Cytokine Receptor-like Factor 1 (CRLF1) and Its Role in Osteochondral Repair.

BACKGROUND: Since cytokine receptor-like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. METHODS: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow-derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno-associated virus (AAV) or AAV containing CRLF1 was determined by morphological, histological, and micro computer tomography (CT) analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were determined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes using real-time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. RESULTS: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondrogenic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and cardiotrophin-like Cytokine (CLC) stimulated catabolic events via STAT3 activation. CONCLUSION: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.

Ginsenoside Rc alleviates osteoporosis by the TGF-ß/Smad signaling pathway.

Osteoporosis is a common chronic bone disorder in postmenopausal women. Ginsenosides are primary active components in ginseng and the effects of various ginsenoside variants in osteoporosis treatment have been widely revealed. We planned to explore the impact of ginsenoside Rc on bone resorption in an osteoporosis rat model. We used ovariectomized rats to assess the potential impact of ginsenoside Rc on osteoporosis. µ-CT was implemented for analyzing the microstructure of the distal left femur in rats. H&E staining together with Masson staining were applied for bone histomorphometry evaluation. ELISA kits were implemented to detect serum concentrations of TRACP-5b, OCN, CTX, as well as PINP. Ginsenoside Rc treatment lessened the serum levels of TRACP-5b as well as CTX, while increasing serum levels of OCN, and PINP of OVX rats. Moreover, we found that ginsenoside Rc contributed to the synthesis of type I collagen via increasing Col1a1 and Col1a2 levels in femur tissues of ovariectomized rats. Our findings also revealed that ginsenoside Rc activated the TGF-ß/Smad pathway by increasing TGF-ß as well as phosphorylated Smad2/3 protein levels. Ginsenoside Rc alleviates osteoporosis in rats through promoting the TGF-ß/Smad pathway.

Effect of experimental pulmonary arterial hypertension on renal and bone parameters of rats submitted to resistance exercise training.

Pulmonary arterial hypertension (PAH) is characterized by right ventricular failure and diminished cardiac output, potentially leading to renal and bone impairments. In contrast, resistance exercise training (RT) offers cardiovascular and bone health benefits. This study aimed to assess the impacts of stable PAH induced by monocrotaline (MCT) and RT on renal morphometry, as well as bone morphometry and biomechanical properties in male Wistar rats. Four experimental groups, untrained control (UC, n=7), trained control (TC, n=7), untrained hypertensive (UH, n=7), trained hypertensive (TH, n=7), were defined. After the first MCT or saline injection (20 mg/kg), trained rats were submitted to a RT program (i.e., Ladder climbing), 5 times/week. Seven days later the rats received the second MCT or saline dose. After euthanasia, renal and femoral histomorphometry and femoral biomechanical properties were assessed. PAH reduced renal glomerular area and volume, which was prevented by the RT. While PAH did not harm the femoral morphometry, structural and mechanical properties, RT improved the femoral parameters (e.g., length, percentage of trabeculae and bone marrow, ultimte and yield loads). Experimental stable PAH promotes renal but not bone damages, whereas RT prevents renal deteriorations and improves the femoral morphological and biomechanical properties.

Bulky malignant peripheral nerve sheath tumour of the left thigh in a pregnant woman presenting with a pathological fracture of the proximal femur.

Malignant peripheral nerve sheath tumour (MPNST) is an aggressive soft tissue sarcoma with a poor prognosis, affecting most commonly the extremities. The lungs constitute the most frequent location for distant metastases. Half of all MPNSTs arise in patients with neurofibromatosis type 1, while approximately 10% are radiation induced and the rest are sporadic.The authors present a pregnant woman in her 40s with a sporadic MPNST of the lower limb and with lung metastases at diagnosis. Treatment consisted of interilioabdominal amputation, followed by adjuvant chemotherapy. Partial response and disease stabilisation were achieved with chemotherapy.Surgical resection with negative margins is the only potentially curative therapy, while radiation therapy and chemotherapy might be useful in the neoadjuvant or adjuvant setting, but their advantage in survival is not demonstrated. In the reported case, chemotherapy permitted the achievement of partial response and stabilisation of the disease.

Idiopathic Avascular Necrosis of the Capitate Treated with a Medial Femoral Trochlea Vascularized Osteochondral Flap: A Case Report.

