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

BackgroundOpen 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.MethodsA retrospective study was conducted with 31 patients (25 males and 6 females) with a mean follow-up of 40.5 ± 27.44 months. 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.ResultsMean 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%).ConclusionThe surgical protocol described here enabled us to achieve good functional results and was in concordance with similar studies done previously.Supplementary InformationThe online version contains supplementary material available at 10.1007/s43465-021-00381-x.     

The Effect of Etidronate on late Development of Heterotopic Ossification After Spinal Cord Injury

Abstract

Forty patients with spinal cord injury (SCI) and heterotopic ossification (HO) were treated with etidronate and followed after therapy to determine the effects of long-term medication on heterotopic bone formation. Eighteen patients had tetraplegia and 22 had paraplegia. Early diagnosis of HO (positive bone scintigraphy and negative radiographic findings of HO) was established by 3-phase bone scintigraphy using 99m technetium-labeled methylene diphosphonate. All patients underwent treatment with etidronate, first with intravenous administration of 300 mg/day for 3 days followed by an oral administration of 20 mg/kg/day for 6 months. Eleven patients (27.5%) developed radiographic evidence of HO from 1.5 to 6 years after therapy. A low degree of HO was found in these patients; 8 had grade I and 3 had grade II ectopic ossification (Brooker’s scale). The analysis of data showed that 2 different types of ectopic bone may form in the later stages after SCI. In 5% of patients, HO was found in the same anatomical site initially and finally, suggesting a “rebound” in mineralization of bone matrix not prevented by the administration of etidronate. The other type of HO was found in the majority of patients (95%) where the localization of HO showed different involvement of joints than initially, indicating de novo appearance of HO following SCI. The data suggest that etidronate given for a prolonged period in higher doses has, in addition to an inhibitory effect on crystal formation, a cellular effect on bone-forming cells.     

Heterotopic Ossification of Rectal Adenocarcinoma: Report of a Case

Heterotopic ossification of gastrointestinal tract tumors is rare. We report the case of a 67-year-old man with heterotopic ossification of a rectal adenocarcinoma. The patient presented with intermittent abdominal pain and frequent diarrhea, and colonoscopic examination showed a large polypoid tumor partially obstructing the rectal lumen. Abdominal computed tomography (CT) revealed a large tumor in the rectal lumen with calcified spots. We performed low anterior resection of the rectum, and histologic examination showed a well-differentiated adenocarcinoma with heterotopic ossification infiltrating the full thickness of the rectum. Local recurrence and liver metastases were found 2 months after surgery, and the patient died 3 months later. Such a rapidly progressive course of rectal adenocarcinoma with heterotopic ossification is very unusual.     

Heterotopic Ossification of the Extensor Tendons in the Hand Associated with Traumatic Spinal Cord Injury

ABSTRACT

Heterotopic ossification (HO) occurs in spinal cord injury (SCI), most frequently in the large joints such as hips, shoulders, knees, and elbows. It always occurs below the level of neurologic lesion. In the upper extremities, HO associated with SCI usually involves the flexor side of the involved joint. HO has only been reported once to involve the hands and rarely develops parallel to the long bones. We present a 44-year-old male with C5 traumatic SCI who developed HO involving the extensor tendons of one hand. The HO was discovered four months after the SCI and involved the extensor sheaths of the second, third, and fourth digits, from the metacarpal-phalangeal joint to the proximal inter-phalangeal joint. The patient had been improving neurologically with poor to fair extension of the right wrist allowing for tenodesis finger flexion, but with the onset of HO he lost some functional grasp. Diagnosis, possible etiology, and treatment (including options of radiation therapy and surgery) are discussed.     

