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

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

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

Heterotopic ossification (HO) is a relatively common complication of total hip arthroplasty (THA), but is rather rare after total knee arthroplasty (TKA). In both cases, it is usually asymptomatic and is most commonly identified as an incidental finding on post-operative radiographs. However, in severe cases it can result in decreased range of motion and pain. There are several risk factors that have been shown to be associated with development of HO. These include male gender, ceramic-on-ceramic bearings, prior stroke, and hypertrophic osteoarthritis. Heterotopic ossification can be treated with physical therapy during the maturation phase (12 to 24 weeks), but surgical intervention is required if the stiffness persists. All heterotopic bone should be excised with careful attention to neurovascular structures. Patients should begin prophylaxis following HO excision and prior to any subsequent surgeries. Heterotopic ossification prophylaxis consists of NSAIDs, radiotherapy, or a combination of both modalities. These therapies are not without complications, therefore, routine administration of prophylaxis for all patients is not indicated. Several new pathways of inhibiting extra-skeletal bone formation in HO are under investigation (retinoid acid receptor agonists, apyrase, and LDN-193189). Future studies should focus on identification of patients at risk for HO as well as better therapeutic options with less side effects

The incidence of clinically significant (Brooker stage 3–4) heterotopic ossification (HO) after THA is 3–7%. Risk factors include male gender, old age, a history of HO, Paget's disease, post-traumatic arthritis, osteonecrosis and rheumatoid arthritis. Prophylaxis for high-risk patients consists of 1) radiotherapy given as one dose of 7–8 Gy either pre-operatively (<4 hours) or post-operatively (within 72 hours) or 2) NSAIDS. Treatment of clinically significant HO includes intensive physiotherapy during the maturation phase of the disease and surgical excision in conjunction with a combination of radiotherapy and indomethacin once the HO has matured. Less invasive surgical approaches may be associated with a reduced incidence of HO

The incidence of clinically significant (Brooker stage 3–4) heterotopic ossification (HO) after THA is 3–7%. Risk factors include male gender, old age, a history of HO, Paget's disease, post-traumatic arthritis, osteonecrosis and rheumatoid arthritis. Prophylaxis for high-risk patients consists of 1) radiotherapy given as one dose of 7–8 Gy either pre-operatively (< 4 hours) or post-operatively (within 72 hours) or 2) NSAIDS. Treatment of clinically significant HO includes intensive physiotherapy during the maturation phase of the disease and surgical excision in conjunction with a combination of radiotherapy and indomethacin once the HO has matured. Less invasive surgical approaches may be associated with a reduced incidence of HO

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) is the formation of lamellar bone in extra-skeletal soft tissues. Its exact pathogenic mechanism remains elusive. Previous studies demonstrate observation only of HO at the microscopic scale. This study uses scanning electron microscopy (SEM), Back-scatter electron (BSE) imaging and mechanical testing to detail the organic and non-organic elements of HO, compared to normal bone, to guide stem cell and bio-modelling research into HO. Samples analysed were 5 military blast related HO patients, 5 control cadaveric samples (age and sex matched). Samples were imaged using SEM, BSE and the I13 beam Synchrotron x-ray diffraction scanner using validated quantitative and qualitative techniques of measurement. Appearances seen in HO compared to normal bone were characterised by the presence of a hyper-vascular network and high lacunae (osteocyte) counts, two distinct zones of bone mineral density distribution, with a tendency for hypermineralisation with kurtosis of the grey scale plots (mineral content as a weight percentage of Ca. 2+. was calibrated to atomic weight of C, Al and HA). Direction of dependence and collagen orientation in HO suggest isotropic properties. This research demonstrates that HO is bone, however its characteristics suggest a high metabolic turnover and disorganised ultra-structure consistent with an inflammatory origin

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. 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

