Surgical Treatment of Heterotopic Ossification of the Bilateral Shoulder and Elbow Joints Caused by Burn Injury: A Case Report.

CASE: A 27-year-old man sustained chemical burns affecting 54% of his body caused by steam and acetic acid at a dyeing factory. He developed restricted bilateral elbow and shoulder motion because of heterotopic ossification (HO) beginning 3 months after the incident. The skin healed within 1 year, but ankylosis developed because of progressing ossification. We performed HO surgical excision in 4 stages. Two years after the final surgery, the function of both upper extremities had recovered. CONCLUSION: For HO caused by severe burns, improvement in upper extremity function can be achieved even if surgery is performed after skin healing.

Post-traumatic Coracoclavicular Ligament Ossification: A Case Report and Surgical Technique.

CASE: A patient presented with complete coracoclavicular ligament ossification after an unnoticed acromioclavicular joint Rockwood Type IV dislocation. He had full passive range of motion in the glenohumeral joint but was disabled by a loss of both active (80°) and passive (90°) abduction due to insufficient passive scapulo-thoracic motion. He was treated with an arthroscopic osteotomy of the coracoclavicular ligament ossification. CONCLUSION: One year after the surgery, active abduction was improved by 45° (80°-125°) with no recurrence of the ossification on the radiographs. Arthroscopic osteotomy of complete coracoclavicular ligament ossification seems effective in restoring abduction in these patients. LEVEL OF EVIDENCE: IV.

Delayed femoral artery injury caused by heterotopic ossification: a rare case report and review of the literature.

BACKGROUND: Arterial injury caused by heterotopic ossification (HO) following fractures is rarely reported, yet it can have catastrophic consequences. This case report presents a unique instance of femoral artery injury and hematoma organization, occurring a decade after intramedullary nail fixation for a femoral shaft fracture complicated by HO. CASE PRESENTATION: A 56-year-old male presented with right femoral artery injury and organized hematoma, a decade after suffering bilateral femoral shaft fractures with mild head injury in a traffic accident. He had received intramedullary nailing for the right femoral shaft fracture and plate fixation for the left side in a local hospital. Physical examination revealed two firm, palpable masses with clear boundaries, limited mobility, and no tenderness. Peripheral arterial pulses were intact. Radiography demonstrated satisfactory fracture healing, while a continuous high-density shadow was evident along the inner and posterior aspect of the right thigh. Computed tomography angiography identified a large mixed-density mass (16.8 × 14.8 × 20.7 cm) on the right thigh's medial side, featuring central calcification and multiple internal calcifications. The right deep femoral artery coursed within this mass, with a smaller lesion noted on the posterior thigh. Surgical consultation with a vascular surgeon led to planned intervention. The smaller mass was completely excised, but the larger one partially, as it encased the femoral artery. The inability to remove all HO was due to excessive bleeding. Postoperatively, the patient experienced no complications, and one-year follow-up revealed a favorable recovery with restoration of full right lower limb mobility. CONCLUSION: This case underscores the potential gravity of vascular injury associated with heterotopic ossification. Surgeons should remain vigilant regarding the risk of vascular injury during HO excision.

Development and validation of a nomogram for predicting heterotopic ossification following spinal cord injury.