Comparing Options for Heterotopic Ossification Prophylaxis following Elbow Trauma: A Systematic Review and Meta-Analysis

Introduction  Heterotopic ossification (HO) can be a potentially serious and devastating complication following traumatic injury to the elbow. HO prophylaxis options include nonsteroidal anti-inflammatory drugs (NSAIDs) and radiation therapy (RT) but neither has been proven more effective. The purpose of this review is to compare effectiveness and outcomes between NSAID and RT prophylaxis for HO about the elbow following a traumatic injury. Materials and Methods  We performed a systematic review of PubMed and Cochrane Library for cases of HO prophylaxis following elbow trauma utilizing PRISMA guidelines to determine the most effective form of prophylaxis. Outcomes of interest included recurrence of HO, range of motion (ROM), and Mayo elbow performance index (MEPI). A total of 36 articles and 826 elbows of which 203 received RT and 623 received NSAID were identified and included in the final analysis. Results  Rates of HO formation or recurrence following elbow trauma were similar between radiation and NSAID prophylaxis (15.6% vs. 22.2%, respectively p = 0.457). ROM was similar in flexion and extension arc (109.0 degrees in radiation vs. 112.8 in NSAIDs, p = 0.459) and in pronation and supination arc (118.9 degrees radiation vs. 134.7 degrees NSAIDs, p = 0.322). MEPI scores were 79.19 in the radiation group and 88.82 in the NSAIDs group at the final follow-up. Conclusion  There is no statistical difference in HO development, recurrence, or final ROM between NSAIDs and RT prophylaxis following trauma to the elbow. We recommend the choice of modality based on patient characteristics, cost, and surgeon preference. Level of Evidence  Level III.     

False-Negative Triple-Phase Bone Scans in Spinal Cord Injury to Detect Clinically Suspect Heterotopic Ossification: A Case Series

Abstract

Background/Objective: Heterotopic ossification (HO) is a complication seen in patients after spinal cord injury (SCI). Triple-phase nuclear bone scanning is the most sensitive test for the detection of HO. This retrospective study assesses whether patients with clinically suspected HO but negative triple-phase nuclear bone scans develop delayed positive nuclear bone scans.

Methods: Case series: A cohort of patients with SCI and clinically suspected HO who underwent triple phase nuclear bone scans over a period of 2 years was identified from retrospective chart review of an acute inpatient SCI rehabilitation service. A subgroup of 7 patients with initially negative but subsequently positive triple-phase nuclear bone scans was identified, and the following data were collected: date, mechanism, admission level, and admission completeness of injury as well as date, number, and results of bone scans. Laboratory studies were also collected during the time of imaging.

Results: Over a 2-year period, 343 patients were admitted to the SCI rehabilitation service; 60 patients were suspected of having HO and underwent a total of 85 triple-phase nuclear bone scans. Seven patients were identified with initially negative but subsequently positive bone scans.

Conclusions: In patients with clinically suspicious HO but negative bone scans, follow-up scans are indicated to identify initial false-negative studies.     

Heterotopic Ossification Prophylaxis After Total Hip Arthroplasty: Randomized Trial of 400 vs 700 cGy

Background

Heterotopic ossification (HO) is a known complication following total hip arthroplasty. Radiation is an effective prophylaxis, but an optimal protocol has yet to be determined. We performed a randomized, double-blinded clinical trial in high-risk patients to determine the efficacy of 400 vs 700 cGy doses of radiation.

Low-Dose Aspirin Administered for Venous Thromboembolism Prophylaxis Reduces the Incidence of Heterotopic Ossification in Total Joint Arthroplasty

BackgroundHeterotopic ossification (HO) is a common complication following total joint arthroplasty (TJA). However, the pathophysiology of HO is not entirely understood. Inflammation may play a significant role in the pathogenesis of HO as nonsteroidal anti-inflammatory drugs are effective in the prevention of HO. The purpose of this study is to examine if aspirin (ASA), when used as venous thromboembolism (VTE) prophylaxis, influenced the rate of HO formation following TJA.MethodsWe queried our longitudinally maintained database to identify all patients who underwent primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) for osteoarthritis between January 2016 and June 2018 with at least 3-month radiographic follow-up. In total, 1238 THAs and 1051 TKAs were included for analysis. Radiographs were reviewed and HO formation graded according to the Brooker classification. Patient demographic and VTE prophylaxis data were collected and reviewed for accuracy. Univariate and multivariate analysis was performed to evaluate the effect of ASA on HO formation.ResultsThe overall rate of HO was 37.5% after THA and 17.4% after TKA. Patients receiving ASA were less likely to develop HO after THA (34.8% vs 45.5%; P < .001), as well as HO after TKA (13.4% vs 18.4%; P = .047) compared to patients receiving non-ASA VTE prophylaxis. The rate of HO formation trended to be lower, albeit not statistically significantly, in patients receiving low-dose ASA (81 mg) vs high-dose ASA (325 mg).ConclusionPatients undergoing primary TJA receiving ASA for VTE prophylaxis were less likely to develop HO compared to patients who were administered non-ASA VTE prophylaxis.     

