Heterotopic ossification of the elbow in patients with burns

Tsionos, Ioannis; Leclercq, Caroline; Rochet, Juliana

doi:10.1302/0301-620x.86b3.14480

Cited by 105 publications

(77 citation statements)

References 30 publications

(34 reference statements)

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“…These treatments options include nonsteroidal antiinflammatory drugs (NSAIDs) and radiotherapy (often in combination), although adverse effects have been associated with their use [8,9,20,57]. Surgical excision of HO is another therapeutic option, although recurrence of HO at the surgical site may ensue [10,13,65]. Furthermore, contemporary treatment options are not engineered specifically to impede the biological mechanisms responsible for the production of bone in soft tissue.…”

Section: Introductionmentioning

confidence: 99%

Cationic Nanogel-mediated Runx2 and Osterix siRNA Delivery Decreases Mineralization in MC3T3 Cells

Shrivats

Hsu

Averick

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Heterotopic ossification (HO) may occur after musculoskeletal trauma, traumatic brain injury, and total joint arthroplasty. As such, HO is a compelling clinical concern in both military and civilian medicine. A possible etiology of HO involves dysregulated signals in the bone morphogenetic protein osteogenic cascade. Contemporary treatment options for HO (ie, nonsteroidal antiinflammatory drugs and radiation therapy) have adverse effects associated with their use and are not biologically engineered to abrogate the molecular mechanisms that govern osteogenic differentiation. Questions/purposes We hypothesized that (1) nanogelmediated short interfering RNA (siRNA) delivery against Runt-related transcription factor 2 (Runx2) and osterix (Osx) genes will decrease messenger RNA expression; (2) inhibit activity of the osteogenic marker alkaline phosphatase (ALP); and (3) inhibit hydroxyapatite (HA) deposition in osteoblast cell cultures. Methods Nanogel nanostructured polymers delivered siRNA in 48-hour treatment cycles against master osteogenic regulators, Runx2 and Osx, in murine calvarial preosteoblasts (MC3T3-E1.4) stimulated for osteogenic differentiation by recombinant human bone morphogenetic protein (rhBMP-2). The efficacy of RNA interference (RNAi) therapeutics was determined by quantitation of messenger RNA knockdown (by quantitative reverse transcription-polymerase chain reaction), downstream protein knockdown (determined ALP enzymatic activity assay), and HA deposition (determined by OsteoImage TM assay). Results Gene expression assays demonstrated that nanogelbased RNAi treatments at 1:1 and 5:1 nanogel:short interfering RNA weight ratios reduced Runx2 expression by 48.59% ± 19.53% (p \ 0.001) and 43.22% ± 18.01% (both p \ 0.001). The same 1:1 and 5:1 treatments against both Runx2 and Osx reduced expression of Osx by 51.65% ± 10.85% and 47.65% ± 9.80% (both p \ 0.001). Moreover, repeated 48-hour RNAi treatment cycles against Runx2 and Osx rhBMP-2 administration reduced ALP activity after 4 and 7 days. ALP reductions after 4 days in culture by nanogel 5:1 and 10:1 RNAi treatments were 32.4% ± 12.0% and 33.6% ± 13.8% (both p \ 0.001). After 7 days in culture, nanogel 1:1 and 5:1 RNAi treatments produced 35.9% ± 14.0% and 47.7% ± 3.2% reductions in ALP activity. Osteoblast mineralization data after 21 days suggested that Two of the authors (ARS, EH) contributed equally.

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Section: Introductionmentioning

confidence: 99%

Cationic Nanogel-mediated Runx2 and Osterix siRNA Delivery Decreases Mineralization in MC3T3 Cells

Shrivats

Hsu

Averick

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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“…Surgical excision has become the preferred treatment for HO of the elbow causing functional impairment [13,19,[22][23][24][25][26][27][28][29][30][31]. Although restoration of normal motion is unlikely, multiple studies have reported improved elbow outcome scores and increased range of motion after operative treatment [13,16,19,22,29,30,32]. Classically, functional elbow range of motion for activities of daily living has been defined as a functional motion arc of 100° (30°-130° of flexion and 50° of pronation to 50° of supination) [33].…”

Section: Discussionmentioning

confidence: 99%

Elbow Heterotopic Ossification Excision in Patients with Worker’s Compensation Claims

