This review aimed to provide a comprehensive analysis of the etiology, epidemiology, pathology, and conventional treatment of heterotopic ossification (HO), especially emerging potential therapies. HO is the process of ectopic bone formation at non-skeletal sites. HO can be subdivided into two major forms, acquired and hereditary, with acquired HO predominating. Hereditary HO is a rare and life-threatening genetic disorder, but both acquired and hereditary form can cause severe complications, such as peripheral nerve entrapment, pressure ulcers, and disability if joint ankylosis develops, which heavily contributes to a reduced quality of life. Modalities have been proposed to treat HO, but none have emerged as the gold standard. Surgical excision remains the only effective modality; however, the optimal timing is controversial and may cause HO recurrence. Recently, potential therapeutic strategies have emerged that focus on the signaling pathways involved in HO, and small molecule inhibitors have been shown to be promising. Moreover, additional specific targets, such as small interfering RNAs (siRNAs) and non-coding RNAs, could be used to effectively block HO or develop combinatorial therapies for HO.
Humans ; Ossification, Heterotopic/genetics*

OBJECTIVE: To explore short-term effectiveness of floating island laminectomy surgery in treating thoracic spinal stenosis and myelopathy caused by ossification of the ligamentum flavum. METHODS: A total of 31 patients with thoracic spinal stenosis and myelopathy caused by ossification of the ligamentum flavum between January 2019 and April 2022 were managed with floating island laminectomy surgery. The patients comprised 17 males and 14 females, aged between 36 and 78 years, with an average of 55.9 years. The duration of symptoms of spinal cord compression ranged from 3 to 62 months (mean, 27.2 months). The lesions affected T _1-6 in 4 cases and T _7-12 in 27 cases. The preoperative neurological function score from the modified Japanese Orthopaedic Association (mJOA) was 4.7±0.6. Surgical duration, intraoperative blood loss, and complications were recorded. The thoracic MRI was conducted to reassess the degree of spinal cord compression and decompression after operation. The mJOA score was employed to evaluate the neurological function and calculate the recovery rate at 12 months after operation. RESULTS: The surgical duration ranged from 122 to 325 minutes, with an average of 204.5 minutes. The intraoperative blood loss ranged from 150 to 800 mL (mean, 404.8 mL). All incisions healed by first intention after operation. All patients were followed up 12-14 months, with an average of 12.5 months. The patients' symptoms, including lower limb weakness, gait disorders, and pain, significantly improved. The mJOA scores after operation significantly increased when compared with preoperative scores ( P<0.05), gradually improving with time, with significant differences observed among 1, 3, and 6 months ( P<0.05). The recovery rate at 12 months was 69.76%±11.38%, with 10 cases exhibiting excellent neurological function and 21 cases showing good. During the procedure, there were 3 cases of dural tear and 1 case of dural defect. Postoperatively, there were 2 cases of cerebrospinal fluid leakage. No aggravated nerve damage, recurrence of ligamentum flavum ossification, or postoperative thoracic deformity occurred. CONCLUSION The floating island laminectomy surgery is safe for treating thoracic spinal stenosis and myelopathy caused by ossification of the ligamentum flavum, effectively preventing the exacerbation of neurological symptoms. Early improvement and recovery of neurological function are achieved.
Humans ; Male ; Spinal Stenosis/diagnostic imaging* ; Female ; Laminectomy/methods* ; Ligamentum Flavum/pathology* ; Middle Aged ; Aged ; Thoracic Vertebrae/surgery* ; Adult ; Decompression, Surgical/methods* ; Treatment Outcome ; Ossification, Heterotopic/surgery* ; Spinal Cord Compression/etiology* ; Spinal Cord Diseases/etiology* ; Magnetic Resonance Imaging

