Nontraumatic Osteonecrosis Research Articles

Exosomal miR-214-3p reprograms BMSC fate: A novel intercellular mechanism linking vascular insufficiency to impaired bone regeneration in nontraumatic ONFH.

Avascular necrosis (AVN), or osteonecrosis, is a debilitating condition caused by reduced blood flow leading to bone tissue death. While commonly linked to trauma, corticosteroid use, and alcohol abuse, emerging evidence suggests that microvascular thrombosis and hypercoagulability may significantly contribute to its development. Prothrombotic condi-tions can obstruct bone microcirculation, resulting in tissue necrosis without infection or malignancy. This study explores the role of coagulation abnormalities as potential risk factors for AVN through a cross-sectional, observational, and analytical approach. A total of 28 patients with non-traumatic osteonecrosis were recruited from a tertiary care center. Each underwent comprehensive coagulation testing to assess thrombotic risk. The study also analyzed demographic and behavioral factors such as age, sex, alcohol intake, and smoking. Preliminary results revealed a high incidence of procoagulant abnormalities, supporting the theory that impaired hemostasis may underlie ischemic bone damage. These findings highlight the importance of including coagulation profiles in the diagnos-tic and prognostic assessment of AVN, promoting a more integrative approach to manag-ing patients at risk for this condition.

Background: Bushen Zhuanggu Formula (BZF), derived from the classic Yougui Pills, has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head (NONFH), particularly by promoting bone repair. However, its underlying mechanisms remain unclear. Objective: This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH. Materials and methods: A total of 518 potential BZF targets were identified from the ETCM v2.0 database. Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls. A drug target-disease gene interaction network was constructed to identify candidate BZF targets involved in NONFH pathogenesis. In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH. Results: Network analysis identified key pathways associated with blood circulation obstruction, immune-inflammatory imbalance, and abnormal bone metabolism. Protein kinase C alpha (PKCA), Ras proto-oncogene (RAS), mitogen-activated protein kinase 3 (ERK), ETS proto-oncogene 1 (ETS1), and receptor activator of nuclear factor-κB ligand (RANKL) formed a signaling axis implicated in NONFH pathogenesis. BZF treatment alleviated joint inflammation, preserved trabecular bone morphology, reduced bone loss, and promoted bone repair. Mechanistically, BZF significantly downregulated the expression of PKCA, RAS, ERK, ETS1, and RANKL, improved blood circulation, and inhibited osteoclast activation while promoting osteoblast activation. Conclusion: BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis, thereby reversing dysregulated bone metabolism.

ABSTRACTJianpi‐Huogu Prescription (JHP), integrating the classic Chinese herbal formulas Linggui‐Zhugan Decoction and Si‐Wu Decoction, has shown clinical efficacy in treating early nontraumatic osteonecrosis of the femoral head (NONFH). In this study, 299 chemical constituents of JHP were identified using ultra‐performance liquid chromatography–quadrupole‐time of flight mass spectrometry. Pharmacological evaluations in rats with early NONFH demonstrated that JHP attenuated femoral head pathological changes, improved gait parameters, increased mechanical pain thresholds, reduced serum levels of triglycerides, total cholesterol, low‐density lipoprotein, very‐low‐density lipoprotein, and the TXB₂/6‐keto‐PGF₁α ratio while elevating high‐density lipoprotein, decreased serum inflammatory cytokines (IL‐1β, IL‐6, TNF‐α) and the RANKL/OPG ratio, and restored bone trabecular morphology and reduced the number of bone marrow adipocytes. Mechanistically, through transcriptomic profiling, network calculations and experimental validation, JHP downregulated NMNAT1, NMNAT3, and NAMPT in the femoral head, thereby reducing NAD+ synthesis, increased ATP production (evidenced by a decreased ADP/ATP ratio) and upregulated STK11 expression, activated p‐HMGCR while suppressing ACAT1 thus inhibiting cholesterol synthesis and lipid accumulation, and surface plasmon resonance confirmed direct binding of its active components (ligustilide, 5,6,4′‐trihydroxy‐7,3′‐dimethoxyflavone, (Z)‐3‐butylidenephthalide, senkyunolide H, ferulic acid, guanosine) to NMNAT1. In conclusion, JHP ameliorates early NONFH by regulating lipid metabolism, improving hypercoagulability, and restoring bone homeostasis through the NMNAT1/NMNAT3/NAMPT/STK11/HMGCR/ACAT1 axis.

