Since the initial reporting in China, coronavirus disease 2019 (COVID-19) infection has spread globally, infecting people in almost every country and affecting the lives of millions^1-3). Although most patients experience mild symptoms and an uneventful course, severe respiratory illness requiring oxygen and/or ventilatory support can occur^4,5). Testing of multiple drugs in the treatment of COVID-19 patients including antiviral drugs, refurbished antiviral drugs, and immune modulating agents has been conducted^6-8). While the majority of these medications failed to provide any benefit for COVID-19 patients, some studies indicated that steroids could reduce mortality in COVID-19 patients requiring oxygen support⁹⁾. This led to a rapid adoption of steroids in the management of moderate to severe cases of COVID-19 throughout the world.

Although the upper respiratory tract is the initial site of infection, viral replication within the cells of the lower respiratory tract and secondary viremia can occur in patients with moderate or severe COVID-19¹⁰⁾. This is associated with a proinflammatory state with high serum levels of cytokines (tumor necrosis factor-α [TNF-α], interleukin-1 [IL-1], and IL-6) and chemokines (IL-8), often called the cytokine storm¹¹⁾. Glucocorticoid, a naturally occurring steroid, can exhibit anti-inflammatory properties by stimulating the synthesis and release of anti-inflammatory molecules and inhibiting the production of pro-inflammatory substances¹²⁾. Glucocorticoids bind with intracellular receptors, and these complexes interact with various transcription factors such as nuclear factor-κB (NF-κB), which can alter the expression of various genes involved in inflammation^13,14). Glucocorticoids can also suppress proliferation, maturation, and differentiation of various immune cells including macrophages, monocytes, T cells, and B cells^15,16). While the use of steroids has saved the lives of many patients infected with COVID-19, these drugs are not without side effects. Among these side effects, osteonecrosis (or avascular necrosis), particularly that of the femoral head, can be irreversible and has been associated with significant functional limitations^17,18). Although steroids were already being used for management of many pathologies, the COVID-19 pandemic has led to a large-scale increase in the use of ster-oids¹⁹⁾. While the course of steroids in these patients is short, development of osteonecrosis might still occur in many patients as a result of the COVID-19 pandemic.

An increase in COVID-19 related steroid induced osteonecrosis is expected in the coming years, thus a thorough understanding of the scope of the problem is essential. Due to the delay between steroid therapy and osteonecrosis, current literature on the characteristics of osteonecrosis in COVID-19 patients is limited. In this review, we discuss the association between steroids and osteonecrosis, indications for steroid therapy in COVID-19 patients, and incidence, diagnosis, and treatment of osteonecrosis secondary to steroids in COVID-19.

1. Evidence Supporting Steroid Use in COVID-19

Corticosteroids have been used for the treatment and prevention of acute respiratory distress syndrome (ARDS) with mixed results^20,21). In an meta-analysis of nine trials, Peter et al.²²⁾ who were not able to determine a definitive role for steroids in ARDS, reported an association of preventive steroids (four studies) with a trend towards increased risk of developing ARDS and increased risk of mortality in patients who subsequently developed ARDS. In patients’ who were administered steroids after onset of ARDS (five studies), a trend towards reduction in mortality and a decrease in ventilator requirement was observed. Steroids were also used during the severe acute respiratory syndrome (SARS) epidemic, although the evidence was inconclusive²²⁾. Because severe inflammatory response is the dominant pathophysiology of COVID-19, similar to SARS, steroids were introduced early in the pandemic.

