Heterotopic ossification is defined as the presence of lamellar bone at locations where bone normally does not exist. The condition must be distinguished from metastatic calcifications, which mainly occur in hypercalcaemia, and dystrophic calcifications in tumours. It is a frequent complication following central nervous system disorders (brain injuries, tumours, encephalitis, spinal cord lesions), multiple injuries, hip surgery and burns. In addition to this acquired form, hereditary causes also exist, such as fibrodysplasia ossificans progressiva, progressive osseous heteroplasia and Albright's hereditary osteodystrophy. Although these conditions are extremely rare, they can provide useful information on the physiopathology of heterotopic ossification, and thus lead to novel and causal treatment modalities. Heterotopic ossification is no trivial complication. A limitation of the range of joint motion may have serious consequences for the daily functioning of people who are already severely incapacitated because of their original lesion. Increased contractures and spasticity, pressure ulcers and increasing pain further compromise the patient's capabilities. Consequently, we feel that attention should be paid to the pathogenesis and particularly the prevention and treatment of this disorder.

/pdf/heterotopic-ossification-a-review-376ufydohs.pdf

Heterotopic ossification: a review.

Heterotopic ossification is the formation of bone in the soft tissues. Soft tissue bone deposition may range from the minimal and inconsequential to massive and clinically significant. In some clinical settings it is a predictable finding with an unpredictable course and in other settings it may be diagnostically confounding. Heterotopic ossification may be encountered in clinically disparate disease processes and circumstances. We review the genetic, neurogenic, post-traumatic, post-surgical and “reactive” causes of heterotopic ossification and discuss some current concepts of its pathogenesis.

Heterotopic ossification: a review

➤ Heterotopic ossification occurs most commonly after joint arthroplasty, spinal cord injury, traumatic brain injury, blast trauma, elbow and acetabular fractures, and thermal injury.➤ The conversion of progenitor cells to osteogenic precursor cells as a result of cell-mediated interactions with the local tissue environment is affected by oxygen tension, pH, availability of micronutrients, and mechanical stimuli, and leads to heterotopic ossification.➤ Radiation and certain nonsteroidal anti-inflammatory medications are important methods of prophylaxis against heterotopic ossification.➤ Well-planned surgical excision can improve patient outcomes regardless of the joint involved or the initial cause of injury.➤ Future therapeutic strategies are focused on targeted inhibition of local factors and signaling pathways that catalyze ectopic bone formation.

/pdf/heterotopic-ossification-basic-science-principles-and-1p2gsg0d85.pdf

Heterotopic Ossification: Basic-Science Principles and Clinical Correlates.

Background: Although infrequently reported in amputees previously, heterotopic ossification has proven to be a common and problematic clinical entity in our recent experience in the treatment of traumatic and combat-related amputations related to Operation Enduring Freedom and Operation Iraqi Freedom. The purpose of the present study was to report the prevalence of and risk factors for heterotopic ossification following trauma-related amputation as well as the preliminary results of operative excision.

Methods: We identified 330 patients with a total of 373 traumatic and combat-related amputations who had been managed at our centers between September 11, 2001 and November 30, 2005. We reviewed the medical records and radiographs of 187 patients with 213 amputations who had adequate radiographic follow-up. Additional analysis was performed for twenty-four patients with twenty-five limbs that required excision of symptomatic lesions. The mechanism and zone of injury, amputation level, timing of excision, use of prophylaxis against recurrence, and other confounding variables were examined. Outcomes were assessed by determining clinical and radiographic recurrence rates, perioperative complications, preoperative and follow-up pain medication requirements, and the ability to be fit with a functional prosthesis.

Results: Heterotopic ossification was present in 134 (63%) of 213 residual limbs, with twenty-five lesions requiring excision. A final amputation level within the zone of injury was a risk factor for both the development and the grade of heterotopic ossification (p < 0.05). A blast mechanism was predictive of occurrence (p < 0.05) but did not correlate with grade. All patients who had been managed with excision were tolerating the prosthetic limb at an average of twelve months of follow-up. Twenty-three limbs demonstrated no evidence of recurrence, and two limbs had development of clinically asymptomatic, radiographically minimal recurrences. Six patients experienced wound-related complications that required reoperation, and two patients required subsequent minor revision surgery. There was a significant decrease in the use of pain medication following surgery (p < 0.05).

Conclusions: Heterotopic ossification following trauma-related amputation is more common than the literature would suggest, particularly following amputations that are performed within the initial zone of injury and those that are due to blast injuries. Many patients are asymptomatic or can be successfully managed with modification of the prosthesis. For patients with refractory symptoms, surgical excision is associated with low recurrence rates and decreased medication requirements, with acceptable complication rates.

Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

Heterotopic ossification following traumatic and combat-related amputations. Prevalence, risk factors, and preliminary results of excision.

Heterotopic ossification is a debilitating condition that can result from traumatic injury, surgery, or genetic disease. We investigated the cellular origins of heterotopic skeletogenesis in the mouse using lineage tracing and bioassays of heterotopic ossification based on intramuscular transplantation. We identified, characterized, and purified a tissue-resident stem/progenitor cell population that exhibits robust osteogenic potential and represents a major cell-of-origin for heterotopic ossification. These progenitors reside in the interstitium of skeletal muscle and other tissues, and are distinct from the endothelium, which does not exhibit osteogenic activity in response to bone morphogenetic protein 2 (BMP2) stimulation. Intramuscular transplantation, together with clonal analysis in culture, revealed that these progenitors are multipotent, exhibiting the capacity for both BMP-dependent skeletogenic differentiation and spontaneous adipogenic differentiation. Identifying the cells-of-origin responsible for heterotopic ossification provides a potential therapeutic target to treat, mitigate, or prevent this disabling condition.

Multipotent progenitors resident in the skeletal muscle interstitium exhibit robust BMP-dependent osteogenic activity and mediate heterotopic ossification.

通过复习异位骨化的相关文献,详细介绍了异位骨化的发病机制、分类、发生率、分型、发病因素、临床表现、诊断、预防及治疗方法.异位骨化是指在正常情况下没有骨组织的软组织内形成的新生骨,在组织学上,成熟的异位骨化与骨痂一致.其形成一般需三个条件:①成骨诱导物;②成骨的前体细胞;③允许成骨的组织环境.早期表现包括关节周围疼痛、发热、红肿,逐渐出现关节活动受限.三相核素骨扫描是早期检测异位骨化的最敏感指标,并可以判断病变的活动性和成熟度.非甾体类消炎药(NSAIDs)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的药物.手术切除是异位骨化形成后导致严重关节功能障碍患者的唯一治疗手段。

Heterotopic ossification

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Heterotopic ossification