Neurogenic heterotopic ossification (NHO) is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury. Ectopic bone forms around joints in characteristic patterns, causing pain and limiting movement especially around the hip and elbow. Clinical sequelae of neurogenic heterotopic ossification include urinary tract infection, pressure injuries, pneumonia and poor hygiene, making early diagnosis and treatment clinically compelling. However, diagnosis remains difficult with more investigation needed. Our pathophysiological understanding stems from mechanisms of basic bone formation enhanced by evidence of systemic influences from circulating humor factors and perhaps neurological ones. This increasing understanding guides our implementation of current prophylaxis and treatment including the use of non-steroidal anti-inflammatory drugs, bisphosphonates, radiation therapy and surgery and, importantly, should direct future, more effective ones

Aims. Acquired heterotopic ossification (HO) is a debilitating disease characterized by abnormal extraskeletal bone formation within soft-tissues after injury. The exact pathogenesis of HO remains unknown. It was reported that BRD4 may contribute to osteoblastic differentiation. The current study aims to determine the role of BRD4 in the pathogenesis of HO and whether it could be a potential target for HO therapy. Methods. Achilles tendon puncture (ATP) mouse model was performed on ten-week-old male C57BL/6J mice. One week after ATP procedure, the mice were given different treatments (e.g. JQ1, shMancr). Achilles tendon samples were collected five weeks after treatment for RNA-seq and real-time quantitative polymerase chain reaction (RT-qPCR) analysis; the legs were removed for micro-CT imaging and subsequent histology. Human bone marrow mesenchymal stem cells (hBMSCs) were isolated and purified bone marrow collected during surgeries by using density gradient centrifugation. After a series of interventions such as knockdown or overexpressing BRD4, Alizarin red staining, RT-qPCR, and Western Blot (Runx2, alkaline phosphatase (ALP), Osx) were performed on hBMSCs. Results. Overexpression of BRD4 enhanced while inhibition of Brd4 suppressed the osteogenic differentiation of hBMSCs in vitro. Overexpression of Brd4 increased the expression of mitotically associated long non-coding RNA (Mancr). Downregulation of Mancr suppressed the osteoinductive effect of BRD4. In vivo, inhibition of BRD4 by JQ1 significantly attenuated pathological bone formation in the ATP model (p = 0.001). Conclusion. BRD4 was found to be upregulated in HO and Brd4-Mancr-Runx2 signalling was involved in the modulation of new bone formation in HO. Cite this article: Bone Joint Res 2021;10(10):668–676

Heterotopic ossification (HO) is perhaps the single most significant obstacle to independence, functional mobility, and return to duty for combat-injured veterans of Operation Enduring Freedom and Operation Iraqi Freedom. Recent research into the cause(s) of HO has been driven by a markedly higher prevalence seen in these wounded warriors than encountered in previous wars or following civilian trauma. To that end, research in both civilian and military laboratories continues to shed light onto the complex mechanisms behind HO formation, including systemic and wound specific factors, cell lineage, and neurogenic inflammation. Of particular interest, non-invasive in vivo testing using Raman spectroscopy may become a feasible modality for early detection, and a wound-specific model designed to detect the early gene transcript signatures associated with HO is being tested. Through a combined effort, the goals of early detection, risk stratification, and development of novel systemic and local prophylaxis may soon be attainable.