In a large multicenter randomized trial (RECOVERY trial), patients were assigned to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days (n=2,104) or to receive usual care alone (n=4,321)⁹⁾. The use of dexamethasone resulted in lower 28-day mortality among patients who received either invasive mechanical ventilation or oxygen alone at randomization but not among those who received no respiratory support. This study was the first major study to demonstrate a survival benefit for any one treatment modality used in management of COVID-19. This led to changes in guidelines for treatment of COVID-19 worldwide with the addition of steroids in the protocol for treatment of moderate to severe COVID-19. A number of trials on steroids including the DEXA-COVID-19, CAPE COVID, REMAP-CAP, etc. which were underway at the time of publication of the results of RECOVERY were suspended^23-25). However, the results of the trials were finally included in the meta-analysis published by the World Health Organization (WHO) Rapid Evidence Appraisal for COVID-19 Therapies (RE-ACT) working group²⁶⁾. In their meta-analysis of seven randomized trials that included 1,703 patients of whom 647 died, lower 28-day all-cause mortality was observed among patients who received corticosteroids compared to those who received usual care or placebo (odds ratio 0.66, 95% confidence interval 0.53-0.82, P<0.001). Among the four trials that recruited critically ill patients who were and were not receiving invasive mechanical ventilation at randomization, the authors reported that the association between corticosteroids and lower mortality was less marked in patients receiving invasive mechanical ventilation²⁶⁾.

2. Indications for Steroids in COVID-19

According to the WHO panel, a strong recommendation was made for systemic (i.e., intravenous or oral) corticosteroid therapy (e.g., 6 mg of dexamethasone orally or intravenously daily or 50 mg of hydrocortisone intravenously every 8 hours) for 7 to 10 days in patients with severe and critical COVID-19²⁷⁾. The WHO panel also made a conditional recommendation not to use corticosteroid therapy in patients with non-severe COVID-19. As the quality evidence on reduction in the risk of death was moderate, the panel concluded that all or almost all fully informed patients with severe or critical COVID-19 would choose treatment with systemic corticosteroids, and other perspectives (i.e., costs, equity, feasibility of implementation), and patient values and preferences would not alter decisions²⁷⁾. Patients with critical COVID-19 were defined as those who fulfilled the criteria for ARDS, sepsis, septic shock, or other conditions that would normally require administration of life-sustaining therapies, such as mechanical ventilation (invasive or non-invasive) or vasopressor therapy. Severe COVID-19 was defined by the presence of any of the following: oxygen saturation <90% on room air; respiratory rate >30 breaths per minute in adults and children >5 years old, ≥60 in children less than 2 months, ≥50 in children 2-11 months, and ≥40 in children 1-5 years old; or signs of severe respiratory distress (i.e., accessory muscle use, inability to complete full sentences; and in children, very severe chest wall indrawing, grunting, central cyanosis, or any other general danger signs)²⁷⁾.

The recommended dosing by WHO is shown in Table 1. The dose was based on the findings of the RECOVERY trial which used low dose steroids. However, other studies have also evaluated higher doses of steroids (approximately 2 mg/kg of methylprednisolone) and superior results with regard to COVID-19 have been reported^28,29). Therefore, many centres use higher doses of steroids and for a prolonged duration, which can lead to an increased cumulative dose.

Table 1 . Recommended Dosage and Duration for Steroids in Severe/Critical COVID-19 according to WHO.

Medication	Dose
Dexamethasone (preferred)	6 mg once a day
Hydrocortisone	50 mg every 8 hours or 100 mg every 12 hours
Prednisone	40 mg once a day
Methylprednisolone	8 mg every 6 hours or 16 mg every 12 hours

Duration: 7-10 days. Route: oral or intravenous..

COVID-19: coronavirus disease 2019, WHO: World Health Organization..

1. Pathomechanism of Steroid Induced Osteonecrosis

Although the precise mechanism of steroid induced osteonecrosis has not been clearly determined, the primary pathology is related to decreased vascular supply. Certain anatomical locations such as the femoral head are at higher risk of vascular insults due to the precarious blood supply³⁰⁾. In addition to the femoral head, other bones can also be affected by steroids. However, based on the higher rate reported for hips, steroids likely act as a second hit to the already compromised blood supply. A number of hypotheses including fat embolization, intravascular coagulation, osteocyte apoptosis, and fat cell hypertrophy have been postulated as potential mechanisms for steroid induced bone necrosis³¹⁾. The final pathway of all these events is assumed to be a compromise in the vascularity of bone and bone marrow, leading to ischemic necrosis and weakening of the bone, weakening its capacity to withstand normal physiologic loads, finally leading to development of microfractures and collapse of the bone³²⁾ (Fig. 1).

