Effectiveness of various interventions for non-traumatic osteonecrosis: a pairwise and network meta-analysis.

Background: Osteonecrosis of the femoral head (ONFH) is acknowledged as a prevalent, challenging orthopedic condition for patients. Purpose: This study aimed to evaluate the efficacy of various interventions for non-traumatic ONFH and provide guidance for clinical decision-makers. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases from inception to February 2023 for relevant randomized controlled trials evaluating treatments for femoral head necrosis, without language restrictions. Quality evaluation was performed using the Cochrane risk-of-bias assessment tool, and analysis was performed using Stata 15.1. Results: Eleven randomized controlled trials were included in this study. The meta-analysis results revealed that CellTherapy [MD= -3.46, 95%CI= (-5.06, -1.85)], InjectableMed [MD= -3.68, 95%CI= (-6.11, -1.21)], ESWT [MD= -2.84, 95%CI= (-4.23, -1.45)], ESWT+InjectableMed [MD= -3.86, 95%CI= (-6.22, -1.53)] were significantly more effective in improving VAS pain score than CD+PTRI, as well as CD+BG+CellTherapy, and CD+BG. Furthermore, CD+BG+CellTherapy was better than CD+BG [MD= -0.97, 95%CI= (-1.71, -0.19)]. The SUCRA ranking for HHS score indicated that CellTherapy (77%) has the best effectiveness rate, followed by ESWT+InjectableMed (72.2%), ESWT (58.3%), InjectableMed (50%), CD+PTRI (31.4%), and CD+BG (11%). In terms of WOMAC and Lequesne scores, the meta-analysis showed no statistically significant differences between the experimental group CD+BG+CellTherapy and the control group CD+BG. Conclusion: CellTherapy and non-surgical ESWT combined with medication or CellTherapy have the best effect on ONFH. Surgical CD+BG combined with CellTherapy is more effective than CD+BG alone. ESWT+InjectableMed is recommended for short-term or acute onset patients, while ESWT is recommended for long-term patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024540122.

Xanthoma combining osteonecrosis in knee joint: a case report.

Xanthoma typically occurs in the subcutaneous tissues, with rare cases of xanthoma in the joints. However, the case of knee joint osteonecrosis combined with xanthoma is even more uncommon. In this article, we described a 50-year-old female patient who suffered xanthoma in the knee joint on the basis of osteonecrosis of the knee joint. The primary clinical symptoms were knee joint pain and limited mobility. The patient initially received conventional treatment for osteonecrosis. However, there was no significant improvement. Later, we found a synovial xanthoma in the patient's knee. Finally, she underwent arthroscopic excision of the knee joint synovial xanthoma. Following the procedure, her VAS score decreased from 7 to 2, and knee joint mobility increased from 10-103° to 10-140°. Through our follow-up, the patient did not exhibit symptom recurrence. This case is valuable as it provides a feasible therapeutic approach for future clinical applications.

Causal relationship between telomere length and osteonecrosis: Bidirectional two-sample Mendelian randomization analysis.

Recent mounting evidence suggests that shortening of telomere length (TL) is associated with impaired bone health; yet, a genetic causal relationship between TL and osteonecrosis remains uncertain. This study aimed to investigate the potential causal relationship between TL and osteonecrosis using bidirectional two-sample Mendelian randomization (MR). Genome-wide association study summary statistics for TL were sourced from the IEU Open genome-wide association study project, while osteonecrosis data were obtained from the FinnGen Biobank database. A range of MR methodologies-including inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode-were utilized for analysis, along with the MR-Egger intercept method for horizontal pleiotropy assessment, and Cochran Q and leave-one-out methods for heterogeneity testing. The forward MR analysis indicated a significant causal relationship between TL and osteonecrosis, suggesting that genetically predicted shorter TL is associated with an elevated risk of developing osteonecrosis (OR = 0.611, 95% confidence interval 0.394-0.948, P = .028). The reverse MR analysis revealed no significant influence of osteonecrosis on TL (OR = 0.999, 95% confidence interval 0.994-1.005, P = .802). Analyses for heterogeneity and horizontal pleiotropy yielded robust results. Our study demonstrates that individuals with shorter TL have an increased risk of developing osteonecrosis, whereas osteonecrosis has no effect on TL.

