We retrospectively reviewed 89 consecutive patients (45 men and 44 women) with a mean age at the time of injury of 58 years (18 to 97) who had undergone external fixation after sustaining a unilateral fracture of the distal humerus. Our objectives were to determine the incidence of heterotopic ossification (HO); identify risk factors associated with the development of HO; and characterise the location, severity and resultant functional impairment attributable to the presence of HO. . HO was identified in 37 elbows (42%), mostly around the humerus and along the course of the medial collateral ligament. HO was hazy immature in five elbows (13.5%), mature discrete in 20 (54%), extensive mature in 10 (27%), and complete bone bridges were present in two elbows (5.5%). Mild functional impairment occurred in eight patients, moderate in 27 and severe in two. HO was associated with less extension (p = 0.032) and less overall flexion-to-extension movement (p = 0.022); the flexion-to-extension arc was < 100º in 21 elbows (57%) with HO compared with 18 elbows (35%) without HO (p = 0.03). HO was removed surgically in seven elbows. . The development of HO was significantly associated with sustaining a head injury (p = 0.015), delayed internal fixation (p = 0.027), the method of fracture fixation (p = 0.039) and the use of bone graft or substitute (p = 0.02).HO continues to be a substantial complication after internal fixation for distal humerus fractures. Cite this article: Bone Joint J 2014;96-B:1681–7

Introduction and aims: Flanged sockets have been in use since 1976.Experimental evidence has shown that they offer an advantage in terms of cement pressurization at the time of implantation. Radiological demarcation at the cement-bone interface has been shown to be significantly reduced in early radiographs with flanged sockets.The Opera Cup with its contoured flange containing a series of tangential rings was developed in Manchester.We present our early results with this cup.

Method: 140 patients had primary hip arthroplasty performed between July1997 and November 2000.

Ten had bilateral surgery.92 (66%) were female and 48 (34%) were male.The mean age at operation was 58 (range 34–90).The mean length of follow up was 50 months (range 36–76).

Standardised anteroposterior radiographs of the pelvis were compared at one year with the three to six year reviews.Radiological demarcation of the acetabular component was assessed using the Hodgkinson grading system by the senior author.

Results: 150 sockets were reviewed.62% had no demarcation at one year (grade 0).This figure fell to 56% at the three to six year review.Grade 1 changes were seen in 36% at one year rising to 41% at the three to six year review.

92% of sockets showed no increase in demarcation during the review period whilst 3% had developed evidence of radiological loosening with grades 2 to 4.

Conclusion: The development and progression of radiolucent lines are associated with aseptic socket loosening.Our results compare favourably with published studies.Long term follow up is needed to make more accurate comparisons.

Aims. Heterotopic ossification (HO) is a common complication after elbow trauma and can cause severe upper limb disability. Although multiple prognostic factors have been reported to be associated with the development of post-traumatic HO, no model has yet been able to combine these predictors more succinctly to convey prognostic information and medical measures to patients. Therefore, this study aimed to identify prognostic factors leading to the formation of HO after surgery for elbow trauma, and to establish and validate a nomogram to predict the probability of HO formation in such particular injuries. Methods. This multicentre case-control study comprised 200 patients with post-traumatic elbow HO and 229 patients who had elbow trauma but without HO formation between July 2019 and December 2020. Features possibly associated with HO formation were obtained. The least absolute shrinkage and selection operator regression model was used to optimize feature selection. Multivariable logistic regression analysis was applied to build the new nomogram: the Shanghai post-Traumatic Elbow Heterotopic Ossification Prediction model (STEHOP). STEHOP was validated by concordance index (C-index) and calibration plot. Internal validation was conducted using bootstrapping validation. Results. Male sex, obesity, open wound, dislocations, late definitive surgical treatment, and lack of use of non-steroidal anti-inflammatory drugs were identified as adverse predictors and incorporated to construct the STEHOP model. It displayed good discrimination with a C-index of 0.80 (95% confidence interval 0.75 to 0.84). A high C-index value of 0.77 could still be reached in the internal validation. The calibration plot showed good agreement between nomogram prediction and observed outcomes. Conclusion. The newly developed STEHOP model is a valid and convenient instrument to predict HO formation after surgery for elbow trauma. It could assist clinicians in counselling patients regarding treatment expectations and therapeutic choices. Cite this article: Bone Joint J 2022;104-B(8):963–971