Humeral head avascular necrosis (AVN) can cause significant shoulder morbidity and represents the second most common site of nontraumatic osteonecrosis after the femoral head. The pathophysiology centers on disrupted blood supply, ultimately leading to bone death and structural compromise. It is associated with various etiologies, including trauma, iatrogenic factors, hematologic conditions, lifestyle factors, certain environmental exposures, and systemic diseases. Diagnosis relies on a combination of clinical assessment and radiographic evaluation, with magnetic resonance imaging serving as the most sensitive modality for early detection. The Cruess classification system guides treatment decisions. Although conservative measures are used in early stages, they carry a risk of progression, as they do not alter the disease course-unlike surgical techniques such as core decompression. Arthroplasty is reserved for later stages with evidence of collapse, with research suggesting that the use of pyrocarbon in hemiarthroplasty may help reduce glenoid erosion. This review provides a comprehensive overview of humeral head osteonecrosis, emphasizing its etiology, clinical evaluation, imaging findings, and treatment strategies. It highlights the growing support for early operative intervention over conservative management, emerging treatment modalities such as biologic augmentation and allografting, and promising new materials like pyrocarbon in hemiarthroplasty to mitigate glenoid erosion.

In this case report, a 45-year-old woman with no major risk factors for non-traumatic caput femoris osteonecrosis (ACFN) presented with severe bilateral hip pain and limited mobility. Previously healthy without excessive alcohol consumption, her only relevant history included intermittent corticosteroid injections for allergies during adolescence. Diagnostic imaging revealed joint deterioration and ACFN. She ultimately required bilateral total hip arthroplasty with positive results. This case underscores the importance of early diagnosis and treatment of ACFN.

JOURNAL/mgres/04.03/01612956-202603000-00001/figure1/v/2025-06-28T140100Z/r/image-tiff Avascular necrosis of the femoral head is a condition resulting from disrupted blood supply, leading to ischemia and bone tissue necrosis. Core decompression (CD) restores the blood supply through pressure relief, whereas hyperbaric oxygen (HBO) enhances tissue oxygenation and promotes bone repair. Their combined use may complement each other in improving blood supply, promoting bone healing, and inhibiting disease progression, thus achieving a better therapeutic effect. To assess and compare the efficacy of HBO and/or CD for treating mild to moderate femoral head avascular necrosis, a retrospective study was conducted on patients diagnosed with Ficat stage II non-traumatic osteonecrosis between January 2017 and January 2022 at the Affiliated Central Hospital of Shenyang Medical University, China. A total of 72 patients were divided into HBO, CD, and combination groups, with 24 patients in each group. After 1 year of follow-up, 90% of patients in the HBO group, 85% in the CD group, and 95% in the combination group showed satisfactory improvements in hip joint function. The SF-36 quality of life questionnaire scale scores also significantly improved in all three groups, with the combination group showing the most significant improvement. These findings suggest that HBO offers promising potential for treating non-traumatic femoral head necrosis, with efficacy similar to that of CD. The combination group showed the most significant improvement in both hip joint function and quality of life.

Changes in Hip Arthroplasty Practice Decreased Dislocation Risk After Primary Arthroplasties Performed for Nontraumatic Osteonecrosis of the Femoral Head.

How Are Diabetes, Statins, and Immunosuppressive Medications Linked to Non-Traumatic Osteonecrosis of the Femoral Head in Kidney Transplant Recipients?

