Neurological phenotypes and treatment outcomes in Eagle syndrome: systematic review and meta-analysis.

Background: Eagle syndrome is caused by an elongated styloid process affecting carotid arteries and cranial nerves. Pain, dysphagia, tinnitus, paresthesia (classic subtype), and neurovascular events (vascular subtype) may be triggered by head movements or arise spontaneously. However, Eagle syndrome remains underappreciated in the neurological community. We aimed to determine the most common neurological and non-neurological clinical presentations in patients with Eagle syndrome and to assess the clinical outcome post-surgical resection in comparison to non-surgical therapies. Methodology: We conducted a systematic review of patient-level data on adults with Eagle syndrome, following PRISMA guidelines. We extracted data on demographics, presenting symptoms, neurological deficits, radiological findings, and treatments, including outcomes and complications, from studies in multiple indexing databases published between 2000 and 2023. The study protocol is registered with PROSPERO. Results: In total, 285 studies met inclusion criteria, including 497 patients with Eagle syndrome (mean age 47.3 years; 49.8% female). Classical Eagle (370 patients, 74.5%) was more frequent than vascular Eagle syndrome (117 patients, 23.5%, p < 0.0001). Six patients (1.2%) presented with both variants and the subvariant for four patients (0.8%) was unknown. There was a male preponderance (70.1% male) in the vascular subtype. A history of tonsillectomy was more frequent in classic (48/153 cases) than in vascular (2/33 cases) Eagle syndrome (Odds Ratio 5.2, 95% CI [1.2-22.4]; p = 0.028). By contrast, cervical movements as trigger factors were more prevalent in vascular (12/33 cases) than in classic (7/153 cases) Eagle syndrome (Odds Ratio 7.95, 95% CI [2.9-21.7]; p = 0.0001). Headache and Horner syndrome were more frequent in vascular Eagle syndrome and dysphagia and neck pain more prominent in classic Eagle syndrome (all p < 0.01). Surgically treated patients achieved overall better outcomes than medically treated ones: Eighty-one (65.9%) of 123 medically treated patients experienced improvement or complete resolution, while the same applied to 313 (97.8%) of 320 surgical patients (Odds Ratio 1.49, 95% CI [1.1-2.0]; p = 0.016). Conclusions: Eagle syndrome is underdiagnosed with potentially serious neurovascular complications, including ischemic stroke. Surgical treatment achieves better outcomes than conservative management. Although traditionally the domain of otorhinolaryngologist, neurologist should include this syndrome in differential diagnostic considerations because of the varied neurological presentations that are amenable to effective treatment.

iMSC-mediated delivery of ACVR2B-Fc fusion protein reduces heterotopic ossification in a mouse model of fibrodysplasia ossificans progressiva.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease caused by a gain-of-function mutation in ACVR1, which is a bone morphogenetic protein (BMP) type I receptor. Moreover, it causes progressive heterotopic ossification (HO) in connective tissues. Using FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) and mouse models, we elucidated the underlying mechanisms of FOP pathogenesis and identified a candidate drug for FOP. METHODS: In the current study, healthy mesenchymal stem/stromal cells derived from iPSCs (iMSCs) expressing ACVR2B-Fc (iMSCACVR2B-Fc), which is a neutralizing receptobody, were constructed. Furthermore, patient-derived iMSCs and FOP mouse model (ACVR1R206H, female) were used to confirm the inhibitory function of ACVR2B-Fc fusion protein secreted by iMSCACVR2B-Fc on BMP signaling pathways and HO development, respectively. RESULTS: We found that secreted ACVR2B-Fc attenuated BMP signaling initiated by Activin-A and BMP-9 in both iMSCs and FOP-iMSCs in vitro. Transplantation of ACVR2B-Fc-expressing iMSCs reduced primary HO in a transgenic mouse model of FOP. Notably, a local injection of ACVR2B-Fc-expressing iMSCs and not an intraperitoneal injection improved the treadmill performance, suggesting compound effects of ACVR2B-Fc and iMSCs. CONCLUSIONS: These results offer a new perspective for treating FOP through stem cell therapy.

