Systematic Review Evaluates Femoral Head Avascular Necrosis Linked to COVID-19

A comprehensive systematic review published in Archives of Orthopaedic and Trauma Surgery has updated the clinical evidence regarding avascular necrosis of the femoral head occurring after COVID-19 infection, synthesizing 55 studies comprising 864 documented patient cases. The investigators evaluated observational data across multiple biomedical databases to clarify the clinical profile, underlying risk factors, diagnostic timelines, radiological disease stages, and therapeutic outcomes associated with this debilitating bone disorder in individuals who survived infection with the coronavirus. Their findings emphasize that while avascular necrosis of the femoral head represents a recognized post-infection musculoskeletal complication, early diagnosis remains critical for preserving hip joint integrity and maintaining functional mobility before structural bone collapse necessitates surgical arthroplasty.

The global COVID-19 pandemic, caused by the novel coronavirus, affected a large proportion of the worldwide population with acute manifestations predominantly characterized by fever, cough, and dyspnea, as well as olfactory and gustatory disturbances including hyposmia, anosmia, and hypogeusia. Clinicians also identified a broad spectrum of less common systemic symptoms involving headache, dizziness, and impaired consciousness, alongside gastrointestinal complaints such as diarrhea, nausea or vomiting, anorexia, and gastrointestinal bleeding. Severe acute illness further involved cardiac complications including myocarditis, cardiac arrhythmias, and heart failure, with advanced age, preexisting underlying diseases, and immunosuppressive agents significantly elevating the risk of severe disease forms. Clinical literature noted that between 5 percent and 58 percent of COVID-19 patients may develop osteonecrosis across joints including the femoral condyles, tibial condyles, humeral head, talus, and calcaneus, with the femoral head most frequently affected.

Underlying pathophysiological mechanisms contributing to osteonecrosis following COVID-19 infection include direct damage to bone vasculature alongside the therapeutic administration of glucocorticoids during acute disease management. Systemic corticosteroids were utilized to counter oxygen desaturation, cytokine storms, and moderate to severe COVID-19, functioning as a double-edged sword due to their potential to induce bone necrosis. Lv and colleagues reported that 39 percent of COVID-19 patients treated with corticosteroids developed femoral head osteonecrosis three to four months after initiating treatment. Furthermore, researchers noted that post-COVID-19 avascular necrosis involves multiple additional biological mechanisms beyond steroid exposure, including a pronounced hypercoagulable state and thrombotic complications, the formation of fat emboli, hyperlipidemia, direct endothelial injury, activation of the complement pathway leading to hypercoagulability, and mast cell activation syndrome. General factors contributing to femoral avascular necrosis also include fractures, dislocations, skeletal trauma, hemoglobinopathies, systemic lupus erythematosus, alcohol consumption, smoking, and pregnancy, all converging to impair skeletal blood supply.

Pathologically, femoral head avascular necrosis is characterized by necrosis of the bone marrow architecture and the loss of osteocytes resulting from insufficient blood supply to bone tissue. In response to ischemic bone injury, increased osteoclastic activity leads to the biological clearance of necrotic trabeculae, which subsequently produces progressive trabecular bone weakening within the femoral head. Microscopic structural fractures within the weakened trabecular bone culminate in subchondral bone collapse, generating debilitating clinical symptoms including localized joint pain, progressive limitation of range of motion, and gait imbalance.

To conduct their updated systematic review, the authors adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, systematically searching PubMed, Scopus, EMBASE, PsycINFO, Web of Science, and Google Scholar on April 1, 2024. Two independent researchers executed search strategies combining MeSH terms and text words covering COVID-19 terminology, viral vaccines, and avascular necrosis nomenclature, while evaluating gray literature encompassing academic theses, reference lists, and conference abstracts. Search results were imported into EndNote files by each investigator, duplicate citations were removed, and eligible full texts were retrieved following initial title and abstract evaluations. The search yielded 1,229 records, from which 161 full-text articles were evaluated, ultimately leaving 55 studies meeting inclusion criteria. Two researchers independently extracted data items into standardized spreadsheets, including first author, publication country, publication year, participant totals, sex distribution, patient age, past medical history, corticosteroid therapy details, magnetic resonance imaging stage, and follow-up duration, with a third researcher resolving discrepancies.

Methodological quality across the 55 included studies was evaluated using the Newcastle-Ottawa Scale checklist for cohort studies, case reports, and case series, yielding study quality scores ranging between 5 and 8. Among the included investigations, four studies were cross-sectional studies, six were retrospective studies, and the remaining 45 studies were case reports or case-series investigations. Regarding geographic distribution, the largest proportion of studies originated from India, which contributed 22 studies accounting for 40.0 percent of the total, followed by Turkey, which accounted for 10.9 percent of the included literature. Eligible study designs specified by inclusion criteria encompassed cross-sectional studies, case reports, case series, or cohort studies, whereas studies lacking definite clinical data and review articles were systematically excluded from analysis. In total, the 55 analyzed studies documented 864 individual patient cases presenting with avascular necrosis of the femoral head following COVID-19 infection.