This meta analysis address the relationship between infection developing after total hip arthroplasty (THA) and heterotopic ossification (HO). To identify the gaps in available knowledge, we screened for full-length peer-reviewed research articles listed in PubMed, Embase, and Web of Science over the past 20 years. The following search terms and Boolean operators were used: heterotopic ossification AND infection AND (hip replacement OR hip arthroplasty). The search resulted in the identification of as few as 14 articles describing periprosthetic joint infection (PJI) and HO after THA. Data summarized from 6 studies suitable for further meta-analysis yielded a cumulative sample size of 753 observations, with 186 recorded events of HO. The pooled RR was estimated at 2.22 (95% CI: 1.00 to 4.91, p = 0.0497), suggesting a more than twofold risk of HO compared to the group without PJI. In conclusion, there is a clear association between a higher risk of HO and PJI. Basic research findings support the hypothesis that bacterial pathogen-associated molecular patterns (PAMPs) can lead to osteogenesis through a toll-like receptor (TLR) and nuclear factor kappa B (NF-κB) pathway in the course of HO development. Together, these results suggest that HO prophylaxis should always be prescribed in PJI after THA. Moreover, during revisions following THA for presumed non-septic reasons, the presence of HO warrants consideration for infection, as there is a potential heightened risk of pathologic ossification induced by PAMPs. Keywords: heterotopic ossification; total hip arthroplasty; total hip replacement; periprosthetic joint infection; bacteria. Authors Ł. Pulik and P. Łęgosz contributed equally to this work

Heterotopic ossification is the formation of lamellar bone in soft tissues and is a common complication of high-energy combat injury. This disabling condition can cause pain, joint ankylosis, and skin ulceration in the residua of amputees. This project is aimed at developing a novel treatment to dissolve hydroxyapatite in heterotopic ossification and prevent the crystallisation of this this mineral at sites of ectopic bone formation. Previously reported results demonstrated that hexametaphosphate could dissolve hydroxyapatite at physiological pH. Further work has been undertaken to investigate the mechanism of this dissolution and establish a means of temporal control of action. In addition, physicochemical analyses of samples of human heterotopic ossification have yielded important insights into the nature of this pathological tissue. Techniques include mapped micro X-ray fluorescence, mapped Raman spectroscopy, scanning electron microscopy, and micro computed tomography. Formulation engineering work has begun in order to develop an appropriate delivery vehicle for this agent. This includes rheological testing and hexametaphosphate elution profiles. Finally, micro CT analysis has shown that hexametaphosphate is able to dissolve human heterotopic ossification tissue. In summary, this work has moved us closer towards our goal of a novel injectable agent for the treatment and prevention of heterotopic ossification

Severe heterotopic ossification (grade III and IV) after contemporary total hip arthroplasty (THA) requiring excision is very uncommon. We performed a systematic review of the literature, and report a new case series with operative treatment after primary uncemented THA. A systematic review identified papers describing patients who had excision of heterotopic ossification (HO) after contemporary THA, defined as performed after 1988. Concepts of hip arthroplasty, heterotopic ossification, and surgical excision were searched in MEDLINE, Embase, and Scopus, from database inception to November 2022. Inclusion criteria were: articles that included specific patient data on grade of heterotopic ossification, operative procedure, and prophylaxis. Studies were screened for inclusion by two independent reviewers. Extracted data included demographic data, interval from index surgery to excision, clinical results, and complications. One surgeon performed reoperation for ankylosis of primary THA in three patients with severe pain and deformity. Seven case series or case report studies were included. There were 41 patients, with grade III or IV HO, that had excision, and in five patients, revision of a component was also performed. Perioperative prophylaxis was irradiation alone in 10 patients, irradiation and indomethacin in 10, and indomethacin alone in 21 patients. At a mean follow-up time of 14.8 months, definition of the results was not uniform, and range of motion was improved, but relief of pain was inconsistent. There was one dislocation, one gastrointestinal complication, and two recurrences. Treatment of the three patients, with wide excision of peri-articular bone, selective exchange of components, and peri-operative irradiation prophylaxis, was successful in improving motion and deformity. There is insufficient data on the treatment of severe symptomatic HO after contemporary THA. Prophylaxis with low-dose irradiation was successful to prevent recurrence. Multicenter studies will be needed to determine the optimum timing and prognosis for treatment

