Avascular necrosis as a part of ‘long COVID-19’

Discussion

Corticosteroid use is considered to be one of the most common cause for the development of AVN. The pathogenesis of steroid-induced AVN is not well established, but postulated mechanisms include fat emboli, fat hypertrophy, hypercoagulable condition, vascular endothelial dysfunction and abnormality of the bone marrow stem cell.9

There is a lack of consensus about the dosage and duration of steroids required to develop AVN. Some authors have reported that a cumulative dose of 2000 mg prednisone (or its equivalent) was required for AVN development.10 Some studies have shown that 700 mg is the minimum dose required to develop AVN.11 However, McKee et al have shown that in their series of 15 patients who developed AVN, mean steroid dose in prednisone equivalents was 850 mg with a range of 290 mg–3300 mg.12 The mean dose of prednisolone equivalent steroid taken in our series was 758 mg (range 400–1250 mg).

Controversy exists about the time after the steroid administration to the development of AVN symptoms. In a case report of a 23-year-old male patient who developed shoulder AVN after receiving oral dexamethasone (equivalent to 700 mg of prednisolone), the authors have reported that the patient developed symptoms 2 years after the administration of steroids.11 McKee et al, in their study, have reported a mean time of 16.6 months (range 6–33 months) from the administration of corticosteroids to the development of AVN.12 Literature review shows that the interval between corticosteroid intake and development of symptomatic AVN is usually 6 months to 1 year.13 14 The mean time duration for the development of AVN post COVID-19 diagnosis in our series was 58 days (range 45–67 days).

Treatment objective in AVN is to obtain pain relief, retard disease progression, prevent collapse and restore joint function. Multitude treatment options are available for managing AVN ranging from conservative, medical to surgical modalities, however no standardised protocol exists. Various medical therapies tried in the past including iloprost, nifedipine and hyperbaric oxygen therapy have not shown significant benefits.7 Therefore, arthroplasty remains the mainstay of treatment. Although it provides good outcome but when performed at a young age will necessitate at least one revision in the future. Successful use of bisphosphonates for the treatment of AVN in adults was first reported by Agarwala et al.8 The authors have shown that bisphosphonates not only give good clinical outcome but also retard progression of the disease and the need for a surgery. Subsequently, various authors have published the role of bisphosphonates in management of AVN and it is now considered to be as one of the standard options of treatment of AVN.

In our case series, AVN occurred with a low mean steroid dosage of 758 mg with a minimum dose of 400 mg compared with the literature which shows that a mean cumulative dose of 2000 mg steroid is required for the development of AVN. Further, the patient developed AVN very early with a mean range of 58 days after COVID-19 diagnosis compared with the literature which shows that it generally takes 6 months to 1 year to develop AVN post steroid exposure.

Post COVID-19, there is a greater propensity to develop AVN, mainly if the patient has been on steroids. The literature suggests the mean dose of steroid in prednisone equivalents of 2000 mg is required to cause AVN, but we feel that due to the COVID-19 virus, the sensitivity to develop AVN is higher and to a smaller cumulative dose of steroids.

Steroids are life-saving and have to be administered. However, AVN, being picked up early, may decrease the patient’s morbidity by bisphosphonate combination therapy. The most sensitive and least invasive test to diagnose early AVN is an MRI of the hips. Hence, it is recommended that on early suspicion, early MRI should be advised.