Heterotopic ossification (HO) is a common occurrence after multiple forms of extensive trauma. These include arthroplasties, traumatic brain and spinal cord injuries, extensive burns in the civilian setting, and combat-related extremity injuries in the battlefield. Irrespective of the form of trauma, heterotopic bone is typically endochondral in structure and is laid down via a cartilaginous matrix. Once formed, the heterotopic bone typically needs to be excised surgically, which may result in wound healing complications, in addition to a risk of recurrence. Refinements of existing diagnostic modalities, like micro- and nano-CT are being adapted toward early intervention. Trauma-induced HO is a consequence of aberrant wound healing, systemic and local immune system activation, infections, extensive vascularization, and innervation. This intricate molecular crosstalk culminates in activation of stem cells that initiate heterotopic endochondral ossification. Development of animal models recapitulating the unique traumatic injuries has greatly facilitated the mechanistic understanding of trauma-induced HO. These same models also serve as powerful tools to test the efficacy of small molecules which specifically target the molecular pathways underlying ectopic ossification. This review summarizes the recent advances in the molecular understanding, diagnostic and treatment modalities in the field of trauma-induced HO.

Introduction: NSAIDs inhibit osteogenesis and may result in delayed union or nonunion. The purpose of this meta-analysis was to determine whether their use leads to delayed union or nonunion. Methods: We systematically reviewed the literature reporting the effect of NSAIDs on bone healing. We included studies of pediatric and adult patients NSAID exposure and healing bone. The outcomes of interest were delayed union, nonunion, or pseudarthrosis with at least six months of follow-up. A maximum likelihood random-effects model was used to conduct meta-analysis and meta-regression. Results: NSAID exposure increased delayed union or nonunion (odds ratio [OR], 2.07; confidence interval [CI], 1.19 to 3.61). No effect was noted in pediatrics (OR, 0.58; CI, 0.27 to 1.21) or low dose/short duration of exposure (OR, 1.68; CI, 0.63 to 4.46). Conclusion: Analysis of the literature indicates a negative effect of NSAIDs on bone healing. In pediatric patients, NSAIDs did not have a significant effect. The effect may be dose or time dependent because low-dose/short-duration exposure did not affect union rates.

A pressing clinical need exists for 63% to 65% of combat-wounded service members and 11% to 20% of civilians who develop heterotopic ossification (HO) after blast-related extremity injury and traumatic injuries, respectively. The mammalian target of rapamycin pathway is a central cellular sensor of injury. We evaluated the prophylactic effects of rapamycin, a selective inhibitor of mammalian target of rapamycin signaling, on HO formation in a rat model of blast-related, polytraumatic extremity injury. Rapamycin was administered intraperitoneally daily for 14 days at 0.5 mg/kg or 2.5 mg/kg. Ectopic bone formation was monitored by micro-computed tomography and confirmed by histologic examination. Connective tissue progenitor cells, platelet-derived growth factor receptor-α-positive cells, and α-smooth muscle actin-positive blood vessels were assayed at postoperative day 7 by colony formation and immunofluorescence. Early gene expression changes were determined by low-density microarray. There was significant attenuation of 1) total new bone and soft tissue ectopic bone with 0.5 mg/kg (38.5% and 14.7%) and 2.5 mg/kg rapamycin (90.3% and 82.9%), respectively, 2) connective tissue progenitor cells, 3) platelet-derived growth factor receptor-α-positive cells, 4) α-smooth muscle actin-positive blood vessels, and 5) of key extracellular matrix remodeling (CD44, Col1a1, integrins), osteogenesis (Sp7, Runx2, Bmp2), inflammation (Cxcl5, 10, IL6, Ccl2), and angiogenesis (Angpt2) genes. No wound healing complications were noted. Our data demonstrate the efficacy of rapamycin in inhibiting blast trauma-induced HO by a multipronged mechanism.

BackgroundThe use of biologic mesh to repair abdominal wall defects in contaminated surgical fields is becoming the standard of practice. However, failure rates and infections of these materials persist clinically. The purpose of this study was to determine the mechanical properties of biologic mesh in response to a bacterial encounter.MethodsA rat model of Staphylococcus aureus colonization and infection of subcutaneously implanted biologic mesh was used. Samples of biologic meshes (acellular human dermis (ADM) and porcine small intestine submucosa (SIS)) were inoculated with various concentrations of methicillin-resistant Staphylococcus aureus [105, 109 colony-forming units] or saline (control) prior to wound closure (n = 6 per group). After 10 or 20 days, meshes were explanted, and cultured for bacteria. Histological changes and bacterial recovery together with biomechanical properties were assessed. Data were compared using a 1-way ANOVA or a Mann-Whitney test, with p<0.05.ResultsThe overall rate of staphylococcal mesh colonization was 81% and was comparable in the ADM and SIS groups. Initially (day 0) both biologic meshes had similar biomechanical properties. However after implantation, the SIS control material was significantly weaker than ADM at 20 days (p = 0.03), but their corresponding modulus of elasticity were similar at this time point (p>0.05). After inoculation with MRSA, a time, dose and material dependent decrease in the ultimate tensile strength and modulus of elasticity of SIS and ADM were noted compared to control values.ConclusionThe biomechanical properties of biologic mesh significantly decline after colonization with MRSA. Surgeons selecting a repair material should be aware of its biomechanical fate relative to other biologic materials when placed in a contaminated environment.

