MRI spectrum of avascular necrosis of femoral head in patients treated for COVID-19

INTRODUCTION

The occurrence of bone death following reduced blood supply or complete stoppage of blood supply is known as avascular necrosis (AVN). The affected bone portion then disintegrates and eventually collapses. The femur is one of the commonly affected bones. Excess use of corticosteroids is one of the most common medical causes of AVN. Affected patients usually complain of gradually increasing pain and reducing the range of movement. Treatment varies from guided physiotherapy to medications and eventually surgery if needed.^[1]

By May 28, 2021, a total of 168,599,045 confirmed COVID-19 cases, including 3,507,477 deaths, have been reported worldwide to the World Health Organization.^[2] Indian contribution to this global statistics has been 27,555,457 confirmed cases and about 318,895 deaths.^[3] However, no data pertaining to the occurrence or presentation of AVN in the femur of patients who have been treated for COVID-19 are available as of now.

Tremendous diagnostic data are available for diagnosing COVID-19 pneumonia, and numerous guidelines are being put forth for timely diagnosis and prompt treatment.^[4]

However, diagnostic data and imaging guidelines for patients treated for COVID and suffering from hip pain are not available. Hence, this retrospective study was done to analyze the spectrum of AVN of the femoral head as seen in MRI images of patients treated for COVID-19.

MATERIAL AND METHODS

RESULTS

Demographic and clinical characteristics: These are listed in [Table 1]. Imaging features are shown in Figure 1.

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Figure 1:

(a) Coronal MRI T1W image: Normal appearance of femoral heads, (b) coronal MRI STIR image: Bilateral Stage I AVN of femoral heads, (c) coronal MRI T1W image: Bilateral Stage II AVN of femoral head, and (d) coronal MRI T1W image: Right Stage III AVN of femoral head, left Stage II.

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Imaging features of MRI: These are listed in [Table 2].

The mean interval between the onset of initial symptoms and MRI was 2–4 weeks.

No positive findings to suggest any femoral head AVN as per the Ficat and Arlet classification were seen in 94% of cases.

• Stage IV AVN was seen in 0 cases (0%).

• Stage I AVN was seen in 6 cases (3%).

• Stage II AVN was seen in 4 cases (2%).

• Stage III AVN was seen in 2 cases (1%).

DISCUSSION

Globally, corticosteroids are being widely used for treating COVID-19 infection. Reports of high dose and/or long duration of steroid usage in these patients leading to steroid-induced AVN of the femoral head (SANFH) are on the rise. Hence, valid usage of steroids backed by the timely diagnosis of possible SANFH for its prevention and timely treatment is pertinent.^[6] SANFH has a poor prognosis as it can lead to a subchondral collapse in a short time.

Glucocorticoids affect the emulsification of very-low-density lipoprotein cholesterol in the blood which if incomplete adds to lipoprotein globules resulting in small fat emboli that occlude peripheral blood vessels cause ischemic necrosis of the bone tissue. Simultaneously, free fatty acids from hydrolysis of the fat emboli damage the capillary endothelial cells resulting in vasculitis and also encourage intravascular coagulation further speeding up the AVN.^[7] Glucocorticoids impair the response of the blood vessels to vasoactive substances causing vascular constriction affecting the femoral head causing further femoral head ischemia.^[8] MicroRNA (miR)-596 in cases diagnosed as SNFHN is found to be upregulated, thereby impairing the repair of the osteonecrotic bone as it inhibits the proliferation and osteogenic differentiation of the bone marrow stromal cells.^[9] miR-17-5p and miR-210 are also believed to be involved in the pathogenesis of SANFH.^[10,11]

It has been reported that as many as, about 39% of patients with COVID-19 developed SIFHN in a few months of glucocorticoid treatment.^[12] In fact, few patients who were on corticosteroids for less than a month too or even at lesser doses as well reported AVN.^[13] Some studies implicate the virus itself as an independent factor leading to AVN through S protein per se.^[14,15]

It has been opined by recent researchers^[6] that patients with mild COVID-19 illness should not be administered corticosteroids. Only those having severe disease should be put on steroids that too as low dosage as needed for treatment. The level of dosage may vary from region to region and locality to locality.^[6]

As the recovery rate from COVID-19 is thankfully increasing, it has to be remembered that we would see more and more post-convalescence complications like AVN^[16] which can thereby significantly hamper the return to normalcy in such patients. Long-term follow-up and big data in this aspect are our current constraints; hence, the sooner we assess any new onset large joint pain in such patients the better we are in diagnosing and treating AVN.^[16]

Prompt diagnosis ensures timely treatment. Hence, periodic MRI scans for possible AVN of the hip, especially in high-risk patients, have been found to be 93–100% sensitive.^[17] It has been found that the onset time of post-glucocorticoid usage AVN can start occurring anywhere from 3 weeks to 3 months.^[18,19] MRI scans are recommended at 3, 6, and 12 months after steroid administration.^[20]

If left untreated, AVN becomes irreversible and damages the hip permanently. Some medications like levodopa reduce osteocyte apoptosis and enhance repair by increasing insulin-like growth factor-1.^[21] Alendronate sodium inhibits the bone resorption capacity of osteoclasts and delays AVN.^[22] Hyperbaric oxygen treatment for 6 weeks promotes angiogenesis and improves the function of osteoblasts and osteoclasts and gives symptomatic relief.^[23,24] An year of extracorporeal shock wave therapy (ESWT) was found to significantly reduce pain and improve functionality.^[25] Combined therapy (alendronate sodium, ESWT, and HBO) can delay and even prevent the development of AVN.^[26]

The present study assessed MRI hip imaging features in patients suffering from hip or back pain that had received standard treatment for COVID-19 pneumonia in a sample of 200 patients.

No significant hip joint findings were noted in maximum cases 188/200 (94%). We found an abnormal (positive) MRI hip status in 12/200 (06%) of patients. Maximum patients presented between 2 and 4 weeks of symptoms of hip or back pain.

Stage IV AVN was seen in 0 cases (0%). This is because all the cases were detected earlier due to the timely presentation of affected patients. Stage I AVN was the most common and seen in 6 cases (3%). This represents edema. Most of the patients were in the younger age group <40 years and hence presented earlier.

Stage II AVN was seen in 4 cases (2%). This was seen more in the middle and elderly age group (40–60 years of age). Stage III AVN was seen in 2 cases (1%). This was seen more in the elderly age group (>60 years of age).

The most commonly affected age group in the present study was <40 years of age. It is likely that this particular age group after getting treated for COVID-19 returned to their office work and daily chores as they belonged to the active working-age group. Positive inclusion criteria but no positive findings on MRI scans in a large number of patients indicate that the patients underwent MRI in a very early phase so hip lesions were not developed till that time. It is also possible that though the patients had symptoms, they might not be due to problems in the hip per se.

The study highlights the necessity to be vigilant for the possibility of AVN of the hip in these cases so that they are timely diagnosed early on and treated properly as per prevalent scientific norms.

The study is limited by its small sample size and absence of follow-up scans. The exact amount and duration for which patients received steroid treatment during COVID-19 infection could not be ascertained. The radiological and histopathological correlation could not be established due to the wanting of femoral biopsy permissions. Furthermore, recently, reported BOLD-MRI which is of more usage in early detection of AVN over conventional MRI techniques^[27] could not be used for lack of availability.

CONCLUSION

Newer data about evolving AVN of hips in patients that received treatment for COVID-19 in the recent past are emerging. Gradually, cases are bound to increase. Hence, the medical fraternity should be aware of this possibility and inform the patients about this entity for timely diagnosis and management.