OBJECTIVE: Heterotopic ossification (HO) following spinal cord injury (SCI) can severely compromise patient mobility and quality of life. Precise identification of SCI patients at an elevated risk for HO is crucial for implementing early clinical interventions. While the literature presents diverse correlations between HO onset and purported risk factors, the development of a predictive model to quantify these risks is likely to bolster preventive approaches. This study is designed to develop and validate a nomogram-based predictive model that estimates the likelihood of HO in SCI patients, utilizing recognized risk factors to expedite clinical decision-making processes. METHODS: We recruited a total of 145 patients with SCI and presenting with HO who were hospitalized at the China Rehabilitation Research Center, Beijing Boai Hospital, from June 2016 to December 2022. Additionally, 337 patients with SCI without HO were included as controls. Comprehensive data were collected for all study participants, and subsequently, the dataset was randomly partitioned into training and validation groups. Using Least Absolute Shrinkage and Selection Operator regression, variables were meticulously screened during the pretreatment phase to formulate the predictive model. The efficacy of the model was then assessed using metrics including receiver-operating characteristic (ROC) analysis, calibration assessment, and decision curve analysis. RESULTS: The final prediction model incorporated age, sex, complete spinal cord injury status, spasm occurrence, and presence of deep vein thrombosis (DVT). Notably, the model exhibited commendable performance in both the training and validation groups, as evidenced by areas under the ROC curve (AUCs) of 0.756 and 0.738, respectively. These values surpassed the AUCs obtained for single variables, namely age (0.636), sex (0.589), complete spinal cord injury (0.681), spasm occurrence (0.563), and DVT presence (0.590). Furthermore, the calibration curve illustrated a congruence between the predicted and actual outcomes, indicating the high accuracy of the model. The decision curve analysis indicated substantial net benefits associated with the application of the model, thereby underscoring its practical utility. CONCLUSIONS: HO following SCI correlates with several identifiable risk factors, including male gender, youthful age, complete SCI, spasm occurrence and DVT. Our predictive model effectively estimates the likelihood of HO development by leveraging these factors, assisting physicians in identifying patients at high risk. Subsequently, correct positioning to prevent spasm-related deformities and educating healthcare providers on safe lower limb mobilization techniques are crucial to minimize muscle injury risks from rapid iliopsoas muscle extension. Additionally, the importance of early DVT prevention through routine screening and anticoagulation is emphasized to further reduce the incidence of HO.

Personalizing Prophylactic Radiotherapy for Hip Heterotopic Ossification: An AMSTAR-2 Compliant Review of Meta-analyses.

BACKGROUND/AIM: Heterotopic ossification (HO) is a common complication following total hip arthroplasty. Various prophylactic treatments have been proposed, including radiotherapy (RT). This review summarizes the evidence from meta-analyses on the efficacy of RT in preventing hip HO. MATERIALS AND METHODS: A literature search was conducted on PubMed. The quality of the meta-analyses was assessed using the AMSTAR-2 tool. RESULTS: Seven meta-analyses were included. One meta-analysis reported a significant reduction in HO occurrence after RT compared to the control group. Comparing RT and non-steroidal anti-inflammatory drugs, one and two meta-analyses showed significantly greater efficacy of RT in preventing severe HO and better outcomes in patients receiving drugs, respectively. Regarding RT settings, the postoperative and preoperative RT were each supported by one meta-analysis. Furthermore, two meta-analyses showed an advantage of multi-fractionated RT over single fraction RT. The overall confidence rate of the meta-analyses was moderate, low, and critically low in one, three, and three meta-analyses, respectively. CONCLUSION: RT is a confirmed prophylactic intervention for HO. However, the precise optimization of timing, dosage, and fractionation requires elucidation. Future research should focus on the development of predictive models through large-scale data collection and advanced analytics to refine individualized treatment strategies and assess RT comparative effectiveness with drugs.

From inflammation to bone formation: the intricate role of neutrophils in skeletal muscle injury and traumatic heterotopic ossification.

Neutrophils are emerging as an important player in skeletal muscle injury and repair. Neutrophils accumulate in injured tissue, thus releasing inflammatory factors, proteases and neutrophil extracellular traps (NETs) to clear muscle debris and pathogens when skeletal muscle is damaged. During the process of muscle repair, neutrophils can promote self-renewal and angiogenesis in satellite cells. When neutrophils are abnormally overactivated, neutrophils cause collagen deposition, functional impairment of satellite cells, and damage to the skeletal muscle vascular endothelium. Heterotopic ossification (HO) refers to abnormal bone formation in soft tissue. Skeletal muscle injury is one of the main causes of traumatic HO (tHO). Neutrophils play a pivotal role in activating BMPs and TGF-ß signals, thus promoting the differentiation of mesenchymal stem cells and progenitor cells into osteoblasts or osteoclasts to facilitate HO. Furthermore, NETs are specifically localized at the site of HO, thereby accelerating the formation of HO. Additionally, the overactivation of neutrophils contributes to the disruption of immune homeostasis to trigger HO. An understanding of the diverse roles of neutrophils will not only provide more information on the pathogenesis of skeletal muscle injury for repair and HO but also provides a foundation for the development of more efficacious treatment modalities for HO.

Heterotopic ossification following COVID-19 infections: systematic literature review of case reports and case series.

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.