CASE: Capitate avascular necrosis should be entertained in a differential diagnosis of young, active adults with midcarpal wrist pain. We present a case study of a 30-year-old laborer who developed avascular necrosis (AVN) of his right proximal capitate. Grip strength and wrist motion were limited on examination, with advanced imaging confirming AVN. A diagnostic arthroscopy confirmed the pathology. Treatment was completed with a medial femoral trochlea vascularized flap for cartilaginous resurfacing. At 10-month follow-up, the patient's capitate was healed with stable fixation, and he is working full-time as a laborer without restrictions. CONCLUSION: AVN of the capitate is a unique and challenging articular pathology that requires a thoughtful preoperative evaluation and meticulous surgical technique to reconstruct. The medial femoral trochlea (MFT) vascularized bone transfer with cartilaginous resurfacing is 1 available treatment option. This flap is harvested from the medial femur using microsurgical techniques, based on the descending genicular artery. Using a 2-surgeon approach, simultaneous dissection of the AVN is completed at the wrist. This flap is a vascularized option that can be used for both AVN and nonunion with structural deformity before salvage surgeries.

Ischiofemoral impingement syndrome: A five-case series report.

Gluteal pain is a frequent cause of medical attention in the daily clinical practice. It can be caused by multiple pathologies, being ischiofemoral impingement syndrome among those included in its differential diagnosis. Encompassed within the deep gluteal syndromes, this entity occurs as a consequence of the entrapment of the neuromuscular structures between the lesser femoral trochanter and the ischial tuberosity, causing pain in the root of the lower limb, with irradiation towards the thigh or the gluteal region and poor tolerance to deambulation and sedestation. The magnetic resonance imaging of the hip is fundamental for its diagnosis, and its management consists on medical treatment at onset. Despite not being a frequent diagnosis in the clinical practice in Rheumatology, keeping it in mind helps improving its prognosis by establishing an early and adequate treatment.

No Difference in Bone Tunnel Enlargement and Clinical Outcome between Cortical Suspension and Hybrid Femoral Fixation in Hamstring Anterior Cruciate Ligament Reconstruction.

OBJECTIVE: The best method for femoral fixation in anterior cruciate ligament reconstruction (ACLR) remains controversial. The study assesses the bone tunnel enlargement and clinical outcome in hamstring ACLR using cortical suspension or hybrid (cortical suspension and compression) femoral fixation. METHODS: From January 2010 to December 2021, 102 patients who underwent quadruple hamstring ACLR using cortical suspension (39 patients) or hybrid (63 patients) fixation on the femoral side were retrospectively analyzed. Clinical evaluation was conducted using the international knee documentation committee score, the Lysholm score, the Tegner activity level scale, the knee injury and osteoarthritis outcome score (quality of life score), the Lachman test, and the side-to-side difference by the KT-1000 arthrometer. The complications after the surgery were also evaluated. These data were compared at baseline and last follow-up. The diameters of the femoral tunnel were calculated at three sites: the width of the entrance of the femoral tunnel, 1 cm proximal to the entrance of the femoral tunnel and the largest diameter of the femoral tunnel on magnetic resonance imaging (MRI) coronal images. Bone tunnel widening data were contrasted between MRI images conducted at least 2 years and within 2 weeks after surgery. The morphology of bone tunnel enlargement was also observed and recorded. The categorical parameters were analyzed using the χ2-test and Fisher's exact test. The continuous variables conforming to a normal distribution were analyzed using Student's t-test, and the Mann-Whitney U-test was undertaken between the two groups without normal distribution. RESULTS: Both cortical suspension and hybrid femoral fixation in quadruple hamstring ACLR achieved significantly improved patient-reported outcome scores and knee stability compared to preoperative data. However, no significant differences were found between these two methods in clinical evaluations, postoperative complications, and patient-reported outcome scores. Although the mean diameter of the enlarged bone tunnel was lowered by an additional bioabsorbable interference screw fixation near the joint line, a statistically insignificant difference was found between the hybrid and cortical suspension fixation on the femoral side. There was no statistical difference in the distribution of enlarged bone tunnel morphology between groups. CONCLUSIONS: No significant difference was found in the bone tunnel enlargement and clinical outcome between cortical suspension and hybrid femoral fixation in ACLR using hamstring autograft.