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

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

Aims. Heterotopic ossification (HO) is a potentially devastating complication of the surgical treatment of a proximal humeral fracture. The literature on the rate and risk factors for the development of HO under these circumstances is lacking. The aim of this study was to determine the incidence and risk factors for the development of HO in these patients. Methods. A retrospective analysis of 170 patients who underwent operative treatment for a proximal humeral fracture between 2005 and 2016, in a single institution, was undertaken. The mean follow-up was 18.2 months (1.5 to 140). The presence of HO was identified on follow-up radiographs. Results. The incidence of HO was 15% (n = 26). Our multivariate model revealed that male sex (odds ratio (OR) 3.57, 95% confidence interval (CI) 1.30 to 9.80 compared to female) and dislocation as the initial injury (OR 5.01, 95% CI 1.31 to 19.22) were significantly associated with the formation of HO (p < 0.05) while no significant associations were seen for the age of the patient, the characteristics of the injury, or the type of operative treatment. Conclusion. This retrospective radiological study is the first to investigate the association between the method of surgical treatment for a proximal humeral fracture and the formation of HO postoperatively. We found that male sex and dislocation as the initial injury were risk factors for HO formation, whereas the method of surgical treatment, the age of the patient, and the pattern of the fracture were not predictive of HO formation. While additional studies are needed, these findings can help to identify those at an increased risk for HO formation under these circumstances. Cite this article: Bone Joint J 2020;102-B(4):539–544

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 (HO) is defined as aberrant bone formation in extraskeletal locations. In this process, local stromal cells of mesenchymal origin abnormally differentiate, resulting in pathologic cartilage and bone matrix deposition. However, the specific cell type and mechanisms beyond this process are not well understood, in part due to the heterogeneity of progenitor cells involved. Here, a combination of single cell RNA sequencing (scRNA-Seq) and lineage tracing, defined the extent to which synovial / tendon sheath progenitor cells contribute to HO. For this purpose, a Tppp3 (tubulin polymerization-promoting protein family member 3) inducible reporter model was used, in combination with either Scx (Scleraxis) or Pdgfra (Platelet derived growth factor receptor alpha) reporter animals. Both arthroplasty-induced and tendon injury-mouse experimental HO models were utilized. ScRNA-Seq of tendon-induced traumatic HO suggested that Tppp3 is a progenitor cell marker for either osteochondral or tendon or cells. After HO induction, Tppp3 reporter+ cell population expanded in number and contributed to cartilage and bone formation in tendon and joint-associated HO. Using double reporter animals, we found that both Pdgfra+Tppp3+ and Pdgfra+Tppp3- progenitor cells produced HO-associated cartilage. Finally, the examination of human samples showed a significant population of TPPP3+ cells overlapping with osteogenic markers in areas of HO. Overall, these results provide novel observations that peritenon and synovial progenitor cells undergo abnormal osteochondral differentiation and contribute to heterotopic bone formation after trauma

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

Aims. Dystrophic calcification (DC) is the abnormal appearance of calcified deposits in degenerating tissue, often associated with injury. Extensive DC can lead to heterotopic ossification (HO), a pathological condition of ectopic bone formation. The highest rate of HO was found in combat-related blast injuries, a polytrauma condition with severe muscle injury. It has been noted that the incidence of HO significantly increased in the residual limbs of combat-injured patients if the final amputation was performed within the zone of injury compared to that which was proximal to the zone of injury. While aggressive limb salvage strategies may maximize the function of the residual limb, they may increase the possibility of retaining non-viable muscle tissue inside the body. In this study, we hypothesized that residual dead muscle tissue at the zone of injury could promote HO formation. Methods. We tested the hypothesis by investigating the cellular and molecular consequences of implanting devitalized muscle tissue into mouse muscle pouch in the presence of muscle injury induced by cardiotoxin. Results. Our findings showed that the presence of devitalized muscle tissue could cause a systemic decrease in circulating transforming growth factor-beta 1 (TGF-β1), which promoted DC formation following muscle injury. We further demonstrated that suppression of TGF-β signalling promoted DC in vivo, and potentiated osteogenic differentiation of muscle-derived stromal cells in vitro. Conclusion. Taken together, these findings suggest that TGF-β1 may play a protective role in dead muscle tissue-induced DC, which is relevant to understanding the pathogenesis of post-traumatic HO. Cite this article: Bone Joint Res 2020;9(11):742–750

Aims. Heterotopic ossification (HO) occurs after arthroplasty, especially total hip arthroplasty. In this study we describe the incidence, evolution, morphology and clinical consequences of HO following reverse shoulder arthroplasty. Patients and Methods. This is a single-centre retrospective study of 132 consecutive patients who received a Delta III or Delta Xtend reverse total shoulder arthroplasty between 2006 and 2013 for the treatment of cuff tear arthropathy. There were 96 women and 36 men. Their mean age at the time of surgery was 69 years (49 to 89) and the mean follow-up was 36 months (12 to 84). The incidence, evolution, morphology and clinical consequences of HO using the Constant-Murley score (CS) were analysed. A modified Brooker classification of HO of the hip was used. Results. HO was seen in 39 patients (29.5%). A total of 31 of these patients (81.6%) began to develop HO by three months post-operatively. According to the Hamada classification, 11 patients had grade 1a, eight had grade 1b, six had grade 1c and 14 had grade 2 HO. The HO evolved over a mean of 8.3 months (3 to 21). Patients with HO had a lower mean CS at three (p = 0.017), six (p < 0.001) and 12 months (p < 0.001) post-operatively. HO was not associated with notching (p = 0.675). Conclusion. HO after reverse shoulder arthroplasty is a non-progressive condition without long-term clinical consequences. Only grade 2 HO is clinically relevant with a negative effect on the function of the shoulder during its development. Cite this article: Bone Joint J 2016;98-B:1215–21