The purpose of this study was to determine if the incidence of heterotopic ossification following total hip replacement decreases with increasing experience of the surgeon. A comparison of the incidence of heterotopic ossification between 196 patients having primary total hip replacement in 1989–1990 and a second group of 180 patients between 1999–2000 was performed. The surgery was done by one surgeon. Radiographs taken at least six months post operatively were assessed, and graded using both the Hamblen and Brooker classification systems. No patients were given specific prophylaxis. The groups were well matched. There was a statistically significant reduction in the incidence of Grade 2 and 3 heterotopic ossification in the 1999–2000 patient group. There did not appear to be any identifiable reason for this except increased surgeon experience. The incidence in the 1999–2000 group was well below reported figures from other studies. The incidence of heterotopic ossification following total hip replacement is falling and the fall may be related to improved surgical technique

Heterotopic ossification is a recognised complication of surgery on the hip joint that can adversely affect the outcome. The aim of this study was to determine the incidence of heterotopic ossification following surgical hip dislocation and debridement for femoro-acetabular impingement using Ganz trochanteric flip osteotomy approach. We also compared the incidence of heterotopic ossification between two subgroups of patients; in the first group, a shaver burr was used to reshape the femoral head and in the second group, an osteotome was used. Methods: We reviewed postoperative radiographs of all patients who underwent surgical hip dislocation and debridement during the period between March 2003 and July 2007. We excluded patients with radiographic follow-up of less than one year. Brooker classification was used to grade heterotopic ossifications. Results: Ninety eight patients (mean age 35 years, range 12–65 years) were included with a mean radiological follow-up of 23 months (range 12–61 months). The overall incidence of heterotopic ossification was 31%. None of the patients developed Brooker grade III or IV heterotopic ossifications. The incidence of heterotopic ossifications in the shaver burr group (n=57) and in the osteotome group (n=41) was 30% and 32%, respectively. Conclusions: Heterotopic ossification of minor grade is a common complication of surgical hip dislocation using trochanteric flip osteotomy approach. The use of a shaver burr did not result in higher rates of heterotopic ossifications despite the formation of large amounts bone debris

Aim. The aim of the study was to define the peculiarities of bone remodeling and identify specific parameters to development to heterotopic ossification. Materials and methods. Markers of bone formation (Osteocalcin, serum type 1 procollagen (N-terminal) (tP1NP)) and bone resorption (serum collagen type 1 cross-linked C-telopeptide (β-CTx)) were determined by the electrochemiluminiscence immunoassay “ECLIA” for Elecsys user cobas immunoassay analyser. In the study were included 23 patients with spinal cord injury – first group (average age 26.8 ± 3.9, duration of spinal cord injury from 3 to 12 months) and 23 healthy people's appropriate age and gender (average age 30.6 ± 6.0, years). In the first group included 11 patients with spinal cord injury with the presence of heterotopic ossification – subgroup I and 12 patients with spinal cord injury without heterotopic ossification – subgroup II. Results. The results of examination showed that patients of first group had significantly higher bone markers than control group: P1NP (256.7±48.2 ng/ml vs 49.3±5.1 ng/ml, p<0.001), serum β-CTx (1.47±0.23 ng/ml vs 0.45±0.04 ng/ml, p<0.0001), osteocalcin (52.2±9.8 ng/ml vs 24.9±2.08 ng/ml, p<0.001). There were obtained that levels of bone remodeling markers in patients with HO were significantly higher in comparison with patients without HO: P1NP (404.9±84.9 ng/ml vs 133.2±15.7 ng/ml, p<0.001), serum β-CTx (1.75±0.23 ng/ml vs 0.28±0.14 ng/ml, p<0.0001), osteocalcin (87.1±18.9 ng/ml vs 29.4±3.7 ng/ml, p<0.001). Conclusion. The bone formation and bone resorption markers in patient of first group were significantly higher than in healthy individuals of appropriate age. The rate of bone turnover markers in patient with HO was considerably higher than in patient without HO and the process of formation dominated over the resorption in patient with HO

