Deep learning-based quantification of osteonecrosis using magnetic resonance images in Gaucher disease.

Gaucher disease is one of the most common lysosomal storage disorders. Osteonecrosis is a principal clinical manifestation of Gaucher disease and often leads to joint collapse and fractures. T1-weighted (T1w) modality in MRI is widely used to monitor bone involvement in Gaucher disease and to diagnose osteonecrosis. However, objective and quantitative methods for characterizing osteonecrosis are still limited. In this work, we present a deep learning-based quantification approach for the segmentation of osteonecrosis and the extraction of characteristic parameters. We first constructed two independent U-net models to segment the osteonecrosis and bone marrow unaffected by osteonecrosis (UBM) in spine and femur respectively, based on T1w images from patients in the UK national Gaucherite study database. We manually delineated parcellation maps including osteonecrosis and UBM from 364 T1w images (176 for spine, 188 for femur) as the training datasets, and the trained models were subsequently applied to all the 917 T1w images in the database. To quantify the segmentation, we calculated morphological parameters including the volume of osteonecrosis, the volume of UBM, and the fraction of total marrow occupied by osteonecrosis. Then, we examined the correlation between calculated features and the bone marrow burden score for marrow infiltration of the corresponding image, and no strong correlation was found. In addition, we analyzed the influence of splenectomy and the interval between the age at first symptom and the age of onset of treatment on the quantitative measurements of osteonecrosis. The results are consistent with previous studies, showing that prior splenectomy is closely associated with the fractional volume of osteonecrosis, and there is a positive relationship between the duration of untreated disease and the quantifications of osteonecrosis. We propose this technique as an efficient and reliable tool for assessing the extent of osteonecrosis in MR images of patients and improving prediction of clinically important adverse events.

Artificial intelligence can be used in the identification and classification of shoulder osteoarthritis and avascular necrosis on plain radiographs: a training study of 7,139 radiograph sets.

BACKGROUND AND PURPOSE: Knowledge concerning the use AI models for the classification of glenohumeral osteoarthritis (GHOA) and avascular necrosis (AVN) of the humeral head is lacking. We aimed to analyze how a deep learning (DL) model trained to identify and grade GHOA on plain radiographs performs. Our secondary aim was to train a DL model to identify and grade AVN on plain radiographs. PATIENTS AND METHODS: A modified ResNet-type network was trained on a dataset of radiographic shoulder examinations from a large tertiary hospital. A total of 7,139 radiographs were included. The dataset included various projections of the shoulder, and the network was trained using stochastic gradient descent. Performance evaluation metrics, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to assess the network's performance for each outcome. RESULTS: The network demonstrated AUC values ranging from 0.73 to 0.93 for GHOA classification and > 0.90 for all AVN classification classes. The network exhibited lower AUC for mild cases compared with definitive cases of GHOA. When none and mild grades were combined, the AUC increased, suggesting difficulties in distinguishing between these 2 grades. CONCLUSION: We found that a DL model can be trained to identify and grade GHOA on plain radiographs. Furthermore, we show that a DL model can identify and grade AVN on plain radiographs. The network performed well, particularly for definitive cases of GHOA and any level of AVN. However, challenges remain in distinguishing between none and mild GHOA grades.

Examining the Efficacy of Arthroscopic Scaphocapitate Arthrodesis for Advanced Kienbock's Disease: Clinical and Radiological Outcomes.

