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T1 weighted non-contrast MRI (left-red arrow) of dystrophic calcifications show hypointense signal in patchy patterns. These appear as calicified hazy patches on CT (right-red arrow).
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Background
Heterotopic Ossification (HO) is a common condition referring to ectopic bone formation in soft tissues. It has two major etiologies, acquired (more common) and genetic. The acquired form is closely related to tissue trauma. The exact pathogenesis of this disease remains unclear; however, there is ongoing research in prophylactic and the...
Context in source publication
Context 1
... On plain film, DC appears as amorphous calcification with a hazy ill-defined appearance that can increase in density over time. 53 CT will similarly show peripheral amorphous hyperdensities, with MRI showing hypointense signals in T1 and T2 weighted images ( Figure 6). 54 The distinguishing difference between DC and HO is organization. ...
Citations
... However, in the context of a chronic, stable, intra-articular lesion with a 2.5-year post-traumatic history, the utility of acute-phase diagnostic modalities is limited. Further, once mature lamellar HO forms, MRI is the modality of choice and can be considered diagnostic if it shows cancellous fat that is hyperintense on T1-and T2weighted images [7,8]. Prophylaxis with NSAIDs is widespread practice despite multiple randomized controlled trials that showed little to no improvement in HO formation compared to placebo or radiation [9][10][11]. ...
Heterotopic ossification is ectopic lamellar bone formation within soft tissue and can result in significant functional limitations. There are multiple underlying etiologies of HO including musculoskeletal trauma and traumatic brain injury. Intra-articular HO of the knee is rare and is typically located within the cruciate ligaments. We report a case of a 24-year-old female who presented with worsening right knee pain and limited knee extension two and a half years after a motor vehicle crash with multiple lower extremity fractures. Physical examination of the knee revealed anterior pain, limited extension, and a palpable infrapatellar prominence. Imaging showed a retropatellar tendon, intra-articular excrescence of bone proximal to the anterior tibial plateau. Diagnostic arthroscopy with a 70° arthroscope identified HO at the proximal anterior tibial plateau, which was excised with a high-speed burr under direct visualization. At the three-month follow-up, the patient remained asymptomatic and returned to sport. Retropatellar tendon, intra-articular anterior knee HO is a rare but debilitating clinical entity that can be successfully and safely managed with excision under direct visualization using a 70° arthroscope.
... It occurs most commonly following traumatic brain or spinal cord injuries, intense trauma, severe thermal injuries, surgeries (e.g. hip arthroplasty), and immobilisation [3,4]. ...
... HO is frequently divided into two groups: acquired HO, which is the most common, and rare genetic cases of fibrodysplasia ossificans progressiva and progressive osseous heteroplasia [3,4]. Three conditions are required for HO to develop: a local environment compatible with osteogenesis, an osteogenic precursor, and a triggering event [4,21]. ...
... HO is frequently divided into two groups: acquired HO, which is the most common, and rare genetic cases of fibrodysplasia ossificans progressiva and progressive osseous heteroplasia [3,4]. Three conditions are required for HO to develop: a local environment compatible with osteogenesis, an osteogenic precursor, and a triggering event [4,21]. Factors influencing the environment are pH, oxygen tension, micronutrients availability, and mechanical stimuli [22]. ...
Background
This review aims to study the clinical characteristics, diagnostic results, treatments, and outcomes in patients with heterotopic ossification following COVID-19 infection.
Methods
A literature search for eligible articles was conducted using MEDLINE/Pubmed, Global Health, and Scopus databases (January 12th, 2023), including all case reports and case series from any country and language. The criteria for inclusion in this review were cases of COVID-19 infection subsequently developing heterotopic ossification.
Results
This systematic review analysed 15 reports (n = 20 patients) documenting cases of heterotopic ossification following COVID-19 infection. 80% of the patients were male, with a median age of 59 years. All patients required intensive care unit stay with an average duration of 48.5 days. Mechanical ventilation was necessary for all patients and 30% of them underwent tracheostomy. Common symptoms included stiffness and pain, most frequently affecting multiple locations (70%), with the hips and shoulders being predominantly involved. X-rays were the most commonly used imaging modality, followed by computed tomography. Although treatment was given, some of the patients continued to experience symptoms, particularly stiffness.
Conclusion
20 patients who developed heterotopic ossification after COVID-19 have been reported, the majority of which had at least two independent risk factors for this condition. The link between those two clinical entities is therefore uncertain, requiring further investigation. It is nonetheless important to suspect heterotopic ossification in patients with severe COVID-19 infection, prolonged immobilisation, mechanical ventilation, who develop joint pain and stiffness, as this condition can significantly impact patients’ quality of life.
Protocol registration
CRD42023393516.
