Post-traumatic Heterotopic Ossification Research Articles

Posttraumatic proximal radioulnar synostosis: Current concepts on the clinical presentations, classifications, and open surgical approaches

In the forearm, posttraumatic heterotopic ossification usually forms as a proximal radioulnar synostosis. It can occur after soft tissue injury involving the interosseous membrane or after surgery involving the radio and ulna, such as distal biceps tendon repair. It can also be induced by radial head dislocation or fracture. Screening radiography can be used to select the appropriate time for excision. The synostosis can be resected when the ectopic bone margin and trabeculation appear mature on radiographs. An interval of 6–12 months from the injury is generally recommended based on ectopic bone maturity. Selection of the surgical approach depends on site, extension (elbow joint or proximal radioulnar joint), severity of the initial articular surface, and periarticular tissue injury. The posterolateral approach is indicated for synostoses: at or distal to the bicipital tuberosity, at the level of the radial head, and proximal radioulnar joint. The posterior global approach is recommended when the forearm synostosis is associated with complete bony ankylosis of the elbow involving the distal aspect of the humerus. After surgical resection of a proximal radioulnar synostosis, the exposed bone surfaces can be covered with interposition material to minimize recurrence.

LncRNA MEG3 Promotes Osteogenic Differentiation of Tendon Stem Cells Via the miR-129-5p/TCF4/β-Catenin Axis and thus Contributes to Trauma-Induced Heterotopic Ossification.

Heterotopic ossification (HO) is one of the most intractable conditions following injury to the musculoskeletal system. In recent years, much attention has been paid to the role of lncRNA in musculoskeletal disorders, but its role in HO was still unclear. Therefore, this study attempted to determine the role of lncRNA MEG3 in the formation of post-traumatic HO and further explore the underlying mechanisms. On the basis of high-throughput sequencing and qPCR validation, elevated expression of the lncRNA MEG3 was shown during traumatic HO formation. Accordingly, in vitro experiments demonstrated that lncRNA MEG3 promoted aberrant osteogenic differentiation of tendon-derived stem cells (TDSCs). Mechanical exploration through RNA pulldown, luciferase reporter gene assay and RNA immunoprecipitation assay identified the direct binding relationship between miR-129-5p and MEG3, or miR-129-5p and TCF4. Further rescue experiments confirmed the miR-129-5p/TCF4/β-catenin axis to be downstream molecular cascade responsible for the osteogenic-motivating effects of MEG3 on the TDSCs. Finally, experiments in a mouse burn/tenotomy model corroborated the promoting effects of MEG3 on the formation of HO through the miR-129-5p/TCF4/β-catenin axis. Our study demonstrated that the lncRNA MEG3 promoted osteogenic differentiation of TDSCs and thus the formation of heterotopic ossification, which could be a potential therapeutic target.

The Kinesin Gene KIF26B Modulates the Severity of Post-Traumatic Heterotopic Ossification.

The formation of pathological bone deposits within soft tissues, termed heterotopic ossification (HO), is common after trauma. However, the severity of HO formation varies substantially between individuals, from relatively isolated small bone islands through to extensive soft tissue replacement by bone giving rise to debilitating symptoms. The aim of this study was to identify novel candidate therapeutic molecular targets for severe HO. We conducted a genome-wide scan in men and women with HO of varying severity following hip replacement for osteoarthritis. HO severity was dichotomized as mild or severe, and association analysis was performed with adjustment for age and sex. We next confirmed expression of the gene encoded by the lead signal in human bone and in primary human mesenchymal stem cells. We then examined the effect of gene knockout in a murine model of osseous trans-differentiation, and finally we explored transcription factor phosphorylation in key pathways perturbed by the gene. Ten independent signals were suggestively associated with HO severity, with KIF26B as the lead. We subsequently confirmed KIF26B expression in human bone and upregulation upon BMP2-induced osteogenic differentiation in primary human mesenchymal stem cells, and also in a rat tendo-Achilles model of post-traumatic HO. CRISPR-Cas9 mediated knockout of Kif26b inhibited BMP2-induced Runx2, Sp7/Osterix, Col1A1, Alp, and Bglap/Osteocalcin expression and mineralized nodule formation in a murine myocyte model of osteogenic trans-differentiation. Finally, KIF26B deficiency inhibited ERK MAP kinase activation during osteogenesis, whilst augmenting p38 and SMAD 1/5/8 phosphorylation. Taken together, these data suggest a role for KIF26B in modulating the severity of post-traumatic HO and provide a potential novel avenue for therapeutic translation.