Posttraumatic proximal radioulnar synostosis: Current concepts on the clinical presentations, classifications, and open surgical approaches.

In the forearm, posttraumatic heterotopic ossification usually forms as a proximal radioulnar synostosis. It can occur after soft tissue injury involving the interosseous membrane or after surgery involving the radio and ulna, such as distal biceps tendon repair. It can also be induced by radial head dislocation or fracture. Screening radiography can be used to select the appropriate time for excision. The synostosis can be resected when the ectopic bone margin and trabeculation appear mature on radiographs. An interval of 6-12 months from the injury is generally recommended based on ectopic bone maturity. Selection of the surgical approach depends on site, extension (elbow joint or proximal radioulnar joint), severity of the initial articular surface, and periarticular tissue injury. The posterolateral approach is indicated for synostoses: at or distal to the bicipital tuberosity, at the level of the radial head, and proximal radioulnar joint. The posterior global approach is recommended when the forearm synostosis is associated with complete bony ankylosis of the elbow involving the distal aspect of the humerus. After surgical resection of a proximal radioulnar synostosis, the exposed bone surfaces can be covered with interposition material to minimize recurrence.

Malvidin attenuates trauma-induced heterotopic ossification of tendon in rats by targeting Rheb for degradation via the ubiquitin-proteasome pathway.

The pathogenesis of trauma-induced heterotopic ossification (HO) in the tendon remains unclear, posing a challenging hurdle in treatment. Recognizing inflammation as the root cause of HO, anti-inflammatory agents hold promise for its management. Malvidin (MA), possessing anti-inflammatory properties, emerges as a potential agent to impede HO progression. This study aimed to investigate the effect of MA in treating trauma-induced HO and unravel its underlying mechanisms. Herein, the effectiveness of MA in preventing HO formation was assessed through local injection in a rat model. The potential mechanism underlying MA's treatment was investigated in the tendon-resident progenitor cells of tendon-derived stem cells (TDSCs), exploring its pathway in HO formation. The findings demonstrated that MA effectively hindered the osteogenic differentiation of TDSCs by inhibiting the mTORC1 signalling pathway, consequently impeding the progression of trauma-induced HO of Achilles tendon in rats. Specifically, MA facilitated the degradation of Rheb through the K48-linked ubiquitination-proteasome pathway by modulating USP4 and intercepted the interaction between Rheb and the mTORC1 complex, thus inhibiting the mTORC1 signalling pathway. Hence, MA presents itself as a promising candidate for treating trauma-induced HO in the Achilles tendon, acting by targeting Rheb for degradation through the ubiquitin-proteasome pathway.

Ossification of Bilateral Sacrotuberous Ligaments: Two Cases Report and Literature Review.

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.

Fulminant Heterotopic Ossification of the Lower Extremity After Gunshot Injury and Blunt Trauma: A Case Report.

Traumatic heterotopic ossification (HO) of the lower extremity is relatively rare but is of major importance in clinical practice. They are defined as posttraumatic abnormal formations of bone within soft tissue outside of the skeletal system. This article describes the clinical case of a 31-year-old male patient who suffered 2 traumatic events within 12 months-a gunshot wound in the lumbar spine/gluteal region followed by a severe traumatic brain injury with intracranial hemorrhage in a traffic accident as a pedestrian. Clinically, the patient was bedridden because of complete stiffening of the lumbar spine, both hip joints, and the left knee joint. After preoperative diagnosis, 3 surgical ablations of the HO were performed on both the hip joints and the left knee joint. In addition, physiotherapeutic exercise, postoperative nonsteroidal anti-inflammatory drug administration (25 mg of indomethazine for 6 weeks, 3 times a day), and perioperative radiation with 7 Gy for each operation were advised. After 4 years of follow-up, the patient showed significant improvement. In HO treatment, prophylactic local radiotherapy (pre- and postoperative radiation with a local single dose of 7 Gy) and postoperative administration of nonsteroidal anti-inflammatory drugs are often recommended. For therapeutic purposes, surgical resection is still indicated for pronounced cases.

Intersections of Fibrodysplasia Ossificans Progressiva and Traumatic Heterotopic Ossification.