Historically, osteonecrosis of the femoral head (ONFH) was a major problem following kidney transplantation, occurring in up to 5%-11% of recipients. The development of new immunosuppressive agents permitted steroid minimization protocols, and consequently, the incidence of ONFH has decreased. We studied ONFH trends over four decades and evaluated risk factors in two immunosuppressive eras, pre- and post-2001. Steroid minimization protocols at our center started in 2000. We reviewed records of 1st kidney transplants from January 1985 to May 2024 and compared ONFH incidence and risk factors between the two eras: Era 1 (January 1985-December 31, 2000) and Era 2 (January 2001-May 2024). Cox regression was used to assess for independent factors associated with a higher or lower incidence of ONFH. ONFH incidence in Era 1 was 7.2%; Era 2, 1.1% (p<0.001). In Era 1, increased risk was associated with heavier weight (HR: 1.017, 95% CI: 1.010-1.023, p<0.001) and mTOR inhibitors (HR: 4.258, 95% CI: 1.726-10.506, p=0.002); and decreased risk with diabetes (HR: 0.362, 95% CI: 0.270-0.486, p<0.001), and statins (HR: 0.452, 95% CI: 0.327-0.625, p<0.001). In Era 2, increased risk was associated with steroid use (HR: 2.096, 95% CI: 1.071-4.100, p=0.031) and decreased risk with mycophenolate (HR: 0.471, 95% CI: 0.237-0.935, p=0.032). The incidence of ONFH in KTRs has dramatically decreased in the modern immunosuppressive era. Diabetes, statin use, and immunosuppressive medications, specifically mTOR inhibitors and mycophenolate, appear to have varying impacts depending on the immunosuppressive era.

ObjectiveTo investigate the role of serum β C-terminal telopeptide of type 1 collagen (β-CTx) and N-terminal mid-fragment of osteocalcin (N-MID) concentration in non-traumatic osteonecrosis of the femoral head (NONFH).Materials and methodsIn this retrospective case-control study, serum β-CTx and N-MID levels were measured in 64 NONFH patients and 64 healthy controls. Propensity score matching (PSM) was used to balance the baseline characteristics of the two groups. The study was conducted at Linyi People’s Hospital between January 2023 and February 2024. The primary outcomes included the differences in serum β-CTx and N-MID levels between the two groups, their correlations with clinical parameters, and their diagnostic performance for NONFH.ResultsThe serum concentration of β-CTx and N-MID was significantly higher in NONFH patients compared to healthy controls (β-CTx: 0.70 ± 0.30 ng/ml vs. 0.36 ± 0.16 ng/ml, P < 0.001; N-MID: 21.35 ± 8.24 ng/ml vs. 13.27 ± 3.87 ng/ml, P < 0.001). No significant differences were observed in serum β-CTx and N-MID levels among different etiological subgroups or ARCO stages. Pearson analysis revealed a positive correlation between serum β-CTx and N-MID levels, as well as β-CTx and pain duration. The ROC curve analysis showed that β-CTx had an AUC of 0.876 (95% CI 0.815–0.938) with a cut-off value of 0.505 ng/ml, sensitivity of 90.63%, and specificity of 76.56%. N-MID had an AUC of 0.860 (95% CI 0.797–0.924) with a cut-off value of 17.050 ng/ml, sensitivity of 84.38%, and specificity of 78.13%.ConclusionSerum β-CTx and N-MID levels are significantly elevated in patients with NONFH and may serve as potential biomarkers for the diagnosis of NONFH. Further studies with larger sample sizes are needed to validate these findings and explore their clinical applications.