Figure 1. Patho-mechanism of steroid induced osteonecrosis.

Hypertrophy of adipocytes has been demonstrated in in-vitro models after steroid administration³³⁾. According to one postulate, hypertrophy of adipocytes can result in an expanded cell volume, which can decrease the blood circulation in the contained bone spaces leading to bone necrosis. This hypothesis led to testing of lipid lowering agents in the treatment of osteonecrosis, although their effects in humans have not been established^32,34). In addition, fat emboli deposits within the subchondral vasculature can activate the complement pathway, leading to immune complex deposition and activation of the coagulation cascade³⁵⁾. Steroid induced apoptosis of osteocytes has also been suggested as a potential mechanism of osteonecrosis³⁶⁾.

2. Association between Dose of Steroids and Risk of Osteonecrosis

The risk of osteonecrosis increases with both the dose and duration of steroid therapy. However, no limits have been established with respect to the dosage or duration below which development of osteonecrosis is thought to not occur. The RECOVERY trial used low dose dexamethasone for a period of 7-10 days, which translates to approximately 60 mg of cumulative dose of dexamethasone (400 mg of prednisone). This dose is much lower than the dose of steroids administered for conditions such as transplant recipients, lupus, inflammatory conditions, etc., which require administration of steroids for a much longer time and at higher doses³⁷⁾. Hedri et al.³⁸⁾, who conducted a cohort study of patients post renal transplant, reported development of osteonecrosis in 4.6% of 326 patients with a mean cumulative dose of 30 and 17 gm prednisone in the osteonecrosis and non-osteonecrosis groups, respectively. By contrast, in another cohort study reported by Griffith et al.³⁹⁾, the incidence of osteonecrosis was 5% in 254 SARS patients with mean dose of 4.5 and 2.2 gm, respectively. However, development of osteonecrosis can occur even at lower doses. Agarwala et al.⁴⁰⁾ reported osteonecrosis of the femoral head in three patients after receiving treatment for COVID-19 infection. The mean dose of prednisone used in these cases was 758 mg and one patient had a cumulative dose of only 400 mg. McKee et al.⁴¹⁾, who studied 15 patients who developed osteonecrosis following short course steroid therapy for different indications, reported a mean prednisone dose of 850 mg with development of osteonecrosis with a dose as low as 290 mg. Some of the major studies examining the association between dose of steroids and risk of osteonecrosis are shown in Table 2^38-40,42-49) along with the cumulative doses (in prednisone equivalents) of steroids received.

Table 2 . Dose of Steroids among Patients Developing Osteonecrosis among Different Diagnoses.

Study	Type of study	Diagnosis	No. of patients (osteonecrosis; no osteonecrosis)	Cumulative dose of prednisone equivalent (g) (osteonecrosis; no osteonecrosis)
Agarwala et al.40) (2021)	Case series	COVID-19	3; NA	0.75; NA
Griffith et al.39) (2005)	Cohort	SARS	12; 242	4.50; 2.22
Zhang et al.47) (2008)	Cohort	SARS	43; 71	6.25; 4.0
Guo et al.42) (2014)	Cohort	SARS	130; 409	5.7; 3.1
McAvoy et al.43) (2010)	Case control	BMT	74; 147	7.0; 1.8
Torii et al.44) (2001)	Cohort	BMT	19; 81	10.3; 4.0
Uea-areewongsa et al.45) (2009)	Case control	SLE	20; 20	20.3; 17.2
Mok et al.46) (2000)	Case control	SLE	11; 22	26.6; 21.8
Lieberman et al.48) (2000)	Cohort	Liver transplant	4; 199	10.5; 9.7
Lieberman et al.49) (2008)	Cohort	Cardiac transplant	6; 198	5.6; 5.8
Hedri et al.38) (2007)	Cohort	Renal transplant	15; 311	30.3; 17.8

COVID-19: coronavirus disease 2019, SARS: severe acute respiratory syndrome, BMT: bone marrow transplant, SLE: systemic lupus erythematosus, NA: not applicable..