Modular intercalary prosthetic reconstruction for malignant and metastatic tumours of the proximal femur.

To illustrate the surgical technique and explore clinical outcomes of the reconstruction for the malignant and metastatic bone tumour of proximal femur with metallic modular intercalary prosthesis. Sixteen patients who underwent modular intercalary prosthetic reconstruction after tumour resection were included from April 2012 and October 2020. Prosthesis and screws parameters, resected bone length and residual bone length, clinical outcomes and survivorship were analyzed. All patients were followed up for an average of 19 months (range 1-74). In our series, 12 patients died of the progression of the primary disease at the final follow-up. The cumulative survivorship since the treatment of proximal femoral metastasis was 78.6% (11 patients) at 6 months and 38.5% (5 patients) at 1 year. The mean MSTS score was 22.25 ± 4.55 among all patients. There were no cases of loosening or breakage of the prostheses, plates or screws, despite the various measurements of prostheses and residual bones. Modular intercalary prosthetic reconstruction was an effective method for malignant tumour of the proximal femur, including the advantages of providing early pain relief, quickly restoring postoperative function, required a short operation time, and preserving the adjacent joints.

Cyclosporine a inhibits bone regeneration and induces bone loss in a rat model.

Cyclosporine A (CSA) is an immunosuppressant that has been extensively studied for its side effects on inhibiting osseointegration of titanium implants. However, the impact of CSA on bone healing in postmenopausal osteoporosis remains unknown. Therefore, this study aimed to investigate the effect of CSA on bone repair in an ovariectomized (OVX) rat model through both in vitro and in vivo experiments. We examined the interventions of CSA on osteoblast progenitor cells MC3T3-E1 and assessed their effects on biological function using RT-qPCR, CCK-8 assay, alizarin red staining, and alkaline phosphatase staining. Furthermore, we evaluated the effects of CSA on bone regeneration and bone mass in both OVX rat models and femoral diaphysis bone defect models. The results from the CCK-8 experiment indicated a positive influence of experimental doses of CSA on osteogenic differentiation of MC3T3-E1 cells. ALP expression levels and calcified nodules were also evaluated, suggesting that CSA intervention promoted osteogenic differentiation in MC3T3-E1 cells. Additionally, specific gene expressions including OPN, Runx-2, OC, and Col1a1 were up-regulated after CSA intervention. Biomechanical parameters aligned with histological analysis as well as micro-CT scans confirmed worse bone microstructure and strength following CSA intervention. Our findings preliminarily suggest that whether it is normal or osteoporotic bones, CSA has adverse effects on bone health which are associated with elevated-bone turnover.

The influence of femoral lytic tumors segmentation on autonomous finite element analysis.

BACKGROUND: The validated CT-based autonomous finite element system Simfini (Yosibash et al., 2020) is used in clinical practice to assist orthopedic oncologists in determining the risk of pathological femoral fractures due to metastatic tumors. The finite element models are created automatically from CT-scans, assigning to lytic tumors a relatively low stiffness as if these were a low-density bone tissue because the tumors could not be automatically identified. METHODS: The newly developed automatic deep learning algorithm which segments lytic tumors in femurs, presented in (Rachmil et al., 2023), was integrated into Simfini. Finite element models of twenty femurs from ten CT-scans of patients with femoral lytic tumors were analyzed three times using: the original methodology without tumor segmentation, manual segmentation of the lytic tumors, and the new automatic segmentation deep learning algorithm to identify lytic tumors. The influence of explicitly incorporating tumors in the autonomous finite element analysis on computed principal strains is quantified. These serve as an indicator of femoral fracture and are therefore of clinical significance. FINDINGS: Autonomous finite element models with segmented lytic tumors had generally larger strains in regions affected by the tumor. The deep learning and manual segmentation of tumors resulted in similar average principal strains in 19 regions out of the 23 regions within 15 femurs with lytic tumors. A high dice similarity score of the automatic deep learning tumor segmentation did not necessarily correspond to minor differences compared to manual segmentation. INTERPRETATION: Automatic tumor segmentation by deep learning allows their incorporation into an autonomous finite element system, resulting generally in elevated averaged principal strains that may better predict pathological femoral fractures.