... Heterotopic ossification (HO), also known as paraosteoarthropathy, myositis ossificans, and heterotopic calcification, is defined as the abnormal formation of mature lamellar extraskeletal bone in soft tissues, such as skeletal muscles, articular capsules, ligaments, and tendons (1)(2)(3). In human medicine, HO is divided into two major types-acquired and genetic (4). The acquired form is the most frequent, is closely associated with tissue trauma in 75% of cases, and can be seen after joint surgery, musculoskeletal or central nervous system injury, and burns (5,6). ...
... Finally, a necessary environment that is conducive to the continued production of heterotopic bone must be present. Of these four factors, signaling agents appear to play the most important role in the formation of heterotopic bone, and recent progress has been made in the understanding of these agents in human medicine (4,(32)(33)(34)(35)(36)(37). In our case, the owner did not describe any traumatic event, but an injury during the first year of life may be speculated. ...
This case report describes a 17-month-old Pudelpointer with recurring motor impairment localized to the left thoracic limb. A neurological exam highlighted lameness in that limb, accompanied by pre-scapular swelling. Radiographs and magnetic resonance imaging detected an osseous structure in soft tissues close to the fifth cervical vertebra, and subsequent surgery uncovered adjacent cervical spinal nerve impingement. Histology of the bony structure revealed heterotopic ossification in paravertebral muscles. Mild bone re-formation at the operating site was detected after a 2-year period, but the patient was asymptomatic. This article reports the first case of heterotopic ossification with spinal nerve entrapment in a dog and adds a new differential diagnosis to the causes of neurogenic lameness in dogs.
... 16,17 However, existing literature indicates that HO in peripheral tissue is relatively frequent after orthopedic surgeries, severe burns, brain or spinal cord injuries, and blast injuries encountered in combat. 16,[18][19][20] Nonetheless, post-traumatic or post-operative calcification of the STL remains a rare occurrence. Shaul et al. reported a case illustrating this phenomenon, where calcification was described as a consequence of inflammatory repair and vascular degeneration. ...
... 6,11,14,21 The definitive diagnostic tools for HO are CT and X-ray. 19,20 Differential Diagnosis It is crucial to distinguish hip pain or discomfort caused by other conditions, such as sciatica, lumbar disc degeneration, piriformis syndrome, sacroiliitis, ischiogluteal bursitis, STL injury, hematoma, and bone tumor. Notably, ischiogluteal bursitis, once known as "weaver's bottom," shares similar clinical features. ...
... 25,26 Surgical resection was a choice for some cases. 19 area. 11 It is hypothesized that surgical resection might risk damaging the ligament, potentially leading to pelvic instability. ...
Ossification of the sacrotuberous ligament is a rare occurrence in soft tissue, with only 15 cases reported in the past few decades. We reported two cases of bilateral ossification in sacrotuberous ligaments and provided a concise review of the literature on this pathology. Clinical data, radiographic outcomes, and diagnostic and treatment details were obtained. This study aimed to summarize this disease's characteristics and investigate its pathogenesis through a review of literature from the last thirty years. This condition is often incidentally confirmed in elderly males via imagiological examination or gross anatomy and presents a low morbidity rate. Its pathogenesis may be related to stress concentration, excessive intake of element ions, injury repair, and improper operative technique. The majority of patients may not exhibit any clinical symptoms or signs and typically do not require medical interventions. It may be complicated with pudendal nerve entrapment syndrome. The long‐term effects of surgical resection and the most effective treatment approach remain areas for further research.
... In our case, the first CT scan, showing the inflammatory change with faint multilayered curvilinear hyperdense rims, helped diagnose the myositis ossificans prior to the characteristic circumferential calcification with a radiolucent center shown in the second CT scan. Serial CT scans may be beneficial for detecting and tracking of changes across the clinical course of myositis ossificans [10]. Other imaging studies, such as ultrasonography, bone scintigraphy, and magnetic resonance imaging, also help diagnose myositis ossificans. ...
... As the ossification matures in patients with myositis ossificans, a more active approach can be adopted with resistive strengthening exercises to improve a range of motion [4]. Surgical intervention is reserved for failed medical management, such as intractable pain, neurovascular compromise, and limitation of range of motion in the mature phase [4,10,16]. Surgery should be performed after complete maturation, and recurrence is known to occur if the myositis ossificans is excised while it is metabolically active [17]. ...
