Radiation prophylaxis for heterotopic ossification about the hip joint—a multicenter study

Seegenschmiedt, M. H.; Makoski, H. B.; Micke, Oliver

doi:10.1016/s0360-3016(01)01640-6

Cited by 91 publications

(44 citation statements)

References 47 publications

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“…However, these treatments are not biologically engineered to target the molecular mechanisms responsible for bone formation and have notable adverse effects [8,9,20,57]. RNAi, however, may be harnessed to silence master osteogenic factors Runx2 and Osx and consequently prevent the aberrant mineralization of muscle tissue without significant offtarget effects (ie, HO).…”

Section: Discussionmentioning

confidence: 99%

“…Current treatments for patients with HO emphasize reducing inflammation and/or inactivating tissue-resident stem cells at the trauma site to minimize pathological bone formation. 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].…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

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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“…However, the time of RT and the dose-response effect of RT on the incidence of HO is still a matter for investigation [5,8,11,13,[21][22][23]. On the other hand, NSAIDs have been extensively used perioperatively for the prevention of HO after THA.…”

Section: Discussionmentioning

confidence: 99%

Prevention of heterotopic ossification in high-risk patients with total hip arthroplasty: the experience of a combined therapeutic protocol

Pakos

Pitouli

Tsekeris

et al. 2006

International Orthopaedics (SICO

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The combination of radiotherapy and indomethacin for the prevention of heterotopic ossification (HO) in high-risk patients undergoing total hip arthroplasty (THA) has not been reported. The aim of this study was to present the experience of our department with this combined therapeutic protocol. Fifty-four patients who underwent THA received a single dose of 7 Gy of postoperative radiotherapy and 75 mg of indomethacin for 15 days. Patients were analysed for clinical and radiographical evidence of HO development at 1 year postoperatively. The overall radiographical incidence of HO was 20.4% (95%

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“…Radiation therapy (RT) is well-established in high-risk patients for prevention of HO development for the hip [1]. There are multiple randomized controlled trials showing that 7 Gy in 1 fraction within 72 hours of surgery decreases the risk of development of HO in these patients [2] [3] [4].…”

Section: Introductionmentioning

confidence: 99%

Radiation Therapy Prophylaxis for Heterotopic Ossification in Non-Hip Sites

Patel¹,

Tzou²,

Single³

et al. 2018

JCT

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Radiation prophylaxis for heterotopic ossification about the hip joint—a multicenter study

Cited by 91 publications

References 47 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

Prevention of heterotopic ossification in high-risk patients with total hip arthroplasty: the experience of a combined therapeutic protocol

Radiation Therapy Prophylaxis for Heterotopic Ossification in Non-Hip Sites

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