OBJECTIVE: To investigate the technical key points and effectiveness of ultrasonic bone scalpel-assisted anterior controllable antedisplacement and fusion (ACAF) for treating cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: Between June 2022 and December 2024, 11 OPLL patients underwent ultrasonic bone scalpel-assisted ACAF. The cohort included 8 males and 3 females, aged 49-74 years (mean, 56.7 years). The OPLL classification included 5 cases of mixed-type, 4 cases of segmental-type, and 2 cases of continuous-type cases. Ossification involved 2-5 spinal segments (mean, 3.2). Disease duration ranged from 2 to 18 months (mean, 6.2 months). The operation time, intraoperative blood loss, and complications were recorded. Pain improvement was assessed using the visual analogue scale (VAS) score, and neurological function was evaluated using Japanese Orthopaedic Association (JOA) score. Postoperative cervical CT and MRI were performed to measure spinal canal encroachment rate, spinal canal area, and spinal cord sagittal diameter. RESULTS: All operations were successfully completed. The operation time ranged from 174 to 360 minutes (mean, 255.9 minutes). The intraoperative blood loss ranged from 170 to 530 mL (mean, 345.9 mL). The C ₅ nerve root palsy occurred in 1 patient. No cerebrospinal fluid leakage, aggravated spinal cord injury, or recurrent/superior laryngeal nerve injuries occurred. All patients were followed 3-12 months (mean, 7.2 months). At last follow-up, VAS scores significantly decreased and JOA scores significantly increased compared to preoperative values ( P<0.05). According to the JOA improvement rate, the effectiveness was rated as excellent in 2 cases, good in 8, and fair in 1, with an excellent and good rate of 90.9%. Radiological re-examination revealed no implant loosening, screw breakage, or aggravated spinal stenosis. Postoperative spinal canal encroachment rate significantly decreased, while spinal canal area and spinal cord sagittal diameter significantly increased compared to preoperative measurements ( P<0.05). CONCLUSION For the treatment of cervical OPLL via ACAF, the intraoperative application of ultrasonic bone scalpel-assisted osteotomy enables precise vertebral groove creation and mobilization of the vertebra-ossification complex, thereby enhancing surgical safety and achieving satisfactory short-term effectiveness.
Humans ; Middle Aged ; Male ; Female ; Ossification of Posterior Longitudinal Ligament/diagnostic imaging* ; Aged ; Cervical Vertebrae/diagnostic imaging* ; Spinal Fusion/instrumentation* ; Treatment Outcome ; Ultrasonic Surgical Procedures/instrumentation* ; Operative Time

OBJECTIVE: To investigate the effect of expansive open-door laminoplasty combined with single lateral mass screw fixation on the posterior longitudinal ligament ossification and cervical instability and its effect on sagittal balance. METHODS: A retrospective analysis of 65 patients with the posterior longitudinal ligament with cervical instability from May 2012 to July 2018 was conducted. The patients were divided into two groups according to the surgical method. Thirty-four patients were treated with open-door laminoplasty including 19 males and 15 females, aged 49 to 60 years old with an average age of (54.4±4.77) years old;symptoms lasted 8 to 39 months with an average of (21.0±8.2) months. Thirty-one patients were treated with single-door laminoplasty combined with single mass screw fixation including 17 males and 14 females, aged 50 to 59 years old with an average age of (55.4±3.2) years;symptoms lasted 7 to 48 months with an average of (23.7±13.1) months. General information of the two groups, including operation time, intraoperative blood loss, and postoperative complications was recorded. Sagittal vertical axis(SVA), C₀-C₂ and C₂-C₇ cobb angle were measured by X-ray before operation and at the last follow-up. Clinical efficacy was evaluated using the Japanese Orthopaedic Association(JOA) score. RESULTS: Surgery was successful in all patients. The operation time (109±15) min in the single-door laminoplasty combined with lateral mass screw fixation group was longer than that in the single-door group(128±16) min(P<0.05). There was no significant difference in intraoperative blood loss, postoperative axial symptoms and follow-up time between two groups(P>0.05). At the latest follow-up, both groups showed significant improvement in the motor and sensory components of the JOA score and the total JOA score compared to pre-surgery(P<0.05) and no significant change in bladder function score(P>0.05). There was no significant difference between two groups(P>0.05). At the latest follow-up, the C₀-C₂ Cobb angle increased in both groups compared to preoperative and more the single-door laminoplasty group(P<0.05). The angle of the C₂-C₇ Cobb angle decreased in both groups, and the reduction was greater in the single-door laminoplasty combined with lateral mass screw fixation group(P<0.05). There was a significant increase in C₂-C₇ SVA in the single-door laminoplasty group(P<0.05) and no significant change the single-door laminoplasty combined with lateral screw fixation group(P>0.05). CONCLUSION Posterior cervical laminoplasty with unilateral lateral mass screw fixation combined with single-door vertebral plate shaping surgery improves the neurological function and quality of life in patients with cervical spondylotic myelopathy complicated by ossification of the posterior longitudinal ligament and cervical instability. Compared with single-door vertebral plate shaping surgery, postoperative cervical lordosis and forward-tilt can be improved.
Humans ; Middle Aged ; Male ; Female ; Laminoplasty/methods* ; Ossification of Posterior Longitudinal Ligament/physiopathology* ; Bone Screws ; Cervical Vertebrae/physiopathology* ; Retrospective Studies ; Joint Instability/surgery*

