Keywords
heterotopic ossification - joint pain and stiffness - immobility - osteoporosis
Introduction
Heterotopic ossification (HO) is a condition with an unclear cause that leads to abnormal
bone growth in muscles and soft tissues. This can result in pain, joint stiffness,
and difficulty with movement, ultimately affecting a person's quality of life. [1]
[2]
[3] HO is defined as the abnormal formation of lamellar bone in soft tissues, often
containing bone marrow. It has been associated with musculoskeletal trauma, surgery,
burns, neurologic injury, immobilization, and congenital and metabolic disorders.[4]
[5] More recently, it has also been reported as one of the sequelae of critical illness.[6]
[7]
Presentation of Cases
A 66-year-old man with history of severe COVID-19 infection requiring mechanical ventilation
for 1 month developed pain and stiffness of his right knee and left elbow after being
discharged to the rehabilitation facility. When he presented for bone scan, he denied
fever, chills, night sweats, changes in weight, or any other past medical problems
except for the COVID-19 infection incident. Focused physical examination revealed
right knee medial-sided bony mass with limited range of motion, but otherwise neurovascularly
intact. The medial aspect of the left elbow also revealed palpable hard mass with
tenderness, joint stiffness, and limited range of motion. For preoperative plan of
joint surgeries, a three-phase bone scintigraphy was performed using radiopharmaceutical
technetium-99m-methylenediphosphonate (99mTc-MDP). The phases of bone scan—the immediate vascular perfusion phase, the intermediate
blood pool activity, and the delayed radiotracer uptake in the bone—are noted to be
increased in HO, denoting the active dystrophic calcification process. [Fig. 1A-1 to A-5] shows the beginning of hypervascularity in the medial aspect of the right knee.
The three-phase bone scan performed with 740 MBq (20 mCi) of 99mTc-MDP showed increased vascularity, hyperemia, and delayed image with increased tracer
uptake in the medial aspect of right knee. The elbow X-ray and CT of the elbow are
shown in [Fig. 1B-1] and [B-2]. Multifocal HO involving the left elbow, bilateral hips, and right knee is shown
in [Fig. 1C-1, C-2].
Fig. 1 (A-1) First phase of the three-phase bone scan. (A-2) Radiograph of the right knee showed bone formation in the medial condyle and medial
supracondylar cortex of the right femur. (A-3) The second phase (upper panels) and third phase (lower panels) of the three-phase
bone scan. (A-4) Single photon emission tomography with computed tomography (SPECT-CT) of the area
of interest showed increased radiotracer uptake near the medial epicondyle of the
right femur. Distal right femur showed an osteoporotic change compared with the left
distal femur on the low-dose CT axial image. Bone scan was obtained 7 months after
initial COVID-19 infection with severe respiratory illness. (A-5) Magnified SPECT-CT image of the knees. (B-1) X-ray images of the patient's left elbow showed mature bone formation in the distal
left humerus and presurgical evaluation of 3D CT left elbow (posterior view) revealed
similar findings. (B-2) SPECT-CT of the left elbow bone scan demonstrates active heterotopic ossification.
(C-1) Planar anterior and posterior whole body bone images. Radiotracer dose administered
intravenously in the right arm. (C-2) SPECT-CT of the pelvis (10 months post-ICU stay with mechanical ventilation) and
the patient indicated hip pain.
Fig. 2 (A) Very early stage, cross-sectional computed tomography (CT) image of the pelvis.
(B) Nine days later, there is development of visible sclerosis in the left buttock without
touching the neighboring bones. (C) Seven months later, CT image of the pelvis showing soft tissue sclerosis (heterotopic
ossification), advanced stage, demonstrating bony ankylosis between the proximal left
femur and pelvic bone.
The second patient is a 57-year-old woman with COVID-19 who developed acute inflammatory
demyelinating polyradiculopathy/Guillain–Barre syndrome,[8]
[9] progressing from headache and ataxia to quadriparesis. The pelvic CT scans at three
different time points (early January, mid-January, and then July, all in the same
year, 2021) demonstrated HO at three different stages of progression, starting with
nearly negligible sclerotic changes in the soft tissue of the left buttock ([Fig. 2A]), progressing to visible sclerosis ([Fig. 2B]), and, finally, expansion of HO, touching neighboring bones ([Fig. 2C]).
Discussion
HO is clinically identified by pain, swelling, and progressive stiffening of the affected
site. The pathophysiology of HO includes a cascade of stimulation of local and systemic
factors that induce pathologic recruitment and differentiation of osteoprogenitor
cells and further proliferation of osteoblasts. The etiology of HO is multifactorial,
which includes, but is not limited to, trauma, neurological insult, tissue hypoxia,
and hypermetabolic status.[10]
[11] Calcium homeostasis is reported to be perturbed. Very few case reports implicate
critical illness like COVID-19 infection as the inciting factor of HO.[12]
[13] Complications of HO include severe morbidity, pressure ulcers, and peripheral nerve
entrapments. Hence, early diagnosis of HO is extremely important. Three-phase bone
scintigraphy is the most sensitive imaging modality for the diagnosis of HO. This
coupled with the use of single-photon emission computed tomography with computed tomography
(SPECT-CT) further increases the diagnostic accuracy of the three-phase bone scan
in identifying active disease. This modality not only helps in early diagnosis of
HO but also identifies the active dystrophic calcification process.[14] Early diagnosis of HO helps direct therapy toward preventing the formation of HO
through rigorous physical therapy and the use of nonsteroidal anti-inflammatories.
Identification of the ongoing pathophysiological process in the patient helps the
clinician to avoid choosing a surgical approach as a treatment option. Surgical resection
is usually delayed till HO achieves maturity to decrease intraoperative hemorrhage
and postoperative recurrence. COVID-19 infection is associated with thrombogenic tendencies,
causing coagulopathy prone to develop local tissue damage. Further surgical intervention
can be helped in the area for minimizing postarthroplasty complications utilizing
a comprehensive approach that considers preoperative optimization, including preoperative
densitometry, optimization of bone quality through at least 3 months of bone-strengthening
medications if low bone mineral density is found, and early diagnosis of HO decreasing
surgical complications can improve patient outcomes, reduce health care cost, and
enhance patient satisfaction.