A new prognostic nomogram for heterotopic ossification formation after elbow trauma : the Shanghai post-Traumatic Elbow Heterotopic Ossification Prediction (STEHOP) model.

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. 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. 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. 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 J2022;104-B(8):963-971.

Functional Characterization of Posttraumatic Heterotopic Ossification of Tibiofibular Syndesmosis with Dynamic Bone Scan and Single-Photon Emission Computed Tomography/Computed Tomography.

A 53-year-old man was investigated for ongoing right ankle pain and lateral malleolus swelling following a traumatic inversion injury 12 weeks prior. The initial ankle radiograph was normal with no evidence of fracturing. The follow-up radiograph showed bridging ossification in the distal tibiofibular syndesmosis. As the pain did not subside, posttraumatic heterotopic ossification (HO) was suspected, and triple-phase dynamic bone imaging with technetium 99m-methylene diphosphonate was performed to guide further management. The bone scan revealed intense focal tracer activity centered on the HO of the tibiofibular syndesmosis, with no evidence of occult fracturing confirming HO as a pain generator.

Role of Kinesiotherapy in the Prevention of Heterotopic Ossification: A Systematic Review.

The role of kinesiotherapy in heterotopic ossification remains unclear. The goal of this study was to revisit the literature on the preventive role of kinesiotherapy against heterotopic ossification formation and maturation. A systematic review was performed in MEDLINE, OVID, Scopus, and Cochrane databases. A high-quality clinical trial is missing from the literature. Of 9617 studies primarily identified, nine studies offered the proper data and were included. They infer that satisfactory results on neurogenic heterotopic ossification prevention were achieved with passive exercises, including continuous passive motion, that were initiated early and at a painless range of motion. On the contrary, for elbow posttraumatic heterotopic ossification and major joints burn-associated heterotopic ossification, active range of motion is indicated as early as possible. Because of the very low quality of the studies included in this review, firm conclusions cannot be drawn about the effectiveness of kinesiotherapy. Nevertheless, it is recommended that controlled passive range of motion exercises (especially continuous passive motion) be applied early and pain-free especially in the neurogenic heterotopic ossification patients while active range of motion in painless limits is beneficial in the heterotopic ossification prevention of traumatic elbows or burn joints.

Three-Dimensional Modeling of the Structural Microenvironment in Post-Traumatic War Wounds

BACKGROUND:The development of post-traumatic heterotopic ossification (HO) is a common, undesirable sequela in patients with high-energy (war-related) extremity injuries. While inflammatory and osteoinductive signaling pathways are known to be involved in the development and progression of post-traumatic HO, features of the structural microenvironment within which the ectopic bone begins to form remain poorly understood. Thus, increasing our knowledge of molecular and structural changes within the healing wound may help elucidate the pathogenesis of post-traumatic HO and aid in the development of specific treatment and/or prevention strategies.METHODS:In this study, we performed high-resolution microscopy and biochemical analysis of tissues obtained from traumatic war wounds to characterize changes in the structural microenvironment. In addition, using an electrospinning approach, we modeled this microenvironment to reconstitute a three-dimensional type I collagen scaffold with non-woven, randomly oriented nanofibers where we evaluated the performance of primary mesenchymal progenitor cells.RESULTS:We found that traumatic war wounds are characterized by a disorganized, densely fibrotic collagen I matrix that influences progenitor cells adhesion, proliferation and osteogenic differentiation potential.CONCLUSION:Altogether, these results suggest that the structural microenvironment present in traumatic war wounds has the potential to contribute to the development of post-traumatic HO. Our findings may support novel treatment strategies directed towards modifying the structural microenvironment after traumatic injury.