Introduction. Stiffness after total knee arthroplasty (TKA) has been reported to occur due to component malpositioning and/or oversizing, improper femoral component (FC) flexion and tibial component (TC) slope, tight extension gap, inaccurate joint line placement, deficient posterior osteophyte resection, heterotopic ossification (HO), poor patellofemoral joint reconstruction, poor posterior condylar offset restoration, and/or posterior cruciate ligament (PCL) under-resection or retraction. However, the importance of these potential factors for stiffness are not well documented in the medical literature. The aim of this study was therefore to evaluate specific radiographic parameters in patients who had stiffness after primary TKA. Material and Methods. An IRB-approved retrospective chart review was performed to identify patients that were revised due to stiffness after TKA. We defined stiffness as 15º or more of flexion contraction, less than 75º of flexion or a range of motion (ROM) of 90º with the chief complaint of limited ROM and pain. Patients with history of previous revisions and/or ORIF, infection, or isolated polyethylene exchange were excluded. Patients with a minimum of 1 year radiographic follow-up were included. Radiographic measurements were performed as described by the Knee Society TKA Roentgenographic Evaluation System (KSRES). Two blinded observers performed all measurements. Descriptive data is reported as mean (range). Inter-observer correlations were reported using Intraclass correlations coefficient (ICC). Results. A total of 44 patients met the inclusion criteria. Of those, 13 (30%) were male and 31 (70%) were female. Mean BMI was 33.9 kg/m2 (19.5–58). ICCs ranged from good to excellent (>0.8) for all measurements performed. Coronal FC and TC alignments were 95.29º (82.4º–100.6º) and 89.16º (84.4º–94.2º) respectively. HO ranged from 0 to 3 (0:43%, 1:36%, 2:11%, 3:10%). FC-Flexion and TC-slope were 10.17 (3.5–19.8) and 86.7 (61.2–99.2) respectively. Insall-Salvati ratio was 1.01 (0.58–2.04). Posterior condylar offset (CO) ratio was 0.51 (0.34–1.11). Anterior CO ratio was 0.2 (0–0.34). Anterior femoral cortex notching ranged from 0 to 3 (0:39%, 1:43%, 2:14%, 3:4%). Femoral posterior osteophytes were observed in 32% of patients. A gap between the anterior flange and the femoral cortex was observed in 45% of patients. The patella was resurfaced in 93% of patients with a mean patellar tilt and patellar displacement of 5.34º (−8.9º to 5.34º) and 9.88% (−5 to 41%) respectively. Conclusion. To our knowledge this is the first study reporting specific radiographic data on postoperative stiffness following primary TKA. From the observed radiographic measurements, the increased mean femoral component flexion, the high amount of postoperative HO and posterior osteophytes, and the anterior cortical and component gap suggest possible risk factors influencing the occurrence of postoperative stiffness. Future focus will include a matched control population of patients in order to establish statistical significance of all observed values