BackgroundFerroptosis is implicated in various musculoskeletal conditions, including non-traumatic osteonecrosis of the femoral head (NT-ONFH).ObjectiveThe objective of this study was to explore the levels of two crucial proteins associated with ferroptosis, namely Glutathione peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11 (SLC7A11), in both serum and femoral head samples, and to correlate their expression levels with the clinical severity of NT-ONFH.MethodsThe study included 136 NT-ONFH patients and an equal number of healthy controls. In addition, 68 subjects suffering from femoral neck fractures (FNF) were included in the study. The serum concentrations of GPX4 and SLC7A11 were quantified using the enzyme-linked immunosorbent assay. The GPX4 and SLC7A11 levels among tissue samples were identified through immunohistochemical staining, western blot analysis, and quantitative real-time polymerase chain reaction (qRT-PCR). The radiographic severity of the condition was evaluated utilizing the Association Research Circulation Osseous (ARCO) classification system, while the symptomatic severity was assessed utilizing the Visual Analogue Scale (VAS) alongside the Harris Hip Score (HHS).ResultsPatients diagnosed with NT-ONFH had considerably reduced serum concentrations of GPX4 and SLC7A11 in comparison to individuals in the healthy control group. Negative correlations of serum GPX4 and SLC7A11 levels with the ARCO stages were observed. A total of 73 ONFH and 68 FNF patients underwent total hip replacement. The mRNA and protein levels of GPX4 and SLC7A11 were lower in the necrotic areas compared to the non-necrotic areas and FNF femoral head tissues. Subsequent Receiver operating characteristic (ROC) curve analysis suggested that the decreased levels of both serum and local GPX4 and SLC7A11 could serve as potential biomarkers for the progression of ONFH. Furthermore, serum and local GPX4 and SLC7A11 levels were found to be negatively linked to the VAS score but positively related to the HHS score.ConclusionThe levels of GPX4 and SLC7A11, both in serum and at the local site, were inversely correlated with the progression of NT-ONFH. Targeting ferroptosis and its associated proteins through potential therapeutic interventions could be a viable strategy to mitigate the severity of NT-ONFH.

A nationwide multicenter follow-up cohort study of hip-replacement arthroplasties performed for nontraumatic osteonecrosis of the femoral head (ONFH) was conducted to clarify factors associated with need for reoperation. We analyzed 7393 arthroplasties including 6284 total hip arthroplasties (THAs), 886 bipolar hemiarthroplasties (BPs), 188 total resurfacing arthroplasties, and 35 hemi-resurfacing arthroplasties (hRSs). The identified risk factors were combined systemic steroid use and excessive alcohol consumption (both ONFH-associated factors), a lateral approach, alumina BPs (aBPs), and hRSs, which were reported previously. The present study performed further analyses separately for THAs and BPs to clarify risk factors in each surgical group. A Cox proportional-hazard model identified the following risk factors: the acetabular-articulating materials of conventional polyethylene (cPE) and metal in the THAs and both ONFH-associated factors, minimum-incision surgery (MIS), and aBPs in the BPs. The risk factors were specific to each surgical group. In the ONFH patients, when performing THA, cPE and metal are not recommended as the acetabular-articulating material. When performing BP, patients with both ONFH-associated factors should be treated carefully, and the employment of MIS and use of aBP are not good strategies.

Osteonecrosis: A More Appropriate Term than Avascular Necrosis-Pathophysiologic Rationale.

Background and purposeNontraumatic osteonecrosis of the femoral head (ONFH) patients are at a higher dislocation risk after primary total hip arthroplasties (THAs) than osteoarthrosis patients. It has not been clear how large prosthetic heads should be to reduce dislocation. A nationwide multicenter follow-up cohort study of THAs performed for ONFH aimed to evaluate risk factors associated with dislocation and whether larger head size could reduce the dislocation risk.MethodsA multivariable logistic regression model analyzed factors associated with dislocation in 5,983 THAs performed for ONFH between 1996 and 2022 with a median of 7.1 (0.5–27)-year follow-up. Patient age at surgery was 52 years and BMI was 22.9, as medians. A posterior approach was employed in 59%. The head diameter was 22 mm in 4%, 26 mm in 15%, 28 mm in 24%, 32 mm in 36%, and ≥ 36 mm in 21%.Results288 THAs (4.8%) dislocated. Younger (1st quartile, ≤ 41 years) patient age (odds ratio [OR] 1.45 CI [95% confidence interval] 1.02–2.07 vs. 2nd quartile), higher BMI (OR 1.05, CI 1.02–1.08 per 1), posterior approach (OR 3.33, CI 1.96–5.56 vs. anterior or anterolateral approach, OR 2.27 CI 1.59–3.23 vs. lateral approach), and smaller heads were identified as risk factors. However, ≥ 36-mm heads were not different from 32-mm heads (OR 1.06 CI 0.69–1.63).ConclusionRisk factors associated with dislocation were younger patient age, higher BMI, posterior approach, and smaller heads; however, 32-mm heads were large enough to reduce dislocation.

