Current therapy in the management of heterotopic ossification of the elbow: a review with case studies.

Heterotopic ossification, or the appearance of ectopic bone in para-articular soft tissues after surgery, immobilization, or trauma, complicates the surgical and physiatric management of injured joints. The chief symptoms of heterotopic ossification are joint and muscle pain and a compromised range of motion. Current therapies for prevention or treatment of heterotopic ossification include surgery, physical therapy, radiation therapy, and medical management. Unlike heterotopic ossification of the hip, heterotopic ossification of the elbow has not been extensively investigated, leaving its optimal management ill-defined. To remedy this deficiency, we review risk factors, clinical anatomy, physical findings, proposed mechanisms, and current practice for treatment and prevention of heterotopic ossification. We then consider and draw conclusions from four cases of elbow injury treated at our institutions (three complicated by heterotopic ossification) in which treatment included surgery, radiation therapy, physical therapy, and medical therapy. We summarize our institutional practices and conclude with a call for a randomized clinical trial to better define optimal management of heterotopic ossification of the elbow.     

Treatment of heterotopic ossification by extracorporeal shock wave: 26 patients]

OBJECTIVES: To evaluate the effects of extracorporeal shockwave therapy (ESWT) on heterotopic ossification leading to functional limitations in the short and medium term. METHODS: Twenty-six patients with heterotopic ossification received sessions of ESTW (4000 shocks, 3/s), with an energy ranging from 0.54 to 1.06 mJ/mm2, once a week for 4 consecutive weeks. Intermediary assessments performed 1 month after the last session related to pain (on a visual analog scale [VAS]), range of motion, functional independence (FIM), walking distance (whenever possible), radiology, and blood calcium and alkaline phosphatase levels. Eighteen patients with total hip arthroplasty (THA) were followed up by quiz, at 11 months, on average. RESULTS: Heterotopic ossification was neurogenic in 5 patients and nonneurogenic in 21. The length of evolution of ossification was 32+/-21 months. The measurements showing significant improvement in the short term were pain, with a mean decrease of 4.32 to 1.14 on a VAS; joint flexion, with an mean increase of 8.18+/-11.9 degrees; and walking distance, with a mean increase from 1126 to 2776 m. The treatment was tolerated for the most part. THA cases showed a decline in factors initially shown to be improved. However, the long-term results were superior to clinical status before treatment. CONCLUSION: ESWT might be an interesting treatment for heterotopic ossification and can be a complement to usual medical treatment, physiotherapy, and before surgery.     

Heterotopic ossification in Guillain-Barré syndrome]

INTRODUCTION: Heterotopic ossification are frequent in central nervous disease, on the opposite just a few cases have been described in peripheral disorders.PURPOSE: To describe three cases of Guillain-Barré syndrome complicated by heterotopic ossification.METHODS: From the detailed case reports and a review of the literature.RESULTS: The authors report three cases of heterotopic ossification in Guillain-Barré syndrome. Each of them had serious symptom and had to go in intensive care. Two of them had encephalopathy. A patient had compression of ulnar nerve as complication of heterotopic ossification. In all cases the consequence of the heterotopic ossifications lead to a great functional handicap. DISCUSSION: Heterotopic ossification is a frequent complication in central neurologic lesions such spinal cord injury or brain injury. Just a few cases following peripheral nerve disorders have been reported. Serious neurologic deficit and encephalopathy may influence the apparition of heterotopic ossifications in patients suffering from Guillain-Barre syndrome. This possibility of complication must be known by the clinicians who should have a special attention to such patients.     

Heterotopic ossification in children with burns: two case reports.

Heterotopic ossification is the formation of ectopic bone in soft tissue, and has been reported as a rare complication in pediatric burn patients. At our hospital, two 86% body surface area burn patients developed heterotopic ossification in the shoulder, elbows, distal femur, proximal tibia, fibula, and ribs approximately four months after the burn injury. These two rare and unusual cases are presented documenting the clinical involvement, radiological studies, laboratory data, as well as treatment of their heterotopic ossification. Discussion will focus on the incidence, diagnosis, pathophysiology, and treatment of heterotopic ossification in burn patients and how this information relates to the specific diagnosis and management of the complication of heterotopic ossification in the burn child.     

Deep venous thrombosis associated with heterotopic ossification.

