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

We report the case of an 82-year-old man who underwent fasciectomy for a severe Dupuytren’s contracture, during which an ossified lesion was encountered within the contracture and surrounding the neurovascular bundle. The abnormal tissue was removed with difficulty and heterotopic ossification was confirmed histologically. We believe this is the first report of heterotopic ossification in Dupuytren’s disease

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

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

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. 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

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

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.

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

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 following joint replacement in the lower limb occurs in 3% to 90% of cases. Higher grades of heterotopic ossification can result in significant limitation of function and can negate the benefits of joint replacement. The understanding of the pathophysiology of this condition has improved in recent years. It would appear to be related to a combination of systemic and local factors, including over-expression of bone morphogenetic protein-4. There is currently little evidence to support the routine use of prophylaxis for heterotopic ossification in arthroplasty patients, but prophylaxis is recommended by some for high-risk patients. Radiotherapy given as one dose of 7 Gy to 8 Gy, either pre-operatively (< four hours before) or post-operatively (within 72 hours of surgery), appears to be more effective than indometacin therapy (75 mg daily for six weeks). In cases of prophylaxis against recurrent heterotopic ossification following excision, recent work has suggested that a combination of radiotherapy and indometacin is effective. Advances in our understanding of this condition may permit the development of newer, safer treatment modalities

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.

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

We evaluated the incidence of heterotopic ossification following total ankle replacement to determine whether the degree of ossification was associated with the clinical outcome. We evaluated 90 ankles in 81 consecutive patients who underwent total ankle replacement, and heterotopic ossification was assessed according to proportional involvement of the ankle joint. Correlation analysis was used to investigate the association between heterotopic ossification and outcome. . No significant association was found between the formation of heterotopic ossification and the clinical outcome. The degree of heterotopic ossification in the posterior ankle joint was not significantly correlated with posterior ankle pain (p = 0.929), the American Orthopaedic Foot and Ankle Society score (p = 0.454) or range of movement (p = 0.283). . This study indicates that caution should be observed in attributing symptoms and functional limitation to the presence of heterotopic ossification in the posterior ankle joint when considering excision of heterotopic bone after total ankle replacement

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

Our study was designed to compare the effect of indometacin with that of a placebo in reducing the incidence of heterotopic ossification in a prospective, randomised trial. A total of 121 patients with displaced fractures of the acetabulum treated by operation through a Kocher-Langenbeck approach was randomised to receive either indometacin (75 mg) sustained release, or a placebo once daily for six weeks. The extent of heterotopic ossification was evaluated on plain radiographs three months after operation. Significant ossification of Brooker grade III to IV occurred in nine of 59 patients (15.2%) in the indometacin group and 12 of 62 (19.4%) receiving the placebo. We were unable to demonstrate a statistically significant reduction in the incidence of severe heterotopic ossification with the use of indometacin when compared with a placebo (p = 0.722). Based on these results we cannot recommend the routine use of indometacin for prophylaxis against heterotopic ossification after isolated fractures of the acetabulum

We examined whether a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) was as effective as a non-selective inhibitor (ibuprofen) for the prevention of heterotopic ossification following total hip replacement. A total of 250 patients were randomised to receive celecoxib (200 mg b/d) or ibuprofen (400 mg t.d.s) for ten days after surgery. Anteroposterior radiographs of the pelvis were examined for heterotopic ossification three months after surgery. Of the 250 patients, 240 were available for assessment. Heterotopic ossification was more common in the ibuprofen group (none 40.7% (50), Brooker class I 46.3% (57), classes II and III 13.0% (16)) than in the celecoxib group (none 59.0% (69), Brooker class I 35.9% (42), classes II and III 5.1% (6), p = 0.002). Celecoxib was more effective than ibuprofen in preventing heterotopic bone formation after total hip replacement

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 which may develop around the elbow in patients with burns may lead to severe functional impairment. We describe the outcome of early excision of such heterotopic ossification in 28 patients (35 elbows), undertaken as soon as the patient’s general and local condition allowed. The mean age at operation was 42 years. The mean area of burnt body surface was 49%. The mean pre-operative range of movement was 22° in flexion/extension and 94° in pronation/supination. The mean time between the burn and operation was 12 months with the median being 9.5. The mean follow-up period was for 21 months. At the last review, the mean range of movement was 123° in flexion/extension and 160° in pronation/supination. Clinical evidence of recurrence was seen in four patients, occurring within the first two months after operation. Nevertheless, three of these elbows gained 60° or more in flexion/extension and in pronation/supination. Based on this experience, we recommend early surgical treatment of heterotopic ossification of the elbow in patients with severe burns