Aspectos clínicos, radiográficos e estratégias terapêuticas da Síndrome de Eagle: revisão de literatura / Clinical, radiographic aspects and therapeutic strategies of Eagle Syndrome: literature review

Objetivo: Este trabalho tem como propósito fornecer uma análise abrangente das características anatômicas, clínicas e radiográficas da Síndrome de Eagle, além de abordar os métodos de diagnóstico e estratégias terapêuticas. Materiais e métodos: Foi realizada uma busca por artigos científicos publicados no período de 2016 a 2024, utilizando as bases de dados Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) e Google Scholar. A coleta de artigos foi realizada nos idiomas inglês e português, utilizando as palavras-chave: "síndrome de eagle", "síndrome estiloide", "síndrome da artéria carótida", "estilalgia", "eagle syndrome", "styloid syndrome", "carotid artery syndrome" e "stylalgia". Conclusão: Os profissionais devem estar atentos à síndrome de Eagle em casos de dor unilateral ao realizar atividades como engolir, bocejar e chorar, sem causa aparente, especialmente em mulheres adultas que não encontram alívio com analgésicos. Devido à frequência de casos assintomáticos, a realização precoce de exames radiológicos desempenha um papel crucial na avaliação diagnóstica. É essencial que profissionais de Otorrinolaringologia, Neurologia e Odontologia estejam cientes dessa síndrome, pois está associada a uma significativa deterioração na qualidade de vida. (AU)

Objective: This work aims to provide a comprehensive analysis of the anatomical, clinical and radiographic characteristics of Eagle Syndrome, in addition to addressing diagnostic methods and therapeutic strategies. Materials and methods: A search was carried out for scientific articles published between 2016 and 2024, using the Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) and Google Scholar databases. Articles were collected in English and Portuguese, using the keywords: "eagle syndrome", "styloid syndrome", "carotid artery syndrome", "stilalgia", "eagle syndrome", "styloid syndrome", "carotid artery syndrome" and "stylalgia". Conclusion: Professionals should be aware of Eagle syndrome in cases of unilateral pain when performing activities such as swallowing, yawning and crying, without an apparent cause, especially in adult women who do not find relief with analgesics. Due to the frequency of asymptomatic cases, early radiological examinations play a crucial role in diagnostic evaluation. It is essential that Otorhinolaryngology, Neurology and Dentistry professionals are aware of this syndrome, as it is associated with a significant deterioration in quality of life. (AU)