Post-Traumatic Heterotopic Ossification With Incidental Hyperparathyroidism

Background: Heterotopic ossification (HO) is a rare disease characterised by abnormal bone growth in non-osseous tissues, causing pain, immobility and impaired quality of life. Although still being elucidated, the underlying pathophysiology may relate to local macrophage-driven inflammation in response to trauma1. Case: A 35-year-old man involved in a motor vehicle accident (MVA) fractured over twenty bones (multiple vertebrae, ribs and complex open book pelvic fracture with shattered left acetabulum) with extensive soft tissue injuries requiring multiple surgeries. Past medical history included a renal calculus three years earlier. His serum corrected calcium on admission was elevated at 2.87mmol/L (2.10-2.60mmol/L). Peri-operative fluid over-resuscitation necessitated boluses of intravenous furosemide, and serum calcium transiently normalised before rapidly incrementing and peaking at 3.04 mmol/L. Serum parathyroid hormone post-operatively was inappropriately high at 9.4pmol/L (1.0–7.0pmol/L) and 25-hydroxyvitamin D low at 24nmol/L (50-150nmol/L). Oral vitamin D replacement was commenced and he received intravenous pamidronate (3x60mg infusions) which briefly restored normocalcaemia. Neck ultrasound and sestamibi scintigraphy demonstrated a left parathyroid adenoma, and he underwent parathyroidectomy. Histology revealed a single parathyroid adenoma. He has been normocalcaemic since surgery. Despite excellent overall recovery, mobility at the left hip remained restricted in all planes of movement. He could not perform simple activities such as putting on his shoe. Plain radiographs showed HO lateral to the left acetabulum, femoral head and neck, with bony bridging to the left ilium on computed tomography. Bone turnover markers (BTMs) measured eleven months post-MVA (and pamidronate) were elevated, with CTX of 750ng/L (100-600ng/L) and P1NP of 207ug/L (15-80ug/L). BTMs gradually reduced over time, plateauing two years post-MVA (CTX 480ng/L and P1NP 103ug/L). Surgery with pre-operative radiotherapy to remove the left hip HO is now planned. Discussion: This man had multiple recognised risk factors for HO, including male sex, trauma followed by immobilisation and pelvic fracture. His hyperparathyroidism may have predisposed HO development through excess calcium-phosphate product promoting soft tissue calcification. Bisphosphonates may also increase the risk2. Elevated BTMs have been demonstrated in the early phase of HO; further research may elucidate whether BTMs can guide timing of surgical intervention relative to the pathophysiological processes driving HO.

Expression and significance of related genes in the early stage of post-traumatic heterotopic ossification in a rat model of Achilles tenotomy.

This study aims to determine expression profiles of relevant genes in the early stages of post-traumatic heterotopic ossification (HO) in a rat model of Achilles tenotomy. A total of 80 male Sprague-Dawley rats were randomly assigned to two groups: the HO group and the control group. Tenotomy was performed in the Achilles tendon of the rats in the HO group, and no intervention was conducted in the control group. On the 3rd, 5th, 8th, and 14th days after the operation, 8 rats were taken from each group at each time point, and the Achilles tendon and surrounding tissue specimens were collected. Gene expressions of TGF-β, BMP, GDF, IL, and MMP families as well as TNF-α, HIF-1α chordin, gremlin, noggin, and NODAL were analyzed by qRT-PCR. The relevant genes that were highly expressed at different time points were screened, and immunohistochemical staining was then used to verify their expression. At the 10th week, HO formation was explored by radiographic and histological examination in the remaining 8 rats of each group. Both the radiographic and histological analyses indicated that all the rats developed HO in the HO group (100%), whereas no HO occurred in the control group. Surrounding tissues obtained from the HO group showed significantly higher gene expressions of TGF-β1, BMP-1, IL1β, HIF-1α, and MMP-2 but lower expressions of BMP-4, GDF-8, and TNF-α compared with the control group. In addition, immunohistochemical staining confirmed the higher protein expression levels of relevant genes in the HO group. TGF-β1, BMP-1, IL-1β, HIF-1α, MMP-2, BMP4, GDF-8, and TNF-α may be associated with the formation of traumatic HO; and BMP4, GDF-8, and TNF-α may play a protective role in the early stage of HO. In this study, we investigated the expression levels of the related cytokines in the early stages of traumatic HO in the Achilles tendon tenotomy rat model to better understand the pathogenesis of HO.

