.46±22.67)°, and (116.58±32.47)°, with statistical significance (P<0.05). The HOOS (20.37±1.39) and HHS (89.74±3.28) scores at the 3-year postoperative were significantly improved from preoperative scores (12.36±1.58) and (50.27±6.15), respectively, with statistical significance (P<0.05). CONCLUSION The direct anterior approach for window decompression and bone grafting surgery can relieve joint pain, improve joint function, and enhance X-ray preserved angles, effectively preventing femoral head collapse, making it an effective surgical method for treating ONFH classified as L1, L2 according to CJFH and stagesⅡ, ⅢA, ⅢB according to ARCO.
Humans ; Middle Aged ; Male ; Female ; Adult ; Decompression, Surgical/methods* ; Bone Transplantation ; Femur Head Necrosis/surgery* ; Follow-Up Studies ; Aged ; Retrospective Studies

Steroid-induced osteonecrosis of the femoral head (SONFH) is avascular necrosis of the femoral head caused by long-erm use of corticosteroids, and its pathogenesis is complex and affected by changes in the dynamic balance of the bone microenvironment. With the deepening of research, the role of bone microenvironment in the pathogenesis of SONFH has been gradually revealed. In the case of excessive use of glucocorticoids (GCs), the bone microenvironment changes significantly, causing imbalance in bone lipid metabolism, microcirculation disorders and disorders of immune regulation, which promotes the increase of the number and activity of osteoclasts, and interferes with the differentiation of osteoblasts and adipoblasts. Through the regulation of PI3K/AKT, OPG/RANKL/RANK, MAPK, JAK/STAT, Hedgehog and other signaling pathways, it eventually leads to osteocyte apoptosis, bone microvascular rupture and destruction of trabecular bone structure, which in turn leads to osteonecrosis, bone density reduction and bone microstructure destruction due to bone microcirculation ischemia, and finally leads to necrosis of the femoral head. This article reviews the role of bone microenvironment homeostasis in GCs-induced ONFH and the regulatory mechanism of bone microenvironment, which is helpful to reveal the pathogenesis of SONFH and provide a theoretical basis for exploring effective intervention strategies.
Humans ; Femur Head Necrosis/physiopathology* ; Animals ; Signal Transduction ; Bone and Bones/metabolism* ; Glucocorticoids/adverse effects* ; Cellular Microenvironment

Osteonecrosis of the mandible is also called avascular necrosis of the jaw, and it is a rare complication of bisphosphonates. It is characterized with pain, swelling, exposure of bone, local infection and pathologic fractures of the jaw. With the widespread usage of bisphosphonates in bone metastasis of malignant tumors and osteoporosis, this rare complication has received more attention in recent years. Here, we reported a case of bisphosphonates-related osteonecrosis of the jaw (BRONJ) caused by intravenous zoledronic acid for osteoporosis. A 62-year-old female patient with 7-year history of Sjögren's syndrome and 3-year history of osteoporosis developed BRONJ after 3-year treatment of zoledronic acid. Two months before she went to the Peking University International Hospital, she visited the dentist for periodontal purulent secretion and extracted one tooth from the right mandible. However, the condition was not improved and she felt persistent pain and swelling in the right mandible. Hence, she received repeated root curettage, but there was no improvement. Finally, she was diagnosed with osteonecrosis of the mandible based on the digital volume tomography scan, which showed right mandibular osteonecrosis bone destruction. She underwent surgical debridement of the necrotic bone and administered intravenous antibio-tics at the Peking University International Hospital. Histopathological analysis of the bone biopsy further confirmed the diagnosis of BRONJ. Her condition was improved successfully during a 3-year follow-up. Osteonecrosis of the mandible become more common with the increased use of bisphosphonates. Recent study has reported that osteonecrosis of the mandible is more likely to occur in patients with Sjögren's syndrome. In addition, age, long-term and irregular administration of glucocorticoids, irregular oral examination and treatment also might be the risk factors in the pathogenesis of osteonecrosis of the mandible. For the elder osteoporosis patients who would receive or had received bisphosphonate-related drugs, oral health status and the disease states associated with necrosis of the mandible such as Sjögren's syndrome should be comprehensively measured and fully evaluated during the whole process. Furthermore, to better understand and prevent or reduce the occurrence of this complication, we reviewed the patho-genesis, diagnosis, treatment, and prevention of BRONJ.
Humans ; Female ; Middle Aged ; Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology* ; Diphosphonates/administration & dosage* ; Zoledronic Acid ; Imidazoles/administration & dosage* ; Bone Density Conservation Agents/adverse effects* ; Osteoporosis/drug therapy*

Bisphosphonates(BP),a class of commonly used medications for treating osteoporosis and bone malignancies,significantly affect bone metabolism.When dental implants are placed in patients receiving BP,the potential impacts of BP on the formation and long-term maintenance of implant osseointegration cannot be ignored.In addition,the influence of dental implants on the occurrence of BP-related osteonecrosis of the jaw is garnering attention.This article explores the influences of BP on the stability of dental implants based on a review of previous animal and clinical studies,discusses the impact of dental implants on the occurrence of BP-related osteonecrosis of the jaw,and proposes suggestions for the dental implant treatment of patients taking BP in clinical practice.This review is expected to provide a theoretical basis for the related research and clinical treatment.
Humans ; Dental Implants ; Animals ; Diphosphonates/pharmacology* ; Osseointegration/drug effects* ; Bisphosphonate-Associated Osteonecrosis of the Jaw

OBJECTIVE: To review the advancement made in the understanding of valgus impacted proximal humeral fracture (PHF). METHODS: The domestic and foreign literature about the valgus impacted PHF was extensively reviewed and the definition, classification, pathological features, and treatment of valgus impacted PHFs were summarized. RESULTS: PHF with a neck shaft angle ≥160° is recognized as a valgus impacted PHF characterized by the preservation of the medial epiphyseal region of the humeral head, which contributes to maintenance of the medial periosteum's integrity after fracture and reduces the occurrence of avascular necrosis. Therefore, the valgus impacted PHF has a better prognosis when compared to other complex PHFs. The Neer classification designates it as a three- or four-part fracture, while the AO/Association for the Study of Internal Fixation (AO/ASIF) categorizes it as type C (C1.1). In the management of the valgus impacted PHF, the selection between conservative and surgical approaches is contingent upon the patient's age and the extent of fracture displacement. While conservative treatment offers the advantage of being non-invasive, it is accompanied by limitations such as the inability to achieve anatomical reduction and the potential for multiple complications. Surgical treatment includes open reduction combined with steel wire or locking plate and/or non-absorbable suture, transosseous suture technology, and shoulder replacement. Surgeons must adopt personalized treatment strategies for each patient with a valgus impacted PHF. Minimally invasive surgery helps to preserve blood supply to the humeral head, mitigate the likelihood of avascular necrosis, and reduce postoperative complications of bone and soft tissue. For elderly patients with severe comminuted and displaced fractures, osteoporosis, and unsuitable internal fixation, shoulder joint replacement is the best treatment option. CONCLUSION Currently, there has been some advancement in the classification, vascular supply, and management of valgus impacted PHF. Nevertheless, further research is imperative to assess the clinical safety, biomechanical stability, and indication of minimally invasive technology.
Aged ; Humans ; Bone Plates ; Bone Wires ; Fracture Fixation, Internal/adverse effects* ; Fractures, Comminuted/surgery* ; Humeral Fractures ; Osteonecrosis ; Retrospective Studies ; Shoulder Fractures/surgery* ; Treatment Outcome