Most Fractures Treated Nonoperatively in Individuals With Fibrodysplasia Ossificans Progressiva Heal With a Paucity of Flareups, Heterotopic Ossification, and Loss of Mobility.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic disorder with episodic and progressive heterotopic ossification. Tissue trauma is a major risk factor for flareups, heterotopic ossification (HO), and loss of mobility in patients with FOP. The International Clinical Council on FOP generally recommends avoiding surgery in patients with FOP unless the situation is life-threatening, because soft tissue injury can trigger an FOP flareup. Surprisingly little is known about flareups, HO formation, and loss of mobility after fractures of the normotopic (occurring in the normal place, distinct from heterotopic) skeleton when treated nonoperatively in patients with FOP. QUESTIONS/PURPOSES: (1) What proportion of fractures had radiographic evidence of union (defined as radiographic evidence of healing at 6 weeks) or nonunion (defined as the radiographic absence of a bridging callus at 3 years after the fracture)? (2) What proportion of patients had clinical symptoms of an FOP flareup because of the fracture (defined by increased pain or swelling at the fracture site within several days after closed immobilization)? (3) What proportion of patients with fractures had radiographic evidence of HO? (4) What proportion of patients lost movement after a fracture? METHODS: We retrospectively identified 36 patients with FOP from five continents who sustained 48 fractures of the normotopic skeleton from January 2001 to February 2021, who were treated nonoperatively, and who were followed for a minimum of 18 months after the fracture and for as long as 20 years, depending on when they sustained their fracture during the study period. Five patients (seven fractures) were excluded from the analysis to minimize cotreatment bias because these patients were enrolled in palovarotene clinical trials (NCT02190747 and NCT03312634) at the time of their fractures. Thus, we analyzed 31 patients (13 male, 18 female, median age 22 years, range 5 to 57 years) who sustained 41 fractures of the normotopic skeleton that were treated nonoperatively. Patients were analyzed at a median follow-up of 6 years (range 18 months to 20 years), and none was lost to follow-up. Clinical records for each patient were reviewed by the referring physician-author and the following data for each fracture were recorded: biological sex, ACVR1 gene pathogenic variant, age at the time of fracture, fracture mechanism, fracture location, initial treatment modality, prednisone use at the time of the fracture as indicated in the FOP Treatment Guidelines for flare prevention (2 mg/kg once daily for 4 days), patient-reported flareups (episodic inflammatory lesions of muscle and deep soft connective tissue characterized variably by swelling, escalating pain, stiffness, and immobility) after the fracture, follow-up radiographs of the fracture if available, HO formation (yes or no) as a result of the fracture determined at a minimum of 6 weeks after the fracture, and patient-reported loss of motion at least 6 months after and as long as 20 years after the fracture. Postfracture radiographs were available in 76% (31 of 41) of fractures in 25 patients and were independently reviewed by the referring physician-author and senior author for radiographic criteria of fracture healing and HO. RESULTS: Radiographic healing was noted in 97% (30 of 31) of fractures at 6 weeks after the incident fracture. Painless nonunion was noted in one patient who sustained a displaced patellar fracture and HO. In seven percent (three of 41) of fractures, patients reported increased pain or swelling at or near the fracture site within several days after fracture immobilization that likely indicated a site-specific FOP flareup. The same three patients reported a residual loss of motion 1 year after the fracture compared with their prefracture status. HO developed in 10% (three of 31) of the fractures for which follow-up radiographs were available. Patient-reported loss of motion occurred in 10% (four of 41) of fractures. Two of the four patients reported noticeable loss of motion and the other two patients reported that the joint was completely immobile (ankylosis). CONCLUSION: Most fractures treated nonoperatively in individuals with FOP healed with few flareups, little or no HO, and preservation of mobility, suggesting an uncoupling of fracture repair and HO, which are two inflammation-induced processes of endochondral ossification. These findings underscore the importance of considering nonoperative treatment for fractures in individuals with FOP. Physicians who treat fractures in patients with FOP should consult with a member of the International Clinical Council listed in the FOP Treatment Guidelines ( https://www.iccfop.org ). LEVEL OF EVIDENCE: Level IV, therapeutic study.

Suppression of heterotopic ossification in fibrodysplasia ossificans progressiva using AAV gene delivery.

Heterotopic ossification is the most disabling feature of fibrodysplasia ossificans progressiva, an ultra-rare genetic disorder for which there is currently no prevention or treatment. Most patients with this disease harbor a heterozygous activating mutation (c.617 G > A;p.R206H) in ACVR1. Here, we identify recombinant AAV9 as the most effective serotype for transduction of the major cells-of-origin of heterotopic ossification. We use AAV9 delivery for gene replacement by expression of codon-optimized human ACVR1, ACVR1R206H allele-specific silencing by AAV-compatible artificial miRNA and a combination of gene replacement and silencing. In mouse skeletal cells harboring a conditional knock-in allele of human mutant ACVR1 and in patient-derived induced pluripotent stem cells, AAV gene therapy ablated aberrant Activin A signaling and chondrogenic and osteogenic differentiation. In Acvr1(R206H) knock-in mice treated locally in early adulthood or systemically at birth, trauma-induced endochondral bone formation was markedly reduced, while inflammation and fibroproliferative responses remained largely intact in the injured muscle. Remarkably, spontaneous heterotopic ossification also substantially decreased in in Acvr1(R206H) knock-in mice treated systemically at birth or in early adulthood. Collectively, we develop promising gene therapeutics that can prevent disabling heterotopic ossification in mice, supporting clinical translation to patients with fibrodysplasia ossificans progressiva.

[Research progress of traumatic heterotopic ossification].