Aims. The aim of this study was to assess the efficacy of non-selective and selective non-steroidal anti-inflammatory drugs (NSAIDs) in preventing heterotopic ossification (HO) after total hip arthroplasty (THA). Methods. A thorough and systematic literature search was conducted and 29 studies were found that met inclusion criteria. Data were extracted and statistical analysis was carried out generating forest plots. Results. Non-selective NSAIDs showed a significant decrease in the odds for forming HO after THA (odds ratio (OR) -1.35, confidence interval (CI) -1.83 to -0.86) when compared with placebo. Selective NSAIDs also showed a significant decrease in the odds for forming HO after THA when compared with placebo (OR -1.58, CI -2.41 to -0.75). When comparing non-selective NSAIDs with selective NSAIDs, there was no significant change in the odds for forming HO after THA (OR 0.22, CI -0.36 to 0.79). Conclusion. Our meta-analyses of all available data suggest that both non-selective and selective NSAIDs are effective HO prophylaxis and can be used routinely after THA for pain control as well as prevention of HO. Indomethacin may serve as the benchmark among non-selective NSAIDs and celecoxib among selective NSAIDs. There was no difference in the incidence of HO between non-selective and selective NSAIDs, allowing physicians to choose either based on the clinical scenario and patient-specific factors. Cite this article: Bone Joint J 2018;100-B:915–22

Aims. We aimed to assess the influence of ethnicity on the incidence of heterotopic ossification (HO) after total hip arthroplasty (THA). . Patients and Methods. We studied the six-month post-operative anteroposterior radiographs of 1449 consecutive primary THAs (1324 patients) and retrospectively graded them for the presence of HO, using the Brooker Classification. . Results. Based on multivariate analysis, African-American ethnicity was an independent risk factor for HO formation following THA with an adjusted odds ratio (OR) of 2.6 (95% confidence interval (CI) 1.3 to 5.2, p = 0.007) for severe HO and 1.9 (95% CI 1.3 to 2.7, p < 0.001) for any grade of HO. . Conclusion. Given the increased risk of HO formation, particularly high grade HO, and the potentially poorer outcomes associated with HO, it is important to consider using prophylaxis against HO in patients of African-American ethnicity undergoing THA. Take home message: African Americans are at an increased risk for developing heterotopic ossification and thus may benefit from HO prophylaxis. . Cite this article: Bone Joint J 2016;98-B:761–6

Aim. The primary aim of this retrospective study was to identify the incidence of heterotopic ossification (HO) following elective and trauma elbow arthroplasty. The secondary aim was to determine clinical outcomes with respect to the formation of heterotopic ossification. Patients and Methods. A total of 55 total elbow arthroplasties (TEAs) (52 patients) performed between June 2007 and December 2015 were eligible for inclusion in the study (29 TEAs for primary elective arthroplasty and 26 TEAs for trauma). At review, 15 patients (17 total elbow arthroplasties) had died from unrelated causes. There were 14 men and 38 women with a mean age of 70 years (42 to 90). The median clinical follow-up was 3.6 years (1.2 to 6) and the median radiological follow-up was 3.1 years (0.5 to 7.5). Results. The overall incidence of HO was 84% (46/55). This was higher in the trauma group (96%, 25/26) compared with the elective arthroplasty group (72%, 21/29) (p = 0.027, Fisher’s exact test). Patients in the trauma group had HO of higher Brooker class. The presence of HO did not significantly affect elbow range of movement within the trauma or elective groups (elective arthroplasty, Mann–Whitney U test, p = 0.070; trauma arthroplasty, p = 0.370, Mann–Whitney U test). Conclusion. HO after total elbow arthroplasty is seen more commonly than previously reported. We have reported a significantly higher rate of HO in TEAs performed for trauma than those performed electively. Cite this article: Bone Joint J 2018;100-B:767–71