The differential diagnosis of the swollen lower extremity in the patient with spinal cord injury includes deep venous thrombosis, fracture, cellulitis, joint sepsis, heterotopic ossification, hematoma formation, and neoplasm. A patient with an asymmetrically swollen limb who was found to have concurrent ipsilateral acute deep venous thrombosis and active heterotopic ossification is described. The diagnostic workup included various laboratory and radiologic studies. Therapy included anticoagulation with heparin and warfarin. To treat the heterotopic ossification, indomethacin, etidronate, and graded range of motion were used. We learned from this patient and several similar cases that acute deep-venous thrombosis and active heterotopic ossification may occur concurrently, and therapeutic anticoagulation did not lead to bleeding within or around the area of active heterotopic ossification. The possibility of a relationship between heterotopic ossification and deep venous thrombosis is presently being studied at our institution.     

环氧化酶2、骨形态形成蛋白2和血管内皮生长因子在异位骨化组织中的表达

背景：研究发现环氧化酶2抑制剂具有预防肘关节周围异位骨化的作用。目的：观察环氧化酶2、骨形态形成蛋白2和血管内皮生长因子在肘关节创伤后异位骨化组织中的表达,并分析其相关性。方法：采用免疫组化SP法检测18例肘关节创伤后异位骨化组织及10例正常骨组织中环氧化酶2、骨形态形成蛋白2和血管内皮生长因子的表达水平,利用HPIAS-1000图像分析系统测定异位骨化组织与正常骨组织中环氧化酶2、骨形态形成蛋白2和血管内皮生长因子的平均吸光度和阳性区域面积百分率,并分析3种蛋白阳性区域面积百分率之间的相关性。结果与结论：异位骨化组织中环氧化酶2、骨形态形成蛋白2和血管内皮生长因子呈高表达;正常骨组织中呈低表达或不表达。图像分析结果显示异位骨化组织中3种蛋白平均吸光度及阳性区域面积百分率显著高于正常骨组织（P〈0.01）。异位骨化组织中环氧化酶2与骨形态形成蛋白2、血管内皮生长因子的阳性区域面积百分率呈正相关（P〈0.01）。提示环氧化酶2、骨形态形成蛋白2和血管内皮生长因子在异位骨化的形成过程中起重要作用,环氧化酶2可能通过诱导骨形态形成蛋白2和血管内皮生长因子的表达从而促进异位骨化组织中的成骨和血管形成。     

Heterotopic ossification

Heterotopic ossification is becoming increasingly recognized as a phenomenon that can complicate trauma to the head and spinal cord. It can be a disabling accompaniment of thermal injury, and it may seriously compromise results in hip arthroplasty and the treatment of acetabular fractures. Etiologic factors, which are imprecise and incompletely understood, vary with the clinical situation. The five cases reported here illustrate the radiologic appearances, complications, and diagnostic problems, including the difficulty in determining the timing of surgical resection. Reported for the first time are cases of neurogenic heterotopic ossification associated with bilateral shoulder involvement and bilateral ulnar nerve entrapment at the elbow. Heterotopic ossification may mimic acute arthritis.     

Orthopedic strategies in the management of the adult head-injured patient

The purpose of this paper is to outline a systematic approach to the care of adult patients with traumatic head injury. The orthopedic management of these individuals is divided in three phases. In the acute period after the initial trauma, musculoskeletal injuries should be diagnosed and treated. Delayed diagnoses of fractures and peripheral nerve injuries are common. Fracture care often differs from the care given to patients without head injuries because open reduction and internal fixation are more frequently indicated. The results of fracture treatment are compromised by spasticity and heterotopic ossification. The second phase is the subacute period during which neurologic recovery is occurring. This period may last up to 18 months. While neurologic recovery is proceeding, heterotopic ossification and spasticity with its resulting deformities are treated. Drugs, casting, and phenol blocks of peripheral nerves and motor points are used in the control of spasticity. Drugs and aggressive range-of-motion exercises aid in maintenance of joint motion when heterotopic ossification is present. When neurologic recovery has stabilized, the third phase begins. At this time, residual limb deformities may be surgically corrected and heterotopic bone may be excised.     