Objective: To review and evaluate the research progress of traumatic heterotopic ossification (HO). Methods: The domestic and foreign related research literature on traumatic HO was widely consulted, and its etiology, pathogenesis, pathological progress, diagnosis, prevention, and treatment were summarized. Results: Traumatic HO is often caused by severe trauma such as joint operation, explosion injury, nerve injury, and burn. At present, it is widely believed that the occurrence of traumatic HO is closely related to inflammation and hypoxia. Oral non-steroidal anti-inflammatory drugs and surgery are the main methods to prevent and treat traumatic HO. Conclusion: Nowadays, the pathogenesis of traumatic HO is still unclear, the efficiency of relevant prevention and treatment measures is low, and there is a lack of specific treatment method. In the future, it is necessary to further study the pathogenesis of traumatic HO and find specific prevention and treatment targets.

Burn-induced heterotopic ossification from incidence to therapy: key signaling pathways underlying ectopic bone formation.

Burn injury is one of the potential causes of heterotopic ossification (HO), which is a rare but debilitating condition. The incidence ranges from 3.5 to 5.6 depending on body area. Burns that cover a larger percentage of the total body surface area (TBSA), require skin graft surgeries, or necessitate pulmonary intensive care are well-researched risk factors for HO. Since burns initiate such complex pathophysiological processes with a variety of molecular signal changes, it is essential to focus on HO in the specific context of burn injury to define best practices for its treatment. There are numerous key players in the pathways of burn-induced HO, including neutrophils, monocytes, transforming growth factor-ß1-expressing macrophages and the adaptive immune system. The increased inflammation associated with burn injuries is also associated with pathway activation. Neurological and calcium-related contributions are also known. Endothelial-to-mesenchymal transition (EMT) and vascularization are known to play key roles in burn-induced HO, with hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) as potential initiators. Currently, non-steroidal anti-inflammatory drugs (NSAIDs) and radiotherapy are effective prophylaxes for HO. Limited joint motion, ankylosis and intolerable pain caused by burn-induced HO can be effectively tackled via surgery. Effective biomarkers for monitoring burn-induced HO occurrence and bio-prophylactic and bio-therapeutic strategies should be actively developed in the future.

Os Trigonum Syndrome.

This article offers an overview of os trigonum syndrome, complications, operative techniques, and the authors' preferred protocol. Os trigonum is an ossicle like many other ossicles in the foot and ankle. Individuals who require repetitive plantarflexion of the ankle for activity may develop symptoms of an enlarged os trigonum. Usually, symptoms will be isolated to the posteriolateral aspect of the ankle. Because of the normal anatomic route of the flexor hallucis longus tendon, its range of motion may also elicit pain to the posterolateral ankle. Conservative, as well as surgical including both endoscopic and open excision, has been described.

Understanding the Implications of the Meniscal Ossicle: Patient Presentation, Treatment, and Outcomes.

The meniscal ossicle is observed in clinical practice, yet there currently is limited information on its potential clinical significance. The purpose of this study was to assess the clinical presentation, imaging findings, and clinical treatment and outcomes of a series of patients identified as having a meniscal ossicle. An institutional database was reviewed to identify knees with a meniscal ossicle. Clinical presentation, magnetic resonance imaging (MRI), treatment, and outcomes were analyzed. Radiographs were graded using Kellgren-Lawrence (KL) scores. MRIs were reviewed for the presence and location of meniscal ossicles and additional knee pathology. Knee arthroplasty rates were recorded with the remaining patients contacted to obtain final International Knee Documentation Committee (IKDC) and Tegner's scores. Failure was defined as conversion to arthroplasty or failing IKDC score (< 75.4). Forty-five meniscal ossicles in 45 patients (26 males and 19 females) with a mean age of 51 years (standard deviation [SD] = 19.0) were included. Pain was the most common presenting symptom (89%). Forty-two patients (93%) had an associated meniscus root tear on MRI. Eighteen percent of patients that did not have an ossicle on initial imaging subsequently developed an ossicle. Mean KL grades progressed significantly from baseline of 1.84 (SD = 1.0) to 2.55 (SD = 0.93 p < 0.01) on final follow-up. Thirty-nine percent of baseline radiographs showed KL grades of less than 2 compared with only 15% of follow-up radiographs (p = 0.04). Mean IKDC score obtained for patients ≤ 60 at an average follow-up of 3.1 years (SD = 3.2) was 65.2 (SD = 19.0). Eight out of 45 patients (18%) had progressed to total knee arthroplasty (TKA) by latest available follow-up. Sixty-two percent of patients met failure criteria at latest available follow-up. The meniscal ossicle is most commonly found in the posterior horn or root of the medial meniscus and is highly suggestive to be sequelae of a posterior root tear. Therefore, the presence of a meniscal ossicle should alert the orthopaedic surgeon to the high likelihood of the patient having a meniscus root tear. These patients have shown to have poor clinical outcomes and worsening arthritis.

