Abstract
Background
One of the complications of COVID-19 infection is avascular necrosis of the femoral head. To date, various studies have reported a wide range of osteonecrosis of the femoral head in patients with COVID-19. The previous systematic review included only 14 studies. So, this systematic review aims to update the findings of these studies.
Methods
Databases such as PubMed, Scopus, EMBASE, PsycINFO, Web of Science, and Google Scholar were systematically searched by two independent researchers on April 1st, 2024.
Results
A literature search revealed 1229 records, 161 full-texts were evaluated, and finally, 55 studies remained for systematic review. Fifty-five studies were included in this systematic review. Four studies were cross-sectional studies, six were retrospective studies, and the remaining (45studies) were case reports or case-series studies. Totally, 864 cases were included. Except for 12 studies, 43 studies reported the administration of steroid therapy in included cases. The most common underlying conditions were hypertension, followed by diabetes. In 274 (31.7%) of included cases, AVN was bilateral, and both hips were involved. In some studies, non-surgical treatments—including supplement therapy, anticoagulant therapy, physiotherapy, and hyperbaric oxygen therapy—were administered. Several studies reported symptomatic improvement in patients treated with the core decompression approach. Total hip arthroplasty (THA) was the most commonly used surgical treatment.
Conclusions
Avascular necrosis of the femoral head in cases that have survived COVID-19 should be considered carefully as early diagnosis helps to preserve the joint and its function.
Keywords: COVID-19, Femur head necrosis, Systematic review
Introduction
Coronavirus was the causative agent of the COVID-19 pandemic that affected a large group of the population worldwide [1]. Advanced age, underlying diseases, and certain medications—such as immunosuppressive agents—increase the risk of infection and its severe forms [2].
The main symptoms of COVID-19 infection were cough, fever, dyspnea, hyposmia, anosmia, and hypogeusia, and less common symptoms such as headache, dizziness, impaired consciousness, GI symptoms(diarrhea, nausea or vomiting, anorexia, GI bleeding), myocarditis, cardiac arrhythmias, and heart failure [3–7]. Musculoskeletal complications, including myalgias, generalized weakness, muscle dysfunction, arthralgias, and osteonecrosis, are reported by affected patients [8–12].
Between 5% and 58% of patients with COVID-19 may develop osteonecrosis in joints such as the femoral and tibial condyles, the humeral head, talus, and calcaneus, with the femoral head being most commonly affected [12, 13].
Possible underlying mechanisms of osteonecrosis include damage to bone vasculature and the administration of glucocorticoids for treatment [14].
Lv et al. reported 39% femoral head osteonecrosis 3–4 months after starting the treatment in patients with COVID-19 who had been treated with corticosteroids [15]. To fight against oxygen desaturation, cytokine storms, and moderate to severe forms of COVID-19, systemic corticosteroids may be applied which play as a double-edged sword [16]. Early diagnosis of femoral head AVN (stage I or II), which accounts for 92–97% of all cases, is associated with a good prognosis when treated promptly [17].
To date, various studies have reported a wide range of osteonecrosis of the femoral head in patients with COVID-19. The previous systematic review included only 14 studies. So, this systematic review aims to update the findings of these studies.
Methods
We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 for reporting our systematic review, and meta-analysis [18].
Eligibility criteria
Inclusion criteria: Cross-sectional studies, case/reports, case series, or cohort studies.
Exclusion criteria: Studies with no definite data, and reviews were excluded.
Information sources
Databases such as PubMed, Scopus, EMBASE, PsycINFO, Web of Science, and Google Scholar were systematically searched by two independent researchers on April 1st 2024. The gray literature, including theses, references list of included studies, and conference abstracts, were searched by researchers, too.
Search strategy
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Word])) OR (Vaccine, COVID 19[Text Word])) OR (2019-nCoV Vaccine*[Text Word])) OR (2019 nCoV Vaccine*[Text Word])) OR (Vaccine, 2019-nCoV[Text Word])) OR (2019 Novel Coronavirus Vaccine*[Text Word])) OR (SARS-CoV-2 Vaccine*[Text Word])) OR (SARS CoV 2 Vaccine*[Text Word])) OR (Vaccine, SARS-CoV-2[Text Word])) OR (Vaccines, 2019-nCoV[Text Word])) OR (Vaccine, COVID-19[Text Word])) OR (SARS Coronavirus 2 Vaccine*[Text Word])) OR (Vaccines, COVID-19 Virus[Text Word])) OR (Virus Vaccines, COVID-19[Text Word])) OR (COVID-19 Virus Vaccine*[Text Word])) OR (COVID 19 Virus Vaccine*[Text Word])) OR (Vaccine, COVID-19 Virus[Text Word])) OR (Virus Vaccine, COVID-19[Text Word])) OR (Vaccines, COVID19 Virus[Text Word])) OR (Virus Vaccines, COVID19[Text Word])) OR (COVID19 Virus Vaccine*[Text Word])) OR (Vaccine, COVID19 Virus[Text Word])) OR (Virus Vaccine, COVID19[Text Word])) OR (Vaccines, COVID19[Text Word])) OR (COVID19 Vaccine*[Text Word])) OR (Vaccine, COVID19[Text Word])) OR (Vaccines, SARS-CoV-2[Text Word])) OR (ChAdOx1 nCoV-19[MeSH Terms])) OR (ChAdOx1 nCoV-19[Text Word])) OR (ChAdOx1 nCoV 19[Text Word])) OR (nCoV-19, ChAdOx1[Text Word])) OR (Oxford-AstraZeneca COVID Vaccine[Text Word])) OR (COVID Vaccine, Oxford-AstraZeneca[Text Word])) OR (Oxford AstraZeneca COVID Vaccine[Text Word])) OR (Vaccine, Oxford-AstraZeneca COVID[Text Word])) OR (Oxford-AstraZeneca COVID-19 Vaccine[Text Word])) OR (COVID-19 Vaccine, Oxford-AstraZeneca[Text Word])) OR (Oxford AstraZeneca COVID 19 Vaccine[Text Word])) OR (Vaccine, Oxford-AstraZeneca COVID-19[Text Word])) OR (ChAdOx1 COVID-19 Vaccine[Text Word])) OR (ChAdOx1 COVID 19 Vaccine[Text Word])) OR (COVID-19 Vaccine, ChAdOx1[Text Word])) OR (Vaccine, ChAdOx1 COVID-19[Text Word])) OR (COVID-19 Vaccine AstraZeneca[Text Word])) OR (AstraZeneca, COVID-19 Vaccine[Text Word])) OR (COVID 19 Vaccine AstraZeneca[Text Word])) OR (AZD1222[Text Word])) OR (AZD-1222[Text Word])) OR (AZD 1222[Text Word])) OR (Covishield[Text Word])) OR (Vaxzevria[Text Word])) OR (2019-nCoV Vaccine mRNA-1273[MeSH Terms])) OR (2019-nCoV Vaccine mRNA-1273[Text Word])) OR (2019 nCoV Vaccine mRNA 1273[Text Word])) OR (mRNA-1273, 2019-nCoV Vaccine[Text Word])) OR (COVID-19 Vaccine Moderna[Text Word])) OR (COVID 19 Vaccine Moderna[Text Word])) OR (Moderna, COVID-19 Vaccine[Text Word])) OR (mRNA-1273[Text Word])) OR (mRNA 1273[Text Word])) OR (Moderna COVID-19 Vaccine RNA[Text Word])) OR (Moderna COVID 19 Vaccine RNA[Text Word])) OR (Moderna COVID-19 Vaccine[Text Word])) OR (COVID-19 Vaccine, Moderna[Text Word])) OR (Moderna COVID 19 Vaccine[Text Word])) OR (Vaccine, Moderna COVID-19[Text Word])) OR (mRNA-1273.211[Text Word])) OR (mRNA 1273.211[Text Word])) OR (TAK-919[Text Word])) OR (TAK919[Text Word])) OR (TAK 919[Text Word])) OR (Spikevax[Text Word])) OR (M-1273[Text Word])) OR (M1273[Text Word])) OR (M 1273[Text Word])) OR (CX-024414[Text Word])) OR (CX024414[Text Word])) OR (CX 024414[Text Word])) OR (Elasomeran[Text Word])) OR (Moderna COVID-19 Vaccine, Bivalent[Text Word])) OR (Moderna COVID 19 Vaccine, Bivalent[Text Word])) OR (BNT162 Vaccine[MeSH Terms])) OR (BNT162 Vaccine[Text Word])) OR (Vaccine, BNT162[Text Word])) OR (COVID-19 Vaccine Pfizer-BioNTech[Text Word])) OR (COVID 19 Vaccine Pfizer BioNTech[Text Word])) OR (Pfizer-BioNTech, COVID-19 Vaccine[Text Word])) OR (Vaccine Pfizer-BioNTech, COVID-19[Text Word])) OR (BNT-162A1[Text Word])) OR (BNT 162A1[Text Word])) OR (BNT162A1[Text Word])) OR (Tozinameran[Text Word])) OR (BNT162B2[Text Word])) OR (BNT-162B2[Text Word])) OR (BNT 162B2[Text Word])) OR (Comirnaty[Text Word])) OR (Pfizer Covid-19 Vaccine[Text Word])) OR (Covid-19 Vaccine, Pfizer[Text Word])) OR (Pfizer Covid 19 Vaccine[Text Word])) OR (Vaccine, Pfizer Covid-19[Text Word])) OR (Abdavomeran[Text Word])) OR (BNT162B1[Text Word])) OR (BNT-162B1[Text Word])) OR (BNT 162B1[Text Word])) OR (Pidacmeran[Text Word])) OR (BNT162C2[Text Word])) OR (BNT-162C2[Text Word])) OR (BNT 162C2[Text Word])) OR (janssen[Text Word])) OR (Gam-COVID-Vac vaccine[Supplementary Concept])) OR (Gam-COVID-Vac vaccine[Text Word])) OR (Gam-COVID-Vac COVID-19 vaccine[Text Word])) OR (Sputnik V COVID-19 vaccine[Text Word])) OR (rAd26[Text Word] AND rAd5[Text Word])) OR (rAd26-rAd5[Text Word])) OR (BIBP COVID-19 vaccine[Supplementary Concept])) OR (BIBP COVID-19 vaccine[Text Word])) OR (sinopharm BIBP COVID-19 vaccine[Text Word])) OR (BIBP vaccine[Text Word])) OR (BBIBP-CorV vaccine[Text Word])) OR (BBIBP-CorV[Text Word])) OR (BIBP-CorV[Text Word])) OR (BBIBP CorV[Text Word])) OR (BBIBPCorV[Text Word])) OR (BBIBP-CorV vaccine antigen[Text Word])) OR (sinopharm’s SARS-CoV-2 Beijing vaccine HB02 strain antigen[Text Word])) OR (SARS-CoV-2 HB02 strain beta-propiolactone inactivated vaccine antigen[Text Word])) OR (Covilo[Text Word])) OR (BBV152 COVID-19 vaccine[Supplementary Concept])) OR (BBV152 COVID-19 vaccine[Text Word])) OR (BBV152 vaccine[Text Word])) OR (BBV152[Text Word])) OR (Covaxin[Text Word])) OR (BBV154 COVID-19 vaccine[Text Word])) OR (BBV154[Text Word])) OR (sinovac COVID-19 vaccine[Supplementary Concept])) OR (sinovac COVID-19 vaccine[Text Word])) OR (sinovac COVID vaccine[Text Word])) OR (CoronaVac[Text Word])) OR (CoronaVac vaccine[Text Word])) OR (sinovac COVID vaccine antigen[Text Word])) OR (SARS-CoV-2 CN2 strain beta-propiolactone inactivated vaccine antigen[Text Word])) OR (inactivated covid-19 cn2 strain vaccine antigen[Text Word])) OR (CoronaVac antigen[Text Word])) OR (Picovacc antigen[Text Word])) OR (Picovacc[Text Word])) OR (EpiVacCorona vaccine[Supplementary Concept])) OR (ZF2001 COVID-19 vaccine[Supplementary Concept])) OR (COVI-VAC[Supplementary Concept])) OR (EpiVacCorona vaccine[Text Word])) OR (EpiVacCorona COVID-19 vaccine[Text Word])) OR (EpiVacCorona[Text Word])) OR (EpiVacCorona-N[Text Word])) OR (Aurora-CoV[Text Word])) OR (Convidecia[Text Word])) OR (ZF2001 COVID-19 vaccine[Text Word])) OR (ZF2001[Text Word])) OR (ZF2001 vaccine[Text Word])) OR (ZF-UZ-VAC2001[Text Word])) OR (ZF-2001[Text Word])) OR (Zifivax[Text Word])) OR (COVI-VAC[Text Word])) OR (CoviLiv[Text Word])) OR (CoviVac[Text Word])) OR (CDX-005[Text Word])) OR (Abdala[Text Word])) OR (COVID-19[MeSH Terms])) OR (SARS-CoV-2[MeSH Terms])) OR (COVID-19[Text