Vascularized Transfer of Second Metacarpal Base for Treatment of Capitate Osteonecrosis.

BACKGROUND: Capitate osteonecrosis is a rare condition that mainly presents in young patients with chronic wrist pain. Treatment aims to address pain, arthritic changes, or carpal instability. METHODS: We present the surgical technique and outcomes of using a vascularized pedicled second metacarpal base transferred on the second dorsal metacarpal artery to treat capitate osteonecrosis in a 20-year-old female secretary, former gymnast, and a 25-year-old female student with acute lymphoblastic leukemia. These patients presented with idiopathic chronic wrist pain with MRI showing capitate osteonecrosis with preserved carpal height and intact articular cartilage. RESULTS: After 2 years of follow-up, both patients endorsed pain resolution and demonstrated preservation of wrist motion and grip strength with evidence of capitate healing on plain radiographs. Case 1 demonstrated grip strength 60 lbs., pinch strength 5 lbs., and wrist flexion-extension arc of 70 to 80°. Case 2 had grip strength 31 lbs., pinch strength 9 lbs., and wrist flexion-extension arc of 40 to 30° on the left. CONCLUSION: Vascularized pedicled second metacarpal base transferred on the second dorsal metacarpal artery can be successfully used in the management of capitate osteonecrosis and offers advantages over other vascularized bone grafts for capitate osteonecrosis.

Designing and additive manufacturing of talus implant for post-traumatic talus avascular necrosis: a case study.

New technologies in additive manufacturing and patient-specific CT-based custom implant designs make it possible for previously unimaginable salvage and limb-sparing operations a practical reality. This study presents the design and fabrication of a lattice-structured implant for talus replacement surgery. Our primary case involved a young adult patient who had sustained severe damage to the talus, resulting in avascular necrosis and subsequent bone collapse. This condition caused persistent and debilitating pain, leading the medical team to consider amputation of the left foot at the ankle level as a last resort. Instead, we proposed a Ti6Al4V-based patient-specific implant with lattice structure specifically designed for pan-talar fusion. Finite element simulation is conducted to estimate its performance. To ensure its mechanical integrity, uniaxial compression experiments were conducted. The implant was produced using selective laser melting technology, which allowed for precise and accurate construction of the unique lattice structure. The patient underwent regular monitoring for a period of 24 months. At 2-years follow-up the patient successfully returned to activities without complication. The patient's functional status was improved, limb shortening was minimized.

The role of NOS3-rs1799983 and NOS3- rs2070744 SNP in occurrence of avascular necrosis as a post COVID-19 complication.

Avascular necrosis (AVN) is a debilitating condition characterized by bone tissue death due to inadequate blood supply, leading to joint dysfunction and collapse. This study investigates the potential association between AVN and COVID-19, focusing on genetic factors such as NOS3 polymorphisms. A total of 180 individuals were included, comprising 120 COVID-19 patients and 60 healthy controls. Clinical, haematological, biochemical, and genetic parameters were assessed. Results revealed significant differences in respiratory and heart rates, haematological counts, and biochemical markers between AVN and control groups. Genetic analysis showed a higher prevalence of the TG genotype and G allele in NOS3 rs1799983 polymorphism among AVN patients. Additionally, NOS3 rs2070744 polymorphism correlated with various clinical parameters, including blood pressure, heart rate, and haematological indices. This study highlights the potential role of genetic factors in predisposing individuals to AVN following COVID-19 infection.

External Auditory Canal Erosion at the 6 O'clock Spot.

OBJECTIVE: To report a common site of external ear canal erosion in multiple pathologies, located inferiorly at 6 o'clock. PATIENTS: Otology patients who came in 2023 for treatment of external auditory canal erosions. INTERVENTION: This clinical capsule is an observational report of the external canal's propensity to erosion at the 6 o'clock location. Patient treatments were canalplasty, mastoidectomy, and medical management. MAIN OUTCOME MEASURE: Documentation of the propensity to erosion at the 6 o'clock location in the external auditory canal. Locations of the niduses of prior series of external auditory canal pathologies are documented. RESULTS: Eight patients are presented with external auditory canal erosion in 10 ears originating at the 6 o'clock position medial to the bony-cartilaginous junction. No other patient with spontaneous canal erosion presented with their nidus of pathology in another canal location. (A review of 42 case series of 291 patients found that keratosis obturans and bisphosphonate-induced osteonecrosis tended to arise from the same 6 o'clock lateral bony canal location, while 26% of necrotizing otitis externa cases arose there.). CONCLUSIONS: The "6 o'clock spot" in the external canal is a common location of canal erosion for spontaneous wax and keratin collections and may be the precursor to keratosis obturans, bisphosphonate-induced osteonecrosis of the ear canal, and necrotizing otitis externa.