Clinical outcomes of total femoral replacement. First Latin American experience.

INTRODUCTION: The femur is frequently affected by primary and metastatic bone tumors. In cases with substantial bone loss, Total Femur Replacement (TFR) remains the only viable limb preservation option. This study investigates the clinical outcomes of TFR patients in a Latin American setting, with a minimum 3-year follow-up. METHODS: Retrospective review identifying cases of TFR at a single center from 2009 to 2020. Patients who had TFR either due to oncological indications or complications arising from oncology-related surgeries were included. Data on the indications for surgery and post-operative complications were recorded. To assess functional status, the Musculoskeletal Tumor Society (MSTS) score and the Toronto Extremity Salvage Score (TESS) were used. RESULTS: Fourteen patients met the inclusion criteria. Diagnoses included eight osteosarcomas, four chondrosarcomas, one Ewing sarcoma, and one giant cell tumor. Ten patients had undergone prior surgeries. Indication for TFR was a complication of a previous surgery in 78.6 % of cases. Post-TFR complications were experienced by 35.7 % of patients, requiring further surgeries. At the 3-year mark, average MSTS and TESS scores were 67.4 % and 70.8 %, respectively. CONCLUSION: Total femur replacement serves as a valuable limb salvage solution for patients with significant femoral defects in oncological scenarios, however, there is a significant risk of complications. Given its potential benefits, it is essential for developing countries to consider incorporating TFR into their healthcare systems.

High Frequencies of Genetic Variants in Patients with Atypical Femoral Fractures.

This study explores the genetic factors associated with atypical femoral fractures (AFF), rare fractures associated with prolonged anti-resorptive therapy. AFF are fragility fractures that typically appear in the subtrochanteric or diaphyseal regions of the femur. While some cases resemble fractures in rare genetic bone disorders, the exact cause remains unclear. This study investigates 457 genes related to skeletal homeostasis in 13 AFF patients by exome sequencing, comparing the results with osteoporotic patients (n = 27) and Iberian samples from the 1000 Genomes Project (n = 107). Only one AFF case carried a pathogenic variant in the gene set, specifically in the ALPL gene. The study then examined variant accumulation in the gene set, revealing significantly more variants in AFF patients than in osteoporotic patients without AFF (p = 3.7 × 10-5), particularly in ACAN, AKAP13, ARHGEF3, P4HB, PITX2, and SUCO genes, all of them related to osteogenesis. This suggests that variant accumulation in bone-related genes may contribute to AFF risk. The polygenic nature of AFF implies that a complex interplay of genetic factors determines the susceptibility to AFF, with ACAN, SUCO, AKAP13, ARHGEF3, PITX2, and P4HB as potential genetic risk factors. Larger studies are needed to confirm the utility of gene set analysis in identifying patients at high risk of AFF during anti-resorptive therapy.

Structural and Mechanical Properties of Human Superficial Femoral and Popliteal Arteries.

The femoropopliteal artery (FPA) is the main artery in the lower limb. It supplies blood to the leg muscles and undergoes complex deformations during limb flexion. Atherosclerotic disease of the FPA (peripheral arterial disease, PAD) is a major public health burden, and despite advances in surgical and interventional therapies, the clinical outcomes of PAD repairs continue to be suboptimal, particularly in challenging calcified lesions and biomechanically active locations. A better understanding of human FPA mechanical and structural characteristics in relation to age, risk factors, and the severity of vascular disease can help develop more effective and longer-lasting treatments through computational modeling and device optimization. This review aims to summarize recent research on the main biomechanical and structural properties of human superficial femoral and popliteal arteries that comprise the FPA and describe their anatomy, composition, and mechanical behavior under different conditions.

Similar complications, implant survival, and function following modular prosthesis and allograft-prosthesis composite reconstructions of the proximal femur for primary bone tumors: a systematic review and meta-analysis.