Treatment methods for post-traumatic elbow stiffness caused by heterotopic ossification.

HYPOTHESIS: Heterotopic ossification (HO) is a common complication of surgically treated elbow fractures that can inhibit range of motion and impair quality of life. Although there are many treatment methods for HO, there is a lack of consensus as to the best option. We hypothesized that contracture release combined with Botox injection would lead to improved functional outcome scores when compared with current treatment methods. METHODS: A retrospective review was conducted of patients who presented to a single surgeon with HO secondary to elbow fracture between 2005 and 2018. A total of 59 patients were identified who met inclusion criteria. Data were classified into 3 groups: contracture release (control - CR), Botox injection with CR (Botox + CR), and radiation therapy with CR (CR + RT). Range of motion measurements were obtained, including flexion, extension, pronation, and supination. RESULTS: A total of 30 patients (30 of 59, 50.8%) received CR, 6 (6 of 59, 9.2%) were treated with CR + RT, and 23 (23 of 59, 40.0%) had CR + Botox. There was a significant difference between pre- and postoperative arc of motion for both CR + RT (P < .01) and CR + Botox (P < .01). In addition, there was a significant difference in pre- and postoperative extension for patients who received intraoperative Botox injections (P < .05). There was no significant difference between pre- and postoperative motion nor extension in the CR group. CONCLUSION: Intraoperative Botox injection with CR is an effective method in the treatment of post-traumatic elbow stiffness caused by HO.

Severe heterotopic ossification after a shoulder arthroscopy : a rare clinical presentation.

Heterotopic ossification is a well-known complication after orthopaedic surgical procedures, with a pre-dilection of the hip and elbow. Heterotopic ossification is a rare complication after shoulder arthroscopy and is rarely clinically significant. We report a case of a 65-year old Caucasian man with a slow and painful recovery after arthroscopic shoulder surgery encompassing rotator cuff repair, biceps tenotomy and acromioplasty, with recurrence of impingement symptoms unresponsive to conservative therapy (physiotherapy and one sub- acromial injection). He developed a severe heterotopic ossification at the acromial insertion of the deltoid and in the coraco-acromial ligament. This was successfully treated by arthroscopic excision of the lesion and postoperative prophylactic therapy with nonsteroidal anti-inflammatory drugs.

The Survey of Cells Responsible for Heterotopic Ossification Development in Skeletal Muscles-Human and Mouse Models.

Heterotopic ossification (HO) manifests as bone development in the skeletal muscles and surrounding soft tissues. It can be caused by injury, surgery, or may have a genetic background. In each case, its development might differ, and depending on the age, sex, and patient's conditions, it could lead to a more or a less severe outcome. In the case of the injury or surgery provoked ossification development, it could be, to some extent, prevented by treatments. As far as genetic disorders are concerned, such prevention approaches are highly limited. Many lines of evidence point to the inflammatory process and abnormalities in the bone morphogenetic factor signaling pathway as the molecular and cellular backgrounds for HO development. However, the clear targets allowing the design of treatments preventing or lowering HO have not been identified yet. In this review, we summarize current knowledge on HO types, its symptoms, and possible ways of prevention and treatment. We also describe the molecules and cells in which abnormal function could lead to HO development. We emphasize the studies involving animal models of HO as being of great importance for understanding and future designing of the tools to counteract this pathology.

A Case Report of Heterotopic Ossification Caused by High-Voltage Electric Injury.