Inhibition of insulin degrading enzyme suppresses osteoclast hyperactivity via enhancing Nrf2-dependent antioxidant response in glucocorticoid-induced osteonecrosis of the femoral head.

BACKGROUND: Osteoclast hyperactivation due to the pathological overproduction of reactive oxygen species (ROS) stimulated by glucocorticoids (GCs) is one of the key drivers behind glucocorticoid-induced osteonecrosis of the femoral head (GIONFH). The insulin degrading enzyme (IDE), a conserved Zn2+ metallo-endopeptidase, facilitates the DNA binding of glucocorticoid receptor and plays a substantial role in steroid hormone-related signaling pathways. However, the potential role of IDE in the pathogenesis of GIONFH is yet undefined. METHODS: In this study, we employed network pharmacology and bioinformatics analysis to explore the impact of IDE inhibition on GIONFH with 6bK as an inhibitory agent. Further evidence was collected through in vitro osteoclastogenesis experiments and in vivo evaluations involving methylprednisolone (MPS)-induced GIONFH mouse model. RESULTS: Enrichment analysis indicated a potential role of 6bK in redox regulation amid GIONFH development. In vitro findings revealed that 6bK could attenuate GCs-stimulated overactivation of osteoclast differentiation by interfering with the transcription and expression of key osteoclastic genes (Traf6, Nfatc1, and Ctsk). The use of an H2DCFDA probe and subsequent WB assays introduced the inhibitory effects of 6bK on osteoclastogenesis, linked with the activation of the nuclear factor erythroid-derived 2-like 2 (Nrf2)-mediated antioxidant system. Furthermore, Micro-CT scans validated that 6bK could alleviate GIONFH in MPS-induced mouse models. CONCLUSIONS: Our findings suggest that 6bK suppresses osteoclast hyperactivity in GCs-rich environment. This is achieved by reducing the accumulation of intracellular ROS via promoting the Nrf2-mediated antioxidant system, thus implying that IDE could be a promising therapeutic target for GIONFH.

Chemotactic recruitment of genetically engineered cell membrane-camouflaged metal-organic framework nanoparticles for ischemic osteonecrosis treatment.

Ischemic osteonecrosis, particularly glucocorticoid-induced osteonecrosis of the femoral head (GIONFH), is primarily due to the dysfunction of osteogenesis and angiogenesis. miRNA, as a therapeutic system with immense potential, plays a vital role in the treatment of various diseases. However, due to the unique microenvironmental structure of bone tissue, especially in the case of GIONFH, where there is a deficiency in the vascular system, it is challenging to effectively target and deliver to the ischemic osteonecrosis area. A drug delivery system assisted by genetically engineered cell membranes holds promise in addressing the challenge of targeted miRNA delivery. Herein, we leverage the potential of miR-21 in modulating osteogenesis and angiogenesis to design an innovative biomimetic nanoplatform system. First, we employed metal-organic frameworks (MOFs) as the core structure to load miR-21-m (miR-21-m@MOF). The nanoparticles were further coated with the membrane of bone marrow mesenchymal stem cells overexpressing CXCR4 (CM-miR-21-m@MOF), enhancing their ability to target ischemic bone areas via the CXCR4-SDF1 axis. These biomimetic nanocomposites possess both bone-targeting and ischemia-guiding capabilities, actively targeting GIONFH lesions to release miR-21-m into target cells, thereby silencing PTEN gene and activating the PI3K-AKT signaling pathway to regulate osteogenesis and angiogenesis. This innovative miRNA delivery system provides a promising therapeutic avenue for GIONFH and potentially other related ischemic bone diseases. STATEMENT OF SIGNIFICANCE.