Word])) OR (COVID 19[Text Word])) OR (SARS-CoV-2 Infection*[Text Word])) OR (Infection, SARS-CoV-2[Text Word])) OR (SARS CoV 2 Infection*[Text Word])) OR (2019 Novel Coronavirus Disease[Text Word])) OR (2019 Novel Coronavirus Infection[Text Word])) OR (2019-nCoV Disease*[Text Word])) OR (2019 nCoV Disease*[Text Word])) OR (Disease, 2019-nCoV[Text Word])) OR (COVID-19 Virus Infection*[Text Word])) OR (COVID 19 Virus Infection*[Text Word])) OR (Infection, COVID-19 Virus[Text Word])) OR (Virus Infection, COVID-19[Text Word])) OR (Coronavirus Disease 2019[Text Word])) OR (Disease 2019, Coronavirus[Text Word])) OR (Coronavirus Disease-19[Text Word])) OR (Coronavirus Disease 19[Text Word])) OR (Severe Acute Respiratory Syndrome Coronavirus 2 Infection[Text Word])) OR (SARS Coronavirus 2 Infection[Text Word])) OR (COVID-19 Virus Disease*[Text Word])) OR (COVID 19 Virus Disease*[Text Word])) OR (Disease, COVID-19 Virus[Text Word])) OR (Virus Disease, COVID-19[Text Word])) OR (2019-nCoV Infection*[Text Word])) OR (2019 nCoV Infection*[Text Word])) OR (Infection, 2019-nCoV[Text Word])) OR (COVID19[Text Word])) OR (COVID-19 Pandemic*[Text Word])) OR (COVID 19 Pandemic*[Text Word])) OR (Pandemic, COVID-19[Text Word])) OR (SARS-CoV-2[Text Word])) OR (SARS Coronavirus 2[Text Word])) OR (Coronavirus 2, SARS[Text Word])) OR (Coronavirus Disease 2019 Virus[Text Word])) OR (2019 Novel Coronavirus*[Text Word])) OR (Coronavirus, 2019 Novel[Text Word])) OR (Novel Coronavirus, 2019[Text Word])) OR (Wuhan Seafood Market Pneumonia Virus[Text Word])) OR (SARS-CoV-2 Virus*[Text Word])) OR (SARS CoV 2 Virus*[Text Word])) OR (Virus, SARS-CoV-2[Text Word])) OR (2019-nCoV[Text Word])) OR (COVID-19 Virus*[Text Word])) OR (COVID 19 Virus*[Text Word])) OR (Virus, COVID-19[Text Word])) OR (Wuhan Coronavirus[Text Word])) OR (Coronavirus, Wuhan[Text Word])) OR (COVID19 Virus*[Text Word])) OR (Virus, COVID19[Text Word])) OR (Viruses, COVID19[Text Word])) OR (Severe Acute Respiratory Syndrome Coronavirus 2[Text Word])))) AND ((((((((((((((((((((((Femur Head Necrosis[MeSH Terms]) OR (Osteonecrosis[MeSH Terms])) OR (Femur Head Necros*[Text Word])) OR (Head Necrosis, Femur[Text Word])) OR (Necrosis, Femur Head[Text Word])) OR (Necrosis, Avascular, of Femur Head[Text Word])) OR (Avascular Necrosis of Femoral Head, Primary[Text Word])) OR (Avascular Necrosis of Femur Head[Text Word])) OR (Femoral Head, Avascular Necrosis Of[Text Word])) OR (Ischemic Necrosis of Femoral Head[Text Word])) OR (Aseptic Necrosis of Femur Head[Text Word])) OR (Necrosis, Aseptic, of Femur Head[Text Word])) OR (Osteonecros*[Text Word])) OR (Bone Necros*[Text Word])) OR (Necroses, Bone[Text Word])) OR (Necrosis, Bone[Text Word])) OR (Necrosis, Avascular, of Bone[Text Word])) OR (Avascular Necrosis of Bone[Text Word])) OR (Bone Avascular Necrosis[Text Word])) OR (Necrosis, Aseptic, of Bone[Text Word])) OR (Aseptic Necrosis of Bone[Text Word])) OR (Bone Aseptic Necrosis[Text Word]))
Selection process, and collection
After searching databases, the obtained results were inserted in the ENDNOTE file by each researcher. The duplicates were deleted, and full-texts of eligible studies were obtained after title/abstract evaluation. Two researchers extracted data from each study and extracted data were entered into the Excel file. In the case of discrepancies, the third one solved the issue.
Data items
The first author of the publication, country of the study, publication year, number of study participants, total female and male population, age, past medical history(PMH), corticosteroid therapy, MRI stage, and duration of follow up.
Study risk of bias assessment
We used the Newcastle–Ottawa scale (NOS) checklist for cohort studies, and case reports, case series [19–21].
Results
A literature search revealed 1229 records, 161 full-texts were evaluated, and finally, 55 studies remained for systematic review (Fig. 1).
Fig. 1.
Flow chart of including studies
Fifty-five studies were included in this systematic review. Four studies were cross-sectional studies, six were retrospective studies, and the remaining (45 studies) were case reports or case-series studies. Most studies were conducted in India (22 studies (40%), followed by the Turkey (10.9%). Except for 12 studies, 43 studies reported administration of steroid therapy in included cases. Totally, 864 cases were included.
The age of included cases ranged from 27 to 71 years, with most patients being male. The most common underlying conditions were hypertension, followed by diabetes. In 274 (31.7%) of included cases, AVN was bilateral, and both hips were involved. Ardakani et al. reported five cases of AVN occurring alongside septic arthritis, with a mean corticosteroid dose of 1695 mg administered for the treatment of COVID-19 infection. All cases underwent surgery, and the outcome was satisfactory [22]. Etta et al. reported a case of AVN that developed four years after a kidney transplant. The patient had received corticosteroid treatment for COVID-19 infection three months prior. Treatment included core decompression, bone grafting, and physiotherapy [23]. Ergun et al. reported a bilateral case of AVN in a female patient who was known for sickle cell anemia and developed AVN two months after COVID-19 infection [24].