This case report described the diagnosis and treatment of a patient with ectopic bone injury due to high-pressure electric shock. A 24-year-old male patient suffered from burns that covered 50% of TBSA, including on limbs and torso, after coming into contact with 10-kV high-voltage electricity. A repeated Meek micrografting technique (MEEK) was applied for wound healing; skin grafts were cut into micrografts and expanded at a ratio of 1:4 to cover large areas after burn trauma. After the injury, right elbow redness, fever, pains, and joint movement disorder were reported by the patient, which might be attributed to excessive exercises and acute scarring. However, these symptoms were not treated immediately. Six months after the injury, his right elbow joint showed 90° locking and a restricted 5° movement capacity. X-ray examination revealed a new bone formation at the inner tibia shin. In addition, 3D CT showed the formation of right tibia, the ruler bone, and the skull of the humming bridge. Under general anesthesia, the right elbow joint was released, the medial collateral ligament was repaired, and the hinge external fixator was fixed. A large number of hyperplastic bone masses were found at the right elbow joint during surgery, specifically in the foot bone hawk's beak nest. No complications after surgery were observed. X-ray examination in February showed disappearance of the bone bridge and normal relationship of the right elbow joint. This case study revealed that electric shock injury could lead to ectopic bone formation, and much attention should be paid on any changes that indicate aseptic inflammation, such as redness, swelling, fever, and pain during the treatment process. Finally, identification of the scar constriction phase could indicate surgical treatment in order to promote the limb rehabilitation process.

[Progress on prevention and treatment of heterotopic ossification].

Heterotopic ossification is the formation of pathological bone in non-skeletal tissues (including muscles, tendons or other soft tissues), and the pathogenesis is not completely clear. It is often caused by musculoskeletal trauma, postoperative bone and joint surgery, or damage of the nervous system, the clinical manifestations are joint swelling, pain, and movement disorders, which often occur around the hips, knees, and elbows. At present, the prevention of heterotopic ossification mainly includes drugs, radiotherapy, molecular biological mechanism intervention, and Chinese medicine-related measures. Among them, drugs and radiotherapy are more effective methods to prevent heterotopic ossification. The intervention of molecular biology mechanism to prevent heterotopic ossification has become a new research direction and focus of attention inrecent years, and is basically at the experimental research stage. The treatment of heterotopic ossification includes various methods such as drugs, physical therapy, and surgery. Among them, surgery is recognized as the most effective treatment, however there are still some controversies and disagreements about the choice of operation time and surgical methods.

Awareness of Heterotopic Ossification in Total Joint Arthroplasty: A Primer.

Heterotopic ossification (HO) is the presence of normal bone in soft tissue where bone should not exist. After direct musculoskeletal trauma of the surrounding soft tissue, HO is hypothesized to develop from a dysfunction of normal lamellar bone formation and remodeling that appears in nonskeletal areas of the body. Acquired HO related to total joint arthroplasty (TJA) of the hip and knee forms outside the joint capsule and can be a challenging condition when it impairs the essential healing process after elective surgery. Although HO is rare after elective TJA and thus clinically immaterial, when clinically relevant HO develops, patients may experience the following: 1) limited ambulation, 2) restricted range of motion, and 3) severe pain and discomfort that may lead to loss of function. Ultimately, patients with clinically relevant HO after elective TJA may require additional treatment, including medication, radiation therapy, manipulation under anesthesia, surgical excision of the HO, and possibly revision TJA. Awareness of HO and an understanding of the associated risk factors along with the various management options will enable health care practitioners and their patients to optimize their surgical outcomes.

The Reduction of Heterotopic Ossification Incidence After Hip Arthroscopy in Patients Treated With Selective Cyclooxygenase 2 Inhibitor (Celecoxib).