Background: Altering wrist biomechanics, Kienbock's disease leads to progressive carpal collapse that results in early arthritis and degenerative changes. By shifting the loading axis toward the radioscaphoid joint, scaphocapitate arthrodesis (SCA) has been reported as a salvage procedure effective in treating symptomatic patients with advanced Kienbock's disease. In this study, we aimed to evaluate the clinical and radiological outcomes of arthroscopic SCA in symptomatic patients with advanced stages of Kienbock's disease. Methods: Between March 2010 and February 2021, we included 15 patients with symptomatic stage IIIA (n=2) and stage IIIB (n=13) Kienbock's disease who were followed up for a minimum of 24 months after arthroscopic SCA with or without lunate excision. The lunate was excised in 6 patients and retained in 9. Visual analog scale (VAS) pain score, grip strength, range of motion (ROM), active flexion-extension arc, and modified Mayo wrist score (MMWS) were measured preoperatively and at each follow-up examination after surgery. Operation-related complications and radiographic changes were also assessed. Results: There were 13 women and 2 men, with a mean age of 57.6 years (range, 21-74 years) at the time of undergoing arthroscopic SCA. Follow-up ranged from 24 to 116 months, with an average of 56.9 ± 32.3 months. Bony union was achieved in all patients. At preoperative examination, wrist ROM (67%) and grip strength (48%) significantly decreased, compared to the contralateral wrist. At the final follow-up, there were significant improvements in VAS, grip strength, and MMWS, whereas the active wrist ROM showed no significant change. Radioscaphoid angle recovered after surgery, while radiographic carpal collapse and ulnar translation of the carpus occurred. In subgroup analysis according to excision of the lunate, there were no significant differences in VAS, MMWS, grip strength, or total ROM. However, increased ulnar translation and decreased radial deviation were noted in the lunate excision group. Conclusions: Arthroscopic SCA achieved significant improvements in pain and wrist function in patients with advanced Kienbock's disease without any complications. Excision of the lunate when performing arthroscopic SCA seemed to induce progressive carpal ulnar translation, with no apparent clinical benefits over retaining it.

Maxillary Osteonecrosis Related with Herpes Zoster: A Case Report and Review of the Literature.

Osteonecrosis of the jaw (ONJ) can occur through various mechanisms including radiation, medication, and viral infections such as herpes zoster. Although herpes zoster is a varicella-zoster virus infection that can affect the trigeminal nerve, it rarely causes oral complications. The author reports a rare case of herpes zoster-related ONJ, followed by a review of the relevant literature pertaining to herpes zoster-related oral complications, including ONJ. A 73-year-old woman presented with a scarred skin lesion on her left midface with an exposed alveolar bone of the left maxilla. Based on her medical records, she received a diagnosis and treatment for herpes zoster six months prior and experienced a few teeth loss in the left maxilla following a fall preceding the onset of herpes zoster. Sequestrectomy of the left maxilla was performed and ONJ was diagnosed. The operative site recovered favorably. Although unusual, several cases of localized extensive ONJ in herpes zoster-infected patients have been reported. This case illustrates the possibility of a rare occurrence of unilateral widespread osteonecrosis of the jaw (ONJ) even in the maxilla associated with herpes zoster. The exact mechanism has not been elucidated; nevertheless, surgeons should consider the possibility of oral and dental complications, including ONJ, related to a history of herpes zoster.

Management of Talus Fractures.

Fractures of the talus are life-changing events. The talus is of vital importance to normal gait. Given its importance, great care is needed in diagnosing and treating these injuries. The threshold for operative treatment and accurate anatomic reduction should be low. Surgical tenets include the avoidance of extensive subperiosteal dissection to minimize vascular disruption. The complications with injuries to the talus are extensive and include avascular necrosis (AVN). Although AVN can prove to be a devastating sequela from this injury, it occurs less frequently than posttraumatic arthritis.

Lithium prevents glucocorticoid-induced osteonecrosis of the femoral head by regulating autophagy.

Autophagy may play an important role in the occurrence and development of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC-ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC-ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC-induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC-ONFH was used for evaluating the therapeutic effect of oral lithium on GC-ONFH and underlying mechanism. Findings demonstrated that GC over-activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over-activated autophagy of GC-treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC-ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over-activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up-regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC-ONFH. Lithium may be a promising therapeutic agent for GC-ONFH. However, the role of autophagy in the pathogenesis of GC-ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC-ONFH, and the efficacy of lithium in the treatment of GC-ONFH and its underlying mechanisms.

Osteonecrosis of the jaw after radiation followed by bevacizumab.