Twenty-five studies reported the stages of AVN among the included cases; however, two of them did not specify the number of cases at each stage. Overall, 89 cases were classified as stage I, 151 as stage II, 74 as stage III, and 14 as stage IV. In some studies, non-surgical treatments—including supplement therapy, anticoagulant therapy, physiotherapy, and hyperbaric oxygen therapy—were administered. Several studies reported symptomatic improvement in patients treated with the core decompression approach. Total hip arthroplasty (THA) was the most commonly used surgical treatment. Umar et al. used a free vascularized fibula graft and reported optimal results in the included patients [25]. Muragesan et al. applied symptomatic treatment in a case with stage II AVN (AVN was diagnosed 11 months after COVID-19 infection) and reported worsening of the symptoms [26].
The quality scores of the included studies ranged from 5 to 8 (Table 1).
Table 1.
Data extracted from included studies
| Study | Year | Country | Study design | Participants | Age | Gender | PMH | Corticosteroid therapy |
|---|---|---|---|---|---|---|---|---|
| Agarwala et al. [27] | 2022 | India | Retrospective study | 48 (88 hips) | Mean (range) 841.3 (100–3520) mg prednisolone equivalents | |||
| Aishwarya et al. [28] | 2025 | India | Retrospective study | 14 | 50% administered corticosteroids | |||
| Annam et al. [29] | 2022 | India | Case report | 2 |
Case 1: 27 Case 2: 69 |
M | - |
Case 1: 430 mg of prednisolone equivalent Case 2: 1040 mg of prednisolone equivalent. |
| Ardakani et al. [22] | 2022 | Iran | Case series | 5 | 38.4 ± 14.44 | 3 F, 2 M |
Case 1: - Case 2: ALL Case 3: breast cancer, radiotherapy, and chemotherapy. Case 4: - Case 5: - |
1695.2 ± 281.76 mg of prednisolone equivalent |
| Assad et al. [30] | 2023 | Iraq | Case series | 17 | 38.65 ± 6.1 | 12 M, 5 F | 8 history of trauma | 14 history of steroid use |
| Bakır and Rumeli [31] | 2024 | Turkey | Case report | 1 | 49 | M | 1250 mg of prednisolone | |
| Beketova et al. [32] | 2022 | Russia | Case report | 3 | 59.33 ± 7.32 | 2 F | 1 sarcoidosis, 2 osteoarthritis, 1 osteoporosis | 2 case corticosteroid |
| Bialik et al. [33] | 2022 | Russia | Case report | 3 | 42.5 ± 12.5 | 1 hypocholesteremia |
630 mg prednisolone 986.9 mg prednisolone |
|
| Darraz et al. [34] | 2024 | Turkey | Case report | 1 | 64 | F | Hypertension, Dyslipidemia | 600 mg of prednisone equivalent |
| Demir et al. [35] | 2025 | Turkey | Cross sectional | 48 | 46.13 ± 13.33 | 17 F, 31 M | 1295.16 ± 857.98 mg prednisolone | |
| Ergün et al. [24] | 2022 | Turkey | Case report | 1 | 51 | F | Sickle cell anemia | - |
| Godoy-Monzón et al. [36] | 2024 | Argentina | Case series | 13(21 hips) |
Mean (range) 47 (36–64) |
480 mg/day | ||
| Haghighatafshar [37] | 2024 | Iran | Case report | 1 | 41 | M | - | |
| Hogea et al. [38] | 2024 | Romania | Retrospective study | 26 | 52.3 ± 8.9 | 9 F, 17 M | 22 patients with comorbidity | 19 patients with corticosteroid therapy |
| Igei et al. [39] | 2025 | japan | Retrospective study | 8 | 47.1 ± 10.8 | 3 F, 5 M | 718.9 ± 447.3 mg | |
| Inneh et al. [40] | 2023 | USA | Case report | 1 | 42 | F | - | - |
| Ivanova et al. [41] | 2023 | Bulgaria | Case report | 1 | 37 | F | Multiple Genetic Coagulation Factor Deficiency | 1952 mg equivalent prednisolone |
| Jagzape et al. [42] | 2023 | India | Case report | 1 | 28 | M | Corticosteroid therapy | |
| Jha et al. [43] | 2024 | India | Case series | 10 | 58.8 ± 11.3 | 6 F, 4 M | 2 diabetes mellitus, 1 hypertension, 1 depression | 4 corticosteroid therapy |
| Kamani et al. [44] | 2022 | India | Case report | 1 | 40 | M | Corticosteroid therapy | |
| Kandari et al. [45] | 2022 | India | Case series | 11 | 45.82 ± 8.33 | 2 F, 9 M | 1 hypertension | 1855.45 ± 254.82 mg corticosteroid |
| Khan et al. [46] | 2024 | India | Cross sectional | 22 | 3 hypertension, 4 Diabetes mellitus | 14 patients steroid therapy | ||
| Kingma et al. [47] | 2022 | USA | Case report | 1 | 60 | M | hypertension, hyperlipidemia, coronary artery disease | |
| Klimenko et al. [48] | 2023 | Russia | Case report | 1 | 59 | - | ||
| Kumar et al. [25] | 2025 | India | Case series | 10 | 29.1 ± 4.94 | 7 M, 3 F | 569 mg | |
| Maharjan et al. [49] | 2022 | Nepal | Case report | 1 | 22 | F | Corticosteroid treatment | |
| Murugesan et al. [26] | 2024 | USA | Case report | 1 | 29 | M | - | - |
| Myasoedov et al. [50] | 2023 | Russia | Cross sectional |
Severe COVID-19: 183 Mild COVID-19: 78 |
Median (IQR) Severe COVID-19: 56 (18) Mild COVID-19: 43 (11) |
Severe COVID-19: 81 F, 102 M Mild COVID-19: 21 F, 57 M |
183 corticosteroid treatment | |
| Panin et al. [51] | 2022 | Russia | Case series | 4 |
Case 1: 42 Case 2: 32 Case 3: 32 Case 4: 30 |
Case 1: M Case 2: M Case 3: F Case 4: F |
Case 1: - Case 2: - Case 3:- Case 4:- |
Case 1: 4000 mg prednisolone equivalent Case 2: 746 mg prednisolone equivalent Case 3: 533 mg prednisolone equivalent Case 4: - |
| Parameswaran et al. [52] | 2025 | India | Case report | 1 | 43 | M | Corticosteroid therapy | |
| Parikh et al. [53] | 2023 | USA | Case series | 3 |