PURPOSE: There is a lack of consensus regarding the best type of reconstruction of the proximal femur following bone tumor resection. The objective of this study was to analyze the complication risks, implant survival, and functional outcomes following modular prosthesis (MP) and allograft-prosthesis composite (APC) reconstruction of the proximal femur after primary bone tumor resections. METHODS: We performed a search in the PubMed and Scopus libraries, obtaining 1 843 studies. We included studies reporting functional outcomes, complications, and implant survival of proximal femur reconstruction with MP or APC following primary bone tumor resection with a 2-year minimum follow-up. We excluded studies analyzing metastatic patients or studies with pooled data in which it was impossible to separate the data of patients with primary bone tumors from those with bone metastases. RESULTS: We analyzed 18 studies (483 patients) reporting on 234 (48%) patients with MP reconstruction and 249 (52%) patients with APC reconstruction. The risk of complications was similar in patients with MP reconstruction (29%; 95% CI [0.11; 0.47]) and APC reconstruction (36%; 95% CI [0.24; 0.47]) (p = 0.48). Implant survival following MP reconstruction ranged from 81 to 86% at 5 years, 75 to 86% at 10 years, and 82% at 15 years. Implant survival following APC reconstruction ranged from 86 to 100% at 5 years and 86% at 10 years, and 86% at 15 years. Functional outcomes following MP reconstruction and APC reconstruction ranged from 24.0 to 28.3 and from 21.9 to 27.8, respectively. CONCLUSION: Patients with primary bone tumor of the proximal femur who underwent MP or APC reconstruction seem to have similar complication risks, implant survival, and functional outcomes.

A novel porous titanium with engineered surface for bone defect repair in load-bearing position.

Porous titanium exhibits low elastic modulus and porous structure is thought to be a promising implant in bone defect repair. However, the bioinert and low mechanical strength of porous titanium have limited its clinical application, especially in load-bearing bone defect repair. Our previous study has reported an infiltration casting and acid corrosion (IC-AC) method to fabricate a novel porous titanium (pTi) with 40% porosity and 0.4 mm pore diameter, which exerts mechanical property matching with cortical bone and interconnected channels. In this study, we introduced a nanoporous coating and incorporated an osteogenic element strontium (Sr) on the surface of porous titanium (named as Sr-micro arch oxidation [MAO]) to improve the osteogenic ability of the pTi by MAO. Better biocompatibility of Sr-MAO was verified by cell adhesion experiment and cell counting kit-8 (CCK-8) test. The in vitro osteogenic-related tests such as immunofluorescence staining, alkaline phosphatase staining and real-time polymerase chain reaction (RT-PCR) demonstrated better osteogenic ability of Sr-MAO. Femoral bone defect repair model was employed to evaluate the osseointegration of samples in vivo. Results of micro-CT scanning, sequential fluorochrome labeling and Van Gieson staining suggested that Sr-MAO showed better in vivo osteogenic ability than other groups. Taking results of both in vitro and in vivo experiment together, this study indicated the Sr-MAO porous titanium could be a promising implant load-bearing bone defect.

Infantile Myofibromatosis of the Femoral Neck: A Case Report.

CASE: A 15-month-old boy who was being followed for developmental dysplasia of the hip because of breech presentation was discovered to have a solitary infantile myofibroma in the left femoral neck. The patient was avoiding weight-bearing on the affected extremity; thus, stabilization of the femoral neck was performed using a proximal femur locking plate. Postoperatively, he achieved all gross motor developmental milestones. CONCLUSION: This report is the first to describe a solitary infantile myofibroma in the femoral neck and demonstrates the utility of operative stabilization of these lesions.

Is seborrheic dermatitis associated with early-stage osteoarthritis?

Seborrheic dermatitis (SD) and osteoarthritis involve similar factors in their pathogenesis. Both of these diseases are associated with an increased frequency of metabolic syndrome and underlying systemic inflammation. This study evaluated the thickness of the distal femoral cartilage using ultrasonography in patients with SD. The study enrolled 60 patients with SD (19 females and 41 males, mean age: 34.07 ±â€…12.56 years) and 60 controls matched for age and sex (20 females and 40 males, mean age: 35.08 ±â€…12.78 years). Ultrasonography was used to measure the distal femoral cartilage thickness (FCT) of the right medial condyle, right lateral condyle, right intercondylar area, left medial condyle, left lateral condyle, and left intercondylar area. FCT values at all points were significantly higher in patients with SD than in the controls (P < .05). Further, all FCT values were significantly higher in patients with moderate SD than in those with mild SD (P < .001). A strong positive correlation was observed between disease severity and FCT measured at right medial condyle (r = .7, P < .001), right lateral condyle (r = .749, P < .001), right intercondylar area (r = .79, P < .001), left medial condyle (r = .624, P < .001), and left intercondylar area (r = .703, P < .001). Further, a moderately positive correlation was observed between disease severity and FCT measured at left lateral condyle (r = .581, P < .001). Increased FCT in patients with SD might be an early indicator of osteoarthritis. However, further studies, especially those evaluating older patients with SD, are required to support our findings.