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by congenital bilateral malformation of the large toe and progressive, extensive, and irreversible heterotopic ossification (HO) of soft tissues throughout the body, leading to severe disabilities. FOP is caused primarily by mutations in activin A receptor type 1 (ACVR1), also known as activin-like kinase 2 (ALK2), which encodes a receptor belonging to the bone morphogenetic protein (BMP) type I family. However, the continuous and complex process of HO in FOP is not yet fully understood, which has impeded the development of therapeutic drugs. Despite surgical removal of HO, which often results in recurrence and expansion of ossification, there is currently no definitive drug treatment available to completely prevent, halt, or reverse the progression of HO in FOP. Currently, researchers are intensively studying the pathogenesis of FOP at various stages and developing promising drug candidates, including saracatinib, palovarotene, and rapamycin. This review provides an overview of progress in understanding the mechanism of FOP and the development of therapeutic drugs, with the goal of providing insights for further research and the development of new treatment methods.
Myositis Ossificans/genetics* ; Humans ; Activin Receptors, Type I/genetics* ; Ossification, Heterotopic ; Mutation ; Sirolimus/therapeutic use* ; Quinolones/therapeutic use* ; Benzodioxoles/therapeutic use* ; Animals ; Quinazolines/therapeutic use*

OBJECTIVE: To evaluate the feasibility, safety, and early effectiveness of percutaneous endoscopic thoracic spine surgery via the trench technique for ventral decompression in central calcified thoracic disc herniation (CCTDH) and thoracic ossification of the posterior longitudinal ligament (T-OPLL). METHODS: Seven patients with single-segment CCTDH or T-OPLL admitted between June 2017 and May 2020 and meeting the selection criteria were retrospectively analyzed. There were 3 males and 4 females with an average age of 51.7 years ranging from 41 to 62 years. There were 2 patients with T-OPLL (T _{1, 2} in 2 cases) and 5 patients with CCTDH (T _{1, 2} in 1 case, T _{7, 8} in 1 case, T _{10, 11} in 2 cases, T _{11, 12} in 1 case). Five patients with thoracic axial pain and intercostal neuralgia had a preoperative visual analogue scale (VAS) score of 6.0 (5.0, 6.5), and 7 patients had a preoperative Japanese Orthopaedic Association (JOA) score of 21 (21.0, 22.0). Transforaminal approach was used in 4 cases and transpedicular approach in 3 cases. Ventral decompression of thoracic spinal cord was performed by thoracic endoscopy combined with trench technique. The operation time, intraoperative blood loss, postoperative hospital stay, and postoperative complications were recorded. Thoracic spine CT and MRI were performed preoperatively and postoperatively to evaluate the surgical decompression, VAS score was used to evaluate the pain of thoracic back and lower limbs, and JOA score was used to evaluate the functional recovery. Modified MacNab criteria was used to evaluate the effectiveness. RESULTS: All surgeries were successfully completed. The operation time ranged from 60 to 100 minutes, with an average of 80.4 minutes; the intraoperative blood loss ranged from 40 to 75 mL, with an average of 57.1 mL; the postoperative hospital stay ranged from 4 to 7 days, with an average of 5.4 days. CT and MRI examinations indicated that the decompression was adequate. All 7 patients were followed up 3-22 months, with an average of 13.3 months. One case developed postoperative wound infection, and 1 case developed pneumonia; the remaining patients did not have any complications such as wound infection or cerebrospinal fluid leakage. Five patients with thoracic axial pain and intercostal neuralgia had VAS scores of 2.0 (1.5, 2.5) at 1 day after operation and 2.0 (1.0, 2.0) at last follow-up, both of which were significantly lower than the preoperative scores ( P<0.05). At 1 day after operation, the JOA scores for all 7 patients were 22.0 (21.0, 24.0), which showed no significant difference compared to the preoperative score ( P>0.05); however, at last follow-up, the score improved to 24.0 (24.0, 26.0), which was significant compared to the preoperative scores ( P<0.05). At last follow-up, the effectiveness was assessed using the modified MacNab criteria, the results were excellent in 2 cases, good in 3 cases, fair in 2 cases, and the excellent and good rate was 71.4%. CONCLUSION Using the trench technique, percutaneous endoscopic thoracic spine surgery can achieve the ventral decompression in CCTDH and T-OPLL, providing a new approach for surgical treatment of CCTDH and T-OPLL.
Humans ; Middle Aged ; Male ; Female ; Thoracic Vertebrae/surgery* ; Decompression, Surgical/methods* ; Adult ; Intervertebral Disc Displacement/surgery* ; Spinal Cord Compression/etiology* ; Treatment Outcome ; Ossification of Posterior Longitudinal Ligament/surgery* ; Endoscopy/methods*