In a systematic review that included 23,561 patients with different diagnoses, Mont et al.³⁷⁾ reported positive associations between mean doses of corticosteroid and osteonecrosis. They found that the risk of osteonecrosis in patients treated with greater than 20 mg per day of steroids (dose used in COVID-19 patients is 40 mg) was significantly higher (odds ratio of 9.1) and that the risk was substantially higher when the cumulative dose of corticosteroid was over 10 gm (odds ratio of 2.4). In addition, they also observed that a 10 mg increase in daily dose resulted in an increase of approximately 3.6% in the rate of osteonecrosis. In a dose-response meta-analysis of 10 studies on 1,137 recovered SARS patients, Zhao et al.⁵⁰⁾ reported close associations between the incidence of osteonecrosis and both the cumulative dose and treatment duration for steroids. They found that the risk of osteonecrosis increased by 1.57 times per 5.0 g increase in the cumulative dose of steroids and increased 1.29 times for each 10-day increment in the treatment duration.

3. Time to Osteonecrosis

Development of osteonecrosis occurs within six months following steroid exposure with early hip involvement in the majority of patients. Agarwala et al.⁴⁰⁾ reported a mean time to osteonecrosis of 58 days after COVID-19 diagnosis. Among SARS patients, Hong and Du⁵¹⁾ reported that the mean time to diagnosis of osteonecrosis was approximately three months. Lv et al.⁵²⁾ reported that among 31 SARS survivors with osteonecrosis of the hip, 28 patients developed osteonecrosis within 3-4 months while it developed in two patients after one year and in one patient after three years. In their cohort, after three years, 10 patients also developed osteonecrosis of other joints. The earlier presentation in the hip joint might be due to the increased biomechanical stress at the femoral head which could have made it more prone to steroid induced changes⁵³⁾.

4. Incidence of Osteonecrosis

Because COVID-19 related osteonecrosis is still emerging, the precise incidence of osteonecrosis in COVID-19 survivors is not known. Higher incidence rates for osteonecrosis of the femoral head and osteoporosis were observed in convalescent SARS patients compared with the general population. The factors influencing femoral necrosis included the degree of healing activity, the dosage summation of corticosteroids, and the length of ictus therapy. The factors influencing bone density included age, dosage summation, and length of ictus therapy.

In a systematic review of 57 studies (23,561 patients), Mont et al.³⁷⁾ reported an overall incidence of osteonecrosis of 6.7% for patients taking high-dose corticosteroids. Based on the indication for steroid therapy, the highest incidence of osteonecrosis was observed for SARS (22%) followed by systemic lupus erythematosus (16%), renal transplant (15%), and bone marrow transplant (7%). These findings suggest that an underlying medical condition can also influence the pathogenesis of osteonecrosis. Because both the SARS and COVID-19 viruses belong to the same family, it is highly possible that COVID-19 survivors can also be at heightened risk of osteonecrosis from the short course of steroid therapy they receive.

The incidence of osteonecrosis in patients with SARS ranged from 5% to 56%^47,52-54) This included osteonecrosis of the hip as well as other joints, although most studies reported that the hip was the most commonly involved site^47,52-55) (Fig. 2). Out of the 71 SARS patients studied by Lv et al.⁵²⁾, 41 patients had osteonecrosis of any joint. Out of these 41 patients, 31 patients had involvement of the hip, while the remaining 10 patients had involvement of other joints (shoulder 8, knee 1, ankle 1). They also reported that the majority of patients had bilateral hip involvement (90%). Involvement of multiple sites is also common. Zhang et al.⁴⁷⁾, who reported development of osteonecrosis in 43 of 114 SARS survivors detected 145 osteonecrotic lesions in 43 patients. Of the 43 affected patients, 30 patients (69.8%) had only one or two areas of osteonecrosis and the other 13 patients (30.2%) had multifocal osteonecrosis affecting three to seven sites. No difference in the risk of developing osteonecrosis was observed between males and females⁵⁰⁾.