Osteonecrosis of the jaw is a recognized complication associated with bevacizumab. Here, we present a patient with squamous cell carcinoma of the tonsil who experienced minimal skin fibrosis following intensity-modulated radiation therapy. Subsequently, the patient developed rectal adenocarcinoma and encountered osteonecrosis of the jaw after receiving two cycles of bevacizumab. Close monitoring, accompanied by thorough examination to detect early signs of osteonecrosis of the jaw, should be considered for patients who have undergone radiation therapy in the head and neck region and are receiving bevacizumab or other medications known to be associated with osteonecrosis of the jaw.

Unraveling the genetic basis of the causal association between inflammatory cytokines and osteonecrosis.

Background: Previous studies have reported that the occurrence and development of osteonecrosis is closely associated with immune-inflammatory responses. Mendelian randomization was performed to further assess the causal correlation between 41 inflammatory cytokines and osteonecrosis. Methods: Two-sample Mendelian randomization utilized genetic variants for osteonecrosis from a large genome-wide association study (GWAS) with 606 cases and 209,575 controls of European ancestry. Another analysis included drug-induced osteonecrosis with 101 cases and 218,691 controls of European ancestry. Inflammatory cytokines were sourced from a GWAS abstract involving 8,293 healthy participants. The causal relationship between exposure and outcome was primarily explored using an inverse variance weighting approach. Multiple sensitivity analyses, including MR-Egger, weighted median, simple model, weighted model, and MR-PRESSO, were concurrently applied to bolster the final results. Results: The results showed that bFGF, IL-2 and IL2-RA were clinically causally associated with the risk of osteonecrosis (OR=1.942, 95% CI=1.13-3.35, p=0.017; OR=0.688, 95% CI=0.50-0.94, p=0.021; OR=1.386, 95% CI=1.04-1.85, p = 0.026). there was a causal relationship between SCF and drug-related osteonecrosis (OR=3.356, 95% CI=1.09-10.30, p=0.034). Conclusion: This pioneering Mendelian randomization study is the first to explore the causal link between osteonecrosis and 41 inflammatory cytokines. It conclusively establishes a causal association between osteonecrosis and bFGF, IL-2, and IL-2RA. These findings offer valuable insights into osteonecrosis pathogenesis, paving the way for effective clinical management. The study suggests bFGF, IL-2, and IL-2RA as potential therapeutic targets for osteonecrosis treatment.

Treatment of AVN-Induced Proximal Pole Scaphoid Nonunion Using a Fifth and Fourth Extensor Compartmental Artery as a Vascularized Pedicle Bone Graft: A Retrospective Case Series.

BACKGROUND Scaphoid nonunion (SN) is a challenging condition in wrist pathology, often resulting in severe consequences if left untreated. Surgical intervention, particularly using vascularized bone grafts (VBGs), is a promising but uncertain approach. The 4+5 extensor compartment artery (ECA) pedicled graft, less commonly used for SN, has potential benefits due to its vascular supply and accessibility to the scaphoid. This study aimed to evaluate the effectiveness of the 4+5 ECA pedicled graft combined with headless compression screw fixation in treating avascular necrosis (AVN)-induced proximal pole SN. Radiological results, functional outcomes, and complications related to this method were assessed. MATERIAL AND METHODS This was a retrospective analysis of 19 proximal pole SN cases with AVN treated using the 4+5 ECA-VBG technique from 2016 to 2022. Patients underwent preoperative evaluation and postoperative follow-up for at least 1 year. Data on surgery, demographics, radiological assessments, and functional outcomes were recorded and analyzed statistically. RESULTS All patients achieved radiographic union within 8.5 weeks postoperatively, with revascularization of proximal pole necrosis. Significant improvements in functional outcomes were observed, including pain reduction, increased wrist range of motion, improved grip and pinch strength, and enhanced wrist scores. No major complications were reported. CONCLUSIONS The 4+5 ECA-VBG technique, with headless compression screw fixation, showed high success rates in treating AVN-induced proximal pole SN. This method offers comprehensive restoration of wrist function and minimal complications, making it a viable option for SN management, especially in AVN cases. Further research is needed to confirm these results and establish standardized protocols for SN treatment.

Association between CDK4/6 inhibitors and drug-related osteonecrosis of the jaw: A pharmacoepidemiological study using the FDA Adverse Events Reporting System.