Across the 864 included patient cases, patient ages ranged from 27 to 71 years, with male patients comprising the majority of reported cases. Comorbidity evaluations demonstrated that the most common underlying medical conditions among patients were hypertension, followed by diabetes mellitus. Anatomical assessment revealed that avascular necrosis was bilateral, involving both hips, in 274 cases, representing 31.7 percent of the analyzed patient cohort, whereas medical literature observes that avascular necrosis occurs predominantly in adults and involves both hips in three-fourths of general presentations. The systematic review identified underlying diseases such as diabetes mellitus, hypertension, and sickle cell anemia as important clinical risk factors for developing avascular necrosis following viral infection. Individual case reports illustrated distinct risk profiles; for instance, Ergun and colleagues reported a bilateral case of avascular necrosis in a female patient with sickle cell anemia who developed hip necrosis two months after COVID-19 infection.

The development of osteonecrosis following corticosteroid therapy depends on daily dose, cumulative dose, maximum dose, and administration route, with cumulative doses exceeding 2 grams generally recognized as capable of inducing osteonecrosis. Kandari and colleagues established a direct link between corticosteroid dosage and treatment duration and the severity and radiological stage of avascular necrosis. Within the systematic review, Nejadhosseinian and colleagues reported a patient who received a cumulative dose of 3,706 milligrams of corticosteroids and subsequently developed bilateral femoral avascular necrosis 20 months after COVID-19 infection. Additionally, Panin and colleagues documented four cases of avascular necrosis developing after COVID-19, including one patient treated with 4,000 milligrams of corticosteroids who developed bilateral necrosis 80 days after infection onset, with non-surgical therapies providing subsequent symptom improvement.

Jyothiprasanth evaluated 17 patients with avascular necrosis between July 2022 and July 2023, having specifically excluded all cases treated with corticosteroids. Within that non-steroid cohort, 14 of the 17 patients developed hip pain and related clinical symptoms immediately after COVID-19 infection, with symptom onset intervals ranging between 7 and 100 days. Male patients represented 71 percent of the cohort, avascular necrosis was bilateral in only three cases, patient ages ranged from 23 to 60 years, and diabetes mellitus alongside hypertension were the most common underlying conditions. In other reports, Ardakani and colleagues detailed five cases of avascular necrosis occurring alongside septic arthritis with a mean corticosteroid dose of 1,695 milligrams administered for COVID-19, all achieving satisfactory surgical outcomes, while Etta and colleagues reported avascular necrosis developing four years post kidney transplant in a patient who received corticosteroids three months prior.

Radiological staging across 25 studies classified 89 cases as stage I, 151 as stage II, 74 as stage III, and 14 as stage IV, with early stages I and II—accounting for 92 to 97 percent of general cases—associated with favorable prognoses under prompt intervention. Non-surgical treatments, including painkillers, physiotherapy, hyperbaric oxygen, vitamin D, and bisphosphonates, yielded symptom improvement, as observed by Agarwala and colleagues and Dhanasekararaja and colleagues. In advanced stages, surgical interventions proved necessary; core decompression provided symptom relief, and Umar and colleagues achieved optimal results using free vascularized fibula grafting. Conversely, Muragesan and colleagues reported symptom worsening in a stage II case under conservative care. Total hip arthroplasty served as the primary surgical treatment for stage III and IV disease, underscored by Aishwarya and colleagues reporting a six-fold post-pandemic increase in arthroplasty rates. Although limited by observational case designs and unstandardized staging data, the 55-study review demonstrates that vigilant early diagnosis is crucial to preserve joint function.

Subject of Research: Systematic review of post-COVID-19 femoral head avascular necrosis

Article Title: Avascular necrosis of the femur following COVID-19: an updated systematic review

Article References: Azadvari, M., Akbari, N., Hatam, S., Rastkar, M., & Razavi, S. Z. E. (2026). Avascular necrosis of the femur following COVID-19: an updated systematic review. Archives of Orthopaedic and Trauma Surgery, 146(1), Article 397. https://doi.org/10.1007/s00402-026-06545-4

Image Credits: AI Generated

DOI: 10.1007/s00402-026-06545-4

Keywords: avascular necrosis, COVID-19, femoral head osteonecrosis, corticosteroid therapy, total hip arthroplasty, orthopaedic surgery, systematic review, bone ischemia, Avascular, necrosis, femur, following