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

1. A clinical study has been made of heterotopic ossification in 273 patients with paraplegia of traumatic and non-traumatic origin treated at the Liverpool Paraplegic Centre over a period of twelve and a half years. 2. The literature is reviewed and theories of etiology are discussed. 3. Etiological factors have been studied. Prominent among these is inadequacy of early treatment leading to urinary infection and to the formation of pressure sores. 4. It is concluded that there is no effective treatment for established heterotopic ossification. 5. The importance of prophylactic treatment is stressed. Special emphasis is placed on adequate primary treatment, correction of hypoproteinaemia and early mobilisation

Heterotopic ossification occurring after the use of commercially available bone morphogenetic proteins has not been widely reported. We describe four cases of heterotopic ossification in patients treated with either recombinant bone morphogenetic protein 2 or recombinant bone morphogenetic protein 7. We found that while some patients were asymptomatic, heterotopic ossification which had occurred around a joint often required operative excision with good results

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

From 1981 to 1986 we treated 413 patients for acute spinal-cord injuries. We reviewed 356 patients followed for a minimum of two years of whom 71 (20%) developed heterotopic ossification around one or more joints. Heterotopic ossification occurred more often in male patients (23%) than in female (10%), and was most frequent in the 20- to 30-year age group. It was also more common after injuries of the lower cervical or thoracic spine than after those of the lumbar spine. Patients with severe neurological deficits (Frankel grades A and B) showed significantly more heterotopic ossification but there was no correlation with the number or severity of associated head and limb injuries. Serum calcium levels did not change significantly in either group for 30 weeks after injury, but the erythrocyte sedimentation rate and the alkaline phosphatase level were significantly increased at six weeks in patients with heterotopic ossification

We present nine patients (five men and four women) who underwent surgical excision of clinically significant heterotopic ossification at the elbow. They also received perioperative radiation therapy using total doses between 600 and 1000 cGy. Five received fractionated radiotherapy, with two fractions of 500 cGy applied on the first two postoperative days, and the remaining four were irradiated with single doses of 600 and 700 cGy. After a mean period of observation of 7.7 months (6 to 13) none had radiological recurrence of heterotopic ossification and eight showed clinical improvement. Assessment of the functional outcome showed a mean improvement in the Morrey score from 33.3 to 84.5 points indicating a high therapeutic efficacy of prophylactic irradiation

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

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

From 1987 to 1991, we treated 53 patients with 54 fractures of the acetabulum by reconstruction through a posterior or an extended iliofemoral surgical approach. For prophylaxis against heterotopic ossification we used perioperative irradiation and indomethacin. Indomethacin was given as daily doses of 25 mg started within 24 hours of operation and continued for four weeks. Irradiation was by either 1200 cGy in three daily doses or by a single 700 cGy dose on the first postoperative day. All patients were followed for at least one year postoperatively and the severity of heterotopic ossification was recorded using the Brooker classification and correlated with hip mobility. The combination therapy proved very effective; 44 fractures showed no heterotopic ossification and ten showed Brooker class I. The functional results were good and there were no complications of this therapy. Irradiation with 1200 cGy did not appear to offer any therapeutic advantage over the 700 cGy dose

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

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

We have developed an animal model to examine the formation of heterotopic ossification using standardised muscular damage and implantation of a beta-tricalcium phosphate block into a hip capsulotomy wound in Wistar rats. The aim was to investigate how cells originating from drilled femoral canals and damaged muscles influence the formation of heterotopic bone. The femoral canal was either drilled or left untouched and a tricalcium phosphate block, immersed either in saline or a rhBMP-2 solution, was implanted. These implants were removed at three and 21 days after the operation and examined histologically, histomorphometrically and immunohistochemically. Bone formation was seen in all implants in rhBMP-2-immersed, whereas in those immersed in saline the process was minimal, irrespective of drilling of the femoral canals. Bone mineralisation was somewhat greater in the absence of drilling with a mean mineralised volume to mean total volume of 18.2% (. sd. 4.5) versus 12.7% (. sd. 2.9, p < 0.019), respectively. Our findings suggest that osteoinductive signalling is an early event in the formation of ectopic bone. If applicable to man the results indicate that careful tissue handling is more important than the prevention of the dissemination of bone cells in order to avoid heterotopic ossification