Figure 2. (A) Plain radiograph showing bilateral osteonecrosis of the femoral head without collapse (arrows) in a 49-year-old male who has taken steroids for coronavirus disease 2019 (COVID-19). (B) Magnetic resonance imaging of the same patient showing osteonecrosis. (C) Plain radiograph showing osteonecrosis of the knee in a 47-year-old female with a history of steroid intake for COVID-19. Adapted from the article of Parikh et al. (Cureus. 2023;15:e35368)⁵⁵⁾ under the terms of the Creative Commons Attribution (CC BY 4.0) license.

The incidence of hip osteonecrosis was pooled using the estimates obtained from studies of SARS patients ^{39,42,47,52,56,57)}. The overall incidence of hip osteonecrosis was 21% based on a random effects model and is depicted using a forest plot in Fig. 3. This result was similar to the incidence of hip osteonecrosis reported by Mont et al.³⁷⁾ (21.8%) in their meta-analysis. Two studies reported an incidence of total hip replacement (THR) in SARS survivors with an overall incidence of 22% among those with osteonecrosis of the hip (Fig. 3).

Figure 3. Forest plot showing the incidence of hip osteonecrosis (A) and the incidence of total hip replacement (B) among severe acute respiratory syndrome survivors who developed hip osteonecrosis from steroids. CI: confidence interval.

5. Projections of Osteonecrosis

Because the numbers of COVID-19 cases are still on the rise, it is important to obtain a future estimate of COVID-19 related osteonecrosis. Based on the incidence of avascular necrosis (AVN) estimated from the study of SARS, and COVID-19 data obtained from the Centers for Disease Control and Prevention (CDC), an approximated projected burden of THR from COVID-19 is shown in Fig. 4. A hospitalization rate of 7.97% was reported by the CDC⁵⁸⁾. According to the CDC data, the number of hospitalized patients requiring admission to intensive care was approximately 22.7%, and the mortality rate was 10.1%, so that approximately 12.6% of patients survived a severe or moderate disease⁵⁹⁾. Because we assumed that these survivors had received steroids, the incidence data obtained from the previous section was used for estimating the burden. Based on this assumption, for every 100,000 COVID-19 infections, approximately 40 THRs is assumed to occur. Even if the incidence of osteonecrosis was halved, there would be at least 20 THRs for every 100,000 COVID-19 infections. However, these are assumptions and conduct of additional research will be required in order to clearly determine the incidence and projections for osteonecrosis and THR in COVID-19 patients. In addition, there could be racial and ethnic differences in the incidence of osteonecrosis that could affect the geographic distribution of prevalence of COVID-19 related osteonecrosis and THRs.

Figure 4. Estimated burden of total hip replacement (THR) from the use of steroids in coronavirus disease 2019 (COVID-19) with 95% confidence interval (CI).

1. Diagnosis

The onset of pain, the initial symptom in a patient with osteonecrosis, is usually insidious and can become aggravated with activity and weight bearing³²⁾. Myalgias and fatigue, which are also common in COVID-19 survivors, have been reported to occur in up to half of symptomatic patients with COVID-19⁶⁰⁾. While the course of myalgia and non-osteonecrosis related joint pain is relatively benign, the symptoms of osteonecrosis can be persistent and debilitating. Therefore, accurate and timely diagnosis is important. Plain X-rays are the most accessible and inexpensive first-line tool for use in the diagnosis of osteonecrosis. Abnormal findings on X-rays include a ‘crescent sign’ indicating subchondral collapse, cystic or sclerotic changes, abnormal contours of the articular surface (for example, loss of sphericity of the femoral head), or degenerative changes in later stages. However, plain radiographs are not sensitive enough for detecting early osteonecrotic lesions.

