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European Spine Journal : Official... Apr 2023Systematic review. (Review)
Review
STUDY DESIGN
Systematic review.
BACKGROUND CONTEXT
Thoracic ossification of the ligamentum flavum (TOLF) has become the principal cause of thoracic spinal stenosis. Dural ossification (DO) was a common clinical feature accompanying with TOLF. However, on account of the rarity, we know little about the DO in TOLF so far.
PURPOSE
This study was conducted to elucidate the prevalence, diagnostic measures, and impact on the clinical outcomes of DO in TOLF by integrating the existing evidence.
METHODS
PubMed, Embase, and Cochrane Database were comprehensively searched for studies relevant to the prevalence, diagnostic measures, or impact on the clinical outcomes of DO in TOLF. All retrieved studies meeting the inclusion and criterion were included into this systematic review.
RESULTS
The prevalence of DO in TOLF treated surgically was 27% (281/1046), ranging from 11 to 67%. Eight diagnostic measures have been put forward to predict the DO in TOLF using the CT or MRI modalities, including "tram track sign", "comma sign", "bridge sign", "banner cloud sign", "T2 ring sign", TOLF-DO grading system, CSAOR grading system, and CCAR grading system. DO did not affect the neurological recovery of TOLF patients treated with the laminectomy. The rate of dural tear or CSF leakage in TOLF patients with DO was approximately 83% (149/180).
CONCLUSION
The prevalence of DO in TOLF treated surgically was 27%. Eight diagnostic measures have been put forward to predict the DO in TOLF. DO did not affect the neurological recovery of TOLF treated with laminectomy but was associated with high risk of complications.
Topics: Humans; Osteogenesis; Ossification, Heterotopic; Ligamentum Flavum; Prevalence; Thoracic Vertebrae; Retrospective Studies
PubMed: 36877368
DOI: 10.1007/s00586-023-07625-4 -
Journal of Shoulder and Elbow Surgery Jun 2023Heterotopic ossification is a frequent complication following surgical treatment of elbow trauma. The use of indomethacin to prevent heterotopic ossification is reported... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Heterotopic ossification is a frequent complication following surgical treatment of elbow trauma. The use of indomethacin to prevent heterotopic ossification is reported in the literature; however, its effectiveness is controversial. The purpose of this randomized, double-blind, placebo-controlled study was to determine whether indomethacin is effective in reducing the incidence and severity of heterotopic ossification after surgical management of elbow trauma.
METHODS
Between February 2013 and April 2018, 164 eligible patients were randomized to receive postoperative indomethacin or placebo medication. The primary outcome was the incidence of heterotopic ossification on elbow radiographs at 1-year follow-up. Secondary outcomes included the Patient Rated Elbow Evaluation score, Mayo Elbow Performance Index score, and Disabilities of the Arm, Shoulder and Hand score. Range of motion, complications, and nonunion rates were also obtained.
RESULTS
At 1-year follow-up, there was no significant difference in the incidence of heterotopic ossification between the indomethacin group (49%) and the control group (55%) (relative risk, 0.89; P = .52). There were no significant differences in postoperative Patient Rated Elbow Evaluation, Mayo Elbow Performance Index, and Disabilities of the Arm, Shoulder and Hand scores or range of motion (P = .16). The complication rate was 17% in both the treatment and control groups (P > .99). There were no nonunions in either group.
CONCLUSION
This Level I study demonstrated that indomethacin prophylaxis against heterotopic ossification in the setting of surgically treated elbow trauma was not significantly different from placebo.
Topics: Humans; Arm Injuries; Elbow; Elbow Joint; Indomethacin; Ossification, Heterotopic; Range of Motion, Articular; Postoperative Complications
PubMed: 36907317
DOI: 10.1016/j.jse.2023.02.119 -
Journal of Extracellular Vesicles Apr 2024Heterotopic ossification (HO) comprises the abnormal formation of ectopic bone in extraskeletal soft tissue. The factors that initiate HO remain elusive. Herein, we...
Heterotopic ossification (HO) comprises the abnormal formation of ectopic bone in extraskeletal soft tissue. The factors that initiate HO remain elusive. Herein, we found that calcified apoptotic vesicles (apoVs) led to increased calcification and stiffness of tendon extracellular matrix (ECM), which initiated M2 macrophage polarization and HO progression. Specifically, single-cell transcriptome analyses of different stages of HO revealed that calcified apoVs were primarily secreted by a PROCR fibroblast population. In addition, calcified apoVs enriched calcium by annexin channels, absorbed to collagen I via electrostatic interaction, and aggregated to produce calcifying nodules in the ECM, leading to tendon calcification and stiffening. More importantly, apoV-releasing inhibition or macrophage deletion both successfully reversed HO development. Thus, we are the first to identify calcified apoVs from PROCR fibroblasts as the initiating factor of HO, and might serve as the therapeutic target for inhibiting pathological calcification.