Lateral distal femoral condyle has more uniform cartilage wear in varus knee osteoarthritis.

Bone resection is highly valued in total knee arthroplasty (TKA), but how to determine the amount of distal femur resection is still controversial. The purpose of this study was to explore how to use lateral condyle as a reference for distal femoral osteotomy in TKA. Magnetic resonance imaging (MRI) and Radiographic images from 118 nonarthritic subjects and 123 osteoarthritis (OA) subjects were used to assess the cartilage wear pattern of the distal femur in varus knees. Measurements were performed on three-dimensional reconstruction after virtual bone cutting. The difference between the resection amount of distal (0°) and posterior (90°) was calculated when the medial condyle was used as a reference in OA patients. The osteotomy amount on lateral was calculated in nonarthritic subjects when the medial condylar osteotomy was consistent with the thickness of the implants. In 43% of OA patients, there was > 1 mm difference between the 0° and 90° in medial condyle cartilage, and no difference was observed in lateral. When using medial condyle as a reference for osteotomy, there was a difference of 1.3 ± 0.56 mm between the resection amount of 0° and 90°, and the difference was 0.24 ± 0.27 mm when using lateral condyle. Statistical analysis showed that there was a linear correlation between the resection amount of lateral condyle and mechanical lateral distal femoral angle (mLDFA) in nonarthritic subjects (r = 0.845, p < 0.001). Lateral distal femoral condyle has more uniform cartilage wear in varus knee osteoarthritis. Using the lateral condyle as the reference for distal femoral osteotomy is more suitable for the cartilage wear pattern of the varus knee. The position of cutting guide can be adjusted by preoperative measurements of mLDFA.

Cervical Lymph Node Metastasis as the Initial Presentation of Femoral Epithelioid Hemangioendothelioma Revealed by 18 F-FDG PET/CT.

ABSTRACT: Femoral epithelioid hemangioendothelioma with cervical lymph node metastasis is rare. We report the FDG PET/CT findings of cervical lymph node metastasis from left femoral epithelioid hemangioendothelioma in a 50-year-old woman with painless enlargement of the left cervical lymph nodes as the initial presentation. Ultrasound and MRI revealed multiple enlarged lymph nodes in the left cervical sheath area. PET/CT showed strong radioactive uptake in the left cervical lymph nodes, and there was additional lesion with increased FDG uptake in the left femur, which was later confirmed as cervical lymph nodes metastasis from left femoral epithelioid hemangioendothelioma by pathological examination.

Obesity impairs revascularization and bone healing in a mouse model of osteonecrosis.

Osteonecrosis of the femoral head (ONFH) is a devastating bone disease that is caused by a disruption of blood supply leading to necrotic cell death. Clinically, it was found that obesity has a high prevalence with ONFH. However, it remains unclear how obesity may directly affect tissue regeneration and bone healing in osteonecrosis (ON). The purpose of this study is to investigate the effects of obesity and weight loss (WL) on ON healing. In this study, we induced obesity and WL in an established surgery-induced ON mouse model via feeding a high-fat diet (HFD) and altering the diet respectively. All mice received a surgical induction of ON of distal femoral epiphysis at the age of 12 weeks. HFD was switched to normal diet (ND) after ON surgery to induce WL. Mouse body weight was recorded weekly. Mouse body composition was scanned by DEXA (Dual-energy X-ray absorptiometry) right after sacrifice at the age of 16 weeks. The distal femoral bone samples were fixed and embedded for histology such as H&E, immunohistochemistry, and TRAP staining. In this study, we found that HFD-induced obesity impaired revascularization and bone remodeling showing decreased vessel areas and reduced osteoblast and osteoclast numbers. WL could rescue obesity-induced bone healing defects. Our study is the first to test the direct effects of obesity and WL on ON bone healing. We believe our work may provide new concepts for osteonecrosis treatment in obese patients.