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

Early total hip replacement (THR) for acetabular fractures offers accelerated rehabilitation, but a high risk of heterotopic ossification (HO) has been reported. The purpose of this study was to evaluate the incidence of HO, its associated risk factors and functional impact. A total of 40 patients with acetabular fractures treated with a THR weres retrospectively reviewed. The incidence and severity of HO were evaluated using the modified Brooker classification, and the functional outcome assessed. The overall incidence of HO was 38% (n = 15), with nine severe grade III cases. Patients who underwent surgery early after injury had a fourfold increased chance of developing HO. The mean blood loss and operating time were more than twice that of those whose surgery was delayed (p = 0.002 and p < 0.001, respectively). In those undergoing early THR, the incidence of grade III HO was eight times higher than in those in whom THR was delayed (p = 0.01). Only three of the seven patients with severe HO showed good or excellent Harris hip scores compared with eight of nine with class 0, I or II HO (p = 0.049). Associated musculoskeletal injuries, high-energy trauma and head injuries were associated with the development of grade III HO. The incidence of HO was significantly higher in patients with a displaced acetabular fracture undergoing THR early compared with those undergoing THR later and this had an adverse effect on the functional outcome. Cite this article: Bone Joint J 2013;95-B:95–100

Currently, there is no animal model in which to evaluate the underlying physiological processes leading to the heterotopic ossification (HO) which forms in most combat-related and blast wounds. We sought to reproduce the ossification that forms under these circumstances in a rat by emulating patterns of injury seen in patients with severe injuries resulting from blasts. We investigated whether exposure to blast overpressure increased the prevalence of HO after transfemoral amputation performed within the zone of injury. We exposed rats to a blast overpressure alone (BOP-CTL), crush injury and femoral fracture followed by amputation through the zone of injury (AMP-CTL) or a combination of these (BOP-AMP). The presence of HO was evaluated using radiographs, micro-CT and histology. HO developed in none of nine BOP-CTL, six of nine AMP-CTL, and in all 20 BOP-AMP rats. Exposure to blast overpressure increased the prevalence of HO. This model may thus be used to elucidate cellular and molecular pathways of HO, the effect of varying intensities of blast overpressure, and to evaluate new means of prophylaxis and treatment of heterotopic ossification. Cite this article: Bone Joint J 2015;97-B:572–6

Heterotopic ossification (HO) is lamellar bone formation that occurs within tissues that do not normally have properties of ossification. The pathoaetiology of HO is poorly understood. We conducted a genome wide association study to better understand the genetic architecture of HO. 891 patients of European descent (410 HO cases) following THA for primary osteoarthritis were recruited from the UK. HO was assessed from plain AP radiographs of the pelvis. Genomic DNA was extracted, genotyped using the Illumina 610 beadchip and referenced using the 1000 Genome Project panel. HO susceptibility case-control analysis and an evaluation of disease severity in those with HO was undertaken using SNPTESTv2.3.0 on>10 million variants. We tested variants most strongly associated with HO in an independent UK THA replication cohort comprising 209 cases and 211 controls. The datasets were meta-analysed using PLINK. In the discovery cohort 70 signals with an index variant at p<9×10–5 were suggestively associated with HO susceptibility. The strongest signal lay just downstream of the gene ARHGAP18 (rs59084763, effect allele frequency (EAF) 0.19, OR1.87 [1.48–2.38], p=2.48×10–8), the second strongest signal lay within the long non-coding (LNC) RNA gene CASC20 (rs11699612, EAF 0.25, OR1.73 [1.1.40–2.16, p=9.3×10–8). In the discovery cohort 73 signals with an index variant at p<9×10–5 were associated with HO severity. At replication, 12 of the leading 14 susceptibility signals showed a concordant direction of allelic effect and 5 replicated at nominal significance. Following meta-analysis, the lead replicating susceptibility signal was the CASC20 variant rs11699612 (p=2.71×10–11). We identify consistent replicating association of variation within the LNC RNA CASC20 with HO susceptibility after THA. Although the function of CASC20 is currently unknown, possible mechanisms include transcriptional, post-transcriptional and epigenetic regulation of downstream target genes. The work presented here provides new avenues for the development of novel predictive and therapeutic approaches towards HO

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

Electron Microscopy and Synchrotron analysis of Heterotopic Ossification (HO) from blast-related amputees' has shown that HO is bone with a disorganised structure and altered remodelling. This research performs mechanical testing of HO to understand its biomechanical properties in an attempt to create an accurate model to predict its morphological appearance. The hypothesis of this work is that HO is mechanically mediated in its formation. Synchrotron mechanical analysis of HO samples was performed to measure Young's modulus, ultimate strength and density distribution. A novel algorithm based on Wolf's law was implemented in a Finite Element (FE) analysis model of HO to take into account the differing mechanical and biological properties measured and the presence of HO outside the skeletal system. An HO modeling factor, which considers boundary conditions, and regulates recruitment of the soft tissue into bone formation, results in a re-creatable formation of HO within the soft tissues, comparable to the appearance of HO seen in military amputees. The results and model demonstrates that certain types of HO are under the control of endogenous and exogenous mechanical stimulus. HO can thus be mechanically exploited in the casualty management and rehabilitation process to achieve better clinical outcomes