Myositis ossificans is uncommon in patients with nontraumatic brain injuries. This report presents a challenging case in which myositis ossificans was diagnosed and treated by medical management in a patient who was unable to complain of any symptoms due to akinetic mutism that occurred after nontraumatic subarachnoid hemorrhage. The patient had intermittent high-grade fever, and laboratory tests showed elevated C-reactive protein and D-dimer levels without clinical signs of infection two months after subarachnoid hemorrhage. Lower-extremity venography using computed tomography was performed to rule out deep venous thrombosis. There was no thrombus, but right vastus medialis muscle showed inflammatory change with faint multilayered curvilinear hyperdense rims. The administration of indomethacin helped prevent abnormal bone formation. For the early detection of myositis ossificans, careful observation of clinical presentation and a high index of clinical suspicion is necessary in brain-injured patients. Further, elevated serum inflammatory markers accompanied by elevated alkaline phosphatase can be a critical clue. Early computed tomography helps identify early ‘string sign’ prior to characteristic ossification. Our report highlights that the myositis ossificans is remediable by early detection and appropriate nonsurgical management.
... Una masa de tejido blando con calcificación suele indicar tofos. Sin embargo, si el mismo fenómeno se produce en el cartílago hialino o fibroso de dos o más articulaciones, lo que se conoce como condrocalcinosis, es un signo diagnóstico de enfermedad por depósito de pirofosfato cálcico (EDPC) (Figura 1C) (20,21). Los meniscos, el fibrocartílago triangular de la muñeca y la sínfisis púbica son ejem-plos de estructuras que contienen cartílago fibroso (22). ...
... Los meniscos, el fibrocartílago triangular de la muñeca y la sínfisis púbica son ejem-plos de estructuras que contienen cartílago fibroso (22). El depósito de hidroxiapatita, que puede estar relacionado con enfermedades sistémicas como la esclerosis sistémica, el lupus eritematoso sistémico y la osteodistrofia renal, causa calcificaciones tendinosas lobuladas alrededor de la articulación (14,21,23). ...
Resumen En este artículo se revisan los hallazgos de la radiografía convencional para distinguir entre patologías inflamatorias y degenerativas en pacientes con dolor articular. Al analizar una radiografía simple en el contexto de un dolor articular inflamatorio, es importante buscar signos clave de artropatía inflamatoria, como osteopenia yuxtaarticular, edema de partes blandas, calcificaciones, pérdida simétrica u homogénea del espacio articular y erosiones, así como hallazgos cardinales en función de la región anatómica evaluada, que ayuden a realizar un diagnóstico más preciso. La radiografía simple seguirá siendo una herramienta esencial para los médicos generalistas, internistas y reumatólogos a pesar de su baja sensibilidad y especificidad para las fases tempranas de las enfermedades. Palabras clave: artritis reumatoide, rayos X, reumatología, artropatía por depósitos de cristales, osteoartritis. Abstract This article reviews conventional radiography's findings for distinguishing inflammatory and degenerative pathologies in patients with joint pain. When analyzing a simple radiograph in the context of inflammatory joint pain, it is important to search for key signs of inflammatory arthropathy, such as juxta-articular osteopenia, soft tissue edema, calcifications, symmetric or homogeneous loss of joint space, and erosions, as well as cardinal findings depending on the anatomical region evaluated, which help make a more accurate diagnosis. Plain radiography will remain an essential tool for general practitioners, internists, and rheumatologists despite its low sensitivity and specificity for early pathologies.
... Radiological diagnosis does not usually precede the onset of symptoms, and there are signs of hyperemia with soft tissue enhancement on contrast-enhanced CT in an early phase, which, due to the absence of visible calcifications, can go unnoticed for up to 3-6 weeks on simple radiography and CT without contrast. During this phase, inflammatory changes can be detected by MRI as a hypointense region on T1 and hyperintense on T2, which enhances after contrast administration 7 . In a second phase, the progressive mineralization of the abnormal tissue causes the signal intensity to become heterogeneous, with progressive loss of signal that can make diagnosis difficult. ...
... In the last phase there is abnormal bone tissue maturation, with periarticular centripetal ossification, appearance of cortical density bone in the periphery and central trabecular bone tissue. In this phase, the MRI findings are usually of central abnormal tissue, hyperintense on T1 and T2, surrounded by cortical bone with low signal intensity 7 . ...
... Heterotopic ossification (HO) merupakan pembentukan tulang baru secara reaktif, yang muncul pada jaringan lunak setelah terjadinya trauma. Keberadaan tulang pada jaringan lunak merupakan keadaan yang tidak normal (Mujtaba et al., 2019), (Ghanem et al., 2020),(R. Zhang et al., 2018). ...