Post-traumatic avascular necrosis of the talus.

In this comprehensive case report, we examine a 29-year-old male who suffered a high-energy vehicular accident, resulting in a type III Hawkins fracture of the talus. This specific fracture type is critically associated with a greater than 90% risk of progressing to avascular necrosis (AVN) of the talus, a severe and debilitating condition. Alongside this, the patient sustained fractures of the medial and lateral malleolus. Due to extensive swelling and severe circulatory disorders, an immediate emergency surgical procedure was necessitated, employing nail fixation as a stabilizing intervention. Over the course of 12 months following the surgery, despite routine post-operative imaging including X-rays and computed tomography (CT) scans, the patient continued to experience significant pain and impairment. This condition led to further investigations, culminating in a magnetic resonance imaging (MRI) that revealed an area of 19.8∕20.9 mm of AVN on the talus dome's upper-lateral facet. Interestingly, earlier CT scans had indicated multiple osteitic lesions, but these findings lacked a clear clinical correspondence, presenting a diagnostic challenge. To resolve this ambiguity and to definitively distinguish between necrosis and infection, a targeted histopathological analysis was deemed necessary. This analysis was conducted on a bone fragment extracted during a follow-up surgical procedure for nail removal. The results from this analysis present an area of bone and myeloid tissue necrosis unequivocally confirming the presence of AVN, effectively ruling out osteitis as a potential diagnosis. This critical diagnostic clarification allowed for a shift in therapeutic strategy, enabling the initiation of a more focused and potentially curative treatment regimen.

Rare presentation of maxillary osteonecrosis and tooth exfoliation induced by herpes zoster infection in a 29-year-old Chinese male: a case report and literature review.

BACKGROUND: We present a case of a 29-year-old male patient without immunodeficiency who suffered from rapid osteonecrosis and tooth exfoliation resulting from herpes zoster (HZ) infection in the left maxillary branch of the trigeminal nerve. Various complications associated with shingles infections have been reported, cases of osteonecrosis and tooth exfoliation due to HZ infection among young people without immunodeficiency are rare. In this case, we focus on the particular manifestation of HZ infection. CASE PRESENTATION: The patient presented with clusters of erythema and papules, along with non-hemorrhagic blisters on the left face and the loss of the left upper incisor. All lesions were localized to the left side of the face without exceeding the midline. After receiving antibacterial and antiviral treatment, successful control over the infection was achieved; however, he experienced the loss of all upper teeth on the left side except for the first and second upper left molars. CONCLUSION: This case highlights that rapid osteonecrosis and tooth exfoliation may occur among young individuals without immunodeficiency after HZ infection. HZ infection of the face should be taken very seriously to obtain prompt treatment to prevent the rare complications of bone necrosis and tooth loss as much as possible.

Results of transosseous suture fixation in four-part valgus impacted fractures of the proximal humerus.

BACKGROUND: The osteonecrosis ratio in valgus impacted fractures of the proximal humerus is low (<10 %), giving osteosynthesis all its meaning. However, the optimal fixation technique remains controversial. After recentering the humeral head, osteosuture is stable enough to allow bone healing in an adequate position as well as a good long-term shoulder functionality. METHODS: Our cohort included 22 patients with a mean age of 65 (28-83). Patients were placed in a beach-chair position. Surgical exposure was done through an anterolateral, transdeltoid approach. Stay sutures were placed on both tuberosities. Elevation of the humeral head was obtained for 9 patients using iliac crest bone graft, for 7 patients using bone substitutes, for 6 without any graft needed. Both tuberosities were approximated and tied together using two horizontal non-absorbable double-threaded sutures. The whole head was also tied to the humeral metaphysis by cerclage wiring using the same suture. Patients were immobilized in a sling for 4 weeks with no passive or active mobilization; then began rehabilitation starting with passive and active-assisted mobilization. Functional outcome was assessed with the Constant score. Radiographic follow-up was used for fracture healing and osteonecrosis signs. RESULTS: All fractures united within the first 3 months. One patient had radiographic signs of osteonecrosis and one had a secondary displaced fracture without osteonecrosis. At an average follow-up of 35 months, the median Constant score was 83.7 % (63-100) in comparison to the uninjured side. DISCUSSION: A preserved posteromedial periosteal hinge in a valgus impacted fracture of the proximal humerus is key to the success of osteosuture. This hinge provides mechanical stability to the humeral head once elevated, as well as blood-supply from the branches of the posterior circumflex humeral artery. Computed Tomography with Three-Dimensional reconstructed images allow for a precise analysis of this hinge as well as the vascularity of the humeral head. Osteosuture being a minimally invasive surgical procedure plays a predominant role in sparing the remaining vascularization of the humeral head. CONCLUSION: Osteosuture in four-part valgus impacted fractures of the proximal humerus is a minimally invasive procedure as well as a reliable technique yielding good long-term results.