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

Abstract Background: Osteonecrosis of the femoral head (ONFH) is the commonest indication for hip replacements in the developing world. Core decompression (CD) has been an effective method in early stages of ONFH with role of various adjuvants like BMAC and PRP widely documented to enhance its efficacy, albeit the associated high. We evaluated the effectiveness of Ibandronate (IB) which is a bisphosphonate as an adjuvant to CD so as to provide a cheaper and effective alternative to the existing adjuvants. Aim: To assess superiority of addition of intraosseous ibandronate to core decompression over core decompression alone in pre-collapse AVN of femoral head in terms of functional outcomes i.e Pain relief and daily activities Methods: A double blinded randomised controlled trial was done and 17 patients between age 18-59 years, with 30 affected hips in the pre-collapse stage, were recruited and divided into 2 groups; CD only and CD + IB groups. Patients were followed up for 1 year and evaluated in terms of visual analogue scale (VAS) and modified Harris hip score (MHHS). Results: The average preoperative MHHS was 67.44 and 75.36 in CD and CD + IB group respectively. In CD only group, MHHS postoperatively at 8 weeks, 3 months, 6 months and one year were 83.4, 80.42, 75.22, 71.71 respectively (p value = 0.165) while VAS score changed from 4.86 preoperatively to 3.60 at 1 year (p value =0.054). In CD + IB group, MHHS Scores were 85.92, 87.92, 87.9, 89.04, 81.75 respectively (p value = 0.050) while VAS score changed from 4.93 preoperatively to 2.33 at 1 year (p value =0.054). In terms of difference between the two groups, at 6 months the MHHS as well as the VAS in the CD + IB group were better significantly (p=0.048 and 0.009 respectively); however, at 1 year, the differences were not significant (p=0.301 and 0.204 respectively) Conclusion: Ibandronate as an intraosseous adjuvant to CD shows promise in terms of significantly improving the functional outcome and pain relief with better results in the early postoperative period (upto 6 months) than CD alone.

BackgroundThe endoplasmic reticulum stress (ER stress) has been involved in various musculoskeletal disorders including non-traumatic osteonecrosis of femoral head (NT-ONFH).ObjectiveThe current study aimed to investigate the association of glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer-binding protein homologous protein (CHOP) expressions in serum and femoral head (FH) tissues with NT-ONFH’s severity.MethodsWe enrolled NT-ONFH patients (n = 150) alongside healthy controls (HCs, n = 150). Meanwhile, 49 patients with femoral neck fracture (FNF) were also enrolled. Serum CHOP and GRP78 levels were determined through enzyme linked immunosorbent assay (ELISA). Local CHOP and GRP78 expressions were detected by immunohistochemistry, western blot, alongside real-time polymerase chain reaction (RT-PCR). Radiographic severity was assessed by FICAT grading system. The visual analogue scale (VAS) together with Harris hip score (HHS) were utilized to determine symptomatic severity.ResultsSerum CHOP and GRP78 levels were markedly increased in NT-ONFH patients than HCs. NT-ONFH patients at FICAT stage 4 showed significant higher serum CHOP and GRP78 levels in contrast with those at stage 3. Furthermore, patients at stage 3 demonstrated higher serum CHOP and GRP78 levels than those at stage 2. There was a positive correlation observed between the serum CHOP and GRP78 levels and the severity of the FICAT stages. A total of 42 ONFH patients at FICAT stage 3, 40 patients at FICAT stage 4, and 49 FNF patients received total hip replacement (THR). The mRNA and protein levels of CHOP and GRP78 were elevated in necrotic area compared to the non-necrotic area of ONFH patients and the FH tissues of FNF patients with statistical significance. The expression levels of CHOP and GRP78 within the local tissues were significantly elevated in patients at FICAT stage 4 as opposed to those at stage 3. Besides, ROC curve analysis indicated that serum and local CHOP and GRP78 expressions may act as indicators of disease progression. The levels of CHOP and GRP78, both in serum and at the local site, were in a positive correlation with VAS scores but an inverse relationship with HHS.ConclusionsSerum and local GRP78 as well as CHOP expressions were positively linked with disease progression in NT-ONFH patients. Potential therapeutics targeting ER stress related protein may serve as a method for alleviating NT-ONFH.

