Screening for Biomarkers of Osteonecrosis of the Femoral Head

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.

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 trial.show_full_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.