Magnetic resonance imaging (MRI) is the most suitable imaging modality for detection of osteonecrosis, particularly during the initial stages. The majority of patients with steroid induced osteonecrosis after SARS had milder forms of osteonecrosis (predominantly stage 1)^47,51). Griffith⁵⁴⁾, who studied 254 SARS survivors receiving steroids, reported osteonecrosis in 12 patients with involvement of the femoral head in 14 patients. All of these patients had normal X-rays, and osteonecrosis was detected by MRI. In their study, all of the femoral heads had stage 1 severity (1A-2, 1B-2, 1C-10) according to the University of Pennsylvania system⁶¹⁾. The higher prevalence of lower stage osteonecrosis among studies on SARS survivors might be a result of the universal use of MRI in these studies resulting in detection of many cases of mild osteonecrosis. It is possible that some of these cases may not have become symptomatic at all. Nevertheless, having a low threshold for ordering an MRI in COVID-19 survivors with joint/bone pain and a history of steroid use is essential.

The diagnosis of osteonecrosis can be established from one or more of the imaging modalities described above, and a history of a previous COVID-19 infection and steroid use can be obtained from history and medical records. However, establishing steroid use as the reason for osteonecrosis can be challenging. Based on a Delphi consensus, Yoon et al.⁶²⁾ reported criteria for diagnosing steroid induced osteonecrosis of the femoral head (Table 3). While the authors described the criteria for diagnosis of hip osteonecrosis, the criteria can potentially be extended to other anatomical regions as well.

Table 3 . ARCO (Association Research Circulation Osseous) Criteria for Diagnosis of Steroid Induced Osteonecrosis.

No.	Criteria
1	Patients should have a history of glucocorticoid use >2 g of prednisolone or its equivalent within a 3-month period.
2	Osteonecrosis should be diagnosed within 2 years after glucocorticoid usage.
3	Patients should not have other risk factor(s) besides glucocorticoids.

A patient should meet all the above criteria to consider as having a steroid induced osteonecrosis..

2. Prevention

Because the options for treatment of osteonecrosis are limited, restricting the use of steroids is important. While steroids can be life-saving and should be used when indicated, it is important to not exceed the duration or dose recommended for COVID-19. Benefits of longer therapy or a higher dose of steroids are not well established, and administration of steroids for patients without severe symptoms should be discouraged. Use of steroid may be unavoidable in some cases, and a history of steroid use is a non-modifiable factor, physicians should counsel patients on other risk factors for osteonecrosis that could be modifiable.

In conduct of a representative survey of over 30,000 Chinese adults, the authors found that high blood levels of triglycerides, total cholesterol, LDL (low-density lipoprotein)-cholesterol, and non-HDL (high-density lipoprotein)-cholesterol, heavy smoking, alcohol abuse and obesity all showed a significant association with an increased risk of osteonecrosis¹⁸⁾. Alcohol, which has been reported as a risk factor for osteonecrosis in multiple studies, is thought to increase adipogenesis in bone marrow leading to increased marrow pressure and osteonecrosis^63,64). Bone mineral density has also shown association with osteonecrosis⁶⁵⁾. Therefore, COVID-19 survivors with a history of steroid use should limit their intake of tobacco and alcohol, control their weight, manage dyslipidemia, and follow a healthy diet with intake of calcium and vitamin D if needed.

3. Treatment

Although multiple treatment modalities have been tried for osteonecrosis, there is no conclusive evidence that any of them will alter the natural progression of the disease. Most of the treatment modalities are focused on osteonecrosis of the hip, which is the most debilitating. Physical therapy, analgesics, and activity modification are the first line therapy, which can provide symptomatic relief to many patients, particularly in the earlier stages. Bisphosphonates are used widely in the management of early stages of osteonecrosis. As the pathogenesis of osteonecrosis involves resorption of devitalized bone tissues, many authors have used bisphosphonates, which are strong anti-resorptive agents⁶⁶⁾. However, a meta-analysis of randomized trials failed to show any benefit with the use of bisphosphonates⁶⁷⁾. Some herbal therapies have also been used for management of osteonecrosis, although the evidence is still limited⁶⁸⁾.