Improvements in elbow motion after resection of heterotopic bone: a systematic review

Complex elbow trauma, severe burn, or a closed head injury render patients at risk for developing heterotopic ossification around the elbow. When heterotopic ossification restricts elbow motion, some patients request surgical resection. We performed a systematic review of the literature to analyze improvement in elbow motion after resection of heterotopic ossification around the elbow. We found that, on average, etiology had little impact on outcome after resection of heterotopic ossification. Resection of heterotopic bone generally leads to improvement of elbow function.     

Palovarotene inhibits connective tissue progenitor cell proliferation in a rat model of combat‐related heterotopic ossification

Heterotopic ossification (HO) develops in the extremities of wounded service members and is common in the setting of high‐energy penetrating injuries and blast‐related amputations. No safe and effective prophylaxis modality has been identified for this patient population. Palovarotene has been shown to reduce bone formation in traumatic and genetic models of HO. The purpose of this study was to determine the effects of Palovarotene on inflammation, progenitor cell proliferation, and gene expression following a blast‐related amputation in a rodent model (n = 72 animals), as well as the ability of Raman spectroscopy to detect early HO before radiographic changes are present. Treatment with Palovarotene was found to dampen the systemic inflammatory response including the cytokines IL‐6 (p = 0.01), TNF‐α (p = 0.001), and IFN‐γ (p = 0.03) as well as the local inflammatory response via a 76% reduction in the cellular infiltration at post‐operative day (POD)‐7 (p = 0.03). Palovarotene decreased osteogenic connective tissue progenitor (CTP‐O) colonies by as much as 98% both in vitro (p = 0.04) and in vivo (p = 0.01). Palovarotene treated animals exhibited significantly decreased expression of osteo‐ and chondrogenic genes by POD‐7, including BMP4 (p = 0.02). Finally, Raman spectroscopy was able to detect differences between the two groups by POD‐1 (p < 0.001). These results indicate that Palovarotene inhibits traumatic HO formation through multiple inter‐related mechanisms including anti‐inflammatory, anti‐proliferative, and gene expression modulation. Further, that Raman spectroscopy is able to detect markers of early HO formation before it becomes radiographically evident, which could facilitate earlier diagnosis and treatment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1135–1144, 2018.

     

Early local delivery of vancomycin suppresses ectopic bone formation in a rat model of trauma‐induced heterotopic ossification

Heterotopic ossification (HO) is a debilitating sequela of high‐energy injuries. It frequently requires surgical excision once symptomatic and there is no practical prophylaxis for combat‐injured patients. In this study, we examined the effect of local vancomycin powder on HO formation in a small animal model of blast‐related, post‐traumatic HO. Male Sprague‐Dawley rats were subjected to a polytraumatic extremity injury and amputation with or without methicillin‐resistant Staphylococcus aureus infection. Animals were randomized to receive a single local application of vancomycin (20 mg/kg) at the time of injury (POD‐0, n = 34) or on postoperative day‐3 (POD‐3, n = 11). Quantitative volumetric measurement of ectopic bone was calculated at 12‐weeks post‐injury by micro‐CT. Bone marrow and muscle tissues were also collected to determine the bacterial burden. Blood for serum cytokine analysis was collected at baseline and post‐injury. Vancomycin treatment on POD‐0 suppressed HO formation by 86% and prevented bone marrow and soft tissue infections. We concurrently observed a marked reduction histologically in nonviable tissue, chronic inflammatory cell infiltrates, bone infection, fibrous tissue, and areas of bone necrosis within this same cohort. Delayed treatment was significantly less efficacious. Neither treatment had a marked effect on the production of pro‐inflammatory cytokines. Our study demonstrates that local vancomycin treatment at the time of injury significantly reduces HO formation in both the presence and absence of infection, with decreased efficacy if not given early. These findings further support the concept that the therapeutic window for prophylaxis is narrow, highlighting the need to develop early treatment strategies for clinical management. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2397–2406, 2017.