Ossification of the posterior longitudinal ligament (OPLL) is a condition comprising ectopic bone formation from spinal ligaments. This disease is a leading cause of myelopathy in the Asian population. However, the molecular mechanism underlying OPLL and efficient preventive interventions remain unclear. Here, we performed single-cell RNA sequencing and revealed that type I interferon (IFN) signaling was activated in the ossified ligament of patients with OPLL. We also observed that IFN-β stimulation promoted the osteogenic differentiation of preosteoblasts in vitro and activated the ossification-related gene SPP1, thereby confirming the single-cell RNA sequencing findings. Further, blocking the IFN-α/β subunit 1 receptor (IFNAR1) using an anti-IFNAR1 neutralizing antibody markedly suppressed osteogenic differentiation. Together, these results demonstrated that the type I IFN signaling pathway facilitated ligament ossification, and the blockade of this signaling might provide a foundation for the prevention of OPLL.
Humans ; Signal Transduction ; Interferon Type I/metabolism* ; Ossification of Posterior Longitudinal Ligament/genetics* ; Gene Expression Profiling ; Single-Cell Analysis ; Osteogenesis/genetics* ; Receptor, Interferon alpha-beta/metabolism* ; Male ; Female ; Cell Differentiation ; Middle Aged

Humans ; Ossification, Heterotopic ; Skin Diseases, Genetic ; Bone Diseases, Metabolic

OBJECTIVE: To evaluate the application of surgical strategies for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) involving the C ₂ segment. METHODS: The literature about the surgery for cervical OPLL involving C ₂ segment was reviewed, and the indications, advantages, and disadvantages of surgery were summarized. RESULTS: For cervical OPLL involving the C ₂ segments, laminectomy is suitable for patients with OPLL involving multiple segments, often combined with screw fixation, and has the advantages of adequate decompression and restoration of cervical curvature, with the disadvantages of loss of cervical fixed segmental mobility. Canal-expansive laminoplasty is suitable for patients with positive K-line and has the advantages of simple operation and preservation of cervical segmental mobility, and the disadvantages include progression of ossification, axial symptoms, and fracture of the portal axis. Dome-like laminoplasty is suitable for patients without kyphosis/cervical instability and with negative R-line, and can reduce the occurrence of axial symptoms, with the disadvantage of limited decompression. The Shelter technique is suitable for patients with single/double segments and canal encroachment >50% and allows for direct decompression, but is technically demanding and involves risk of dural tear and nerve injury. Double-dome laminoplasty is suitable for patients without kyphosis/cervical instability. Its advantages are the reduction of damage to the cervical semispinal muscles and attachment points and maintenance of cervical curvature, but there is progress in postoperative ossification. CONCLUSION OPLL involving the C ₂ segment is a complex subtype of cervical OPLL, which is mainly treated through posterior surgery. However, the degree of spinal cord floatation is limited, and with the progress of ossification, the long-term effectiveness is poor. More research is needed to address the etiology of OPLL and to establish a systematic treatment strategy for cervical OPLL involving the C ₂ segment.
Humans ; Longitudinal Ligaments/surgery* ; Ossification of Posterior Longitudinal Ligament/surgery* ; Treatment Outcome ; Osteogenesis ; Decompression, Surgical/methods* ; Cervical Vertebrae/surgery* ; Laminoplasty/methods* ; Kyphosis/surgery* ; Retrospective Studies

Patients with burns are predisposed to heterotopic ossification and contracture formation. While radiographs and bone scans are used to detect heterotopic ossification, musculoskeletal ultrasound can be used to diagnose and localize the lesion in patients with contractures. A 14-year-old girl with multiple contractures of the limbs from thermal burn injury sustained three years ago underwent in-patient rehabilitation in a sub-acute burn rehabilitation unit. Despite close monitoring and daily therapy sessions, the patient had minimal improvement in the range of motion of bilateral hips. Musculoskeletal ultrasound demonstrated hyperechogenic focus on the posterolateral aspect of the bilateral hips. This report documents the advantage of diagnostic musculoskeletal ultrasound in localizing and guiding the treatment of heterotopic ossification in a burn patient with contractures.
Diagnostic Imaging ; Ossification, Heterotopic ; Burns ; Rehabilitation ; Pediatrics