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

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

OBJECTIVE: To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms. METHODS: Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH. RESULTS: Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent. CONCLUSION At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.
Humans ; Femur Head/pathology* ; Osteonecrosis/therapy* ; Macrophages/pathology* ; Inflammation ; Femur Head Necrosis/pathology*

Background: Avascular necrosis (AVN) of the femoral head results from intraosseous pathology causing functional impairment. Early diagnosis allows conservative treatment like core decompression, delaying total hip arthroplasty. Objective: This meta-analysis aims to summarize platelet-rich plasma's (PRP) impact as an adjunct to core decompression (CD) on treatment outcomes and femoral head preservation in hip AVN. Methods: The study conducted a comprehensive literature search using PubMed, Cochrane Library, Science Direct, Google Scholar and Med Line, including randomized controlled trials (RCTs) and previous meta-analyses from various databases. Using a random effects model, it compared PRP+CD with bone grafting to CD with bone grafting alone in AVN patients, evaluating function, pain scores, disease progression and the need for hip surgery. Results: The meta-analysis examined 1041 records and included three studies. The primary outcomes were function and pain scores using Harris Hip Scoring (HHS) and Visual Analog Scale (VAS). Postoperative HHS scores at final follow-up favored the PRP+CD group significantly over CD alone. Postoperative VAS scores showed a trend towards higher scores in the CD alone group. The PRP+CD group demonstrated higher survival from disease progression compared to CD alone. Overall, the study suggests that PRP+CD led to better functional outcomes and disease progression outcomes than CD alone in AVN of the hip. Conclusion The PRP+CD treatment group showed significant benefits in AVN patients compared to CD alone, including higher HHS scores, improved disease progression survival and reduced need for hip surgery. Although PRP+CD resulted in decreased VAS scores, the difference was not statistically significant.
Osteonecrosis ; Femur Head ; Platelet-Rich Plasma ; Randomized Controlled Trial

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

OBJECTIVE: To investigate the early effectiveness of the Ti-Robot assisted femoral neck system (FNS) in the treatment of elderly Garden type Ⅱ and Ⅲ femoral neck fractures. METHODS: A retrospective analysis was conducted on the clinical data of 41 elderly patients with Garden type Ⅱ and Ⅲ femoral neck fractures who were admitted between December 2019 and August 2022 and met the selection criteria. Among them, 21 cases were treated with Ti-Robot assisted FNS internal fixation (study group), and 20 cases were treated solely with FNS internal fixation (control group). There was no significant difference in baseline data, including gender, age, side, cause of injury, time from injury to surgery, fracture Garden classification, and fracture line classification, between the two groups ( P>0.05). Surgical effectiveness was evaluated based on parameters such as operation time (including incision time and total operation time), reduction level, number of dominant pin insertions, intraoperative fluoroscopy frequency, incision length, whether to extend the incision, need for assisted reduction, postoperative hospital stay, fracture healing time, incidence of osteonecrosis of the femoral head, postoperative visual analogue scale (VAS) score at 1 day, and Harris hip score at last follow-up. RESULTS: The study group showed significantly shorter incision time, fewer dominant pin insertions, fewer instances of extended incisions, fewer intraoperative fluoroscopy frequency, and smaller incisions than the control group ( P<0.05). There was no significant difference in total operation time, reduction level, and assisted reduction frequency between the two groups ( P>0.05). Both groups achieved primary wound healing postoperatively, with no complications such as incision leakage or skin infection. All patients were followed up 12-24 months with an average of 14.6 months. Fractures healed in both groups, with no significant difference in healing time ( P>0.05). There was no significant difference in postoperative hospital stay between the two groups ( P>0.05). The study group showed significantly better VAS score at 1 day after operation and Harris hip score at last follow-up when compared to the control group ( P<0.05). No complication such as internal fixation failure, fracture displacement, or hip joint varus occurred in both groups during the follow-up. Osteonecrosis of the femoral head occurred in 1 patient of the control group, while no was observed in the study group, and the difference in the incidence of osteonecrosis of the femoral head between the two groups was not significant ( P=0.488). CONCLUSION Compared to sole FNS internal fixation treatment, Ti-Robot assisted FNS internal fixation for elderly Garden typeⅡ and Ⅲ femoral neck fractures can reduce incision time, achieve minimally invasive and accurate nail implantation, and decrease intraoperative fluoroscopy frequency, leading to improved postoperative hip joint function recovery.
Humans ; Aged ; Femur Neck ; Robotics ; Retrospective Studies ; Treatment Outcome ; Titanium ; Femoral Neck Fractures/surgery* ; Fracture Fixation, Internal ; Osteonecrosis ; Surgical Wound