Topics: Humans; Endothelial Protein C Receptor; Extracellular Vesicles; Ossification, Heterotopic; Extracellular Matrix; Fibroblasts
PubMed: 38594791
DOI: 10.1002/jev2.12425 -
Journal of Bone and Mineral Metabolism Mar 2022Previous studies on patients with symptoms of spinal ligament ossification, including ossification of the posterior longitudinal ligament (OPLL) and ligamentum flavum...
INTRODUCTION
Previous studies on patients with symptoms of spinal ligament ossification, including ossification of the posterior longitudinal ligament (OPLL) and ligamentum flavum (OLF), have not clarified whether obesity is a cause or consequence of these diseases and were limited by selection bias. Thus, we investigated the association between obesity and the prevalence of spinal ligament ossification in randomly selected asymptomatic subjects.
MATERIALS AND METHODS
Between April 2020 and March 2021, 622 asymptomatic Japanese subjects who underwent computed tomography of neck to pelvis for medical check-up purposes were included. All subjects were divided into the following three groups: normal weight (body mass index [BMI] < 25 kg/m), obese I (25 ≤ BMI < 30 kg/m), and obese II (BMI ≥ 30 kg/m). The relationship between factors affecting the presence of each spinal ligament ossification was evaluated using multivariate logistic regression analysis.
RESULTS
The proportion of subjects with thoracic OPLL was significantly higher in the obese II group than in the other two groups (vs. normal weight, P < 0.001; vs. obese I, P < 0.001). BMI was associated with the prevalence of OLF, cervical OPLL, thoracic OPLL, and ossification of the anterior longitudinal ligament (OALL). BMI was most significantly associated with the prevalence of thoracic OPLL (β, 0.28; 95% confidence interval, 0.17-0.39).
CONCLUSION
BMI was associated with the prevalence of OALL, cervical OPLL, thoracic OPLL, and OLF in asymptomatic subjects, suggesting that obesity is associated with the development of heterotopic ossification of the spinal ligaments.
Topics: Cross-Sectional Studies; Humans; Ligamentum Flavum; Obesity; Ossification of Posterior Longitudinal Ligament; Ossification, Heterotopic; Osteogenesis
PubMed: 35034211
DOI: 10.1007/s00774-021-01292-5 -
FASEB Journal : Official Publication of... Jul 2023Heterotopic ossification occurs as a pathological ossification condition characterized by ectopic bone formation within soft tissues following trauma. Vascularization...
Heterotopic ossification occurs as a pathological ossification condition characterized by ectopic bone formation within soft tissues following trauma. Vascularization has long been established to fuel skeletal ossification during tissue development and regeneration. However, the feasibility of vascularization as a target of heterotopic ossification prevention remained to be further clarified. Here, we aimed to identify whether verteporfin as a widely used FDA-approved anti-vascularization drug could effectively inhibit trauma-induced heterotopic ossification formation. In the current study, we found that verteporfin not only dose dependently inhibited the angiogenic activity of human umbilical vein endothelial cells (HUVECs) but also the osteogenic differentiation of tendon stem cells (TDSCs). Moreover, YAP/β-catenin signaling axis was downregulated by the verteporfin. Application of lithium chloride, an agonist of β-catenin, recovered TDSCs osteogenesis and HUVECs angiogenesis that was inhibited by verteporfin. In vivo, verteporfin attenuated heterotopic ossification formation by decelerating osteogenesis and the vessels densely associated with osteoprogenitors formation, which could also be readily reversed by lithium chloride, as revealed by histological analysis and Micro-CT scan in a murine burn/tenotomy model. Collectively, this study confirmed the therapeutic effect of verteporfin on angiogenesis and osteogenesis in trauma-induced heterotopic ossification. Our study sheds light on the anti-vascularization strategy with verteporfin as a candidate treatment for heterotopic ossification prevention.