A new era for fibrodysplasia ossificans progressiva: a druggable target for the second skeleton

Fibrodysplasia ossificans progressiva (FOP) is a disabling genetic condition that leads to the formation of a second (heterotopic) skeleton, and is the most catastrophic disorder of heterotopic ossification in humans. Throughout childhood and early adult life, FOP progressively immobilizes all of the joints of the normotopic skeleton, rendering movement impossible. At present, there is no effective prevention or treatment. Recently, a recurrent mutation in the glycine-serine activation domain of the activin receptor IA/activin-like kinase-2, a bone morphogenetic protein type I receptor, was reported in all sporadic and familial cases of classic FOP, making this one of the most highly specific disease-causing mutations in the human genome. The discovery of the FOP gene establishes a critical milestone in understanding FOP, reveals a highly conserved druggable target in the TGF-beta/bone morphogenetic protein signaling pathway and compels therapeutic approaches for the development of small molecule signal transduction inhibitors for activin-like kinase-2. Effective therapies for FOP, and possibly for a vast array of more common conditions of heterotopic ossification, will be based on blocking activin-like kinase-2, a critical node in the BMP signaling pathway.     

Do patients with traumatic brain injury benefit from physiotherapy? A review of the evidence

Physiotherapy is an integral component of the management of patients with traumatic brain injury. This paper reviews the evidence that physiotherapy is effective in the management of these patients. The three specific areas addressed here are the effect of physiotherapy on: (1) range of movement, abnormal muscle tone, quality of movement, balance and conscious level; (2) the ability to perform functional tasks; and (3) outcome in areas such as independence in daily living, vocational and social domains. There is evidence that techniques such as casting or splinting may be effective in improving restricted range of movement after traumatic brain injury. However, there is either no research or such limited data that it is not possible to draw any firm conclusions regarding the effect of physiotherapy on quality of movement, balance, conscious level, the ability to perform functional tasks or outcome of this patient group. The need for research into all aspects of physiotherapy management for traumatically brain-injured patients is highlighted.     

成人肘关节骨折术后异位骨化的危险因素分析

【目的】分析成人肘关节骨折内固定术后异位骨化的危险因素。【方法】回顾性研究2001年10月到2010年8月本院成人肘关节骨折患者90例的临床资料,分析其手术后异住骨化的危险因素,包括骨折类型、手术方法、异位骨化发生部位、大小、肘关节功能活动度。时其结果数据采用统计软件SPSSl6分析。【结果】90例符合纳入标准,平均年龄55岁,平均随访190d。患者年龄,性别,外侧副韧带修补,肘关节内外侧双切口与异位骨化的发生率无相关性。肱骨远端骨折对异位骨化的发生有重要的预测意义。【结论】肱骨远端骨折是肘关节附近发生异位骨化的重要危险因素。     

髋关节术后关节周围大量异位骨化的治疗

目的：通过对髋关节术后异位骨化的发生、发展及其引起的后果的分析，探讨对异位骨化的预防和治疗方法。方法：回顾2000年1月至2007年3月56例患者患者髋关节手术（其中髋臼骨折手术46例，髋关节置换术10例）的治疗方法和效果。结果：56例患者中共发生异位骨化21例，发生率37．5％。结论：髋关节术后异位骨化应早预防，早期行放射治疗或者药物治疗。非甾体类消炎药是目前公认的预防人工髋关节置换和髋臼骨折术后异位骨化形成的最有效药物。手术切除是异位骨化形成后导致严重关节功能障碍的唯一治疗手段     

获得性异位骨化动物模型的系统综述

目的 系统综述获得性异位骨化(AHO)相关动物模型,为研究疾病防治方案提供可靠造模方法。方法 检索PubMed、Web of Science、中国知网、万方数据库自建库至2021年11月AHO动物模型相关文献,筛选并提取文献关键内容,采用文献归纳法对各型AHO动物模型进行分析与评价。结果 最终共纳入20篇动物实验研究相关文献,可归纳为创伤后和神经源性两大类异位骨化动物模型,用于模拟AHO的发生发展过程。创伤后异位骨化动物模型主要有肌肉损伤、跟腱切断、肌肉损伤联合关节制动、髋关节损伤、异位植入、爆炸伤和烧伤7种。神经源性异位骨化动物模型主要包括脊髓损伤和脑外伤。目前实验室中常用跟腱切断法和成骨因子植入法造模,此类方法可靠、易行、成功率高,但无法准确解释临床中复杂条件下异位骨化的发病机制。基于爆炸伤、烧伤、神经损伤等条件下造模方法正在完善,为临床研究某些特殊病因所致异位骨化的分子生物学机制及防治方案提供了支持。结论 目前存在的几种造模方法各有利弊,但均无法完整复制人类异位骨化的全部特征,因此,临床上在判定模型的选择方面尚无统一标准。针对疾病的不同病因,选用合适的动物模型,对不同类型AHO在早期制定有效干预措施至关重要。     