Introduction: Heterotopic ossification around the tip of intramedullary nail is a well-known complication of the nailing technique, since the time of Kuntscher. Nevertheless, little attention has been given to it in the current literature. Aim: The evaluation of the incidence, clinical significance and possible risk factors of this complication after intramedullary nailing of femur with reaming. Material – Method: For this purpose we studied the X-rays and medical charts of 30 patients who had undergone the above procedure at the Orthopaedic Departments of both Institutions mentioned above, between 2000 and 2002. The preoperative diagnoses were diaphyseal fracture: 13 patients, subtrochanteric fracture: 7 patients, refracture of femur: 1 patient, non-union: 5 patients, imminent fracture (due to intraosseous lesion): 2 patients, failure of previous fixation: 2 patients. In 18 cases the G.K. nail was used, whereas, in the remaining twelve, the long gamma nail was used. The patients’ follow-up ranged from 6 to 18 months (mean: 11 months). The presence of heterotopic bone around the proximal tip of the nail was graded according to the grading system of Brumback et al. Results: In 12 patients (40%) there was no development of heterotopic bone around the proximal tip of the nail. In 14 patients (47%) minimal and moderate grade of heterotopic ossification was developed (grade I and II). Finally, in 4 patients (13%) there was significant heterotopic bone formation (grade III). None of the above patients presented with any significant limitation of ipsilateral hip joint motion. There was no correlation between type of fracture, type of nail fixation, presence of concomitant injuries, nail prominence above the tip of greater trochanter and the formation of heterotopic bone. The only positive correlation was between male sex and the presence of heterotopic ossification. Conclusion: Heterotopic ossification of minimal and moderate grade is a common complication of the technique of intramedullary nailing of femur, without any further clinical significance. The formation of heterotopic bone of significant degree in the hip region, though it does not results in serious clinical problems for the patient, it will surely make future extraction of the nail difficult

The work of Sloof, Ling and Gie has established allografting as a modern technique in revision total hip arthroplasty. The use of allograft enhances the local bone stock and provides a secure fixation for cemented components. Its association with the problem of heterotopic ossification has not been previously considered. The records and x-rays of 114 patients after revision hip surgery were reviewed. All had been operated upon by three Consultant Orthopaedic Surgeons using standard techniques. 35 patients had undergone revision with impaction allografting of both the femur and acetabulum, 29 had allografting of the femur only, 18 of the acetabulum alone and the final 32 patients (acting as controls) had cemented revision arthroplasty without impaction allografting. Fresh frozen allograft was used in all cases and prepared using a bone mill. No patient was given radiation or Indomethacin after their revision surgery, even if they had pre-existing heterotopic ossification. The immediate pre-operative x-rays and x-rays at least a year post-revision were assessed independently by a musculoskeletal radiologist. He was blinded to the type of revision procedure and graded the heterotopic ossification according to the Brooker Classification. Our results report the incidence of heterotopic ossification after revision hip arthroplasty with fresh frozen allograft when compared with cemented revision arthroplasty from our unit and other studies

Purpose. The ideal timing for a Total Hip Arthroplasty (THA) remains a highly controversial topic in the treatment of displaced acetabular fractures in the elderly with damage to the articular surface of the acetabulum or femoral head. Acute THA offers early rehabilitation but a high incidence of heterotopic ossification has been reported. Its incidence and consequences on the patient's function are not clear. The goal of this study is to compare the incidence of heterotopic ossification following acute THA of acetabular fractures compared to delayed THA, and to evaluate its functional effects on the patient. Method. In this retrospective consecutive case series of acetabular fractures; 20 patients were treated with acute THA and 20 patients were treated with delayed THA after failed conservative or surgical treatment. The incidence of heterotopic ossification (using Brooker's classification) was obtained and functional outcomes were evaluated using SF-12, WOMAC, Harris Hip Score surveys. Results. Heterotopic ossification (HO) was found in 55% (13/20) in the acute THR group compared to 25% (5/20) in the delayed THA group. The relative risk of having significant HO (grades 2–3-4) when the prosthesis was done acutely was 3.4 times higher then when it was delayed. (p=0.01). Furthermore, significant difference in functional outcome was noted in the acute THA group. In fact, seven of eight (7/8) patients in the first subgroup of patients with no HO or grade 1 HO had excellent or good HHS scores. However, only three of eight (3/8) patients with grade 2 or 3 HO showed excellent or good HHS scores. The specific heterotopic ossification grade did not correlate with function. Conclusion. The incidence of HO was significantly higher in patients with acute THA compared to delayed THA for acetabular fractures. Interestingly, in the acute THA group, patients with grades 2 and 3 HO seem to have worst functional outcomes than patients with no HO or grade 1 HO