Case 1: 47 Case 2: 71 Case 3: 49 |
Case 1: F Case 2: M Case 3: M |
Case 1: ESRD, kidney transplant, history prednisone therapy Case 2: hypertension Case 3: lumbar radiculopathy |
Case 1: - Case 2: corticosteroid therapy Case 3: - |
| Petrusevska-Marinkovic et al. [54] | 2024 | North Macedonia | Case report | 2 |
Case 1: 50 Case 2: 37 |
M |
Case 1: 400 mg of prednisolone equivalent Case 2: 1587 mg of prednisolone equivalent |
|
| Sehgal et al. [55] | 2024 | India | Case series | 20 | 6 F, 14 M | 6 Hypertension, 8 Diabetes mellitus | ||
| Seong et al. [56] | 2025 | Uzbekistan | Retrospective study | 84 | 42.5 ± 10.5 | 23 F, 61 M | 9 hypertension, 4 diabetes mellitus | 173 ± 125 mg equivalent dexamethasone |
| Sinha et al. [57] | 2023 | India | Case series | 10 | 58.8 ± 11.3 | 6 F, 4 M | ||
| Sulewski et al. [58] | 2021 | Poland | Case series | 3 | 66.67 ± 3.40 | 2 F, 1 M | 1 diabetes mellitus | - |
| Tewatia et al. [59] | 2022 | India | Case report | 1 | 40 | M | Corticosteroid therapy | |
| Yılmam et al. [60] | 2021 | Turkey | Case report | 1 | 44 | F | congenital torticollis |
dexamethasone 6 mg/day 18 mg dexamethasone in ICU |
| Velchov et al. [61] | 2023 | Bulgaria | Retrospective study | 24 | 56 ± 15 | 7 F, 17 M |
53.33 ± 47.14 prednisolone 6 ± 3.46 dexamethasone |
|
| Agarwala et al. [17] | 2021 | India | Case series | 3 | 37.33 ± 1.25 | 3 M | 758.33 ± 359.59 mg prednisolone equivalent | |
| Dhanasekararaja et al. [62] | 2022 | India | Case series | 22 | 38.82 ± 14.13 | 2 F, 20 M | 4 hypertension, 2 diabetes mellitus, 1 hypothyroidism | 811.08 ± 527.30 mg methylprednisolone equivalent |
| Mahran et al. [63] | 2022 | Egypt | Case series | 4 | 27.75 ± 6.38 | 2 F, 2 M | - | Corticosteroid therapy |
| Nejadhosseinian et al. [64] | 2023 | Iran | Case report | 1 | 39 | M | 3706 mg methylprednisolone | |
| Sehrawat et al. [65] | 2023 | India | Cross sectional | 50 |
Mean (range) 36.3 (20–60) |
5 F, 45 M | 42 cases with corticosteroid therapy | |
| Yoshimura et al. [66] | 2024 | Japan | Case report | 1 | 87 | F | osteoporosis, hypertension, and breast cancer | 1642.6 mg methylprednisolone equivalent |
| Alkindi et al. [67] | 2022 | UAE | Case report | 1 | 29 | M | 200 mg methylprednisolone | |
| Chacko et al. [68] | 2021 | India | Case report | 1 | 23 | M | 860 mg of prednisolone equivalent | |
| Daltro et al. [69] | 2021 | Brazil | Case report | 23 |
Mean (range) 43.5 (25–61) |
8 F, 15 M | 15 patients corticosteroid therapy | |
| Etta et al. [23] | 2022 | India | Case report | 1 | 38 | M | Kidney transplant | Steroid therapy |
| Jayapalan et al. [70] | 2023 | India | Case report | 1 | 31 | M | 608 mg methylprednisolone | |
| Joshi et al. [71] | 2021 | Bangladesh | Case report | 1 | 31 | F | 544 mg methylprednisolone | |
| Jyothiprasanth et al. [72] | 2023 | India | Case series | 17 |
Mean (range) 37 (23–60) |
7 F, 10 M | ||
| Karpur et al. [73] | 2023 | India | Case series | 20 | 6 F, 14 M | 8 diabetes, 6 hypertension | ||
| Shershah et al. [74] | 2023 | India | Case series | 3 | 29.33 ± 1.89 | 1 F, 2 M | 560 mg methylprednisolone | |
| Uysal et al. [75] | 2022 | Turkey | Case report | 1 | 63 | M | - |
| Study | Corticosteroid therapy | Diagnosis | MRI Ficat and Arlet Stage | Interval between COVID-19 infection and AVN | Treatment | Follow-up | Outcome | Quality assessment |
|---|---|---|---|---|---|---|---|---|
| Agarwala et al. [27] | Mean (range) 841.3 (100–3520) mg prednisolone equivalents | Femoral head AVN | 13 stage I, 66 stage II, 9 stage III | Mean (range) 179 (59–459) days | Zoledronic acid, alendronate, calcium, Vitamin D, surgery | Mean (range) 10 (6–13) months |
84 hips with good clinical outcome, 4 surgical intervention VAS Before: 7.03 After: 3.13 HHS Before: 59.14 After: 71.01 |
7/10 |
| Aishwarya et al. [28] | 50% administered corticosteroids | Femoral head AVN | Stage III and IV | Total hip arthroplasty | 8/10 | |||
| Annam et al. [29] |
Case 1: 430 mg of prednisolone equivalent Case 2: 1040 mg of prednisolone equivalent. |
Bilateral femoral head AVN |
Case 1: stage II and IV Case 2: stage II and IV |
Case 1: 15 day Case 2: 2 months |
Case 1: left hip core decompression and conservative management on the right side. Then, total hip replacement surgery and hip core decompression on the left and right hip respectively Case 2: Right hip decompression and left hip replacement |
6/8 | ||
| Ardakani et al. [22] | 1695.2 ± 281.76 mg of prednisolone equivalent |
Case 1: septic arthritis of the left hip joint and femoral head AVN Case 2: septic arthritis of the both hip joints and femoral head AVN Case 3: septic arthritis of the right hip joint and femoral head AVN Case 4: septic arthritis of the both hip joints and femoral head AVN Case 5: septic arthritis of the both hip joints and femoral head AVN |
Case 4: stage IV Case 5: stage II |
45 ± 14.76 days |
Case 1: THA Case 2: arthrotomy, irrigation and debridement for left side and THA for the right side. Case 3: THA Case 4: THA and cement placement for both hip joints Case 5: THA |
2.1 ± 0.73 |
All improved VAS Before: 9.4 ± 0.49 After: 2.8 ± 1.17 |
7/10 |
