Prevention and Treatment Of Heterotopic Ossification After Spinal Cord Injury

Abstract

Background/Objectives: Heterotopic ossification (HO) is a frequent, irreversible complication afterspinal cord injury (SCI). The objective of this article is to explain the etiology of HO; present new advances in prevention, diagnosis, and management of this complication; and provide a suggested algorithm for clinical management.

Etiology: Although still hypothetical, trauma and overexpression of bone morphogenic protein(s) in traumatized soft tissue appear to play important roles as initiating factors of HO.

Prevention: Preventive use of nonsteroidal antiinflammatory agents (NSAIDs) reduces the incidence of HO by a magnitude of 2 to 3.

Management: Early determination of serum creatine phosphokinase may have a diagnostic value in predicting the onset and severity of HO, and an NSAID may be added to etidronate therapy in the initial inflammatory phase of HO formation until C-reactive protein Ieveis return to normal range. Surgery is indicated in a subset of patients, and a regimenthat includes radiation therapy may prevent postoperative recurrence.

Conclusion: Significant progress has been made in the early prevention and management of HO. Further studies are needed to elucidate the etiology.     

Use of Imatinib in the Prevention of Heterotopic Ossification

Background

Heterotopic ossification (HO) is a common complication following orthopedic and trauma surgery, which may have substantial negative effects on the postoperative outcome. Angiogenesis appears to play a critical role in heterotopic ossification. One of the involved signaling molecules is platelet-derived growth factor (PDGF) which may be inhibited by imatinib.

Questions/Purposes

Our goal was to prevent HO by pharmacologically interfering with the molecular signaling pathways involved in the developmental process. We hypothesized that by administering a proven inhibitor of PDGF expression, heterotopic bone formation may be prevented.

Methods

The effect of imatinib on HO formation was studied in a murine model which reliably produces islets of HO within the soft tissue following Achilles tenotomy. The control group underwent Achilles tenotomy only. The imatinib group received imatinib mesylate. After trial completion, the limbs were harvested and scanned by micro-CT. Heterotopic bone volume was then identified and quantified.

Results

The mean volume of heterotopic bone formed in the control group was 0.976mm³ compared to 0.221 mm³ in the imatinib group. The volume of HO in the treatment group was reduced by 85% compared to the control group.

Conclusions

The administration of imatinib was associated with a significantly reduced volume of HO. This may be due to the inhibitory effect of imatinib on the PDGF signaling pathway during development of HO.

Clinical Relevance

The successful reduction of HO formation following imatinib administration has led to further insight concerning the pathogenesis of HO which in the future may lead to new clinical approaches towards the prevention of HO.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-013-9335-y) contains supplementary material, which is available to authorized users.     

颈椎带锁钢板内固定术对颈椎退变性疾病神经功能改善的分析

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Improvements in elbow motion after resection of heterotopic bone: a systematic review

Complex elbow trauma, severe burn, or a closed head injury render patients at risk for developing heterotopic ossification around the elbow. When heterotopic ossification restricts elbow motion, some patients request surgical resection. We performed a systematic review of the literature to analyze improvement in elbow motion after resection of heterotopic ossification around the elbow. We found that, on average, etiology had little impact on outcome after resection of heterotopic ossification. Resection of heterotopic bone generally leads to improvement of elbow function.     

Controlling stem cell-mediated bone regeneration through tailored mechanical properties of collagen scaffolds

Mechanical properties of the extracellular matrix (ECM) play an essential role in cell fate determination. To study the role of mechanical properties of ECM in stem cell-mediated bone regeneration, we used a 3D in vivo ossicle model that recapitulates endochondral bone formation. Three-dimensional gelatin scaffolds with distinct stiffness were developed using 1-Ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) mediated zero-length crosslinking. The mechanical strength of the scaffolds was significantly increased by EDC treatment, while the microstructure of the scaffold was preserved. Cell behavior on the scaffolds with different mechanical properties was evaluated in vitro and in vivo. EDC-treated scaffolds promoted early chondrogenic differentiation, while it promoted both chondrogenic and osteogenic differentiation at later time points. Both micro-computed tomography and histologic data demonstrated that EDC-treatment significantly increased trabecular bone formation by transplanted cells transduced with AdBMP. Moreover, significantly increased chondrogenesis was observed in the EDC-treated scaffolds. Based on both in vitro and in vivo data, we conclude that the high mechanical strength of 3D scaffolds promoted stem cell mediated bone regeneration by promoting endochondral ossification. These data suggest a new method for harnessing stem cells for bone regeneration in vivo by tailoring the mechanical properties of 3D scaffolds.     

Anatomical details of neurogenic heterotopic ossification anterior to the ankylotic hip

Neurogenic heterotopic ossification (NHO) is a common complication in patients with spinal cord injury (SCI) and traumatic brain injury (TBI). Although there are many reports regarding the etiology, pathophysiology, and medical management, few studies elaborate the anatomical details of NHO, which leads to ankylosis of the hip joint. A prospective study on surgical resection of NHO in patients with hip ankylosis was conducted. Radiography and magnetic resonance imaging (MRI) were used to assess the relationship of the NHO block with the blood vessels, peripheral nerve, and surrounding muscles and bones. The anatomical relationships were also assessed and documented during the surgical procedures. NHO, which is anterior to the hip and causes hip ankylosis, settles into tissue planes without involving the tissue itself and does not disrupt the femoral neurovascular structures. The NHO bone block can then fuse to the cortex of adjacent bone. During resection, the normal bony contour should be exposed as a marker to guide the resection in order to avoid iatrogenic fracture.