2018

J Orthopedics Rheumatol

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The effect of worker's compensation claims following the surgical management of symptomatic heterotopic ossification (HO) about the elbow has not previously been evaluated. The purpose of this study is to report on a consecutive series of patients with HO about the elbow, and to compare the results of surgical treatment and a standardized postoperative rehabilitation regimen, with regards to the presence of a worker's compensation claim. A retrospective review of all patients treated operatively for HO of the elbow at a single institution was performed. Forty-six elbows with HO treated surgically were identified. Seventeen of the 46 elbows (37%) had workers' compensation claims at the time of surgery. Other than gender (p=0.007), there was no statistical difference in patient demographics or medical history. There was no statistical difference in postoperative flexion-extension arc between the two groups (p>0.05). There was a 17% (8/46) postoperative complication rate, however there was no difference in frequency of complications between groups (Worker's Comp: 18% vs. Non-Worker's Comp: 17%; p=0.97). Surgical management combined with postoperative HO prophylaxis and a regimented rehabilitation program is an effective treatment for patients with heterotopic ossification of the elbow and workers compensation claims did not adversely affect the postoperative range of motion arc or complications.

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“…Furthermore, we did not have a protocol in place for timing of initial excision, because often the wounds, associated injuries, symptoms, related activity levels, and patient or surgeon preference dictated surgical timing. Many studies now support surgical excision earlier than the 12 to 18 months historically proposed as the requisite delay [9][10][11]14]; however, those series represent excisions about the elbow [25,32] or were performed in conjunction with radiotherapy protocols.…”

Section: Reexcision 11mentioning

confidence: 99%

“…Recently, interest in HO has increased as a result of its high prevalence in combat-related extremity injuries and amputations [9,10,14,15,17]. Studies have reported the prevalence of HO to be as high as 65% in combat-related amputations, and HO can result in pain, wound breakdown, difficulty with prosthesis wear, entrapment of neurovascular structures, and limited ROM [2,4,6,16,18,20,22,23,26,29,31,32,35]. Before operative excision, nonsurgical modalities such as pain control and serial prosthetic socket adjustments should be exhausted; however, up to 41% of affected patients who have undergone amputation will choose to have surgical excision to treat persistent symptoms and failed nonsurgical treatments [7,8,24,27,28].…”

Section: Introductionmentioning

confidence: 99%

What Risk Factors Predict Recurrence of Heterotopic Ossification After Excision in Combat-related Amputations?

Pavey

Polfer

Nappo

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Heterotopic ossification (HO) is common after combat-related amputations and surgical excision remains the only definitive treatment for persistently symptomatic HO. There is no consensus in the literature regarding the timing of surgery, and recurrence frequency, reexcision, and complications have not been reported in large numbers of patients. Questions/purposes (1) What are the rates of symptomatic recurrence resulting in reexcision and other complications resulting in reoperation in patients with HO? (2) Is either radiographic or symptomatic recurrence dependent on timing and type of initial surgery, the experience of the surgeon in performing the procedure, the severity of preexcision HO, the presence of concomitant neurologic injury, or the use of postoperative HO prophylaxis? Methods Between March 2005 and March 2013 our institution treated 994 patients with 1377 combat-related major extremity amputations; of those, 172 amputations underwent subsequent excision of symptomatic HO. The mechanism of injury resulting in nearly all amputations (n = 168) was blast-related trauma. We reviewed medical records and radiographs to collect initial grade of HO, radiographic recurrence, complete compared with partial excision, concomitant neurologic injury, timing to initial surgery, surgeon experience, and use of postexcision prophylaxis with our primary study outcome being a return to the operating room (OR) for repeat excision of symptomatic HO. All 172 combat-related amputations were considered for this study irrespective of followup, which was noted to be robust, with 157 (91%) amputations having Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research 1 editors and board members are on file with the publication and can be viewed on request. All of the authors are employees of the US Government and this work was prepared as part of their official duties. As such, there is no copyright to transfer. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of the Army, Department of Defense, nor the US Government. Nothing in the presentation implies any Federal/Department of Defense/Department of the Navy endorsement. Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained. This work was performed at Walter Reed National Military Medical Center, Bethesda, MD, USA. Conclusions HO is common after combat-related amputations, and patients undergoing surgical excisio...

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Heterotopic ossification of the elbow in patients with burns

Cited by 105 publications

References 30 publications

Cationic Nanogel-mediated Runx2 and Osterix siRNA Delivery Decreases Mineralization in MC3T3 Cells

Cationic Nanogel-mediated Runx2 and Osterix siRNA Delivery Decreases Mineralization in MC3T3 Cells

Elbow Heterotopic Ossification Excision in Patients with Worker’s Compensation Claims

What Risk Factors Predict Recurrence of Heterotopic Ossification After Excision in Combat-related Amputations?

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