Heterotopic ossification (HO) is the formation of bone at extra-skeletal sites. Genetic diseases, traumatic injuries, or severe burns can induce this pathological condition and can lead to severe immobility. While the mechanisms by which the bony lesions arise are not completely understood, intense inflammation associated with musculoskeletal injury and/or highly invasive orthopaedic surgery is thought to induce HO. The incidence of HO has been reported between 3% and 90% following total hip arthroplasty. While the vast majority of these cases are asymptomatic, some patients will present decreased range of motion and painful swelling around the affected joints leading to severe immobility. In severe cases, ectopic bone formation may be involved in implant failure, leading to costly and painful revision surgery. The effects of surgical-related intraoperative risk factors for the formation of HO can also play a role. Prophylactic radiation therapy, and anti-inflammatory and biphosphonates agents have shown some promise in preventing HO, but their effects are mild to moderate at best and can be complicated with adverse effects. Irradiation around surgery could decrease the incidence of HO. However, high costs and the risk of soft tissue sarcoma inhibit the use of irradiation. Increased trials have demonstrated that nonsteroidal anti-inflammatory drugs (NSAID) are effective for the prevention of HO. However, the risk of gastrointestinal side effects caused by NSAID has drawn the attention of surgeons. The effect of the selective COX-2 inhibitor, celecoxib, is associated with a significant reduction in the incidence of HO in patients undergoing THA. Bone morphogenetic proteins (BMP) such as BMP2 identified another novel druggable target, i.e., the remote application of apyrase (ATP hydrolyzing agent) in the burn site decreased HO formation and mitigated functional impairment later. The question is if apyrase can be safely administered through other, such as systematical, routes. While the systemic treatments have shown general efficacy and are used clinically, there may be great benefit obtained from more localised treatment or from more targeted inhibitors of osteogenesis or chondrogenesis. In the surgical setting, prophylaxis for HO is regularly indicated due to the considerable risk of functional impairment. Heterotopic ossification is a well-known complication of total hip arthroplasty, especially when the direct lateral approach is used. Possible intraoperative risks are the size of incision, approach, duration of surgery and gender that can be associated with higher rates of HO or increase of the severity of HO. Like inflammation and tissue damage/ischemia are likely to be the key in the formation of HO, kindness to the soft tissues, tissue preserving surgery, pulse lavage to remove bone inducing factors and avoiding damage to all tissues should be erased as a comorbidity. Incision length, tissue dissection and subsequent localised trauma and ischemia, blood loss, anesthetic type and length of surgery may all contribute to the local inflammatory response. Data suggest that the surgeon may control the extent and nature of HO formation by limiting the incision length and if possible the length of the operation. Currently resection of HO is generally suggested after complete maturation (between 14–18 months), since earlier intervention is thought to predispose to recurrence. Reliable indicators of maturation of HO are diminishing activity on serial bone scans and/or decreasing levels of alkaline phosphatase. Although usually asymptomatic, heterotopic bone formation can cause major disability consisting of pain and a decreased range of motion in up to 7% of patients undergoing THA. Patients benefit from early resection of the heterotopic ossification with a proper and reliable postoperative strategy to prevent recurrence of HO with clinical implications

The causes of a stiff elbow are numerous including: post-traumatic elbow, burns, head injury, osteoarthritis, inflammatory joint disease and congenital. Types of stiffness include: loss of elbow flexion, loss of elbow extension and loss of forearm rotation. All three have different prognoses in terms of the timing of surgery and the likelihood of restoration of function. Contractures can be classified into extrinsic and intrinsic (all intrinsic develop some extrinsic component). Functional impairment can be assessed medicolegally; however, in clinical practice the patient puts an individual value on the arc of motion. Objectively most functions can be undertaken with an arc of 30 to 130 degrees. The commonest cause of a Post-traumatic Stiff elbow is a radial head fracture or a complex fracture dislocation. Risk factors for stiffness include length of immobilisation, associated fracture with dislocation, intra-articular derangement, delayed surgical treatment, associated head injury, heterotopic ossification. Early restoration of bony columns and joint stability to allow early mobilisation reduces incidence of joint stiffness. Heterotopic ossification (HO) is common in fracture dislocation of the elbow. Neural Axis trauma alone causes HO in elbows in 5%. However, combined neural trauma and elbow trauma the incidence is 89%. Stiffness due to thermal injury is usually related to the degree rather than the site. The majority of patients have greater than 20% total body area involved. Extrinsic contractures are usually managed with a sequential release of soft tissues commencing with a capsular excision (retaining LCL/MCL), posterior bundle of the MCL +/− ulna nerve decompression (if there is loss of flexion to 100 degrees). This reliably achieved via a posterior incision, a lateral column exposure +/− ulna nerve mobilisation. A medial column exposure is a viable alternative. Arthroscopic capsular release although associated with a quicker easier rehabilitation is associated with increased neural injury. Timing of release is specific to the type of contracture, i.e. flexion contractures after approx. six months, extension contractures ASAP but after four months, loss of forearm rotation less 6 to 24 months. The use of Hinged Elbow Fixators is increasing. The indications include reconstructions that require protection whilst allowing early movement, persistent instability or recurrent/late instability or interposition arthroplasty. Post-operative rehabilitation requires good analgesia, joint stability and early movement. The role of CPM is often helpful but still being evaluated

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