A Surgical Protocol for Management of Post Traumatic Heterotopic Ossification of Elbow.

Open excision remains the gold standard of treatment for posttraumatic heterotopic ossification (HO) of the elbow. The purpose of this study is to evaluate the functional outcome of early surgical excision done by adhering to a proposed surgical protocol with exclusive posttraumatic HO of the elbow. A retrospective study was conducted with 31 patients (25 males and 6 females) with a mean follow-up of 40.5 ± 27.44months. Excision was done according to our surgical protocol based on the location of HO, associated fractures, stability, need for ulnar nerve transposition, previous operative scar. Improvement in elbow function, Mayo elbow performance score (MEPS) preoperatively and at final follow-up was compared, and statistical analysis was done. Mean flexion-extension arc, supination-pronation arc and MEPS improved by 74.68° ± 29.32°, 26.13° ± 32.93°, 30.48 ± 11.57, respectively. Flexion arc deteriorated by 10.81° ± 10.42° from intraoperative to final follow-up. Improvement at final follow-up was significant in all the cases (P < 0.05). 19 patients had limited HO, and 12 had global HO. Their mean flexion-extension arc increase was 77.63° ± 29.12° and 70° ± 30.3° respectively, and the final mean MEPS score was 96.05 ± 5.16 and 88.75 ± 11.51, respectively. Nine patients had no initial fracture (Group 1), 13 had some fracture (Group 2), nine had a fracture-dislocation of the elbow (Group 3). Their flexion-extension improvement, final MEPS were 88.33° ± 30.82°, 98.33 ± 5, (Group 1); 81.15° ± 16.73°, 92.31 ± 9.27 (Group 2) and 51.67° ± 31.32°, 89.44 ± 9.5 (Group 3), respectively. We had two complications (6.45%). The surgical protocol described here enabled us to achieve good functional results and was in concordance with similar studies done previously. The online version contains supplementary material available at 10.1007/s43465-021-00381-x.

Diagnostic and therapeutic approach to meniscal ossification: a systematic review.

The purpose of this study was to systematically review case reports and case series about meniscal ossicle, to summarize existing evidence. Specifically, to identify the etiology, demographic characteristics, localization, clinical features, diagnostic procedures and treatment options of this rare entity. Although, case reports/ series are of low level of evidence, a systematic review of such studies can provide and help us to gain a better understanding and awareness of meniscal ossicle. Two authors searched three online databases (MEDLINE, SCOPUS and GOOGLE SCHOLAR) from inception until March 2020 for the literature on meniscal ossicle. Inclusion criteria included case series, case reports and case-based reviews, available in full-text version, in English and that concern humans. Reports published in languages other than English were excluded, as well as articles with no electronic full text availability. Case reports using the term "meniscal ossicle" to describe an acute avulsion fracture of the tibial root of the meniscus, were also excluded. Of 453 initial studies, 38 studies satisfied inclusion criteria. In total 169 patients were included of whom 107 (63%) were males and 62 (37%) were females. Mean age was 44years (range 12-87). According to Magnetic resonance imaging findings, in 144 knees (86%) the ossicle was localized at the posterior root or horn of the medial meniscus. 60% of the patients had a history of trauma. The predominant symptom in 87% of patients was knee pain. In all patients was detected an intra-articular density structure in computed radiography. 76% had associated meniscal tear, 61% had intraarticular cartilage loss, 34% meniscal extrusion and 28% anterior cruciate ligament injury. Treatment modalities included conservative regimen in 40 patients, while 59 patients underwent surgical excision. The most possible etiology of meniscal ossicle is posttraumatic heterotopic ossification and small occult bony avulsion fracture. It is commonly observed in individuals complaining about knee pain with history of antecedent trauma. The presence of a meniscal ossicle should alert the physician to the high likelihood of the patient having an associated meniscal tear, articular cartilage loss, ACL injury or meniscal extrusion. Along with the meniscal ossicle, the associated meniscal tear should be treated as well.

