Heterotopic Ossification of Bilateral Hips Post–COVID-19 and Prolonged Immobilization

Case: A 43-year-old healthy man developed hip pain post–coronavirus disease 2019 (COVID-19) immobilization. Imaging confirmed bilateral bridging heterotopic ossification (HO) of the hips, Brooker Class IV. Bilateral HO caused functional arthrodesis (45° flexion: −20° internal rotation). Bilateral HO resection resulted in almost full mobility at 1-year follow-up (90° flexion; 30° internal rotation). Conclusion: Many cases of HO after immobilization for COVID-19 have been reported, but as far as we know, this is the first case report describing surgical intervention as an adequate treatment option for severe restricted mobility caused by HO due to COVID-19–induced prolonged immobilization. Caution and preoperative 3D planning are recommended of HO formation near neurovascular structures.


H
eterotopic ossification (HO) is the abnormal bone deposition in soft tissues, typically around joints, without attachment to the periosteum 1 .This phenomenon is a recognized complication in neurological disorders, orthopedic surgery, musculoskeletal trauma, or prolonged joint immobilization.HO seems to be more prevalent in patients with coronavirus disease 2019 (COVID-19)-induced immobilization possibly due to local myositis, deranged calcium metabolism, and systemic inflammatory condition 2 .While many COVID-19-related HO cases are reported, none describe surgery [2][3][4][5][6][7][8][9] .Surgical resection is recommended only for severe joint limitation severely interfering with quality of life (QoL) and autonomy 1 .Our case reports successful surgical intervention for severe restricted mobility caused by HO due to COVID-19-induced prolonged immobilization.
The patient was informed that data concerning the case would be submitted for publication, and he provided consent.

Case Report
A 43-year-old man without comorbidities was hospitalized for COVID-19 at the only hospital in a city of 200,000 inhabitants.He spent 39 days in intensive care due to worsening symptoms requiring mechanical ventilation (33 days) and prone positioning.After discharge to the general ward, intensive inpatient rehabilitation was needed due to weakness, swallowing disorders, and cognitive disorders.During rehabilitation, the patient experienced acute bilateral groin pain and restricted hip mobility.He had significantly reduced flexion (45°) and internal rotation (220°), greatly impeding his ability to sit and walk.X-rays showed signs of bilateral HO of the hip, Brooker Class IV (Fig. 1) 10 .Further supporting the diagnosis was an elevated level of 277 U/L alkaline phosphatase (normal range 46-116) 11 .The patient was discharged 65 days after admission, and at home, he continued with mobilization and anti-inflammatory medication (diclofenac, 3 times a day 50 milligrams for 29 days).
During the follow-up at our orthopedic clinic, the patient displayed significant hip motion loss, with both hips fixed in extension and limited to 50°of external rotation.This resulted in bilateral functional arthrodesis, causing a waddling gait and preventing sitting in a chair.Radiography and computed tomography (CT) confirmed bilateral medial bridging HO near the iliopsoas and adductor muscles (Fig. 2).Considering the HO extent, severe impairment, and relatively young age of 43 years, it was decided to perform a bilateral surgical resection of HO 8 months after discharge; which is 2 months after the expected completion of osseous maturation 1 .Surgery was initially planned to be performed in 1 session, but due to the extent of HO and time constraints, surgery on the left side was followed 3 weeks later by surgery on the right.

Surgical Treatment
The direct anterior approach was used, given the anteromedial location of HO.After identification of the bone bar, the extraskeletal bone was carefully resected piece by piece using osteotomes, taking into consideration that the large vessels (circumflexa femoris lateralis and profunda femoris) are in proximity (Fig. 3).Intraoperative hip mobilization showed significant improvement in flexion and external rotation.Internal rotation was slightly limited due to impingement but improved after further resection.The operation time was 150 minutes with minimal blood loss.
The same anterior approach was used on the right hip 3 weeks later.As much ossification as possible was again resected in the same manner with consideration of the large vessels, although this time a small side branch, possibly of the profunda femoris, was damaged.The vessel was clipped successfully, and surgicel was left behind.A wound drain was used to monitor potential further postoperative bleeding.Hip mobilization was assessed demonstrating adequate improvement in flexion and external rotation.Initially, internal rotation was still decreased after removal of the HO most likely due to soft tissue stiffness.Subsequent mobilization of the hip joint reduced the tension of the external rotators and capsule which improved internal rotation to 40°.Operation time was also 150 minutes with 1000 mL of blood loss requiring 2 units of packed red blood cells postoperatively.
Each surgical resection was followed by 1 dose of radiotherapy (7 Gray), anti-inflammatory drug treatment (indomethacin, 25 milligrams 3 times a day for 14 days), and intensive mobilization by physiotherapists (3 times a week including swimming and cycling).