Free medial femoral condyle osteocutaneous flap for repairing stage IIIB osteonecrosis of the lunate: a case report.

BACKGROUND: There are several surgical options for osteonecrosis of the lunate, and confirming the effectiveness of various surgical methods remains challenging. Here, we present a case of stage IIIB osteonecrosis of the lunate repaired with a free medial femoral condyle osteocutaneous flap. CASE PRESENTATION: A 43-year-old male construction worker was admitted to our hospital due to right wrist pain, impaired mobility, and pain aggravated by activity for 10 months. The patient was diagnosed with stage IIIB osteonecrosis of the lunate based on the orthopantomogram and magnetic resonance imaging of the right wrist. Considering the patient's medical history, physical examination, auxiliary examination, and wishes, reconstruction was performed using a free medial femoral condyle osteocutaneous flap. After the flap survived completely, the K-wires were removed one month after the operation, the external brace was removed two months after the operation, and functional wrist rehabilitation was initiated. After six months of follow-up, the wrist swelling and pain resolved, and the reconstructed lunate bone was viable. Additionally, the last follow-up was conducted in the sixth month after surgery; the affected hand grip strength improved from about 70% (28 kg) to 80% (32 kg) compared with the healthy side (40 kg); the visual analog scale score decreased from 6.5 points before the operation to 1 point; and the MAYO score increased from 60 points before the operation to 85 points. CONCLUSIONS: The success of this case reinforces the potential of the free medial femoral condyle osteocutaneous flap as a new treatment option for stage IIIB osteonecrosis of the lunate and further expands the existing treatment options. Using a free medial femoral condyle osteocutaneous flap to reconstruct the lunate and restore the carpal anatomy may.

Fat Phagocytosis Promotes Anti-Inflammatory Responses of Macrophages in a Mouse Model of Osteonecrosis.

Osteonecrosis (ON) of the femoral head (ONFH) is a devastating bone disease affecting over 20 million people worldwide. ONFH is caused by a disruption of the blood supply, leading to necrotic cell death and increased inflammation. Macrophages are the key cells mediating the inflammatory responses in ON. It is unclear what the dynamic phenotypes of macrophages are and what mechanisms may affect macrophage polarization and, therefore, the healing process. In our preliminary study, we found that there is an invasion of macrophages into the repair tissue during ON healing. Interestingly, in both ONFH patients and a mouse ON model, fat was co-labeled within macrophages using immunofluorescence staining, indicating the phagocytosis of fat by macrophages. To study the effects of fat phagocytosis on the macrophage phenotype, we set up an in vitro macrophage and fat co-culture system. We found that fat phagocytosis significantly decreased M1 marker expression, such as IL1ß and iNOS, in macrophages, whereas the expression of the M2 marker Arg1 was significantly increased with fat phagocytosis. To investigate whether the polarization change is indeed mediated by phagocytosis, we treated the cells with Latrunculin A (LA, which inhibits actin polymerization and phagocytosis). LA supplementation significantly reversed the polarization marker gene changes induced by fat phagocytosis. To provide an unbiased transcriptional gene analysis, we submitted the RNA for bulk RNA sequencing. Differential gene expression (DGE) analysis revealed that the top upregulated genes were related to anti-inflammatory responses, while proinflammatory genes were significantly downregulated. Additionally, using pathway enrichment and network analyses (Metascape), we confirmed that gene-enriched categories related to proinflammatory responses were significantly downregulated in macrophages with fat phagocytosis. Finally, we validated the similar macrophage phenotype changes in vivo. To summarize, we discovered that fat phagocytosis occurs in both ONFH patients and an ON mouse model, which inhibits proinflammatory responses with increased anabolic gene expression in macrophages. This fat-phagocytosis-induced macrophage phenotype is consistent with the in vivo changes shown in the ON mouse model. Our study reveals a novel phagocytosis-mediated macrophage polarization mechanism in ON, which fills in our knowledge gaps of macrophage functions and provides new concepts in macrophage immunomodulation as a promising treatment for ON.