Dead muscle tissue promotes dystrophic calcification by lowering circulating TGF-β1 level

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

A microRNA Signature for Impaired Wound-Healing and Ectopic Bone Formation in Humans.

Heterotopic ossification (HO) is characterized by the abnormal growth of ectopic bone in soft tissues, frequently occurring within the military population because of extensive orthopaedic combat trauma. MicroRNAs (miRNAs) are small noncoding RNAs that act as post-transcriptional regulators of gene expression. We hypothesized that a clinically relevant miRNA signature could be detected in patients following injury that progressed to form HO (HO+) or did not form HO (HO-). Tissue samples were obtained from injured servicemembers during their initial surgical debridements, and miRNA profiling was performed using a real-time miRNA polymerase chain reaction (PCR) array. Primary mesenchymal progenitor cells (MPCs) were harvested from debrided traumatized human muscle tissue, and cells were isolated and cultured in vitro. Mimic miRNAs were transfected into MPCs, followed by downstream in vitro analyses. The investigation of the miRNA expression profile in the tissue of HO+ compared with HO- patients demonstrated a molecular signature that included the upregulation of miR-1, miR-133a, miR-133b, miR-206, miR-26a, and miR-125b. Transfection of each of these mature miRNAs into MPCs followed by osteogenic induction demonstrated that miR-1, miR-133a, miR-133b, and miR-206 enhanced osteogenic differentiation compared with control treatments. In silico and in vitro analyses identified the transcription factor SOX9 as a candidate downstream target of miR-1 and miR-206 miRNAs. Our data demonstrated a molecular signature of miRNAs in the soft tissue of wounded servicemembers that was associated with the development of HO, providing novel insights into the underlying molecular mechanisms associated with posttraumatic HO. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Activin A does not drive post-traumatic heterotopic ossification.

Heterotopic ossification (HO), the formation of ectopic bone in soft tissues, has been extensively studied in its two primary forms: post-traumatic HO (tHO) typically found in patients who have experienced musculoskeletal or neurogenic injury and in fibrodysplasia ossificans progressiva (FOP), where it is genetically driven. Given that in both diseases HO arises via endochondral ossification, the molecular mechanisms behind both diseases have been postulated to be manifestations of similar pathways including those activated by BMP/TGFβ superfamily ligands. A significant step towards understanding the molecular mechanism by which HO arises in FOP was the discovery that FOP causing ACVR1 variants trigger HO in response to activin A, a ligand that does not activate signaling from wild type ACVR1, and that is not inherently osteogenic in wild type settings. The physiological significance of this finding was demonstrated by showing that activin A neutralizing antibodies stop HO in two different genetically accurate mouse models of FOP. In order to explore the role of activin A in tHO, we performed single cell RNA sequencing and compared the expression of activin A as well as other BMP pathway genes in tHO and FOP HO. We show that activin A is expressed in response to injury in both settings, but by different types of cells. Given that wild type ACVR1 does not transduce signal when engaged by activin A, we hypothesized that inhibition of activin A will not block tHO. Nonetheless, as activin A was expressed in tHO lesions, we tested its inhibition and compared it with inhibition of BMPs. We show here that anti-activin A does not block tHO, whereas agents such as antibodies that neutralize ACVR1 or ALK3-Fc (which blocks osteogenic BMPs) are beneficial, though not completely curative. These results demonstrate that inhibition of activin A should not be considered as a therapeutic strategy for ameliorating tHO.

Color Doppler ultrasound visualizes early post-traumatic heterotopic ossification in animal model