Objectives:Bone scintigraphy is a sensitive imaging method to evaluate patients with suspected osteonecrosis. We assessed the diagnostic performance of combined bone single-photon emission computed tomography/computed tomography (SPECT/CT) (CBS) in patients with known rheumatic disease or other connective tissue disorders and clinical suspicion of osteonecrosis compared to magnetic resonance imaging (MRI).Methods:This prospective diagnostic accuracy study included 70 patients with clinical suspicion of osteonecrosis in any bone who underwent a planar triple-phase bone scan along with a regional SPECT/CT (CBS) and regional MRI. MRI was considered the standard for diagnosing the sensitivity, specificity, predictive values, and accuracy of CBS. Cohen’s kappa statistic of the agreement was also calculated.Results:The distribution of the patients based on the joint regions suspected to have osteonecrosis is as follows: 21 hip, 43 knee, and six ankle. MRI detected osteonecrosis in 30/70 patients. CBS had a sensitivity of 100% (30/70 were detected) and a specificity of 97% (2/40 were false positive). Overall, there was good agreement between the two scans regarding the diagnosis of osteonecrosis (Cohen’s kappa statistic = 0.94). In addition to the suspected sites, CBS detected osteonecrosis in 19 additional asymptomatic sites in 13 patients.Conclusion:The study has demonstrated that CBS, which includes whole-body imaging and SPECT/CT, is highly sensitive in detecting osteonecrosis with accuracy comparable to regional MRI. Its inherent whole-body imaging technique enabled the detection of multifocal osteonecrosis. It can be used as an early investigating modality after routine plain radiography to establish the diagnosis.

Legg – Calve – Perthes disease (LCPD) is the most common femoral head osteonecrosis in children. Until now, the knowledge of etiology, pathogenesis and clinical signs is partial and does not provide a coherent view of the disease. Despite modern advances in understanding and diagnosing of the disease, surgical interventions and stress release remain the standard treatment methods. Now there is a need to develop both new strategies for studying the pathogenesis of the disease and choosing methods of its treatment.The aim. Reproduction and development of morphological criteria for the early stage of Legg – Calve – Perthes disease (stages 1–2 by the modified Waldenström classification system).Materials and methods. The research involved 6 young gray giant rabbits (Flandres) aged 3–4 months. The early stages of LCPD were simulated by the pathophysiological model of Kuzhelivsky I.I. et al. (2016) with paraarticular adrenaline injections along with physical activity. We modified the physical activity regime for the subjects by daily free range for 1.5–3 hours.Results. The experiment confirmed the validity of the modified simulation and designed its morphological criteria. The osteochondropathy process was verified histologically, we also revealed the classic signs of damage to subchondral bone and hyaline cartilage as well as abnormal vascularization of cartilage sites and pathological neoangiogenesis.Conclusion. The technique of non-traumatic osteonecrosis simulation in young rabbits featured initial results in reproducing the pathological links of osteonecrosis process. The cartilage tissue featured the loss of isogeneity in chondrocytes structure and their column-like arrangement; its delamination and replacement with fibrous tissue, including fibroblast-like cells and collagen fibers; cartilage neovascularization and persistent mixed hyperemia. In the bone marrow, only the activation of the red blood cell line was noted. The bone tissue featured the abnormality of osteon structure with a mosaic arrangement of trabeculae as well as lacunar resorption, and osteoblast degeneration.