Surgical treatment can be broadly classified according to two types-head preserving and head sacrificing procedures. The most commonly performed head preserving procedure is core decompression, which is performed for removal of necrotic bone from the femoral head, relieving the pressure within the confined bone spaces, thereby promoting healing. However, recent studies have raised concerns regarding the efficacy of this procedure^62,69). Most studies reporting better outcomes with core decompression included patients with small necrotic portions⁶²⁾. According to consensus, these small lesions are unlikely to progress to collapse even without treatment^62,69). The THR is the most commonly performed head sacrificing procedure. THR, a highly successful procedure, is commonly used as the end stage treatment modality for osteonecrosis of the hip. Although excellent outcomes have been achieved, and that it is considered a cost effective option, replacement surgeries at a younger age may necessitate a revision surgery in the future⁷⁰⁾.

4. Outcomes

Studies reporting on the outcome of osteonecrosis in COVID-19 patients are limited. In a case series of three patients who developed hip osteonecrosis following steroid use for management of COVID-19, Agarwala et al.⁴⁰⁾ reported that at the last mean follow-up period of 70 days, none of the patients required surgery and were tolerating symptoms. All three patients were started on weekly dosages of oral alendronate 70 mg along with intravenous zoledronic acid 5 mg annually, and showed a reduction in the mean visual analogue score for pain, reduced from 8 to 2.7. Zhang et al.⁵⁷⁾ reported that among the 23 limbs in 15 patients with necrosis of the femoral head following steroid use in the setting of SARS, the ARCO (Association Research Circulation Osseous) stage of 16 limbs in ten patients stabilized during the 15-year follow-up period (three in stage IIA, eight in stage IIB, four in stage IIC, and one in stage IIIC). However, the stage of one limb was downgraded from stage IIB to stage IIA, while the stages of six limbs in four patients were upgraded.

THR has been performed successfully in patients with steroid induced osteonecrosis. However, lower implant longevity among patients undergoing THR for management of steroid related osteonecrosis remains a concern⁷¹⁾. Rahman et al.⁷²⁾ reported on the outcome of 31 patients (35 hips) who underwent THR for management of steroid induced osteonecrosis. The average follow-up period was 20 months, and the average age at the time of surgery was 47 years. At follow-up, patients showed significant improvement in patient reported outcome measures. However, the complication rate was high (17%), with six complications in five patients (six of 35 hips) with four patients (four of 35 hips; 11%) requiring reoperations. The slightly higher complication rates reported in these patients may be a reflection of the underlying pathology which may have led to steroid use^71,72).

COVID-19 has affected millions of lives globally. Steroids have been administered to many patients with COVID-19. Despite the low dose, and the shorter duration of the steroid course, development of osteonecrosis in many patients is expected. Although any joint or bone can be affected, the hip is the most commonly affected joint, and the quality of life can also be affected. Multiple treatment modalities for osteonecrosis are available, and some non-operative measures and head preserving procedures can provide a benefit in early stages of osteonecrosis. With severe stages and greater involvement of the head, most procedures have limited value and THR may be required for some patients. Based on the prevalence estimates from SARS patients, we estimated that approximately 40 patients might require a THR for every 100,000 COVID-19 infections. With COVID-19 infections still on the rise, it can be expected that the musculoskeletal disability resulting from COVID-19 infection and steroid use will be a major problem in the coming years. An increase in the need for THR is also expected with the large number of COVID-19 infections. Orthopaedic surgeons and physicians treating COVID-19 survivors should have a high suspicion for osteonecrosis. Conduct of additional research is needed to improve our armamentarium for addressing steroid induced osteonecrosis.

No funding to declare.

No potential conflict of interest relevant to this article was reported.