OBJECTIVE: To investigate the value of CT-based radiomics and clinical data in predicting the efficacy of non-vascularized bone grafting (NVBG) in hip preservation, and to construct a visual, quantifiable, and effective method for decision-making of hip preservation. METHODS: Between June 2009 and June 2019, 153 patients (182 hips) with osteonecrosis of the femoral head (ONFH) who underwent NVBG for hip preservation were included, and the training and testing sets were divided in a 7∶3 ratio to define hip preservation success or failure according to the 3-year postoperative follow-up. The radiomic features of the region of interest in the CT images were extracted, and the radiomics-scores were calculated by the linear weighting and coefficients of the radiomic features after dimensionality reduction. The clinical predictors were screened using univariate and multivariate Cox regression analysis. The radiomics model, clinical model, and clinical-radiomics (C-R) model were constructed respectively. Their predictive performance for the efficacy of hip preservation was compared in the training and testing sets, with evaluation indexes including area under the curve, C-Index, sensitivity, specificity, and calibration curve, etc. The best model was visualised using nomogram, and its clinical utility was assessed by decision curves. RESULTS: At the 3-year postoperative follow-up, the cumulative survival rate of hip preservation was 70.33%. Continued exposure to risk factors postoperative and Japanese Investigation Committee (JIC) staging were clinical predictors of the efficacy of hip preservation, and 13 radiomic features derived from least absolute shrinkage and selection operator downscaling were used to calculate Rad-scores. The C-R model outperformed both the clinical and radiomics models in predicting the efficacy of hip preservation 1, 2, 3 years postoperative in both the training and testing sets ( P<0.05), with good agreement between the predicted and observed values. A nomogram constructed based on the C-R model showed that patients with lower Rad-scores, no further postoperative exposure to risk factors, and B or C1 types of JIC staging had a higher probability of femoral survival at 1, 2, 3 years postoperatively. The decision curve analysis showed that the C-R model had a higher total net benefit than both the clinical and radiomics models with a single predictor, and it could bring more net benefit to patients within a larger probability threshold. CONCLUSION The prediction model and nomogram constructed by CT-based radiomics combined with clinical data is a visual, quantifiable, and effective method for decision-making of hip preservation, which can predict the efficacy of NVBG before surgery and has a high value of clinical application.
Humans ; Bone Transplantation ; Femur Head/surgery* ; Femur ; Osteonecrosis ; Tomography, X-Ray Computed ; Retrospective Studies

Bacterial infection is a common finding in patients, who develop medication-related osteonecrosis of the jaw (MRONJ) by the long-term and/or high-dose use of anti-resorptive agents such as bisphosphonate (BPs). However, pathological role of bacteria in MRONJ development at the early stage remains controversial. Here, we demonstrated that commensal microbiota protects against MRONJ development in the pulp-exposed periapical periodontitis mouse model. C57/BL6 female mice were treated with intragastric broad-spectrum antibiotics for 1 week. Zoledronic acid (ZOL) through intravenous injection and antibiotics in drinking water were administered for throughout the experiment. Pulp was exposed on the left maxillary first molar, then the mice were left for 5 weeks after which bilateral maxillary first molar was extracted and mice were left for additional 3 weeks to heal. All mice were harvested, and cecum, maxilla, and femurs were collected. ONJ development was assessed using μCT and histologic analyses. When antibiotic was treated in mice, these mice had no weight changes, but developed significantly enlarged ceca compared to the control group (CTL mice). Periapical bone resorption prior to the tooth extraction was similarly prevented when treated with antibiotics, which was confirmed by decreased osteoclasts and inflammation. ZOL treatment with pulp exposure significantly increased bone necrosis as determined by empty lacunae and necrotic bone amount. Furthermore, antibiotics treatment could further exacerbate bone necrosis, with increased osteoclast number. Our findings suggest that the commensal microbiome may play protective role, rather than pathological role, in the early stages of MRONJ development.
Animals ; Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control* ; Bone Density Conservation Agents ; Diphosphonates ; Female ; Humans ; Mice ; Microbiota ; Periapical Diseases ; Zoledronic Acid