220 consecutive hip resurfacing procedures were reviewed at a minimum of two years follow up to assess the incidence of heterotopic ossification and its effect on function and clinical outcome. We also reviewed the pre-operative diagnosis, gender and previous surgery. The overall percentage of heterotopic ossification was 58.63%. The incidence of Brooker 1 was 37.27%, Brooker 2 was 13.18% and Brooker 3 was 8.18%. Male osteoarthritics had the highest incidence of heterotopic bone formation. Three males underwent excision of heterotopic bone, two for pain and stiffness and one for decreased range of movement. Both antero-posterior and lateral radiographs were reviewed for evidence of heterotopic bone formation. 12.7% had no evidence of heterotopic bone formation on one view but clearly had on the second view. Overall we found no evidence that heterotopic bone formation affected the clinical or functional outcome of the hip resurfacing at a mean of 3 years follow up

Heterotopic Ossification (HO) is a known complication that can arise after total elbow arthroplasty (TEA). In most cases it is asymptomatic, however, in some patients it can limit range of motion and lead to poor outcomes. The objective of this review was to assess and report incidence, risk factors, prophylaxis, and management of HO after TEA. A systematic search was conducted using MEDLINE, EMBASE, and PubMed to retrieve all relevant studies evaluating occurrence of HO after TEA. The search was performed in duplicate and a quality assessment was performed of all included studies. A total of 1907 studies were retrieved of which 45 studies were included involving 2256 TEA patients. HO was radiographically present in 10% of patients and was symptomatic in 3%. Less than 1% of patients went on to surgical excision of HO, with outcomes following surgery reported as good or excellent as assessed by range of motion and Mayo Elbow Performance Scores (MEPS). TEA due to ankylosis, primary osteoarthritis, and posttraumatic arthritis are more likely to develop symptomatic HO. HO is an uncommon complication following TEA with the majority of patients developing HO being asymptomatic and requiring no surgical management. Routine HO prophylaxis for TEA is not supported by the literature. The effectiveness of prophylaxis in high risk patients is uncertain and future studies are required to clarify its usefulness. The strength of these conclusions are limited by inconsistent reporting in the available literature