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

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

Purpose: The purpose is to evaluate the clinical outcome of patients who underwent excision of motion-limiting radioulnar heterotopic ossification (HO) as a complication of a distal biceps tendon repair. The hypothesis is that there are no measurable clinical losses that persist after excision. Method: Between 1996 and 2005, eight consecutive patients were identified. All were treated with heterotopic ossification excision using a standard surgical technique, a single dose of postoperative radiation, four weeks of indomethacin, and a standard rehabilitation protocol. These individuals were studied and compared to a matched cohort of eight patients who underwent a distal biceps tendon repair with a similar surgical technique that was uncomplicated. At minimum follow-up of one year, all patients in both groups completed the Disabilities of the Arm, Shoulder and Hand (DASH) outcomes questionnaire, were tested for range of motion in elbow flexion/extension and forearm supination/pronation, and underwent biceps isokinetic dynamometry strength testing including elbow flexion and forearm supination. Both peak strength as well as muscle fatigue were quantified. Range of motion and strength comparisons were made both between groups and side-to-side within each group. Results: There were no patients lost to follow-up. At mean follow-up of 56 months, there were no cases of nerve palsy, recurrence, or other complications. All patients in the HO group returned to their original occupation without restrictions. Mean arc of forearm rotation in this group increased from 19 to 151 degrees (p=0.01), but pronation (65 degrees) was less than the unaffected arm (p=0.01). There were no side-to-side differences in motion within the control group, or differences in peak strength or fatigue within either group. When comparing the two groups, there was a trend towards worse functional outcomes on DASH in the HO group than the controls (p=0.09). No differences were identified between the HO and control groups with respect to isokinetic torque, endurance strength or range of motion. Conclusion: When patients develop motion-limiting heterotopic ossification after distal biceps tendon repair, surgical resection can safely lead to a functional recovery of elbow and forearm strength and motion. Level III Evidence, Case-control

We have carried out a prospective, randomised study of prophylaxis for heterotopic ossification (HO) comparing indomethacin for 7 and 14 days, acetylsalicylic acid, and fractional (4 × 3 Gy) or single exposure of 5 or 7 Gy irradiation after operation. We initially had 723 patients (733 hip replacements), but after withdrawals there were 685 hips of which 18.4% developed HO; 14% were grade I, 2.9% grade II and 1.5% grade III of the Brooker classification. We compared the results between these groups with those of a matched control series and found that indomethacin, 2 × 50 mg for 7 and 14 days, and postoperative irradiation of 4 × 3 Gy or 1 × 7 Gy, significantly reduced the development of HO compared with the control group. Patients in the acetylsalicylic acid group and those with a single irradiation of 5 Gy after operation developed significantly more ossification than those in the indomethacin and other irradiation groups. We suggest the use of 2 × 50 mg of indomethacin with mucoprotection for seven days as prophylaxis against HO after total hip replacement for all patients. A single irradiation of 7 Gy is recommended for patients who have developed HO after previous operations or to whom administration of indomethacin is contraindicated

Previous reports of the prevalence of Heterotopic Ossification (HO) in limbs from UK blast-related amputees from Afghanistan, is demonstrated to be 57.1%. With the end of UK military operations in Afghanistan in 2014 the aim of this study is establish the rate of HO, assess causality demographics and ascertain risk factors for the formation of HO during the entire period of operations in Afghanistan. Military databases, case notes and radiographs were scrutinised to quantify and qualify the prevalence and risk factors for the formation of HO. 256 servicemen sustained 398 military trauma related amputations. The overall prevalence of HO was 65.9%. Significant (p<0.05) risks identified for the formation of HO included a blast mechanism of injury, a zone of injury the same as the subsequent amputation, and an increased number of debridements prior to closure. Positive correlation existed between the number of amputations and the presence and grade of HO (p=0.04). HO presents clinical problems to military blast injury patient populations. This study demonstrates that both a blast mechanism of injury and an increased injury load are key factors in the increased prevalence of HO seen in military trauma

