Christopher M. Stutz

Micro-computed tomography assessment of the progression of fracture healing in mice

The mouse fracture model is ideal for research into the pathways of healing because of the availability of genetic and transgenic mice and the ability to create cell-specific genetic mutations. While biomechanical tests and histology are available to assess callus integrity and tissue differentiation, respectively, micro-computed tomography (μCT) analysis has increasingly been utilized in fracture studies because it is non-destructive and provides descriptions of the structural and compositional properties of the callus. However, the dynamic changes of μCT properties that occur during healing are not well defined. Thus, the purpose of this study was to determine which μCT properties change with the progression of fracture repair and converge to values similar to unfractured bone in the mouse femur fracture model. A unilateral femur fracture was performed in C57BL/6 mice and intramedullary fixation performed. Fractured and un-fractured contralateral specimens were harvested from groups of mice between 2 and 12 weeks post-fracture. Parameters describing callus based on μCT were obtained, including polar moment of inertia (J), bending moment of inertia (I), total volume (TV), tissue mineral density (TMD), total bone volume fraction (BV/TV), and volumetric bone mineral density (vBMD). For comparison, plain radiographs were used to measure the callus diameter (D) and area (A); and biomechanical properties were evaluated using either three-point bending or torsion. The μCT parameters J, I, TV, and TMD converged toward their respective values of the un-fractured femurs over time, although significant differences existed between the two sides at every time point evaluated (p<0.05). Radiograph measurement D changed with repair progression in similar manner to TV. In contrast, BV/TV and BMD increased and decreased over time with statistical differences between callus and un-fractured bone occurring sporadically. Similarly, none of the biomechanical properties were found to distinguish consistently between the fractured and un-fractured femur. Micro-CT parameters assessing callus structure and size (J, I, and TV) were more sensitive to changes in callus over time post-fracture than those assessing callus substance (TMD, BV/TV, and BMD). Sample size estimates based on these results indicate that utilization of μCT requires fewer animals than biomechanics and thus is more practical for evaluating the healing femur in the mouse fracture model.

Neuralgic amyotrophy: Parsonage-Turner Syndrome.

p c a p o p n b p t r t m RESCHFELD FIRST DESCRIBED neuralgic amyotrophy in 1887 when he outlined recurrent episodes of the condition in 2 sisters. Multiple eports outlining symptoms mirroring the condition riginally described would follow in the literature beore Parsonage and Turner clearly detailed the clinical spects of the condition in a cohort of 136 patients in 948. Hence, the clinical condition has become comonly known as Parsonage-Turner Syndrome. Shortly hereafter, in 1952, Kiloh and Nevin published a report n the British Medical Journal describing the classic nvolvement of the anterior interosseous nerve with humb and index finger paralysis. In addition to the opular eponym, neuralgic amyotrophy can be found escribed in the literature under such names as acute rachial neuropathy, acute brachial plexitis, brachial lexus neuropathy, idiopathic brachial plexopathy, idopathic brachial neuritis, localized neuritis of the houlder girdle, multiple neuritis of the shoulder girdle, aralytic brachial neuritis, serum neuritis, shoulder irdle neuritis, and the shoulder girdle syndrome.

Surgical and nonsurgical treatment of cubital tunnel syndrome in pediatric and adolescent patients