Topics: Mice; Humans; Animals; Osteogenesis; Achilles Tendon; Verteporfin; beta Catenin; Endothelial Cells; Lithium Chloride; Ossification, Heterotopic
PubMed: 37367700
DOI: 10.1096/fj.202300568R -
Stem Cell Research & Therapy Dec 2022Heterotopic ossification (HO) is the formation of bone in non-osseous tissues, such as skeletal muscles. The HO could have a genetic or a non-genetic (acquired)... (Review)
Review
Heterotopic ossification (HO) is the formation of bone in non-osseous tissues, such as skeletal muscles. The HO could have a genetic or a non-genetic (acquired) background, that is, it could be caused by musculoskeletal trauma, such as burns, fractures, joint arthroplasty (traumatic HO), or cerebral or spinal insult (neurogenetic HO). HO formation is caused by the differentiation of stem or progenitor cells induced by local or systemic imbalances. The main factors described so far in HO induction are TGFβ1, BMPs, activin A, oncostatin M, substance P, neurotrophin-3, and WNT. In addition, dysregulation of noncoding RNAs, such as microRNA or long noncoding RNA, homeostasis may play an important role in the development of HO. For example, decreased expression of miRNA-630, which is responsible for the endothelial-mesenchymal transition, was observed in HO patients. The reduced level of miRNA-421 in patients with humeral fracture was shown to be associated with overexpression of BMP2 and a higher rate of HO occurrence. Down-regulation of miRNA-203 increased the expression of runt-related transcription factor 2 (RUNX2), a crucial regulator of osteoblast differentiation. Thus, understanding the various functions of noncoding RNAs can reveal potential targets for the prevention or treatment of HO.
Topics: Humans; MicroRNAs; RNA, Long Noncoding; Ossification, Heterotopic; Osteogenesis; Cell Differentiation
PubMed: 36522666
DOI: 10.1186/s13287-022-03213-3 -
Neurochemical Research Jul 2024Heterotopic ossification (HO) is a pathological process characterized by the aberrant formation of bone in muscles and soft tissues. It is commonly triggered by... (Review)
Review
Heterotopic ossification (HO) is a pathological process characterized by the aberrant formation of bone in muscles and soft tissues. It is commonly triggered by traumatic brain injury, spinal cord injury, and burns. Despite a wide range of evidence underscoring the significance of neurogenic signals in proper bone remodeling, a clear understanding of HO induced by nerve injury remains rudimentary. Recent studies suggest that injury to the nervous system can activate various signaling pathways, such as TGF-β, leading to neurogenic HO through the release of neurotrophins. These pathophysiological changes lay a robust groundwork for the prevention and treatment of HO. In this review, we collected evidence to elucidate the mechanisms underlying the pathogenesis of HO related to nerve injury, aiming to enhance our understanding of how neurological repair processes can culminate in HO.
Topics: Ossification, Heterotopic; Humans; Animals; Neurotransmitter Agents; Signal Transduction
PubMed: 38416374
DOI: 10.1007/s11064-024-04118-8 -
The American Journal of Sports Medicine Nov 2023Arthroscopic techniques aim to reduce complications and accelerate recovery of the elbow after treatments for posttraumatic stiffness, arthritis diseases, lateral...
BACKGROUND
Arthroscopic techniques aim to reduce complications and accelerate recovery of the elbow after treatments for posttraumatic stiffness, arthritis diseases, lateral epicondylitis, ligament reconstruction, and elbow trauma. However, data on the true prevalence and characteristics of heterotopic ossification (HO) formation after elbow arthroscopy are limited.
PURPOSE
To investigate the prevalence, timing, locational distribution, and risk factors of HO after elbow arthroscopy.
STUDY DESIGN
Cohort study; Level of evidence, 4.
METHODS
Data on 205 patients undergoing elbow arthroscopy by a single senior elbow surgeon at a single institution between May 2011 and January 2022 were retrospectively reviewed. The patients were evaluated at 2 weeks, 8 weeks, 6 months, and then annually after surgery or more frequently if HO developed, with a minimum of 1 year of postoperative follow-up. Postoperative anteroposterior and lateral elbow radiographs were taken at 2 weeks to rule out fracture and at 8 weeks to identify HO. The clinical outcomes were evaluated based on the pain visual analog scale; the shortened version of the Disabilities of the Arm, Shoulder and Hand score; Mayo Elbow Performance Score; and the Single Assessment Numeric Evaluation scores before and after surgery. Bivariate logistic regression analyses were used to determine factors affecting HO prevalence.
RESULTS
Thirteen (12 male, 1 female) of 205 (6.3%) patients developed HO, with 10 (76.9%) with HO that formed on the medial compartment of the elbow. Ten (76.9%) patients were diagnosed at 8 weeks after arthroscopic surgery, 1 (7.7%) at 6 months after surgery, and 2 (15.4%) at 12 months after surgery. HO was not found at 2 weeks after surgery in any patient. The mean follow-up time was 3.5 years (range, 1.0-11.8 years). Eleven asymptomatic patients were treated nonoperatively, and 2 symptomatic patients underwent HO excision arthroscopically or had a combination of open surgery and arthroscopy. Age was a protective factor for HO formation (odds ratio [OR], 0.953; 95% CI, 0.910-0.999; = .047). The risk factors for HO formation were tourniquet time (OR, 1.042; 95% CI, 1.019-1.065; < .001) and surgical time (OR, 1.026; 95% CI, 1.011-1.041; < .001).