PURPOSE: To evaluate the effectiveness of celecoxib, a selective cyclooxygenase 2 inhibitor, in reducing heterotopic ossification (HO) after hip arthroscopic surgery and to evaluate celecoxib's impact on clinical outcomes. METHODS: We performed a retrospective review of patients who received hip arthroscopy performed by the same surgeon between January 1, 2012, and December 31, 2016. Patients who had an allergy to sulfa drugs, had pre-existing HO or previous surgery on the operative side, or failed to complete radiographic follow-up at 6 months postoperatively were excluded. Patients in the treatment group received 400 mg of celecoxib postoperatively for 6 weeks, whereas the control group received no postoperative celecoxib. The incidence of HO was assessed using anteroposterior radiographs obtained at 6 months, 1 year, and 2 years postoperatively. Patients completed the International Hip Outcome Tool 33 survey, and the proportion of patients who met the minimal clinically important difference, substantial clinical benefit (SCB), and absolute SCB was calculated. RESULTS: A total of 559 patients were identified. After application of the exclusion criteria, 454 patients were included in the study (211 in control group and 243 in treatment group). The overall incidence of HO was 20.3% (n = 92). The treatment group had a significantly lower incidence of HO at 6 months (P = .006), 1 year (P < .001), and 2 years (P = .008) postoperatively. At 2 years postoperatively, the treatment group had a significantly higher International Hip Outcome Tool 33 score on average: 64.2 versus 57.3 (P = .023). No significant difference in the proportion of patients reaching the minimal clinically important difference, SCB, or absolute SCB was found at any of the postoperative time points. CONCLUSION: The findings of this study suggest that a prophylactic treatment regimen of 400 mg of celecoxib once daily for 6 weeks significantly reduces the incidence of HO formation after hip arthroscopic surgery; however, it did not impact clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective, comparative case-control study.

Heterotopic ossification: radiological and pathological review.

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 therapeutic treatments that is promising. Conclusions Due to HO potential to cause disability, it is so important to differentiate it from other causes in order to establish the best possible management.

Superparamagnetic iron oxide (SPIO) nanoparticles labeled endothelial progenitor cells (EPCs) administration inhibited heterotopic ossification in rats.

Heterotopic ossification (HO) is a painful disease characterized by unwanted bone ectopic formation outside of the skeleton after injury. SPIO nanoparticles therapy has been widely used in diverse orthopedic diseases. However, the effect of SPIO nanoparticles on heterotopic ossification remains unknown. Here, we prepared the SPIO nanoparticles carrying mothers against decapentaplegic homolog 7 (SMAD7) and evaluated their mechanism function to HO in a rat model. The results revealed that SPIO nanoparticles containing SMAD7 treatment lead to a decrease in epithelial-mesenchymal transition (EMT) relevant protein expression in vitro. Moreover, SPIO nanoparticles labeled EPCs transplantation effectively prevented heterotopic ossification and inhibited endothelial-mesenchymal transition (EndMT) in HO rats. In addition, SPIO nanoparticles labeled EPCs transplantation suppressed osteogenic and adipogenic differentiation of embryonic fibroblasts (EFs) in HO rats. Our results demonstrated that administration of SPIO nanoparticles labeled EPCs could inhibit heterotopic ossification in rats, which might be a potential therapy method for a medical intervention to treat HO in clinic.

A Comparison of Contracture Severity at Acute Discharge in Patients With and Without Heterotopic Ossification: A Burn Model System National Database Study.

This study assesses the association between heterotopic ossification and upper extremity contracture by comparing goniometric measured active range of motion outcomes of patients with and without heterotopic ossification. Data were obtained from the Burn Model System National Database between 1994 and 2003 for patients more than 18 years with elbow contracture at acute discharge. Absolute losses in elbow range of motion were compared for those with and without radiologic evidence of heterotopic ossification (location undefined) and were further examined by burn size subgroups using Wilcoxon rank-sum test. Differences in elbow range of motion were estimated using regression models, adjusted for demographic and clinical variables. Loss of range of motion of shoulder, wrist, forearm, and hand were also compared. From 407 instances of elbow contracture, the subjects with heterotopic ossification were found to have greater median absolute loss of elbow flexion among all survivors (median 50° [IQR 45°] vs 20° [30°], P < .0001), for the 20 to 40% total body surface area burn subgroup (70° [20°] vs 20° [30°], P = .0008) and for the >40% subgroup (50° [45°] vs 30° [32°], P = .03). The adjusted estimate of the mean difference in the absolute loss of elbow flexion between groups was 23.5° (SE ±7.2°, P = .0013). This study adds to our understanding of the potential effect of heterotopic ossification on upper extremity joint range of motion, demonstrating a significant association between the presence of heterotopic ossification and elbow flexion contracture severity. Further study is needed to determine the functional implications of heterotopic ossification and develop treatment protocols.