Introduction and Objective. Heterotopic ossification is the formation of extraskeletal mineralized tissue commonly associated with either trauma or surgery. While several mouse models have been developed to better characterize the pathologic progression of HO, no model currently exists to study HO of the hip, the most common location of acquired HO in patients. Owing to the unique biological mechanisms underpinning the formation of HO in different tissues, we sought to develop a model to study the post-surgical HO of the hip. Materials and Methods. Wild-type mice C57BL/6J mice were used to study the procedure outcomes, while Pdgfra-CreERT2;mT/mG and Scx-GFP reporter animals were used for the lineage tracing experiments (total n=16 animals, male, 12 weeks old). An anterolateral approach to the hip was performed. Briefly, a 2 cm incision was made centered on the great trochanter and directed proximal to the iliac crest and distally over the lateral shaft of the femur. The joint was then reached following the intermuscular plane between the rectus femoris and gluteus medius muscles. After the joint was exposed, the articular cartilage was removed using a micropower drill with a 1.2 mm reamer. The medius gluteus and superficial fascia were then re-approximated with Vicryl 5-0 suture (Ethicon Inc, Somerville, NJ) and skin was then closed with Ethilon 5-0 suture (Ethicon Inc). Live high resolution XR imaging was performed every 2 wks to assess the skeletal tissues (Faxitron Bioptics, Tucson, AZ). The images were then scored using the Brooker classification. Ex-vivo microCT was conducted using a Skyscan 1275 scanner (Bruker-MicroCT, Kontich, Belgium). 3D reconstruction and analysis was performed using Dragonfly (ORS Inc., Montreal, Canada). For the histological analysis of specimens, Hematoxylin and Eosin (H&E), modified Goldner's Trichrome (GMT) stainings were performed. Reporter activity was assessed using fluorescent imaging. Results. Substantial periarticular heterotopic bone was seen in all cases. A periosteal reaction and an initial formation of calcified tissue within the soft tissue was apparent starting from 4 wks after surgery. By XR, progressive bone formation was observed within the periosteum and intermuscular planes during the subsequent 8 weeks. Stage 1 HO was observed in 12.5% of cases, stage 2 in 62.5% of cases, and stage 3 HO in 25% of cases. 3D microCT reconstructions of the treated hip joints demonstrated significant de novo heterotopic bone in several location which phenocopy human disease. Heterotopic bone was observed in an intracapsular location, periosteal location involving the iliac bone and proximal femur, and intermuscular locations. Histological analyses further confirmed these findings. To assess the cells which gave rise to HO in this model, an inducible PDGFRα and constitutive Scx-GFP reporter mice were used. A dramatic increase in mGFP reporter activity was noted PDGFRα within the HO injury site, including in areas of new cartilage and bone formation. Scx-associated reporter activity increased in the soft tissue and periosteal periacetabular areas of injured hips. Conclusions. HO has a diverse set of pathologies, of which joint associated HO after elective surgery is the most common. Here, we present the first mouse model of hip dislocation and acetabular reaming that mimics elements of human periarticular HO. The diverse locations of HO after acetabular reaming (intracapsular, intermuscular and periosteal) suggests the activation of different and specific HO program after surgery. Such a field effect would be consistent with local trauma and inflammation, which is a well-studied contributor to HO genesis. Not surprisingly, joint-associated HO significantly derives from PDGFRα-expressing cells, which has been shown to similarly give rise to intramuscular and intratendinous HO

Heterotopic ossification (HO) is a well-known complication of traumatic elbow injuries. The reported rates of post-traumatic HO formation vary from less than 5% with simple elbow dislocations, to greater than 50% in complex fracture-dislocations. Previous studies have identified fracture-dislocations, delayed surgical intervention, and terrible triad injuries as risk factors for HO formation. There is, however, a paucity of literature regarding the accuracy of diagnosing post-traumatic elbow HO. Therefore, the purpose of our study was to determine the inter-rater reliability of HO diagnosis using standard radiographs of the elbow at 52 weeks post-injury, as well as to report on the rate of mature compared with immature HO. We hypothesized inter-rater reliability would be poor among raters for HO formation. Prospectively collected data from a large clinical trial was reviewed by three independent reviewers (one senior orthopedic resident, one senior radiology resident, and one expert upper extremity orthopedic surgeon). Each reviewer examined anonymized 52-week post-injury radiographs of the elbow and recorded: 1. the presence or absence of HO, 2. the location of HO, 3. the size of the HO (in cm, if present), and 4. the maturity of the HO formation. Maturity was defined by consensus prior to image review and defined as an area of well-defined cortical and medullary bone outside the cortical borders of the humerus, ulna, or radius. Immature lesions were defined as an area of punctate calcification with an ill-defined cloud-like density outside the cortical borders of the humerus, ulna or radius. Data were collected using a standardized online data collection form (CognizantMD, Toronto, ON, CA). Inter-rater reliability was calculated using Fleiss’ Kappa statistic and a multivariate logistic regression analysis was performed to identify risk factors for HO formation in general, as well as mature HO at 52 weeks post injury. Statistical analysis was performed using RStudio (version1.4, RStudio, Boston, MA, USA). A total of 79 radiographs at the 52-week follow-up were reviewed (54% male, mean age 50, age SD 14, 52% operatively treated). Inter-rater reliability using Fleiss’ Kappa was k= 0.571 (p = 0.0004) indicating moderate inter-rater reliability among the three reviewers. The rate of immature HO at 52 weeks was 56%. The multivariate logistic regression analysis identified male sex as a significant risk factor for HO development (OR 5.29, 1.55-20.59 CI, p = 0.011), but not for HO maturity at 52 weeks. Age, time to surgery, and operative intervention were not found to be significant predictors for either HO formation or maturity of the lesion in this cohort. Our study demonstrates moderate inter-rater reliability in determining the presence of HO at 52 weeks post-elbow injury. There was a high rate (56%) of immature HO at 52-week follow-up. We also report the finding of male sex as a significant risk factor for post traumatic HO development. Future research directions could include investigation into possible male predominance for traumatic HO formation, as well as improving inter-rater reliability through developing a standardized and validated classification system for reporting the radiographic features of HO formation around the elbow

