Treatments and Preventative Measures for Trauma‐Induced Heterotopic Ossification: A Review

Juarez, Jessica K; Wenke, Joseph C.; Rivera, Jessica C.

doi:10.1111/cts.12552

Cited by 21 publications

(14 citation statements)

References 72 publications

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“…The role of the inflammatory microenvironment in HO formation has received increasing attention. In the early stage after inflammation and traumatic stimulation, an acute reaction increases the levels of inflammatory factors such as IL-6 and TNF- α at the injury site and induces local inflammatory response and tissue repair [ 28 ]. Meanwhile, signal levels of related signal transduction pathways and osteogenic and chondrogenic induction factors such as OCN, RUNX2, and SOX9 were increased [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Palovarotene Can Attenuate Heterotopic Ossification Induced by Tendon Stem Cells by Downregulating the Synergistic Effects of Smad and NF-κB Signaling Pathway following Stimulation of the Inflammatory Microenvironment

Huang

Lin

et al. 2022

Stem Cells International

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Heterotopic ossification (HO) is defined as the formation of bone tissues outside the bones, such as in the muscles. Currently, the mechanism of HO is still unclear. Tendon stem cells (TSCs) play important roles in the occurrence and development of HO. The inflammatory microenvironment dominated by macrophages also plays an important role in the course of HO. The commonly used clinical treatment methods, such as nonsteroidal anti-inflammatory drugs and radiotherapy, have relatively large side effects, and more efficient treatment methods are needed in clinical practice. Under physiological conditions, retinoic acid receptor (RAR) signal transduction pathway inhibits osteogenic progenitor cell aggregation and chondrocyte differentiation. We focus on palovarotene, a retinoic acid γ-receptor activator, showing an inhibitory effect on HO mice, but the specific mechanism is still unclear. This study was aimed at exploring the specific molecular mechanism of palovarotene by blocking osteogenic differentiation and HO formation of TSCs in vitro and in vivo in an inflammatory microenvironment. We constructed a coculture model of TCSs and polarized macrophages, as well as overexpression and knockdown models of the Smad signaling pathway of TCSs. In addition, a rat model of HO, which was constructed by Achilles tendon resection, was also established. These models explored the role of inflammatory microenvironment and Smad signaling pathways in the osteogenic differentiation of TSCs which lead to HO, as well as the reversal role played by palovarotene in this process. Our results suggest that, under the stimulation of inflammatory microenvironment and trauma, the injured site was in an inflammatory state, and macrophages were highly concentrated in the injured site. The expression of osteogenic and inflammation-related proteins, as well as Smad proteins, was upregulated. Osteogenic differentiation was performed in TCSs. We also found that TCSs activated Smad and NF-κB signaling pathways, which initiated the formation of HO. Palovarotene inhibited the aggregation of osteogenic progenitor cells and macrophages and attenuated HO by blocking Smad and NF-κB signaling pathways. Therefore, palovarotene may be a novel HO inhibitor, while other drugs or antibodies targeting Smad and NF-κB signaling pathways may also prevent or treat HO. The expressions of Smad5, Id1, P65, and other proteins may predict HO formation.

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Section: Discussionmentioning

confidence: 99%

Palovarotene Can Attenuate Heterotopic Ossification Induced by Tendon Stem Cells by Downregulating the Synergistic Effects of Smad and NF-κB Signaling Pathway following Stimulation of the Inflammatory Microenvironment

Huang

Lin

et al. 2022

Stem Cells International

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“…External beam radiation has not been used extensively in hip arthroscopy cases. The usual dose would be 700 cGy one-time dose within < 4 h preoperatively to < 72 h post-operatively [25,26].…”

Section: Prophylaxismentioning

confidence: 99%

Heterotopic Ossification in Hip Arthroscopy: an Updated Review

Kurz

Leroux

Riediger

et al. 2019

Curr Rev Musculoskelet Med

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Purpose of Review Heterotopic ossification (HO) in hip arthroscopy is a common post-operative complication. This review was undertaken to provide an update (2014 present) on the current literature regarding HO in hip arthroscopy. Recent Findings Risk factors for HO post-hip arthroscopy include male gender, mixed impingement, picture, and the size of CAM resection. HO prophylaxis with NSAIDs has been proven to decrease the rate of HO post-hip arthroscopy; however, there is inherent risk to long-standing NSAIDs therapy. HO post-hip arthroscopy is not uncommon as a radiological finding, but symptomatic HO post-hip arthroscopy requiring revision surgery is a rare event, at < 1%. The outcomes for revision surgery for HO excision have fair outcomes. Summary The hip arthroscopist should stratify their patients based on known risk factors, and determine whether NSAIDs prophylaxis is warranted.

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“…Surgical intervention typically involves an osteoplasty and excision of heterotopic bone after the heterotopic bone has matured. Excision of heterotopic bone prior to maturation can result in an increased incidence of recurrence [ 6 ]. The degree of functional limitation should serve as a guide to management strategies, as the most common long-term sequela of HO involves limitations in mobility and joint function.…”

Section: Introductionmentioning

confidence: 99%

The Treatment of Heterotopic Ossification With a Dual Mobility Total Hip Replacement System: A Case Report

Parikh¹,

Tacy²,

Gomez³

et al. 2022

Cureus

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Heterotopic ossification (HO) is the formation of bone within extraskeletal soft tissue. The development of mature lamellar bone within soft tissues can be acquired in cases like trauma. Clinical manifestations of HO primarily include pain at the site of the extraskeletal ossification and limited range of motion or function when it involves a joint. This case report presents a 56-year-old man with severe HO. His past medical history included a traumatic hip dislocation in 1996. He denied any other past medical, family, or surgical history. This patient had severely limited range of motion and difficulty performing activities of daily living like going up and down the stairs and getting up from a seated position. After failing conservative therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy, a non-cemented dual mobility hip replacement system was used to treat this patient. A non-cemented dual mobility hip replacement system was chosen because the patient had significant bone loss and was relatively young. The dual mobility system significantly reduces the risk of dislocation and is a good option for younger patients who require more stability in their hips. The patient progressed well with a full range of motion and no pain. There was no evidence of HO recurrence. Treatment of HO with a total hip replacement, let alone a dual mobility system, is not prevalent throughout the literature. Furthermore, cemented total hip arthroplasty has been associated with increased recurrence of HO, which is why we elected to use a non-cemented technique. Osteoplasty is typically the mainstay of treatment for HO. The purpose of this case report is to introduce an incident of HO treated with a non-cemented dual mobility system and emphasize its use in young, middle-aged, or active patients who have bone loss and require increased stability.

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Treatments and Preventative Measures for Trauma‐Induced Heterotopic Ossification: A Review

Cited by 21 publications

References 72 publications

Palovarotene Can Attenuate Heterotopic Ossification Induced by Tendon Stem Cells by Downregulating the Synergistic Effects of Smad and NF-κB Signaling Pathway following Stimulation of the Inflammatory Microenvironment

Palovarotene Can Attenuate Heterotopic Ossification Induced by Tendon Stem Cells by Downregulating the Synergistic Effects of Smad and NF-κB Signaling Pathway following Stimulation of the Inflammatory Microenvironment

Heterotopic Ossification in Hip Arthroscopy: an Updated Review

The Treatment of Heterotopic Ossification With a Dual Mobility Total Hip Replacement System: A Case Report

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