| Assad et al. [30] | 14 history of steroid use |
14 bilateral hip AVN 1 right hip AVN 1 left hip AVN |
Stage II, III and IV | 6.53 ± 3.81 months | 3 THR, 9 conservative, 5 core decompression | 7/10 | ||
| Bakır and Rumeli [31] | 1250 mg of prednisolone | Bilateral femoral head AVN | 6 months | Hyperbaric oxygen, NSAID, and physiotherapy | Not Improved | 6/8 | ||
| Beketova et al. [32] | 2 case corticosteroid | 1 bilateral, 2 unilateral femoral head AVN |
2 Stage III 2 stage II |
7.67 ± 1.70 months |
Case 1: Ibandronic acid Apixaban Vitamin D, Calcium Case 2: zoledronic acid, calcium, vitamin D Case 3: zoledronic acid, vitamin D, calcium |
6/8 | ||
| Bialik et al. [33] |
630 mg prednisolone 986.9 mg prednisolone |
1 bilateral, 1 left femoral head AVN | Stage II | 8 ± 0 months |
Case 1: zoledronic acid, vitamin D, calcium, dipyridamole, physiotherapy Case 2: ossein hydroxyapatite complex; taking calcium carbonate 600 mg + cholecalciferol 400 IU for 6 months; NMRI − 9 sessions per course; taking NSAIDs |
Case 1: 3 months |
Case 1: VAS: right: 75, left: 60 Before: After: right: 60, left: 10 Case 2: VAS: right: 20, left: 50, Before: After: right: 5, left: 60 |
7/8 |
| Darraz et al. [34] | 600 mg of prednisone equivalent | Bilateral Femoral Head AVN | Stage II and III | 7 months | THA | 2 months | Improved | 7/8 |
| Demir et al. [35] | 1295.16 ± 857.98 mg prednisolone | 39 bilateral femoral head AVN | 21 stage II, 19 stage III, 8 stage IV | 6/9 | ||||
| Ergün et al. [24] | - |
Bilateral AVN of the femoral heads |
Stage I | 2 months | Core decompression | 10 weeks | Improved | 6/8 |
| Godoy-Monzón et al. [36] | 480 mg/day | Femoral head AVN (8 bilateral) | 10 stage I, 6 stage II, 5 stage III |
Mean (range) 30.5 (14–41) days |
3 THA |
HHS Before: 41.2 ± 5.2 After: 86.6 ± 3.4 |
7/10 | |
| Haghighatafshar [37] | - | Femoral head AVN | 9 months | 6/8 | ||||
| Hogea et al. [38] | 19 patients with corticosteroid therapy | 9 Bilateral femoral head necrosis, 17 unilateral | 6/10 | |||||
| Igei et al. [39] | 718.9 ± 447.3 mg | Bilateral femoral head AVN | 1 stage I, 4 stage II, 5 stage IIIA, 6 stage IIIB | 9.25 ± 6.58 months | 8 conservative treatment, 8 surgical treatment. | 6/10 | ||
| Inneh et al. [40] | - | Bilateral femoral head AVN | 5/8 | |||||
| Ivanova et al. [41] | 1952 mg equivalent prednisolone | Bilateral femoral head AVN | 4 months | Left THA | 6/8 | |||
| Jagzape et al. [42] | Corticosteroid therapy | Bilateral femoral head AVN | Physiotherapy treatment | 4 weeks |
VAS Before: 8 After:3 HHS Before: 11 After: 63 |
7/8 | ||
| Jha et al. [43] | 4 corticosteroid therapy | 6 right femoral head, 4 left femoral head | 14.4 ± 4.61 days | All conservative, 4 decompression, 3 arthroplasty | 7.30 ± 2.00 months |
VAS Before: 7.7 ± 0.78 After: 0.5 ± 0.67 |
8/10 | |
| Kamani et al. [44] | Corticosteroid therapy | Bilateral femoral head AVN |
Left stage III and IV Right stage II |
2 months | Core decompression and physiotherapy | 6 weeks |
NPRS Before: 8 After: 2 |
6/8 |
| Kandari et al. [45] | 1855.45 ± 254.82 mg corticosteroid | 5 bilateral, 6 unilateral femoral head AVN | 1 stage I, 8 stage II, 5 stage III, 2 stage IV | 7 months | 8 conservative, 1 THA, 1 THA and conservative, 1 decompression and conservative |
VAS Before: 7.19 ± 0.95 After: 2.69 ± 1.16 HHS Before: 59.25 ± 6.92 After: 77.75 ± 5.91 |
7/10 | |
| Khan et al. [46] | 14 patients steroid therapy | 14 bilateral, 5 left, 3 right femoral head AVN | 6/9 | |||||
| Kingma et al. [47] | Bilateral femoral head AVN | 10 months | bilateral THA | 6/8 | ||||
| Klimenko et al. [48] | - | Bilateral femoral head AVN | Stage II | 9 months |
Conservative therapy Right total hip arthroplasty |
5/8 | ||
| Kumar et al. [25] | 569 mg | 4 bilateral femoral head necrosis, 10 unilateral | 6.36 ± 2.69 months | Free Vascularized fibula graft |
HHS Before: 65.79 ± 4.56 After: 68.28 ± 24.85 |
7/10 | ||
| Maharjan et al. [49] | Corticosteroid treatment | Bilateral femoral head AVN | 7 months |
Core decompression, Alendronate, cefuroxime, clavulanic acid, Non-weight bearing exercises, Mobilization on crutches, Physiotherapy |
2 months | Improved | 7/8 | |
| Murugesan et al. [26] | - | Bilateral femoral head AVN | Stage II | 11 months | Symptomatic treatment (waiting for surgery) | Worsened | 5/8 | |
| Myasoedov et al. [50] | 183 corticosteroid treatment | Femoral head AVN |
Median (IQR) Severe COVID-19: 3 (5) months Mild COVID-19: 8 (7) months |
6/9 | ||||
| Panin et al. [51] |
Case 1: 4000 mg prednisolone equivalent Case 2: 746 mg prednisolone equivalent Case 3: 533 mg prednisolone equivalent Case 4: - |
Bilateral femoral head AVN |
Case 1: 80 days Case 2: 75 days Case 3: 120 days Case 4: 180 days |
Case 1: bilateral decompression, statins, bisphosphonates, and anticoagulants Case 2: anticoagulants and bisphosphonates Case 3: left THA Case 4: anticoagulants and bisphosphonates |
Case 1: 3 months Case 2: 4 weeks |
VAS Case 1: Before: 8 After: 4 Case 2: Before: 8 After: 4 Case 3: - Case 4: - |
8/10 | |
| Parameswaran et al. [52] | Corticosteroid therapy | Bilateral AVN of femoral head with concomitant septic arthritis | 4 months | Bilateral THA | 2 years | improved | 6/8 | |