PURPOSE Few studies have investigated the presence or treatment of cubital tunnel syndrome in pediatric or adolescent patients. We conducted this retrospective investigation to quantify success rates of nonsurgical care and to assess patient outcomes after surgical intervention. METHODS We identified 39 extremities treated for cubital tunnel syndrome between 2000 and 2009 at one institution. We documented patient demographic data, precipitating events, symptomatology, physical examination findings, and treatment for all patients. We assessed patient-rated outcomes with validated measures including the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and the visual analog scale (VAS). RESULTS Subjective complaints at the time of presentation included 16 extremities with ulnar nerve instability at the elbow, 21 extremities with pain at the elbow, and 15 extremities with numbness and tingling in the ring and small fingers. Physical examination revealed 33 extremities with a positive Tinel sign and 20 extremities with a positive elbow flexion-compression test. In the nonsurgical group (9), pretreatment DASH scores averaged 32 and posttreatment DASH scores averaged 11. Pretreatment recall VAS pain scores had a median of 7, and were similar to posttreatment scores, which had a median of 3. In the surgical group (30), DASH scores averaged 46 before surgery and improved to 7 at final follow-up. The VAS pain scores improved from a median of 8 before surgery to 2 after surgery. A total of 30 patients (from both groups) were treated with a trial of nonsurgical care without symptom resolution. CONCLUSIONS Cubital tunnel syndrome in pediatric or adolescent patients is rare. It can be treated successfully with surgical intervention. Although nonsurgical treatment is unlikely to relieve symptoms in this patient population, a trial of nighttime splinting, activity modification, and anti-inflammatory medications remains appropriate for most patients. Surgical intervention is effective for symptom relief if nonsurgical care fails. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic III.

Supraclavicular nerve entrapment and clavicular fracture.

Because the supraclavicular nerve lies in close proximity to the clavicle, it is particularly vulnerable to injury in cases of clavicle fracture and in the surgical treatment of these fractures. The development of painful neuromas after iatrogenic transsection and symptomatic nerve entrapment in fracture callus after healing have previously been described. Reported here is a case of acute supraclavicular nerve entrapment and tension after fracture of the clavicle with significant pain relief after fracture fixation and nerve decompression.

Complex Syndactyly: Aesthetic and Objective Outcomes

PURPOSE Outcome data after the treatment of complex syndactyly are lacking. The purpose of this investigation was to critically analyze and report our results after surgical reconstruction of complex syndactyly. METHODS We included 13 patients and 21 hands (25 webspaces) in this retrospective call-back investigation. There were 17 middle/ring finger and 8 ring/little finger complex syndactylies, each with a defined, isolated osseous bridge between the distal phalanges. We excluded complicated and syndrome-associated syndactylies. Patients returned for clinical examination and subjective assessment at an average of 9 years (range, 2-27 y) after the most recent surgery. Of 21 hands, 6 had undergone a revision surgery. RESULTS The Vancouver Scar Scale scores averaged 3 (range, 0-6), web creep averaged 1.5 (range, 0-3), and total active motion averaged 148° for the affected fingers. In the middle/ring finger syndactylies, the middle finger was most commonly supinated (average, 13°) and ulnarly deviated (average, 9°), and the ring finger was either supinated or pronated and radially deviated (average, 13°). In the ring/little finger syndactylies, the ring finger was most commonly supinated (average, 8°) without deviation, and the little finger was most commonly pronated (average, 8°) and radially deviated (average, 24°). There was a notable nail wall deformity in most fingers. Surgeon visual analog scale scores (range, 0-10, where lower scores are better) averaged 2.8 (range, 0.8-5.0). Patient visual analog scale scores were 0.4 (range, 0-3) for pain, 1.9 (range, 0-10) for appearance, and 1.1 (range, 0-3) for function. CONCLUSIONS Complex syndactyly reconstruction is challenging, and common postsurgical findings include rotational and angular deformity and nail deformity. When deformity was present, the fingers typically rotated away from and deviated toward the site of the previous complex syndactyly. We describe how we have altered our approach based on these findings. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic IV.

The temporal and spatial development of vascularity in a healing displaced fracture