     

Location‐dependent heterotopic ossification in the rat model: The role of activated matrix metalloproteinase 9

Extremity amputation or traumatic injury can often lead to the formation of heterotopic ossification (HO). Studies to induce HO in rat muscle using cell‐based gene therapy show that this process appears to be location dependent. In the present study, HO was induced in mice and rats through injection of immunologically matched cells transduced with either a replication‐defective adenovirus possessing bone morphogenetic protein 2 (BMP2) or an empty adenovirus vector (control). Injection in rat near the skeletal bone resulted in HO, whereas cells injected into the same muscle group but distal from the bone did not result in bone formation. When cells were injected in the same limb at both locations at the same time, HO was formed at both sites. Characterization of the bone formation in rats versus mice demonstrated that different sources of osteogenic progenitors were involved, which may account for the location dependent bone formation observed in the rat. Further experimentation has shown that a potential reason for this difference may be the inability of rat to activate matrix metalloproteinase 9 (MMP9), an essential protease in mice necessary for recruitment of progenitors. Inhibition of active MMP9 in mice led to a significant decrease in HO. The studies reported here provide insight into the mechanisms and pathways leading to bone formation in different animals and species. It appears that not all animal models are appropriate for testing HO therapies, and our studies also challenge the conventional wisdom that larger animal models are better for testing treatments affecting bone. © 2016 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 34:1894–1904, 2016.     

Acute Changes in NADPH Oxidase 4 in Early Post‐Traumatic Osteoarthritis

Knee injuries cause structural damage and acute inflammation that initiates the development of post‐traumatic osteoarthritis (PTOA). NADPH oxidase 4 (Nox4), a member of a family of enzymes that generates reactive oxygen species (ROS), plays a pivotal role in normal development of the musculoskeletal system, but may increase ROS production to harmful levels after joint injury. The role of ROS in both normal joint homeostasis and injury is poorly understood, but inhibition of excessive ROS production by Nox4 after joint injury could be protective to the joint, decreasing oxidative stress, and initiation of PTOA. Knee injuries were simulated using inflammatory cytokines in cultured primary human chondrocytes and a non‐invasive mouse model of PTOA in C57BL/6N and Nox4 knockout mice. There is an acute decrease in Nox4 activity within 24 h after injury in both systems, followed by a subsequent sustained low‐level increase, a novel finding not seen in any other system. Inhibition of Nox4 activity by GKT137831 was protective against early structural changes after non‐invasive knee injury in a mouse model. Nox4 knockout mice had significant differences in structural and mechanical properties of bone, providing further evidence for the role of Nox4 in development of joint tissues and biochemical response after joint injury. Nox4 plays a significant role in the acute phase after joint injury, and targeted inhibition of inflammation caused by Nox4 may be protective against early joint changes in the pathogenesis of PTOA. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2429–2436, 2019     

Late Post‐transplant Anemia in Adult Renal Transplant Recipients. An Under‐recognized Problem?

Post-transplant anemia (PTA), a frequent complication during the first 3-6 months after transplant, is thought to be uncommon during the late post-transplant period. A study population of adults (> 18 years) transplanted during 1995 at Stanford University (n = 88) and University of North Carolina (n = 40) was selected. Data-collection points were 0, 1, 2, 3, 4 and 5 years post transplant. Anemia was defined as a hematocrit < 33 volume percentage. Thirty percent of patients were anemic at some time during the post-transplant period. The prevalence of PTA increased over time; by 5 years post transplant, 26% of the patients were anemic. Anemia occurred in 62.5% of patients converted from azathioprine to mycophenolate mofetil. A multivariate logistic regression model demonstrated a correlation between anemia and serum total CO2 (p = 0.002), BUN (p = 0.04), and creatinine (p = 0.045) at 1 year post transplant. At 5 years post transplant, only serum total CO2 (p = 0.0004) correlated with anemia. Thus, diminished renal excretory function and metabolic acidosis appear to be the most important correlates of late PTA. These findings should be interpreted in view of the fact that the newer immunosuppressive agents may have an even more profound effect on anemia and its recovery after transplantation.