Heterotopic ossification (HO) is a debilitating pathology where ectopic bone develops in areas of soft tissue. HO can develop as a consequence of traumatic insult or as a result of dysregulated osteogenic signaling, as in the case of the orphan disease fibrodysplasia ossificans progressiva (FOP). Traumatic HO (tHO) formation is mediated by the complex interplay of signaling between progenitor, inflammatory, and nerve cells, among others, making it a challenging process to understand. Research into the pathogenesis of genetically mediated HO (gHO) in FOP has established a pathway involving uninhibited activin-like kinase 2 receptor (ALK2) signaling that leads to downstream osteogenesis. Current methods of diagnosis and treatment lag behind pre-mature HO detection and progressive HO accumulation, resulting in irreversible decreases in range of motion and chronic pain for patients. As such, it is necessary to draw on advancements made in the study of tHO and gHO to better diagnose, comprehend, prevent, and treat both.

Heterotopic bone formation in a case of clear cell renal cell carcinoma: A case report.

Renal cell carcinoma (RCC) with heterotopic formation has been reported very rarely. We report this rare entity in a 33-year-old female patient who came to the out-patient department after complaining of pain in the lumbar region of the left side for 2 years. A computed tomography scan showed a heterogeneously enhancing lesion originating from the posterior cortex of the left kidney in the upper pole. It had many chunky calcification foci and was treated with left robotic partial nephrectomy. Histo-pathological examination revealed clear cell RCC with the heterotopic bone formation with a tumor size measuring 5 × 4 × 2.5 cm; the tumor was limited to the kidney, and the tumor resection margin were free of tumor, WHO/ISUP Grade 2. The pathological stage (AJCC 8th edition PTNM) was p T1b p NX p MX. The prognostic implications regarding calcification are poorly addressed in the literature. Patients suffering from osseous metaplasia are often in their early stages of the disease and have a favorable prognosis.

Arthroscopic debridement improves range of motion for heterotopic ossification after total knee replacement: a retrospective cohort study.

The presence of heterotopic ossification (HO) after primary total knee replacement (TKR) is rare and associated with limited mobility and stiffness of the knee. This study aimed to identify if the arthroscopic debridement after TKR could decrease HO and improve the function and range of motion. Thirty HO patients after TKR were retrospectively separated into 2 cohorts. 15 patients of group A accepted the arthroscopic debridement, while 15 patients of group B only had non-operative treatment, mainly including oral nonsteroidal anti-inflammatory drugs (NSAIDs) and rehabilitative treatment. Visual analog scale (VAS) scores, knee society knee scores (KSS), range of motion (knee flexion and knee extension) were obtained before treatment and at 1 month, 3 months, and 6 months after treatment. Radiography of after-treatment was also evaluated to assess the changes in HO. There were 3 males and 27 females with a mean age of 67.4 ± 0.8 years in group A and 68.2 ± 1.3 in group B. The onset time of HO was 3-6 months. The maximum size of the ossification was < 2 cm in 23 knees, 2 cm < heterotopic bone < 5 cm in 6 knees and > 5 cm in 1 knee. The size of HO decreased gradually in all knees by X-ray film at the last follow-up. There were no significant differences in VAS scores after replacement between two groups (p > 0.05). The average range of motion preoperatively in group A was - 15.2-90.6°, which postoperatively increased to - 4.2-110.0°. Meanwhile, the KSS scores and average range of motion of the group A were better than those of the group B at each follow-up time after treatment. Arthroscopic debridement can decrease HO seen from postoperative X-rays, improve the function and range of motion, as well as the pain remission between two groups are comparable. Consequently, arthroscopic resection of HO after TKR is recommended as soon as there is aggravating joint stiffness.

Heterotopic Ossification of Bilateral Hips Post-COVID-19 and Prolonged Immobilization: A Case Report.

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.

Roles of Plasminogen Activator Inhibitor-1 in Heterotopic Ossification Induced by Achilles Tenotomy in Thermal Injured Mice.