| Parikh et al. [53] |
Case 1: - Case 2: corticosteroid therapy Case 3: - |
Case 1: Bilateral femoral head AVN Case 2: left femoral head AVN Case 3: left femoral head AVN |
Case 1: left hip stage IV, right hip stage II Case 2: - Case 3: stage II |
Case 1: - Case 2: core decompression Case 3: bilateral core decompression |
Case 1: - Case 2: improved Case 3: improved |
6/10 | ||
| Petrusevska-Marinkovic et al. [54] |
Case 1: 400 mg of prednisolone equivalent Case 2: 1587 mg of prednisolone equivalent |
Case 1: Bilateral femoral head AVN Case 2: right femoral head AVN |
Case 1: stage I-II Case 2: stage III |
Case 1: 62 days Case 2: 68 days |
Case 1: Alendronate, calcium carbonate, cilostazol, diosmin, and hyperbaric chamber Case 2: NSAID and head decompression |
Case 1: 1 year |
VAS Case 1: Before: 8 After: 3 Case 2: Before: 9 After: 8 |
7/8 |
| Sehgal et al. [55] | Femoral head AVN | 9 stage I, 8 stage II, 3 stage III | 6/10 | |||||
| Seong et al. [56] | 173 ± 125 mg equivalent dexamethasone | 34 unilateral AVN of femoral head, 50 bilateral AVN of femoral head | 12 ± 5.3 months | 6/10 | ||||
| Sinha et al. [57] | Femoral head AVN | 14 ± 4.61 days | 3 arthroplasty, 4 core decompression, 3 conservative therapy | 7 improved | 7/10 | |||
| Sulewski et al. [58] | - | Femoral head AVN | 13.33 ± 6.34 months | 2 arthroplasty, 1 conservative | 7.33 ± 2.05 months |
VAS Before: 7.67 ± 0.47 After: 0.67 ± 0.94 |
8/10 | |
| Tewatia et al. [59] | Corticosteroid therapy | Bilateral hip AVN | 9 months | core decompression | Improved | 6/8 | ||
| Yılmam et al. [60] |
dexamethasone 6 mg/day 18 mg dexamethasone in ICU |
Bilateral hip AVN | 2 months | Hyperbaric oxygen therapy | 5/8 | |||
| Velchov et al. [61] |
53.33 ± 47.14 prednisolone 6 ± 3.46 dexamethasone |
4 bilateral femoral head AVN | 57 ± 12 days | 19 THA, 4 THA and core decompression, 1 core decompression | 6 months |
HHS Before: 59.2 ± 11.4 After: 86.8 ± 7.2 |
9/10 | |
| Agarwala et al. [17] | 758.33 ± 359.59 mg prednisolone equivalent | 2 bilateral, 1 left femoral head AVN | All stage II | 49 ± 5.66 days | Alendronate and zoledronic acid | 70.7 days |
Mean (range) VAS: Before: 8 (6–9) After: 2.7 (1–4) |
8/10 |
| Dhanasekararaja et al. [62] | 811.08 ± 527.30 mg methylprednisolone equivalent | 17 Bilateral, 2 right, 3 left femoral head AVN | 2 THA, 20 conservative therapy |
HHS Before: 63.64 ± 22.64 After: 82.64 ± 9.37 |
8/10 | |||
| Mahran et al. [63] | Corticosteroid therapy | 3 bilateral, 1 left femoral head AVN | 3 core decompression, 1 THA and core decompression | 7/10 | ||||
| Nejadhosseinian et al. [64] | 3706 mg methylprednisolone | Bilateral femoral head AVN | 20 months | Core decompression | 5/8 | |||
| Sehrawat et al. [65] | 42 cases with corticosteroid therapy | 39 Bilateral, 11 Unilateral femoral head AVN |
44 stage I or II 6 stage III or IV |
Mean (range) 359.02 days ( 10–822) |
27 patients bisphosphonate 14 patients core decompression 3 patients core decompression with fibular grafting 6 patients total hip arthroplasty |
Mean (range) 9.79 (6–19) months |
Mean (range) Bisphosphonate: VAS Before: 8(6–10) After: 4 (0–6) HHS Before: 67.7 (42.35-84) After: 88.0 (52–96) Core decompression VAS Before: 8 (4–10) After: 4 (0–6) HHS Before: 59.70 (34.65–87.85) After: 90.0 (49.85-86) THA VAS Before: 8 (6–10) After: 1 (0–6) HHS Before: 47.20 (10.40-56.65) After: 91.50 (80.65–99.75) |
7/9 |
| Yoshimura et al. [66] | 1642.6 mg methylprednisolone equivalent | Unilateral femoral head AVN | 16 months | THA | 3 months | Improved | 7/8 | |
| Alkindi et al. [67] | 200 mg methylprednisolone | Bilateral femoral head AVN | 8 weeks | Core decompression, NSAID, physiotherapy | 6 weeks | Improved | 6/8 | |
| Chacko et al. [68] | 860 mg of prednisolone equivalent | Bilateral femoral head AVN | Stage II | 56 days | Core decompression and bone marrow aspiration | 5/8 | ||
| Daltro et al. [69] | 15 patients corticosteroid therapy | Bilateral femoral head AVN | 132.8 (64–180) days | 3 surgery | 5/8 | |||
| Etta et al. [23] | Steroid therapy | Bilateral femoral head AVN | 8 weeks | core decompression, bone grafting, and physiotherapy | 6 weeks | Improved | 6/8 | |
| Jayapalan et al. [70] | 608 mg methylprednisolone | Bilateral femoral head AVN | 65 days | Core decompression | 5/8 | |||
| Joshi et al. [71] | 544 mg methylprednisolone | Bilateral femoral head AVN | 1 month | 5/8 | ||||
| Jyothiprasanth et al. [72] | 13 unilateral and 4 Bilateral femoral head AVN | 12 Stage II, 9 stage III |
Mean (range) 66 (43–100) days |
5/10 | ||||
| Karpur et al. [73] | 9 stage I, 8 stage II, 3 stage III | 6/10 | ||||||
| Shershah et al. [74] | 560 mg methylprednisolone | Bilateral femoral head AVN | 8.00 ± 4.32 months | 2 THA, 1 core decompression | 6/10 | |||
| Uysal et al. [75] | Bilateral femoral head AVN | Right stage II | 5 months | Alendronate and surgery plan | 5/8 |
Discussion
COVID-19 was associated with a wide range of musculoskeletal problems, such as joint pain, muscle pain, spasticity, and osteonecrosis [76]. One of the concerns after COVID-19 pandemic was AVN development.