The most common toxicities associated with cyclin-dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity. Recent reports have suggested an association between palbociclib and medication-related osteonecrosis of the jaw; however, reports on this association are inconsistent. This study investigated the potential association of palbociclib and abemaciclib with MRONJ using the FAERS. Signals of "Osteonecrosis of jaw" were detected only in females using palbociclib (cROR025: 2.08). Other signals detected included stomatitis-related adverse events with abemaciclib and intraoral soft tissue damage and infection with palbociclib. As previous exploratory studies have reported MRONJ signals for bisphosphonates and denosumab, we calculated the aROR for palbociclib-induced osteonecrosis of the jaw using concomitant bisphosphonates and denosumab as covariates. A signal was detected even after adjusting for sex, age, and concomitant medications as covariates (aROR0025: 5.74). A proper understanding of the differences in CDK selectivity is necessary for the appropriate use of CDK4/6 inhibitors. To the best of our knowledge, this is the first report on CDK4/6 inhibitors and drug-related osteonecrosis of the jaw. We believe that these results will offer new insights into adverse events related to the use of CDK4/6 inhibitors, and may aid in the proper use of CDK4/6 inhibitors.

[Transcriptome data mining combined with clinical and animal experiments for identification of syndrome element marker genes during entire course of steroid-induced osteonecrosis of femoral head].

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.

Infection may play an important role in the pathogenesis of alveolar osteonecrosis following facial herpes zoster: a case report and literature review.

BACKGROUND: Herpes zoster (HZ) is one of the most common skin diseases caused by viruses. Facial HZ develops when the varicella-zoster virus affects the trigeminal nerve, and alveolar osteonecrosis is a rare complication. However, the exact pathogenesis of postherpetic alveolar osteonecrosis remains unclear. CASE DESCRIPTION: We encountered a patient who presented to the dermatology clinic with facial HZ and tooth exfoliation in the upper right jaw, and panoramic radiography revealed decreased bone density and poor alveolar socket healing in his right maxilla. Biopsy of the alveolar process revealed fragments of nonvital lamellar bone, which were devoid of osteoblasts and osteocytes and were surrounded by numerous neutrophils and bacterial aggregates. Thus, the diagnosis of alveolar osteonecrosis following facial HZ was confirmed. He then underwent resection of the osteonecrotic tissue. The pathological findings of postoperative tissue were similar to those of previous biopsies. Varicella-zoster virus and multiple types of bacteria were detected through next-generation sequencing, and the species of bacteria were consistent with the results of bacterial culture. Antibiotics and valaciclovir were administered during the perioperative period. The patient showed good recovery at the 9-month follow-up. CONCLUSIONS: The coexistence of bacterial and viral infection may play an important role in the pathogenesis of alveolar osteonecrosis following HZ. To our knowledge, we are the first to directly explore microbial pathogens in a case of postherpetic alveolar osteonecrosis through next-generation sequencing and bacterial culture. We recommend that oral examinations be carefully conducted for patients who are diagnosed with facial HZ, even if their facial rashes have faded away. We suggest that a prolonged and full-dose antiviral therapy course may be beneficial for the treatment of facial HZ with intraoral lesions. The implementation of dental preventive measures should be considered for patients with facial HZ. The application of antibiotics and excision of necrotic bone may reduce the abundance of bacteria in lesions and improve wound healing.

Sclerotic bone: a sign of bone reaction in patients with medication related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction associated with antiresorptive drugs such as bisphosphonates and denosumab. When dealing with advanced and/or multiple MRONJ lesions undergoing surgical therapy, the extent of surgery is often a topic of discussion. The aim of this study was to identify the differences in bone density in and around the MRONJ lesion before and after surgical treatment to evaluate the needed surgical extend of the modelling osteotomy. In this retrospective study 26 patients with MRONJ lesions that were surgically treated in our department were observed. Length, width and bone density were measured in panoramic radiograph pre and postoperatively with the Imaging processing software Sidexis and ImageJ (Fiji). The necrotic area, the surrounding sclerotic area as well as the healthy contralateral side were observed. Measurements were performed by two independent observers. Pearson correlation was calculated to determine the interobserver variability. Bone density was significantly reduced in the necrotic bone area compared to the healthy unaffected contralateral reference side. The sclerotic bone area surrounding the necrosis showed increased bone density compared to the contralateral unaffected reference side. The density of the sclerotic bone area was increased in the previously affected MRONJ area in the postoperative panoramic radiograph. The pre and postoperative density showed no significant correlation to healing behaviour. The focus of the modelling osteotomy in surgical treatment of mature MRONJ lesions should be predominantly on the parts that appear necrotic and less dense in the panoramic radiograph as sclerotic areas might be an expression of bone reaction.