Abstract. Objectives. The term heterotopic ossification (HO) describes lamellar bone formation within soft tissues following injury. A genome-wide scan of patients after hip arthroplasty has identified that variation within the lncRNA CASC20 is associated with HO susceptibility. Previous findings in our lab have demonstrated upregulation of CASC20 during BMP2-induced osteodifferentiation of adipose-derived stem cells (hMAD) alongside osteodifferentiation markers, RUNX2 and OSX. We hypothesize that CASC20 is a novel regulator of bone formation and aim to investigate CASC20 function in bone formation. Methods. 1) We used miRanda prediction algorithm and the ENCORI database to respectively predict which miRNAs CASC20 interacts with and to select for experimentally validated miRNAs. 2) We characterized the expression and functional role of CASC20-interacting miRNAs by respectively analyzing publicly available datasets (GSE107279 and pubmed.ncbi.nlm.nih.gov/26175215/) and by using Gene Ontology (GO) analysis. 3) We overexpressed CASC20 in hMAD using a lentiviral system and tested the effect of CASC20 overexpression in osteodifferentiation and expression of putative CASC20-interacting miRNAs. Results. 1) We identified 64 experimentally validated miRNAs that are predicted to interact with CASC20. 2) GO analysis revealed that the most frequently targeted molecular functions included SMADs, MAPKK and other kinase activities known to play a central role in osteo and chondrogenesis. We found 10 miRNAs including hsa-miR-485-3p that demonstrated down-regulation in both osteo- and chondrogenesis. 3) We found that CASC20-overexpression augmented the osteodifferentiation of hMAD measured in mineralization using Alizarin Red S. CASC20 overexpression increased the expression of osteogenic marker ALP and decreased the expression of hsa-miR-485-3p. Conclusion. Here we show how CASC20 may regulate bone formation by acting as a competitive endogenous RNA (ceRNA). We are currently using CASC20 overexpression model in osteo- and chondrogenesis, and testing CASC20-miRNA interaction to establish the underlying mechanism for the observed associations