Short-Term Outcomes of Arthroscopic Treatment of Freiberg Disease.

BACKGROUND: Surgical treatment for Freiberg disease (also known as avascular necrosis of the metatarsal head) has not been completely defined. This retrospective study evaluated short-term outcomes after arthroscopic treatment of Freiberg disease. METHODS: From 2015 to 2019, 13 patients (15 feet) diagnosed as having Freiberg disease were enrolled for arthroscopic surgery. Feet were divided based on the Smillie classification system (two with stage I, eight with stage II, three with stage III, one with stage IV, and one with stage V). Arthroscopic interventions, including synovectomy, debridement, chondroplasty, microfracture, and loose body removal, were performed without considering the Smillie classification stage. Radiologic outcomes were evaluated by radiography (preoperatively and 3, 6, and 12 months postoperatively) and magnetic resonance imaging (preoperatively and 12 months postoperatively). Clinical outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) lesser metatarsophalangeal (MTP)-interphalangeal score and the visual analog scale (VAS) score. The MTP joint range of motion was measured using a goniometer preoperatively and postoperatively. RESULTS: Radiologic studies showed no evidence of osteonecrosis progression in postoperative 12-month radiographs of any patients. Postoperative 12-month magnetic resonance images showed reduction of bone marrow edema, irregularity of subchondral bone, and cartilage defects in all patients. Significant improvements in AOFAS and VAS scores occurred at all postoperative time points compared with preoperative scores (P = .001). The MTP joint range of motion also showed improvement at last follow-up (P = .001). CONCLUSIONS: Arthroscopic surgery for Freiberg disease showed excellent clinical outcomes, MTP joint range of motion, and short-term outcomes regardless of stage (Smillie classification) in radiologic evaluation.

Medial Femoral Trochlea Osteochondral Flap Reconstruction of the Previously Unsalvageable Kienbock-Associated Lunate With a Coronal Split.

PURPOSE: Patients with Kienbock disease can present with coronal fracture and collapse of the proximal lunate (Unified B2/Bain grade 1, 2B). Traditionally, this was considered unsalvageable. However, medial femoral trochlea (MFT) osteochondral reconstruction, used to recreate the proximal lunate surface, can be paired with reduction and repair of the coronal plane fracture, thus restoring midcarpal congruity. The purpose of this study was to report radiographic and clinical outcomes following lunate coronal fracture fixation at the time of MFT osteochondral reconstruction. METHODS: This was a retrospective study performed at a single institution. We identified patients with Kienbock disease who underwent MFT osteochondral reconstruction from 2014 to 2023. Patients were included if they had a coronal fracture of the lunate distal articular surface fixed at the time of surgery. Radiographic and clinical parameters were evaluated, including carpal height ratio, union rate, presence of heterotopic ossification, need for revision surgery, and patient-reported outcome measures. RESULTS: Thirty-three patients were included, with a mean age of 27.5 years (range: 15-41); 19 (58%) were women. Mean radiographic follow-up time was 5.8 months, and mean clinical follow-up time was 22.6 months. Union was achieved in 30/33 patients (91%). Carpal height ratio improved from 1.32 to 1.4. Two patients (6%) required reoperation, one for removal of heterotopic ossification and another for conversion to proximal row carpectomy. Patients demonstrated meaningful improvement in brief Michigan Hand Questionnaire and Patient-Reported Outcomes Measurement Information Upper Extremity scores. Range of motion before and after surgery was similar. CONCLUSIONS: Lunate coronal fracture fixation with MFT osteochondral reconstruction represents an additional management option in select patients with Kienbock disease. This technique restores the midcarpal joint during lunate reconstruction and may allow patients to avoid salvage procedures. Early radiographic and clinical outcomes are promising. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.