Penangkapan non-osseous pada pemeriksaan sidik tulang dengan menggunakan radiofarmaka Technetium-99m methylene diphosphonate (Tc-99m MDP) dapat disebabkan karena proses neoplasma, trauma, proses inflamasi, iskemik, dan artefak. Perubahan metabolisme lesi non-osseous dapat diketahui pada pencitraan sidik tulang dengan menggunakan radiofarmaka Tc-99m MDP. Lesi pada jaringan lunak dapat terlihat pada pemeriksaan sidik tulang karena adanya peningkatan aktivitas pada area fokal. Tujuan penulisan telaah pustaka ini adalah untuk mengetahui gambaran penangkapan non-osseous Tc-99m MDP pada pemeriksaan sidik tulang. Metode penelitian ini adalah tinjauan pustaka dari semua literatur mengenai penangkapan non-osseous Tc-99m MDP pada sidik tulang yang dipublikasikan dalam 10 tahun terakhir hingga tahun 2022. Hasil penelitian ini didapatkan bahwa identifikasi yang tepat dari penangkapan Tc-99m MDP pada sidik tulang dapat memberikan petunjuk diagnostik pada proses patologis. Kesimpulan dari telaah pustaka ini adalah pencitraan penangkapan non-osseous Tc-99m MDP pada pemeriksaan sidik tulang dapat memberikan informasi tambahan sehingga dapat mengurangi risiko salah interpretasi dalam membaca hasil pemeriksaan sidik tulang.
... Common pathological mineralizations include uric acid crystals in joints which forms gout, cholesterol crystallization that forms in some atherosclerotic plaques, and calcium phosphate that forms in heterotopic ossification or breast microcalcifications (Grebe and Latz 2013, Ragab et al 2017, Mujtaba et al 2019, Tsolaki and Bertazzo 2019. Unlike kidney stones, which are heterogenous structures of crystals interwoven in organic matrices, these other pathological mineralizations are more homogeneous crystals with minimal organic material (Tsolaki and Bertazzo 2019). ...
Pathological mineralizations form throughout the body and can be difficult to detect using conventional imaging methods. Color Doppler ultrasound twinkling highlights ~60% of kidney stones with a rapid color shift and is theorized to arise from crevice microbubbles as twinkling disappears on kidney stones at elevated pressures and scratched acrylic balls in ethanol. Twinkling also sometimes appears on other pathological mineralizations; however, it is unclear whether the etiology of twinkling is the same as for kidney stones. In this study, five cholesterol, calcium phosphate, and uric acid crystals were grown in vitro and imaged in Doppler mode with a research ultrasound system and L7-4 transducer in water. To evaluate the influence of pressure on twinkling, the same crystals were imaged in a high-pressure chamber. Then, the effect of surface tension on twinkling was evaluated by imaging crystals in different concentrations of surfactant (1%, 2%, 3%, 4%) and ethanol (10%, 30%, 50%, 70%), artificial urine, bovine blood, and a tissue-mimicking phantom. Results showed that all crystals twinkled in water, with cholesterol twinkling significantly more than calcium phosphate and uric acid. When the ambient pressure was increased, twinkling disappeared for all tested crystals when pressures reached 7 MPa (absolute) and reappeared when returned to ambient pressure (0.1 MPa). Similarly, twinkling across all crystals decreased with surface tension when imaged in the surfactant and ethanol (statistically significant when surface tension < 22 mN/m) and decreased in blood (surface tension = 52.7 mN/m) but was unaffected by artificial urine (similar surface tension to water). In the tissue-mimicking phantom, twinkling increased for cholesterol and calcium phosphate crystals with no change observed in uric acid crystals. Overall, these results support the theory that bubbles are present on crystals and cause twinkling, which could be leveraged to improve twinkling for the detection of other pathological mineralizations.
... However, these two methods do not identify mature HO until 6 weeks after trauma, at which point prospective therapies are ineffective. [165][166][167] Edwards et al. 168 distinguished the location of soft tissue endochondral ossification at early stages through high-frequency spectral ultrasound imaging, such that effective interventions could be applied when and where they were needed after injury. Furthermore, the chondrogenic to osteogenic transition occurred in mesenchymal progenitor cells during HO and was correlated with gene expression, as revealed by an analysis using high-frequency spectral ultrasound imaging for the detection of HO anlagen. ...
Although previous RNA sequencing methods have been widely used in orthopedic research and have provided ideas for therapeutic strategies, the specific mechanisms of some orthopedic disorders, including osteoarthritis, lumbar disc herniation, rheumatoid arthritis, fractures, tendon injuries, spinal cord injury, heterotopic ossification, and osteosarcoma, require further elucidation. The emergence of the single-cell RNA sequencing (scRNA-seq) technique has introduced a new era of research on these topics, as this method provides information regarding cellular heterogeneity, new cell subtypes, functions of novel subclusters, potential molecular mechanisms, cell-fate transitions, and cell‒cell interactions that are involved in the development of orthopedic diseases. Here, we summarize the cell subpopulations, genes, and underlying mechanisms involved in the development of orthopedic diseases identified by scRNA-seq, improving our understanding of the pathology of these diseases and providing new insights into therapeutic approaches.