Heterotopic ossification in patients after total hip replacement

Heterotopic ossification (HO) is defined as pathological bone formation in soft tissues, for example in muscles, where physiologically there is no osseous tissue present. It is one of the most common complications of total hip joint replacement surgery. A wide variety of risk factors for heterotopic ossification have been identified to date. Almost 90% of total hip arthroplasty patients are at high risk for HO. There are two primary methods of preventing heterotopic ossification: pharmacotherapy with NSAIDs (non steroid anti-inflammatory drugs) and radiotherapy. Symptomatic heterotopic ossifications are treated by extracorporeal shock wave therapy (ESWT) and surgery, followed by NSAID pharmacotherapy or radiotherapy. The arterioles adjacent to areas of heterotopic ossification are usually embolized prior to the operation. This article describes the state of the art in the prevention and treatment of heterotopic ossifications based on the available literature.     

Warfarin in prevention of heterotopic ossification.

Patients with spinal cord injuries among others, commonly develop neurogenic heterotopic ossification. Current treatment with Didronel (disodium etidronate) inhibits bone matrix mineralization but not matrix production. To eliminate much morbidity and cost, a more efficatious prophylactic treatment is desirable. Because one of the proteins in bone, osteocalcin, is produced by a vitamin K-dependent carboxylation, this raises the possibility that treatment with warfarin may prevent the formation of ectopic bone. In the present study, 227 cases of spinal cord injury were reviewed. Among these patients, 15% were treated with warfarin and another 15% developed heterotopic ossification. None of the patients who were treated with warfarin developed heterotopic ossification, thus suggesting that warfarin may inhibit heterotopic ossification. Further prospective studies are planned.     

Brain injury severity and autonomic dysregulation accurately predict heterotopic ossification in patients with traumatic brain injury

OBJECTIVE: To assess brain injury severity, autonomic dysregulation and systemic infection as risk factors for the occurrence of heterotopic ossification in patients with severe traumatic brain injury. DESIGN: Historic cohort study. SETTING: Radboud University Medical Centre. SUBJECTS: All consecutively admitted patients with severe traumatic brain injury (admission Glasgow Coma Scale score 8 or less) during the years 2002-2003. MAIN MEASURES: The development of clinically relevant heterotopic ossification, defined as painful swelling of joints with redness and decreased range of motion, confirmed radiographically. RESULTS: Seventy-six (64%) of the 119 patients survived and were eligible for further follow-up. Nine patients (12%) developed 20 symptomatic heterotopic ossifications, in one or more joints. Patients with heterotopic ossification had sustained more severe brain injuries, compared to the group without heterotopic ossification. The mean coma duration in the heterotopic ossification group was 28.11 days (SD 20.20) versus 7.54 days (SD 7.47) in the patients without heterotopic ossification (P < 0.001). The occurrence of autonomic dysregulation (relative risk (RR) 59.55, 95% confidence interval (CI) 8.39-422.36), diffuse axonal injury (RR 20.68, 95% CI 4.92-86.91), spasticity (RR 16.96, 95% CI 3.96-72.57) and systemic infection (RR 13.12, 95% CI 3.01-57.17) were all associated with an increased risk of developing symptomatic heterotopic ossification. However, only autonomic dysregulation had a high positive (88.9%, 95% CI 51.7-99.7) and negative (98.5%, 95% CI 91.9-99.9) predictive value with regard to heterotopic ossification. CONCLUSIONS: The occurrence of autonomic dysregulation may predict the chance of developing heterotopic ossification in patients with severe head injury.     