Different factors such as fractures, dislocations, traumas, hemolobinopathies, lipid emboli, systemic lupus erythematosus, alcohol consumption, smoking, administration of medications such as corticosteroids, and pregnancy may lead to the development of avascular necrosis of the femur [77].Femoral head AVN is characterized by necrosis of the bone marrow and loss of osteocytes due to blood insufficiency to the bone [75].
Increased osteoclastic activity will lead to the cleaning of necrotic trabeculae and trabecular bone weakening. Fracture of weakened bone results in subcondral collapse and development of symptoms such as pain, limitation of range of motion, and gait imbalance [78]. The best diagnostic choice is MRI of the hip because detection of volume and location of the infarcted bone will be possible. AVN mostly happens in adults and in the third fourth, it is bilateral [79, 80].
Early diagnosis can slow disease progression and help prevent subchondral collapse and the need for disabling arthroplasty [72].
Agarwala et al. reported three cases of femoral head AVN following COVID-19 infection who were treated with non-surgical medications (alendronate and zolendronic acid) whose symptoms significantly improved during the follow-up [17].
Jyothiprasanth evaluated 17 cases with AVN between July 2022 and July 2023 (They had excluded cases that took corticosteroids). Fourteen out of seventeen cases developed symptoms immediately after COVID-19 infection, such as hip pain. 71% were male, and avascular necrosis (AVN) was bilateral in only three cases. The age of patients ranged from 23 to 60 years, and symptom onset occurred between 7 and 100 days. The most common underlying conditions were diabetes mellitus and hypertension [72].
By including 22 cases, Dhanasekararaja et al. reported significant improvement of symptoms in 20 cases who underwent conservative therapy and two THA. Patients developed osteonecrosis of the femur after corticosteroid therapy for COVID-19 infection (in 17 cases, AVN involved both hips) [62].
Developing osteonecrosis following corticosteroid therapy depends on daily dose, cumulative dose, maximum dose of the medication, and the route of administration [27]. Kandari et al. reported a direct link between dose and treatment duration with corticosteroids and severity and stage of AVN [45].
In general, corticosteroid therapy may induce osteonecrosis when the cumulative dose exceeds 2 g. However, in our review, only Nejadhosseinian et al. reported a case in which a patient received 3706 mg of corticosteroids and developed bilateral femoral AVN 20 months after COVID-19 infection [64].
Panin et al. reported four cases of AVN who developed AVN after COVID-19. One of them was treated with 4000 mg corticosteroid and developed bilateral AVN eighty days after COVID-19 onset. Non-surgical treatment improved the symptoms of those cases [51],
It appears that the development of AVN in patients following COVID-19 may involve additional mechanisms, such as a hypercoagulable state and thrombotic complications, formation of fat emboli, hyperlipidemia, direct endothelial injury, activation of the complement pathway leading to hypercoagulability, and mast cell activation syndrome [81–83].
Underlying diseases such as diabetes mellitus, hypertension, and sickle cell anemia should be considered as risk factors for developing AVN.
Some studies have reported symptom improvement with the use of painkillers, hyperbaric oxygen therapy, vitamin D, zoledronic acid, and physiotherapy. Others have used bisphosphonate therapy and observed significant symptom relief [27]. In advanced stages, such as stage III or IV, surgical treatments including core decompression, bone grafting, and arthroplasty may be performed [79, 80].
To restore hip joint function, total hip arthroplasty (THA) is recommended for patients in stage III or IV. Aishwarya et al. reported a six-fold increase in the rate of THA at their center after the pandemic compared to the pre-pandemic period [28].
This study had some limitations. First, most included studies were case reports or case series. Second, all studies did not report the stage of the AVN, duration of treatment with corticosteroids, or time interval between COVID-19 and AVN development, which may arise a source of bias.
Our study has some strengths. First, it is a comprehensive review including fifty-five studies. Second, we extracted all available data in included studies.
Conclusions
Avascular necrosis of the femoral head in cases that survived from COVID-19 should be considered carefully as early diagnosis helps to preserve the joint and its function.
Acknowledgements
The authors would like to thank the Research Development Center of Sina Hospital for their technical assistance.
Author contributions
Mohaddeseh Azadvari: Study conception, article writing. Nafiseh Akbari: Data gathering, article writing. Sepanta Hatam: Data gathering, article writing. Mohsen Rastkar: Data analysis, article writing. Seyede Zahra Emami Razavi: Study design, supervision, article editing.
Data availability
All data generated or analyzed during this study are included in this published article.
Declarations
Conflict of interest
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Data Availability Statement
All data generated or analyzed during this study are included in this published article.