Background. Heterotopic ossification (HO) is a known complication following total hip arthroplasty, with increased incidence in certain patient populations. Current prophylaxis options include oral non-steroidal anti-inflammatory drugs (NSAIDs) and radiation therapy, but an optimal radiation protocol has yet to be clearly defined. We performed a randomized, double-blinded clinical trial in high-risk total hip arthroplasty patients to determine the efficacy of 400 cGy versus 700 cGy doses of radiation. Methods. 147 patients at high risk for HO undergoing total hip arthroplasty (THA) at Rush-St. Luke's- Presbyterian medical center were randomized to either a single 400 cGy or 700 cGy dose of radiation. High risk was defined as diagnosis of diffuse idiopathic skeletal hyperostosis (DISH), hypertrophic osteoarthritis, ankylosing spondylitis, or history of previous heterotopic ossification. Radiation was administered over a 14 × 6 cm area of soft tissue and given on the first or second post-operative day. A blinded reviewer graded anterior-posterior (AP) and lateral radiographs taken immediately post-operatively and at a minimum of 6 months post-operatively. Progression was defined as an increase in Brooker classification from the immediate post-operative to the long-term post-operative radiograph. Operative data including surgical approach, use of cemented implants, revision surgery, and post-operative range of motion data were also collected. Results. A significantly greater portion of patients who received the 400 cGy dose demonstrated progression of HO than patients who received the 700 cGy dose. No pre-operative factors were associated with a higher rate of progression. Patients who progressed had less flexion on physical exam than patients who did not progress, but this was not clinically significant. Conclusion. To the authors' knowledge this is the largest randomized prospective study to date comparing two single-dosages of radiation treatment. 700 cGy demonstrates superiority over 400 cGy in preventing HO formation following total hip arthroplasty in high-risk patients and may be the more effective treatment in this population

Purpose: Heterotopic ossification is a recognised complication after total hip arthroplasty. Prevalence can reach 53%, particularly if prophylaxis is not given, leading to postoperative pain and limiting the functional prognosis. Non-steroidal antiinflammatory drugs have proven efficacy but also present the risk of gastroduodenal toxicity making postoperative administration hasardous. Recently, selective COX-2 inhibitors have been shown to have a similar antiinflammatory activity with a clear reduction in gastrointestinal disorders. We hypothesised that selective COX-2 inhibitors could be as effective as classical NSAID for the prevention of heterotopic ossifications. Material and methods: This clinical trial was conducted according to a prospective randomised protocol comparing a group of patients given prophylaxis with Celecoxib (Celebrex®) and another group of patients given ibuprofen (Brufen®). All patients scheduled for total elective prostheses were radomised in a prospective manner to one of the two groups, either Celecoxib 200mg b.i.d. or ibuprofen 400mg t.i.d. for ten immediate postoperative days. Radiological assessment was performed by two independent investigators blinded to the study (an orthopaedic surgeon and a radiologist) who scored calcifications according to the Brooker classification (type I to IV) at three months after surgery. Reproducibility of radiogram reading was tested and analysed with a kappa test K=0.74). Results: Two hundred ten patients were randomised and 73 have had their three-month radiograms. The Cele-coxib group included 37 patients: 24 with Brooker stage 0, eleven with stage 1, two with stage 2. The ibuprofren group included 42 patients, 15 with Brooker 0, 16 with Brooker 1; nine with Brooker 2 and two with Brooker 3. The statistical analysis will be performed at the end of this study (June 2002). Discussion: The preliminary results show that Celecoxib appears to have the same efficacy as ipubrofen for the prevention of heterotopic ossification after total hip arthroplasty. There was a clear trend in favour of Celecoxib

The objective of this study was to evaluate the functional outcome of the elbow joint in patients with heterotopic ossification of the elbow joint who underwent surgical excision of pathologic bone. From 5/1994 to 12/2006, 24 patients (33 joints) with heterotopic ossification of the elbow joint were evaluated. All patients were attended in the Intensive Care Unit (ICU). The patient\’s age ranged from 19–48 years (mean; 32 years) The median ICU hospitalization was 3 weeks. In nine patients both elbows were affected. Unilateral involvement was equally noticed to the right (seven cases) and the left elbow (eight cases). The DASH SCORE and the range of motion were used for the evaluation of the results. All patients underwent surgical treatment in order to extract heterotopic bone and to improve the range of motion of the affected elbow joint. Postoperatively 18 out of 33 operated elbow joints (54.54%) demonstrated improvement of the range of motion, whereas no improvement was observed in the remaining 15 elbow joints (45.45%). Higher DASH SCORE was obtained in 19 out of 24 patients (79.17%). Surgical excision of the ectopic bone around the affected elbow significantly improves the range of motion of the joint providing better use of the upper extremity and therefore a superior quality of life in these patients