塞来昔布预防全髋关节置换后的异位骨化

背景:目前吲哚美辛已作为预防全髋关节置换后异位骨化的常用药物,但是该药物常伴有严重不良胃肠道反应,而塞来昔布作为COX-2特异性抑制剂理论上胃肠道不良反应发生较少,但其预防全髋关节置换后异位骨化的作用目前尚缺乏研究。目的:观察COX-2特异性抑制剂塞来昔布预防全髋关节置换后异位骨化的效果,为伴有胃肠道症状患者的临床用药提供依据。方法:选取2010-12/2011-05行全髋关节置换患者50例,年龄55~72(65.40±3.24)岁,左髋19例,右髋31例。随机分为塞来昔布组25例和吲哚美辛组25例,分别给予塞来昔布200mg/d或吲哚美辛75mg/d,连续服用6周。结果与结论:塞来昔布组异位骨化发生率为12.0%,吲哚美辛组异位骨化发生率为16.0%,两组比较差异无显著性意义(P>0.05)。Harris髋关节功能评分优良率塞来昔布组与吲哚美辛组分别为88.0%,76.0%,两组比较差异无显著性意义(P>0.05)。胃肠道不良反应发生率塞来昔布组和吲哚美辛组分别为16.0%,36.0%,两组比较差异有显著性意义(P=0.039)。结果可见塞来昔布预防全髋关节置换后异位骨化是可行的,并且胃肠道不良反应发生率较低。     

Sciatic nerve compression by preexisting heterotopic ossification during general anesthesia in the dorsal lithotomy position

This report documents the 4th patient reported with sciatic nerve compression by heterotopic ossification and the 1st case occurring during general anesthesia. A 25-year-old woman developed right sciatic nerve dysfunction after a 30-minute dilatation and curettage in the dorsal lithotomy position. Postoperative x-rays revealed a large area of heterotopic ossification above the right greater trochanter. The patient had sustained a traumatic midshaft fracture of the right femur seven years previously, which required intramedullary nail fixation. It is postulated that during the D and C in the dorsal lithotomy position, the heterotopic ossification was displaced posteromedically, compressing the sciatic nerve that had already been placed at maximal stretch. The patient recovered partially. Electrodiagnostic studies were of considerable value in localization of the lesion and confirmation of the mechanism of injury. It is concluded that preexisting heterotopic ossification of the hip may compress the sciatic nerve during surgery in the dorsal lithotomy position.     

彩色多普勒超声及X线平片对异位骨化诊断的比较

目的比较彩色多普勒超声(彩超)及X线平片检查对脊髓损伤后异位骨化的早期诊断价值。方法对39例临床可疑异位骨化的脊髓损伤患者,在发生下肢水肿48h内进行首次彩超检查,每周复查,直至出现明确钙化灶。39例患者均同时进行X平片检查。结果脊髓损伤后异位骨化彩超所见:正常肌肉板层状结构肿胀增厚或被紊乱不规则结构取代,回声增强34例;出现弧形或长条形强回声带后伴声影39例;肌层内出现无回声血肿8例。外压性血管狭窄,流速增高4例。动态变化表现为:下肢水肿48h内,受累肌层肌纤维肿胀,回声增强,或病变中央区出现局限、形态不规则的非特异性低回声区;下肢水肿1周出现岛状回声增强区;1～2周后,出现大片弧形或长条形强回声带后伴声影,表面光滑或凹凸不平。下肢水肿1周内,彩超对异位骨化的检出率比X平片明显提高(P<0.01)。结论彩色多普勒超声可在患者起病初期检出阳性表现,是早期诊断异位骨化的可靠方法。     

Heterotopic ossification in rehabilitation patients who have had internal fixation of an acetabular fracture

High-energy trauma patients often have multiple injuries and are frequently seen by a physiatrist following their acute care. Acetabular fractures are common in this patient population. Following surgical treatment of acetabular fractures, a very high incidence of heterotopic ossification can occur. We describe 94 patients who underwent posterior surgical fixation of an acetabular fracture. Of these, 87 received heterotopic ossification prophylaxis in the form of irradiation or indomethacin; 5 did not receive prophylaxis. Seven of the 45 patients who were initially started on indomethacin had their medication discontinued for various reasons. Of the 12 patients who did not receive adequate prophylaxis, 5 developed disabling heterotopic ossification. We present our experience with this patient population, and we discuss the importance of adequate prophylaxis for heterotopic ossification.