Objective To validate the role of color Doppler ultrasound in an animal model to detect early heterotopic ossification (HO) after brain-traumatic/burn/tenotomy. Methods Forty-four rats were randomly divided into two groups. Rats in experimental group (n=22) were operated to build brain-traumatic/burn/tenotomy model and others in control group (n=22) underwent only skin incision injury. Color Doppler ultrasound, X-ray film examination at 2, 3, 4, 6, 8 and 10 weeks post-injury were performed to follow up the progression of HO in both groups respectively. Histology was used to confirm bone formation. Results In the experimental group, disorder structure with a hypoechoiccore in treated Achilles tendon was visualized using color Doppler ultrasound in the 2nd week. Additional tiny hyperechoic foci were observed in the 3rd week, which increased in the fourth week and fused into a mineralized island in the sixth week. No obvious abnormality was found in control group at the aforementioned time point. X-ray could detect heterotopic bone tissue in the sixth week in the experimental group but not in the control group. X-ray and HE stainning had confirmed bone formation in the tenth week in the experimental group. Conclusions Color Doppler ultrasound can detect early HO and continuously follow up the progression of HO. Key words: Ultrasonography; Heterotopic ossification; Animal model; X-ray

In vivo model of human post-traumatic heterotopic ossification demonstrates early fibroproliferative signature

BackgroundThe relationship between the tissue injury healing response and development of heterotopic ossification (HO) is poorly understood. Here we compare a rat blast model and human traumatized muscle from a blast injury to study the early signatures of osteogenesis and fibrosis during the formation of HO.MethodsRat and human tissues were characterized using histology, scanning electron microscopy, immunohistochemistry, as well as gene and protein expression analysis. Additionally, animals and humans were assessed radiographically for HO formation following injury.ResultsMarkers of bone formation were dramatically increased in tissue samples from both humans and rats, and both displayed increased fibroproliferative regions within the injured tissues and elevated expression of markers of tissue fibrosis such as TGF-β1, Fibronectin, SMAD3 and PAI-1. Markers of inflammation and fibrosis (ACTA, TNFα, BMP1 and BMP3) were elevated at the RNA level in both rat and human samples. By day 42, bone formation in the rat blast model appeared similar in radiographs compared to human patients who progressed to develop post-traumatic HO.ConclusionsOur data demonstrates that a similar early fibrotic response is evident in both the rat blast model and the human tissues following a traumatic injury and demonstrates the relevance of this animal model for future translational studies.

Loss of pronation-supination in patients with heterotopic ossification around the elbow

Heterotopic ossification (HO) is a well-recognized cause of limited flexion-extension, but it can also limit pronation-supination. There is a paucity of literature concerning restriction of pronation-supination due to HO. We conducted a retrospective review of patients who had undergone elbow surgery for HO removal between January 1, 2003, and September 27, 2013. Computed tomography scans were reviewed to determine the presence of HO restricting forearm rotation and were rated independently by 4 observers. Each elbow was given 1 of 4 scores according to the likelihood that HO was restricting forearm rotation. Agreement was achieved when 3 or 4 observers thought that HO definitely or probably caused a loss of pronation-supination. Of 132 post-traumatic patients undergoing HO excision for restricted elbow motion, 61 (46%) also lacked a functional arc of pronation and supination (50° and 50°, respectively). Of these 61 patients, 32 (53%) were considered to have lost forearm rotation because of HO. The remaining 29 patients (47%) were thought to have restricted forearm rotation for reasons unrelated to HO. In this study, loss of pronation-supination affected almost half of the patients (61 of 132 [46%]) undergoing HO excision around the elbow. Of these 61 patients, 32 (52%) had HO extending into the proximal forearm and affecting rotation. From our data, one can expect that about one-quarter (24% of patients in this study, or 32 of 132) with post-traumatic HO of the elbow will have a significant functional loss of pronation-supination due to HO extending into the forearm.

Post-traumatic ossifications of the rectus femoris: Arthroscopic treatment and clinical outcome after 2 years

