Screening for Biomarkers of Osteonecrosis of the Femoral Head

Screening of Biomarkers for Osteonecrosis of the Femoral Head and Establishment of a Multidimensional Data Based Early Diagnostic Method

Osteonecrosis of the femoral head (ONFH) presents a rapidly progressive natural disease course. Femoral head collapse may occur within two years, ultimately necessitating total hip arthroplasty and imposing a heavy medical and economic burden on patients. Early intervention can significantly improve the long-term prognosis of ONFH. However, due to the lack of validated biomarkers for early diagnosis, the early diagnostic rate remains low, with a primary diagnostic rate of merely 68.43% at the first visit, accompanied by a high rate of misdiagnosis. This project intends to collect blood samples from patients diagnosed with ONFH and suspected cases in the orthopedic outpatient department of a tertiary Grade A hospital. Diagnostic and differential diagnostic tests will be adopted to evaluate the clinical application value of previously reported candidate biomarkers, so as to screen out biomarkers with excellent diagnostic validity and reliability. Meanwhile, clinical data will be collected to identify independent risk factors, and a multi-dimensional integrated diagnostic model will be further established. The research findings are expected to provide solid data support, theoretical basis and technical reserves for the early prevention, early diagnosis and individualized intervention of osteonecrosis of the femoral head.

Study Overview

• Status: Recruiting
• Conditions: Osteonecrosis of the Femoral Head

Detailed Description

Osteonecrosis of the Femoral Head (ONFH) is a highly disabling disease characterized by osteocyte death caused by interrupted blood supply to the femoral head. The natural course of ONFH progresses rapidly. Femoral head collapse can occur within approximately two years, and ultimately about 30% of patients require total hip arthroplasty. This disease not only severely impairs patients' quality of life but also imposes a heavy medical and economic burden. The global incidence of ONFH is on the rise. Statistics show that there are approximately 20,000 to 30,000 new cases annually in the United States, and around 300,000 new cases in China each year, with young and middle-aged people accounting for the largest proportion. The incidence rate among individuals aged 15 years and above is approximately 10-30 per 100,000 population. The prevalence of ONFH is higher in northern regions than in southern areas, and higher in urban than in rural areas. Such distribution differences may be associated with climate, occupation, medical accessibility, and exposure levels of risk factors.

The etiology and pathogenesis of ONFH are complex and correlated with multiple risk factors including excessive alcohol consumption, glucocorticoid administration, and hip fractures. Long-term or high-dose glucocorticoid use is a major predisposing factor for ONFH, accounting for approximately 40% of all cases. Glucocorticoids may induce femoral head ischemia and subsequent necrosis by increasing blood viscosity, triggering fat embolism, or directly damaging vascular endothelial cells. Long-term heavy drinking (average daily alcohol intake ≥ 40 g) is another high-risk factor, responsible for 20%-30% of cases. Alcohol inhibits osteoblast activity, exacerbates oxidative stress, and disrupts bone microcirculation through lipid metabolism disorders. Traumatic injuries such as femoral neck fracture and hip dislocation directly damage the retinacular blood vessels, contributing to 10%-20% of ONFH cases. Subcapital fractures carry the highest risk of osteonecrosis; completely displaced adduction fractures with severe vascular injury present a necrosis rate of 30%-50%. Delayed reduction (> 24 hours) and improper reduction operations (e.g., excessive traction) after fracture also markedly increase the risk of necrosis. In addition, metabolic disorders including hypertension, diabetes and hyperlipidemia impair bone blood circulation indirectly by exacerbating systemic angiopathy. Cigarette smoking (nicotine) induces vasoconstriction and endothelial dysfunction, thereby accelerating the progression of osteonecrosis. Osteoporosis reduces bone mineral density and the mechanical strength of the femoral head, rendering it susceptible to microfractures caused by minor trauma and further aggravating blood perfusion disturbance.

A variety of therapeutic approaches are available for ONFH, including non-surgical treatments (protective weight-bearing, bisphosphonate medication, hyperbaric oxygen therapy, and platelet-rich plasma treatment), femoral head-preserving surgeries (core decompression, vascularized bone grafting, non-vascularized bone grafting, and stem cell therapy), and emerging experimental therapies such as M2 macrophage-derived exosomes. Treatment efficacy is mainly determined by disease stage, intervention strategies and individual patient differences. Early intervention can significantly improve clinical prognosis, whereas advanced ONFH often requires complex surgical procedures such as total hip arthroplasty. Nevertheless, the early diagnostic rate of ONFH remains low, with only 68.43% of cases correctly diagnosed at the first visit. Meanwhile, the disease has a high misdiagnosis rate and is frequently misdiagnosed as lumbar disc herniation or simple arthritis.

Existing studies on ONFH are predominantly clinical research with notable limitations. Most studies adopt a single research methodology that merely analyzes ONFH from the perspective of biomechanics, while ignoring the interactions of multiple factors such as heredity, metabolism and immunity. Research designs represented by retrospective studies are prone to selection bias and information bias, which limit the generalizability of research findings. In addition, small sample sizes fail to accurately reflect the overall characteristics and epidemiological patterns of ONFH. Furthermore, inconsistent research designs in previous studies lead to heterogeneous indicators and poor data comparability. Therefore, disease-specialized research on ONFH is urgently needed. By adopting a multicenter prospective design, high-risk factors, clinical imaging data and biological samples will be systematically collected. Combined with multi-dimensional influencing factors including biomechanics, biochemistry and genetics, this study aims to explore early diagnostic biomarkers and optimal diagnostic strategies for ONFH, so as to provide evidence for optimizing clinical diagnosis and treatment protocols and establishing individualized predictive models.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Wenjie Ren; Phone Number: 8618937302619; Email: 157121431@qq.com

Study Locations

• China
  • Henan
    • Xinxiang, Henan, China, 453003
      • Recruiting
      • The First Affiliated Hospiatl of Henan Medical University
      • Contact: Tan Lu; Phone Number: 8613663901294; Email: Lutan1982@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patients with suspected osteonecrosis of the femoral head.

Description

Inclusion Criteria:

1. Aged between 18 and 70 years old (inclusive).
2. Patients with suspected ONFH.
3. Those who provide informed consent and volunteer to participate in this study.

Exclusion Criteria:

1. Patients with a clear history of hip trauma.
2. Patients with ONFH secondary to traumatic factors such as femoral neck fracture and hip dislocation.
3. Patients complicated with severe mental illness or cognitive impairment who are unable to cooperate with questionnaire completion.
4. Patients who refuse to sign the informed consent form.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with suspected ONFH; The research subjects shall cover as many types of ONFH patients as possible, including the alcohol-induced type, steroid-induced type and other types. Enrolled patients will be predominantly in the early stage of ONFH. Meanwhile, patients with diseases sharing similar clinical manifestations with ONFH and prone to misdiagnosis shall also be included.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Diagnose based on MRI	MRI was adopted as the gold standard for the diagnosis of ONFH.	on enrollment
Diagnostic biomarkers	To screen potential early diagnostic biomarkers of ONFH in human blood	About 100 days after all sample collected.

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Xinxiang Medical College
• Investigators: Study Chair: Wenjie Ren, The First Affliated Hosptal of Henan Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): April 20, 2026
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): May 30, 2027

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: April 15, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Biomarker; Osteonecrosis of the Femoral Head
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Femur Head Necrosis; Osteonecrosis; Legg-Calve-Perthes Disease
• Other Study ID Numbers: ONFH-XXMU-20260101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No