CONCLUSION
Among 205 patients who underwent elbow arthroscopy, HO was a minor complication of elbow arthroscopy, with a prevalence rate of 6.3%, and was usually located on the medial compartment of the elbow. Although the presence of HO may not affect the clinical outcomes in most patients, it should be carefully monitored for a minimum of 8 weeks postoperatively. Younger age, longer tourniquet time, and longer surgical time contributed to HO formation after elbow arthroscopy.
Topics: Humans; Male; Female; Arthroscopy; Cohort Studies; Retrospective Studies; Elbow; Prevalence; Risk Factors; Elbow Joint; Ossification, Heterotopic; Range of Motion, Articular
PubMed: 37804157
DOI: 10.1177/03635465231198862 -
Journal of ISAKOS : Joint Disorders &... Dec 2023Heterotopic ossification (HO) is a known complication diagnosed following hip arthroscopy. (Review)
Review
INTRODUCTION
Heterotopic ossification (HO) is a known complication diagnosed following hip arthroscopy.
PURPOSE/HYPOTHESIS
This study sought to review the current literature on chemoprophylaxis for HO following hip arthroscopy and to describe what agents and doses are being utilized.
STUDY DESIGN
Systematic Review.
METHODS
A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines on the use of chemoprophylactic medications for HO prevention following hip arthroscopy. Mechanical and radiation prophylaxis were not included in the current analysis.
RESULTS
A total of 203 studies were identified, of which 15 were included with 6463 patients. There was one randomized control trial (RCT) and 4 additional comparative studies. The most commonly utilized chemoprophylactic agents were the following: naproxen (n = 8), celecoxib (n = 3), indomethacin (n = 3), aspirin (n = 1), etoricoxib (n = 1), and etodolac (n = 1), and non-specific non-steroidal anti-inflammatory drugs (NSAIDs) (n = 1). Naproxen was either given at a dose of 500 mg once or twice daily for 2-4 weeks. RCTs and additional comparative studies showed significant HO prevention using chemoprophylactic agents following hip arthroscopy.
CONCLUSIONS
HO is a known and common complication following hip arthroscopy. The current systematic review found significant heterogeneity across the literature with respect to specific chemoprophylactic agents and their dosing regimens aimed to reduce the incidence and severity of HO following hip arthroscopy. Additionally, this review demonstrates that most studies that utilize chemoprophylaxis use NSAIDs with successful reduction in the incidence of HO.
LEVEL OF EVIDENCE
Level IV Evidence.
Topics: Humans; Naproxen; Arthroscopy; Postoperative Complications; Anti-Inflammatory Agents, Non-Steroidal; Ossification, Heterotopic; Chemoprevention
PubMed: 37619960
DOI: 10.1016/j.jisako.2023.08.005 -
BMC Neurology Dec 2019The elongation of the styloid process is historically associated with two variants of the Eagle syndrome. The classic one, mainly characterized by pain and dysphagia,...
BACKGROUND
The elongation of the styloid process is historically associated with two variants of the Eagle syndrome. The classic one, mainly characterized by pain and dysphagia, and the carotid variant characterized by pain and sometimes by cerebral ischemia. We observed a further variant characterized by a styloid elongation coursing adjacent to the transverse process of C1, causing significant compression of the internal jugular vein.
METHODS
We reviewed all the cases of Eagle syndrome, including the jugular variant, admitted in our Hospital in the last six years. We compared symptomatology, associated comorbidities and imaging. Data were statistically analyzed.
RESULTS
Overall 23 patients were admitted to the Hospital for symptomatic elongation of the styloid process, 11 male and 12 females. The jugular variant of the Eagle syndrome is clinically delineated by significant differences, as compared to the classic variant and carotid variants. Headache was the more prominent symptom (p < .009) as well as a documented peri-mesencephalic hemorrhage was the more significant comorbidity (p < .0003). The group classic-carotid variant was characterized by ipsilateral pain respect to the jugular variant (p < .0003). CT angiography with venous phase extended to the neck veins and imaging reconstruction is highly recommended as imaging technique, complemented by color-Doppler ultrasound.
CONCLUSIONS
The elongation of the styloid process may have different paths which creates compression on the surrounding anatomical structures. There may be a possible association of jugular impingement by an elongated styloid process with symptoms.
TRIAL REGISTRATION
Protocol n°45-2013.
Topics: Adult; Female; Humans; Jugular Veins; Male; Middle Aged; Ossification, Heterotopic; Temporal Bone; Young Adult
PubMed: 31864313
DOI: 10.1186/s12883-019-1572-3