Injuries of the rectus femoris tendon origin could result in a chronic tendinopathy, leading to groin pain and loss of function.Conservative treatment with analgesics and physical therapy is the gold standard, but in some cases excessive bone formation after avulsion injuries, can lead to a post-traumatic heterotopic ossification (PHO) and may benefit from surgical removal. MethodsOutcome was evaluated in 16 top soccer players (age 24-43 years) affected by calcification of the proximal rectus who underwent arthroscopic excision (6-12 and 24 months). X-ray and 3D CT was collected for all patients. Hip disability and Osteoarthritis Outcome Score, Oxford Hip Score, Modified Harris Hip Score, together with visual analog scales (VAS) for pain, sport activity level (SAL), and activities of daily living (ADL) were used to evaluate clinical outcome. Technical procedureafter central compartment examination and treatment was accomplished, attention was focused to the ossification of the rectus femoris. A complete exposure of the ossification was achieved; when possible attention was taken in detaching the minimum amount of fibers of the direct head of the rectus femoris from its insertion site. During the entire procedure, both dynamic direct visualization and fluoroscopic evaluation of the amount of resection were performed. ResultsClinical outcome was excellent; the percentage of return to pre-injury level sport was 68.75 % (11 athletes), with significant statistical improvement of MHHS, OHS and all 3 VAS subscales in all patients at 2 years follow-up. ConclusionArthroscopic removal using conventional hip arthroscopic portals represent both effective and safe procedure to adequately treat post-traumatic ossification of the rectus femoris.

Ultrasonography Monitoring of Trauma-Induced Heterotopic Ossification: Guidance for Rehabilitation Procedures.

Traumatic injury is one of varying causes of heterotopic ossification (HO). After HO occurrence, rehabilitation training need alterations to avoid the aggravation of HO. Therefore, monitoring of HO development plays an important role in the rehabilitation procedure. The aims of this study are to evaluate the post-traumatic HO occurring at various joints, to describe the features of HO development in ultrasound images, and to provide a guidance for the orthopedist to make individualized rehabilitation therapy. Eight subjects with the post-traumatic HO were recruited in this study. The joints on the injured side was examined by plain radiography. The joints on the injured side and the corresponding sites on the uninjured sides were scanned by ultrsonography. The HO tissues were segmented automatically using a semi-supervised segmentation algorithm. Then the HO tissues were evaluated in comparison with the corresponding region of the uninjured side. During the development stage of immature HO, ultrasonography was sensitive to observe the involved soft tissue and the calcification of HO. The characteristics of HO tissues in ultrasound image included the hyperechoic mass occasionally accompanied with acoustic shadow and the irregular muscular architecture. It was found that the mean grayscale value of HO was significantly higher (p < 0.001) than that of the uninjured side at the middle and late stages. During the development period of HO, the HO grayscale value gradually increased and the mean grayscale of value of mature HO was significantly higher (p < 0.05) than that of immature HO. According to the information of HO provided by ultrasound, the orthopedist properly adjusted the rehabilitation treatment. The results demonstrated that the visualization of HO using ultrasonography revealed the development of HO in the muscle tissues around the injured joints and thus provide a guidance for the orthopedist to make individualized rehabilitation therapy. Ultrasound could be a useful imaging modality for quantitative evaluation of HO during the rehabilitation of traumatic injury.

Trauma induced heterotopic ossification patient serum alters mitogen activated protein kinase signaling in adipose stem cells.

Post-traumatic heterotopic ossification (HO) is the formation of ectopic bone in non-osseous structures following injury. The precise mechanism for bone development following trauma is unknown; however, early onset of HO may involve the production of pro-osteogenic serum factors. Here we evaluated serum from a cohort of civilian and military patients post trauma to determine early induction gene signatures in orthopaedic trauma induced HO. To test this, human adipose derived stromal/stem cells (hASCs) were stimulated with human serum from patients who developed HO following trauma and evaluated for a gene panel with qPCR. Pathway gene analysis ontology revealed that hASCs stimulated with serum from patients who developed HO had altered gene expression in the activator protein 1 (AP1) and AP1 transcriptional targets pathways. Notably, there was a significant repression in FOS gene expression in hASCs treated with serum from individuals with HO. Furthermore, the mitogen-activated protein kinase (MAPK) signaling pathway was activated in hASCs following serum exposure from individuals with HO. Serum from both military and civilian patients with trauma induced HO had elevated downstream genes associated with the MAPK pathways. Stimulation of hASCs with known regulators of osteogenesis (BMP2, IL6, Forskolin, and WNT3A) failed to recapitulate the gene signature observed in hASCs following serum stimulation, suggesting non-canonical mechanisms for gene regulation in trauma induced HO. These findings provide new insight for the development of HO and support ongoing work linking the systemic response to injury with wound specific outcomes.