Patient-specific implants have been linked to stiffness. The purpose of this study was to evaluate outcomes in patient-specific implants. We performed a retrospective review with a primary outcome of manipulation under anesthesia (MUA); secondary outcomes included Knee Society Scores (KSS), Knee Society Functional Scores (KSFS), range of motion (ROM), and Forgotten Joint Scores (FJS). Pre-operative measurements were similar in both groups. There was one MUA in the CPS and two in the OTS groups. There was no difference in postoperative scores. Our study suggests patient-specific implants have comparable rates of MUA and functional outcomes as conventional implants.

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.

Introduction Noise exposure is an occupational health concern for certain professions, especially military servicemembers and those using power tools on a regular basis. The purpose of this study was to quantify noise exposure during total hip arthroplasty (THA) and total knee arthroplasty (TKA) cases compared to the recommended standard for occupational noise exposure. Materials and Methods A sound level meter was used to record cumulative and peak noise exposure levels in 10 primary THA and 10 primary TKA surgeries, as well as 10 arthroscopy cases as controls. Measurements at the distance of the surgeon were taken in all cases. In TKA cases, measurements were taken at 3 feet and 8 feet from the surgeon, to simulate the position of the anesthetist and circulating nurse, respectively. Results Time-weighted average was significantly higher in THA (64.7 ± 5.2 dB) and TKA (64.5 ± 6.8 dB) as compared to arthroscopic cases (51.1 ± 7.5 dB, P &lt; 0.001) and higher at the distance of the surgeon (64.5 ± 6.8 dB) compared to the anesthetist (52.9 ± 3.8 dB) and the circulating nurse (54.8 ± 11.2 dB, P = 0.006). However, time-weighted average was below the recommended exposure level of 85 dB for all arthroplasty cases. Peak levels did not differ significantly between surgery type or staff role, and no values above the ceiling limit of 140 dB were recorded. Surgeon’s daily noise dose percentage per case was 1.78% for THA and 2.04% for TKA. Conclusion Noise exposure in THA and TKA was higher than arthroscopic cases but did not exceed occupational standards. A daily dose percentage of approximately 2% per case indicates that repeated noise exposure likely does not reach hazardous levels in modern arthroplasty practice.

Background: Biceps tenodesis is a procedure that can address biceps and labral pathology. While there is an increased risk of humeral fracture after biceps tenodesis, it has been described only in case reports. Purpose: To identify the incidence, demographics, and characteristics of humeral shaft fractures after biceps tenodesis. Study Design: Case series; Level of evidence, 4. Methods: The US Military Health System Data Repository was searched for patients with a Current Procedural Terminology code for biceps tenodesis between January 2013 and December 2016. The cohort of identified patients was then searched for those assigned a code for humeral fracture per the International Classification of Diseases, 9th Revision and 10th Revision. The electronic health records and radiographs of patients who were diagnosed with a humeral fracture were then evaluated to confirm that the fracture was related to the biceps tenodesis. Records were then reviewed for patient demographics, radiographs, operative reports, and clinical notes. Results: A total of 15,085 biceps tenodeses were performed between January 2013 and December 2016. There were 11 postoperative and 1 intraoperative humeral fractures. The incidence of fracture was <0.1%. All fractures were extra-articular spiral fractures that propagated through the tenodesis site. Eight patients were treated with functional bracing, 3 with open reduction and internal fixation, and 1 with a soft tissue biceps tenodesis revision. Of 8 patients successfully treated nonoperatively, 6 regained full range of shoulder motion. Only 2 of the 4 patients who required operative treatment regained full range of shoulder motion. Conclusion: Humeral shaft fracture after biceps tenodesis is a rare complication that occurs in 7.9 out of 10,000 cases. Fractures occurred after various methods of fixation, including suture anchor, cortical button, and interference screw. Most patients were initially treated nonoperatively, and those who healed usually achieved full range of motion; however, those who required operative intervention often had restricted range of motion on final follow-up. Future studies should determine risk factors for fracture after biceps tenodesis.