In vivo study of porous NiTi cryotweezers for bone tissue cryotherapy.

This study examined the effects of liquid nitrogen vapor on osteogenesis in the rabbit femur. Cryotweezers made of porous nickel titanium alloy (nitinol or NiTi) obtained by self-propagating high temperature synthesis were used in this experiment. The porous structure of the cryotweezers allows them to hold up to 10 g of liquid nitrogen after being immersed for 2 min, which completely evaporates after 160 s. To study the effects of liquid nitrogen evaporation on osteogenesis, a rabbit femur was perforated. The formed holes were subjected to cryotherapy with varying exposure times. It was found that a 3 s exposure time stimulates osteogenesis, which was manifested in a greater number of osteoblasts in the regenerate compared to the control sample without liquid nitrogen. It was observed that increasing the exposure to 6, 9 or 12 s had a destructive effect, to varying degrees. The most severe damage was exerted by a 12 s exposure, which resulted in the formation of osteonecrosis areas. In the samples exposed to 6 and 9 s of cryotherapy, destruction of the cytoplasm of osteocytes and osteoclasts was observed.

Osteonecrosis of the Knee: The Unintended Consequence of Steroid Abuse.

The anti-inflammatory and immunosuppressive properties of steroids allow their use in a wide variety of rheumatological diseases, asthma, inflammatory bowel disease, cancer therapy, and severe viral infections. Though life-saving or organ-saving, long-term clinical use leads to a vast array of complications. Osteoporosis is the most common orthopedic side effect of steroid abuse, while osteonecrosis is a rare occurrence. The risk of osteonecrosis appears to be dose and duration dependent, but several patient factors also play a major role and usually affect the femoral head followed by the knee joint. The long-term effects of steroids must be explained to all patients on therapy, but this risk is missed in individuals who abuse steroids for recreational or performance-enhancing purposes. We describe a male, aged 29 years, who presented with dull aching bilateral knee pain of 2-years' duration after a long-term steroid abuse for weight and muscle mass gain. Radiological and magnetic resonance imaging studies confirmed osteonecrosis of femoral and tibial condyles and secondary degenerative arthritis of the knee joint. Prompt suspicion, early diagnosis, and intervention in osteonecrosis of knee joints, and termination of steroids may reverse the pathology and prevent progression of disease.

Identifying the causal relationship between immune factors and osteonecrosis: a two-sample Mendelian randomization study.

A wealth of evidence intimates a profound connection between the immune system and osteonecrosis, albeit the specific immune factors underlying this connection remain largely veiled. A bidirectional Mendelian randomization (MR) study was conducted based on genome-wide association study summary data to identify causal links between 731 immune factors and osteonecrosis including drug-induced osteonecrosis. Preliminary MR analysis was accomplished utilizing the inverse-variance weighted method under a multiplicative random effects model, and heterogeneity and potential horizontal pleiotropy were evaluated through Cochrane's Q-test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. Upon false discovery rate correction, the gene-predicted level of one immune factor (CD62L - monocyte %monocyte) exhibited a significant positive correlation with osteonecrosis, while eight immune traits associated with monocytes, dendritic cells, and NK cells demonstrated significant causal effects with drug-induced osteonecrosis. Reverse MR revealed no significant correlations. This MR research provides genetic evidence for the causal associations between a broad spectrum of immune factors and osteonecrosis. Such a study aids in unraveling the intricate interaction patterns between the immune and skeletal systems, elucidating the pathogenesis of osteonecrosis, and identifying potential novel therapeutic approaches.