Discussion
W e identified 21 previously published reports describ- ing 47 patients who developed HO after prolonged     I).Our case report is the first describing surgical intervention as an adequate treatment option for severe restricted mobility caused by HO due to COVID-19-induced prolonged immobilization.
The incidence of HO in patients admitted to the Intensive Care Unit due to acute respiratory distress syndrome is reported to be 5% 28 .Stoira et al. described the development of HO in 10 of 52 patients (19%) who required prolonged mechanical ventilation due to COVID-19, making the incidence seem to be higher than 5% 2 .The authors assumed that prolonged immobilization played a decisive role in HO formation in their patients.However, altered acid-base homeostasis, the systemic inflammatory condition, and local myositis, which may have been caused by COVID-19, might have also contributed to HO occurrence after COVID-19.Recently, 8 case series were published demonstrating HO around the hips, shoulders, elbows, knees, ankles, and ribs in 21 patients with COVID-19 requiring prolonged immobilization [2][3][4][5][6][7][8][9] , of whom were treated with surgery.Unfortunately, the long-term outcomes and HO severity of the conservatively treated patients were not reported, so we are unable to compare our surgical case report with the existing 21 conservative cases.In our patient, severe hip motion loss severely affected his daily activities and QoL.We believe extensive bilateral HO resection was justified and resulted in substantial improvement at the 1-year follow-up.
HO development after prolonged immobilization and critical illness must be recognized at an early stage to prevent functional loss.Besides assessing the range of motion of hips and shoulders, elevated levels of alkaline phosphatase might serve as a useful screening tool 11 .The primary imaging modalities for the diagnosis HO are plain radiographs and bone scans 29 ; furthermore, serial bone scans may be used to observe HO metabolic activity indicating disease maturity and can therefore be an useful tool in determining the adequate time for surgical resection 11 .However, even with bone scans, precise indicators for bone maturity have remained elusive.Moreover, there is a higher risk of HO recurrence when surgical resection is undertaken prematurely.Hence, delaying surgery until the expected bone maturation date, typically 6 months after disease onset for HO due to prolonged immobilization, may be beneficial 1 .In preparation for surgery, CT may be used to delineate the area of HO 29 .These imaging modalities can be used for staging HO severity in hips according to Brooker classification system (Class I-IV), which is often used for surgery planning.
Treatment of HO is challenging.An earlier study showed that nonsteroidal anti-inflammatory drugs, particularly indomethacin, radiotherapy, and bisphosphonates are 3 modalities used as prophylaxis against HO 30 .However, there is no consensus regarding the prophylaxis during prolonged immobilization due to COVID-19.Nevertheless, early and frequent mobilization is believed to be essential.Surgical resection of HO is recommended only when joint limitation severely interferes with QoL and autonomy and when the osseous maturation is finished 1 .
This report describes a healthy patient who developed HO after prolonged immobilization due to COVID-19.While it is Fig. 4 At 1-year postoperative follow-up, the patient demonstrates that he is able to remain in a squatting position.Resected ossification deposits.The deposits were carefully resected using osteotomes.White paper length and width is 21 cm and 13 cm, respectively.Further research is needed to investigate the role of COVID-19 in HO development.Furthermore, the ossification in the iliopsoas in our patient was close to important neurovascular structures that were visible on the CT scan.Although the surgeon was aware of the risks, a small side branch, possibly of the profunda femoris, was damaged during resection leading to a profound bleeding.This indicates the difficulty of ossification removal in the proximity of neurovascular structures.A 3D printed model of the affected area and its relation to the important neurovascular structures might have prevented the damage to this vessel or might have improved the ease of resecting all HO deposits.This case report shows that physicians should be aware of HO in patients with COVID-19 who are hospitalized and immobilized for extended periods, especially with mechanical ventilation.Physical examination and alkaline phosphatase can be useful screening tools.In addition, preoperative 3D models should be considered in surgical resection of HO, especially in HO in the proximity of neurovascular structures.

Conclusion
I n conclusion, to our knowledge, this is the first case report describing surgical intervention in HO of bilateral hips as a complication of COVID-19 prolonged immobilization.Caution is warranted of HO formation near neurovascular structures, in which case preoperative 3D planning may be useful.E-mail address for O.N. van de Langerijt: olafvdl@xs4all.nl

Fig. 1
Fig. 1 Plain anteroposterior radiograph during hospital admission showing the first signs of medial bilateral HO of the hip (Brooker Class IV).HO = heterotopic ossification.

Fig. 5
Fig. 5Postoperative plain anteroposterior radiographs of the hips.Fig. 5-A One day after second surgery, showing significant reduction of ossification near the iliopsoas and adductor muscles, including the vascular clip.Fig. 5-B No new ossification seems to be formed 1-year postoperatively.

TABLE I Literature
Review of Studies (n = 21) Reporting on Patients Who Developed HO After Prolonged Immobilization