Pathogenesis and prevention strategies of heterotopic ossification in total hip arthroplasty: a narrative literature review and results of a survey in Germany

Winkler, Sebastian; Craiovan, Benjamin; Wagner, Ferdinand; Weber, Markus; Grifka, Joachim; Renkawitz, Tobias

doi:10.1007/s00402-015-2174-1

Cited by 32 publications

(31 citation statements)

References 63 publications

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“…Acquired HO (aHO) is a serious complication of traumatic tissue damage [21,22]. aHO is a particularly difficult clinical challenge, since 1) the underlying mechanisms of aHO are likely more variable than in the genetic disorders, and 2) few commonly accepted animal models are available for study of aHO.…”

Section: Bmp/tgf-β Signalingmentioning

confidence: 99%

Conserved signaling pathways underlying heterotopic ossification

Chen

et al. 2018

Bone

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Heterotopic ossification (HO), a serious disorder of extra-skeletal bone formation, occurs as a common complication of trauma or in rare genetic disorders. Many conserved signaling pathways have been implicated in HO; however, the exact underlying molecular mechanisms for many forms of HO are still unclear. The emerging picture is that dysregulation of bone morphogenetic protein (BMP) signaling plays a central role in the process, but that other conserved signaling pathways, such as Hedgehog (HH), Wnt/β-catenin and Fibroblast growth factors (FGF), are also involved, either through cross-talk with BMP signaling or through other independent mechanisms. Deep understanding of the conserved signaling pathways is necessary for the effective prevention and treatment of HO. In this review, we update and integrate recent progress in this area. Hopefully, our discussion will point to novel promising, druggable loci for further translational research and successful clinical applications.

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Section: Bmp/tgf-β Signalingmentioning

confidence: 99%

Conserved signaling pathways underlying heterotopic ossification

Chen

et al. 2018

Bone

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“…AHO formation is largely thought to be related to the inflammatory response to trauma, which in turn cause ectopic bone formation through the up-regulation of pro-osteogenic gene and activation of osteopotent progenitor cell. (Winkler et al, 2015;Pavey et al, 2015) Nf-ҝb signal path is important in inflammatory response,which is activated by many cytokines, such as TNF-α,IL-1. Guo and Caron have proved that the activation of Nf-ҝb promote the expression of Sox9, which induce endochondral ossification.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Nf-ҝb prevents trauma-induced heterotopic ossification in rat model

Ju¹,

Xue

et al. 2017

Preprint

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Background. To find a better prophylactic regimen, the pathogenesis of acquired heterotopic ossification (AHO) must be more understood. To date, AHO formation is largely thought to be related to inflammation, which is activated by trauma, resulting in AHO by up-regulation of pro-osteogenic genes. Methods. Brain-traumatic/burn/tenotomy model is firstly used in experiment. At first, 44 rats were randomly divided into two groups: E group and C group. Two rats in every group were euthanized during second, third, fourth, sixth, eighth, tenth weeks for collecting tendon. The remaining rats survived until tenth week for X-Ray radiation examination to confirm the size of AHO.Then, 124 rats were randomly divided into four group: P group, L group, M group, H group. The three rats of every group were euthanized during every week of the first seven weeks for collecting tendon to detect P65 protein. The remaining rats survived until tenth week for X-Ray examination to confirm the size of AHO. Results. The success rate of Brain-traumatic/Burn/Tenotomy model is 100%. Difference of P65 expression in E group and in C group are statistically significant,and that in E group is higher.Pharmacologic inhibition of Nf-ҝb signaling pathway limits AHO formation, and that The bone formation content of M group is decreased. Conclusion. Brain-traumatic/Burn/Tenotomy model is highly reliable.Results indicate that the Nf-ҝb /p65 signaling response occurs in the forming process of AHO. PDTC limits formation of AHO. The most effective concentration is 6mg/ml for local injection.

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“…NSAIDs target the first step of HO formation, which is the inflammation of muscles and soft tissue due to various factors. Prophylactic intervention with NSAIDs has been widely used, inter alia, after THA, hip arthroscopy, hip resurfacing, open reduction internal fixation, acetabular fracture, elbow dislocation, radial head dislocation, radial head fracture, femoral neck fracture, femoral shaft fracture, clavicular fracture, acromioclavicular joint injury, traumatic brain injury, and spinal cord injury …”

Section: Standard Treatment and Prophylaxismentioning

confidence: 99%

Challenges of heterotopic ossification—Molecular background and current treatment strategies

Łęgosz

Drela

Pulik

et al. 2018

Clin Exp Pharma Physio

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Heterotopic ossification (HO) is an abnormal formation of mature lamellar bone within extraskeletal soft tissues, such as muscles, tendons, and ligaments. This process is thought to be induced by inflammation associated with tissue injuries. HO is classified using two subtypes: resulting from injury or genetically inherited. HO formation is associated with polytrauma patients with traumatic brain injuries and spinal cord injuries. Moreover, HO is also considered to be a post-operative risk factor in some orthopaedic procedures. In this review, we summarize our current understanding of the pathology of different types of HO and discuss its current and future therapies. Thus far, research has revealed cellular and molecular pathways leading to HO formation and proposed several possible mechanisms leading to HO and conserved signalling pathways common in the different HO subtypes. Non-steroidal anti-inflammatory drug treatment and localized low-dose irradiation are currently the only available prophylactic treatments for HO. However, they are not always effective and do not target the osteogenic processes directly. New therapeutic strategies targeting the pathological processes of HO, such as bone morphogenetic protein (BMP) inhibitors like noggin, BMP type 1 receptor inhibitor, and nuclear retinoid acid receptor-gamma (RARγ) agonists, are currently being investigated. In-depth understanding of the HO pathological process could help to develop effective therapeutic strategies.

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Pathogenesis and prevention strategies of heterotopic ossification in total hip arthroplasty: a narrative literature review and results of a survey in Germany

Cited by 32 publications

References 63 publications

Conserved signaling pathways underlying heterotopic ossification

Conserved signaling pathways underlying heterotopic ossification

Inhibition of Nf-ҝb prevents trauma-induced heterotopic ossification in rat model

Challenges of heterotopic ossification—Molecular background and current treatment strategies

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