Heterotopic ossification (HO) is the formation of bone in extraskeletal sites. It is a major problem for combat-related casualties with 64% of such patients showing radiological evidence of the disease. Of these, 19% require surgical excision. Current prophylaxis is problematic due to poor efficacy and unsuitability in a military setting. Our novel anti-HO strategy is to use an inorganic reagent to inhibit the deposition of HA and disperse any pre-formed mineral. Literature review identified several potentially effective agents. These were tested for their ability to disperse solid monoliths of HA. In addition, a standard HA synthetic reaction was performed in the presence of each agent to establish their inhibiting activity. One reagent (a condensed phosphate) dispersed a solid monolith of HA by 38% (mass loss) over 30 days. This reagent was also shown to inhibit HA crystal synthesis yield by 28%. Early work on a hydrogel delivery system has produced favourable results. These preliminary data demonstrate proof of concept that HA may be dispersed and its formation inhibited by a non-toxic polyphosphate. This work will form the justification for development into in vitro osteogenic cell culture models and animal HO models

Heterotopic ossification (HO) of the hip after injury to the central nervous system can lead to joint ankylosis. Surgery is usually delayed to avoid recurrence, even if the functional status is affected. We report a consecutive series of patients with HO of the hip after injury to the central nervous system who required surgery in a single, specialised tertiary referral unit. As was usual practice, they all underwent CT to determine the location of the HO and to evaluate the density of the femoral head and articular surface. The outcome of surgery was correlated with the pre-, peri- and post-operative findings. In all, 183 hips (143 patients) were included of which 70 were ankylosed. A total of 25 peri-operative fractures of the femoral neck occurred, all of which arose in patients with ankylosed hips and were associated with intra-articular lesions in 18 and severe osteopenia of the femoral head in seven. All the intra-articular lesions were predicted by CT and strongly associated with post-operative complications. The loss of the range of movement before ankylosis is a more important factor than the maturity of the HO in deciding the timing of surgery. Early surgical intervention minimises the development of intra-articular pathology, osteoporosis and the resultant complications without increasing the risk of recurrence of HO

Anterior decompression and fusion has been standard treatment for cervical disc herniation and myelopathy with disc degeneration. Since cervical total disc replacement (TDR) has been introduced with early favorable results and ideal mechanism, it has gained its popularity recently. But varying degrees of heterotopic ossification (HO) around the operated segment have been noted in the literatures. The theoretical advantages of TDR are the maintenance of intervertebral motion and prevention of adjacent segment degeneration. It is questionable that if HO occurs after TDR, mobility of operated segments would be restricted then clinical outcome worse. Purpose of this study is to determine prevalence of HO and to investigate that the presence of HO would limit motion and subsequently negatively affect clinical outcome following cervical TDR. We analyzed 29 patients (30 levels) who were treated with cervical TDR by 2 spine specialists using 4 types of prostheses (Mobi-C: 13 levels, ProDisc: 10, Bryan: 5, Prestige LP: 2) consecutively from July 2004 to June 2007. Postoperative mean follow-up period was 21.4 (12–36) months. We assessed presence of HO and segmental ROM radiographically and clinical outcome by VAS, ODI after 1.5, 3, 6 months, and every year postoperatively in principle. All subjects were divided by 3, which were group A (no HO, McAfee class 0), group B (class I and II), and group C (class III and IV), then compared with each other. HO was detected on 14 levels (46.7%) in the 30 levels after at mean of 8.2 (4–18) months after operation. There were 15 levels(53.3%) of group A (no HO, class 0), 7 levels of group B (class I HO:3, II: 4), and 7 levels of group C (class III: 3, IV: 4). Segmental flexion-extension ROM of group A was 10.1 (5.6–16.2)°, group B is 8.3 (3.5–14.4)°, and group C is 3.1 (0.0–6.6)° (p< 0.001, multiple comparison test with post hoc Bonferroni correction). And no difference in the clinical outcomes, VAS and ODI, was found compared with each other among group A, B, and C (p> 0.05). Nonetheless, longer term follow-up should be performed to investigate whether clinical outcomes would be changed and occur adjacent level degeneration as time goes on. In addition, further study for prevention of HO may be needed as in HO of other joint replacement surgery not to lose superior mechanism to fusion treatment