Heterotopic ossification (HO) is the process by which ectopic bone forms at an extraskeletal site. Inflammatory conditions induce plasminogen activator inhibitor 1 (PAI-1), an inhibitor of fibrinolysis, which regulates osteogenesis. In the present study, we investigated the roles of PAI-1 in the pathophysiology of HO induced by trauma/burn treatment using PAI-1-deficient mice. PAI-1 deficiency significantly promoted HO and increased the number of alkaline phosphatase (ALP)-positive cells in Achilles tendons after trauma/burn treatment. The mRNA levels of inflammation markers were elevated in Achilles tendons of both wild-type and PAI-1-deficient mice after trauma/burn treatment and PAI-1 mRNA levels were elevated in Achilles tendons of wild-type mice. PAI-1 deficiency significantly up-regulated the expression of Runx2, Osterix, and type 1 collagen in Achilles tendons 9 weeks after trauma/burn treatment in mice. In in vitro experiments, PAI-1 deficiency significantly increased ALP activity and mineralization in mouse osteoblasts. Moreover, PAI-1 deficiency significantly increased ALP activity and up-regulated osteocalcin expression during osteoblastic differentiation from mouse adipose-tissue-derived stem cells, but suppressed the chondrogenic differentiation of these cells. In conclusion, the present study showed that PAI-1 deficiency promoted HO in Achilles tendons after trauma/burn treatment partly by enhancing osteoblast differentiation and ALP activity in mice. Endogenous PAI-1 may play protective roles against HO after injury and inflammation.

An Autopsy Case of COVID-19 with New Diffuse Pulmonary Ossification.

We present the case of a 61-year-old man who developed coronavirus disease 2019 (COVID-19) and died during treatment for relapsing polychondritis. The patient was intubated and treated with steroid pulse therapy, remdecivir, antibacterial agents, baricitinib, and tocilizumab. However, his respiratory condition worsened, and he died 108 days after disease onset. An autopsy revealed diffuse alveolar damage in the fibrotic phase in all lung lobes, diffuse pulmonary ossification, and cytomegalovirus-infected cells in the middle lobe of the right lung. We herein discuss the clinical features and pathological findings of COVID-19 in immunosuppressed patients.

Heterotopic Ossification of the Abdomen: A Rare Sequela Following Trauma and Damage Control Laparotomy.

Heterotopic ossification (HO) of the abdomen is a rare yet highly morbid complication following blunt and penetrating trauma requiring damage control laparotomy. We present the case of a 22-year-old man, 20 months after life-threatening motor vehicle crash with major vascular injury requiring multiple abdominal surgeries. The patient was initially treated at a community hospital and subsequently developed a chronic left lower quadrant enterocutaneous fistula, accompanied by a gradually worsening diffuse abdominal pain. He was referred to our tertiary care center with extensive skin breakdown and an inability to control the fistula despite numerous wound care consultations. He also had severe abdominal deformities due to HO in the abdominal wall, peritoneum, paraspinal muscles, and parapelvic regions. As HO is largely underreported, it is crucial to refer those patients, once medically stabilized, to tertiary care centers for surveillance and possible treatment when symptomatic.

The significance of heterotopic ossification following total ankle arthroplasty: a systematic review and meta-analysis.

PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate the prevalence and clinical significance of heterotopic ossification (HO) following total ankle replacement (TAR). METHODS: During August 2023, the PubMed, Embase and Cochrane library databases were systematically reviewed to identify clinical studies reporting HO following TAR. Data regarding surgical characteristics, pathological characteristics, subjective clinical outcomes, ankle range of motion, radiographic outcomes, reoperation rates were extracted and analysed. RESULTS: Twenty-seven studies with 2639 patients (2695 ankles) at a weighed mean follow-up time of 52.8 ± 26.9 months were included. The pooled prevalence rate was 44.6% (0.25; 0.66). The implant with the highest rate of HO was the INBONE I (100%) and BOX (100%) implants. The most common modified Brooker staging was grade 1 (132 patients, 27.0%). Random effects models of standardized mean differences found no difference in American orthopedic foot and ankle society (AOFAS) scores, visual analog scale scores (VAS) and ankle range of motion (ROM) between patients with HO and patients without HO. Random effects models of correlation coefficients found no correlation between AOFAS, VAS and ROM and the presence of HO. The surgical intervention rate for symptomatic HO was 4.2%. CONCLUSION: This systematic review and meta-analysis found that HO is a common finding following TAR that is not associated with inferior clinical outcomes. Surgical intervention was required only for moderate-to-severe, symptomatic HO following TAR. This study is limited by the marked heterogeneity and low level and quality of evidence of the included studies. Further higher quality studies are warranted to determine the precise prevalence and impact of HO on outcomes following TAR.