There is little in the literature reporting on the incidence of heterotopic ossification (HO) after hip resurfacing arthroplasty. HO has long been recognized as a complication of THA, with a reported incidence that ranges between 5 – 90 %. We investigated the incidence of HO in a group of hip resurfacing patients, and compared this against the incidence of HO in a comparable group of patients managed with a conventional THA. We retrospectively reviewed patients who had a hip resurfacing procedure from January 2004 to December 2007 carried out by a single surgeon. To act as our comparative group, we selected a closely matched group of patients in terms of age and sex who underwent a THA over the same time period, under the same surgeon. 47 cases of resurfacing, 23 were female and 24 male. The 47 cases of the selected THA group consisted of 24 females and 23 males. Therefore the two groups were of a similar sex make up. Within the resurfacing group of patients, the ages ranged from 31 to 68 years, with the mean being 55.4 years, and the median being 56.5 years. The THA group possessed an age range of from 31 to 68 years, with the mean being 55.4 years, and the median being 56.5 years. The resurfacing group of patients had 5 cases showing HO, giving an overall rate of 10.6 percent. 3 were of the grade I variety, while 2 were grade II. The THA group had 6 cases showing HO, giving an overall rate of 12.8 percent. 5 of these were of the grade I variety, while 1 was of the grade III variety. We used a two tailed Fischer’s Exact test set at the 5th percentile significance level to compare the overall rate of HO occurrence between the 2 groups, namely 10.6 percent versus 12.8 percent. This gave a p value of 0.238. Therefore we can state that there is no significant difference in the rate of HO formation between the resurfacing and THA patients

Indomethacin is commonly administered for the prophylaxis of heterotopic ossification (HO) after the surgical treatment of acetabular fractures. Non-steroidal anti-inflammatory drugs such as indomethacin, have been associated with delayed healing of fractures and mechanically weaker callus. Our aim was to determine if patients with an acetabular fracture, who received indomethacin for prophylaxis against HO, were at risk of delayed healing or nonunion of any associated fractures of long bones. We reviewed 282 patients who had had open reduction and internal fixation of an acetabular fracture. Patients at risk of HO were randomised to receive either radiation therapy (XRT) or indomethacin. Of these patients, 112 had sustained at least one concomitant fracture of a long bone; 36 needed no prophylaxis, 38 received focal radiation and 38 received indomethacin. Fifteen patients developed 16 nonunions. When comparing patients who received indomethacin with those who did not, a significant difference was noted in the rate of nonunion (26% v 7%; p = 0.004). Patients with concurrent fractures of the acetabulum and long bones who receive indomethacin have a significantly greater risk of nonunion of the fractures of the long bones when compared with those who receive XRT or no prophylaxis

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

Resurfacing arthroplasty of the hip is currently enjoying a resurgence in popularity. There are many reasons why resurfacing may be indicated, but one is that the absence of proximal femoral reaming at surgery may reduce the occurrence of heterotopic ossification (HO) after surgery. The objective of this study was to compare the prevalence of postoperative HO for patients undergoing two different types of hip surgery, resurfacing arthroplasty or total hip replacement. Data were gathered from 43 consecutive patients undergoing metal on metal hip resurfacing (MoM-R) and 37 consecutive patients undergoing metal on metal total hip replacement (MoM-THR) with a minimum of six months’ follow up. The Brooker classification was used to grade HO from postoperative radiographs1. We found that, when undergoing MoM-R, women had a lower chance of developing HO than men (p=0.04). In addition, women who received a MoM-R had a reduced incidence of developing HO than women who received a MoM-THR (p=0.04). There were no differences in the incidence of postoperative HO between men undergoing either MoM-R or MoM-THR. It can be concluded from this study that resurfacing does reduce the incidence of HO in women and that care must be taken when selecting women to undergo total hip replacement in preference to hip resurfacing. This study has highlighted the need to inform patients of HO as a common complication when consenting for hip arthroplasty, and has established an 18% rate of postoperative HO for hip resurfacing arthroplasty