Underlying vascular disease is an important pathophysiologic factor shared among many co-morbid conditions associated with poor fracture healing, such as diabetes, obesity, and age. Determining the temporal and spatial patterns of revascularization following a fracture is essential for devising therapeutic strategies to augment this critical reparative process. Seminal studies conducted in the last century have investigated the pattern of vascularity in bone following a fracture. The consensus model culminating from these classical studies depicts a combination of angiogenesis emanating from both the intact intramedullary and periosteal vasculature. Subsequent to the plethora of experimental fracture angiography in the early to mid-20th century there has been a paucity of reports describing the pattern of revascularization of a healing fracture. Consequently the classical model of revascularization of a displaced fracture has remained largely unchanged. Here, we have overcome the limitations of animal fracture models performed in the above described classical studies by combining novel techniques of bone angiography and a reproducible murine femur fracture model to demonstrate for the first time the complete temporal and spatial pattern of revascularization in a displaced/stabilized fracture. These studies were designed specifically to i) validate the classical model of fracture revascularization of a displaced/stabilized fracture, ii) assess the association between intramedullary and periosteal angiogenesis and iii) elucidate the expression of VEGF/VEGF-R in relation to the classical model. From the studies, in conjunction with classic studies of angiogenesis during fracture repair, we propose a novel model (see abstract graphic) that defines the process of bone revascularization subsequent to injury to guide future approaches to enhance fracture healing. This new model validates and advances the classical model by providing evidence that during the process of revascularization of a displaced fracture 1) periosteal angiogenesis occurs in direct communication with the remaining intact intramedullary vasculature as a result of a vascular shunt and 2) vascular union occurs through an intricate interplay between intramembranous and endochondral VEGF/VEGF-R mediated angiogenesis.

Fractures of the Distal Radius and Ulna: Metaphyseal and Physeal Injuries

Fractures of the distal radius account for 80 percent of pediatric forearm fractures. The rapid growth of the distal radial physis and the on-going transformation of the metaphysic explain the propensity for fractures in this location and the potential for fracture remodeling. Fractures of the distal ulna are less common and usually occur in conjunction with fractures of the distal radius. In general both injuries can be managed by closed treatment and casting. Indications for skeletal fixation and/or open reduction are discussed. Complications are infrequent but not insignificant and usually treatable with early recognition and appropriate intervention.

Coagulopathies in Orthopaedics: Links to Inflammation and the Potential of Individualizing Treatment Strategies

Summary: Orthopaedic patients are at risk for developing pathologic imbalances of coagulation factors characterized by phases of both hypocoagulability and hypercoagulability. Complications from “hypocoagulability” include life-threatening hemorrhage, wound hematoma, and poor wound healing. Complications due to “hypercoagulability” include deep venous thrombosis, pulmonary embolus, and disseminated intravascular coagulation. In addition, coagulation imbalance that favors the production of procoagulant factors may lead to excessive inflammation and contribute to systemic inflammatory response syndrome, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Optimally, the goal of individualized treatment of coagulopathies in orthopaedic patients should be to achieve efficient healing while avoiding the morbidities associated with imbalance of coagulation and inflammation. Such individualized and time-sensitive measures of coagulation status require rapid, accurate, qualitative, and quantitative assessment of the critical balance of the coagulation system. Commonly used coagulation tests (prothrombin time and activated partial thromboplastin time) are incapable of determining this balance. An alternative to is to perform thrombin generation assays. The greatest advantage of thrombin generation assays over traditional coagulation tests is their ability to detect hypercoagulability, the balance of procoagulant and anticoagulant factors, and the effect of all pharmaceutical anticoagulants. Further clinical investigations are warranted to develop and refine the thrombin generation assays to help predict clinical complications related to coagulation imbalances. In addition, future testing will help define the prothrombotic period allowing for appropriate initiation and cessation of anticoagulant pharmaceuticals. These subsequent studies have the potential to allow the development of a real-time coagulation monitoring strategy that could have paramount implications in the management of postoperative patients.

2010 Young Investigator Award winner: Therapeutic aprotinin stimulates osteoblast proliferation but inhibits differentiation and bone matrix mineralization.

Study Design. Analysis of the effect of antifibrinolytics on in vitro bone formation. Objective. As the direct effect of antifibrinolytics on bone formation is unknown, we examined whether antifibrinolytics routinely used in spine surgery, namely, aprotinin and aminocaproic acid, affect osteoblast function in vitro. Summary of Background Data. Antifibrinolytics are used in spine surgery to prevent intraoperative blood loss and decrease the need for transfusion. They are either delivered systemically or included as a component of most tissue sealants. Although the role of the fibrinolytic system in wound healing is well established, reports of indirect effects on normal bone biology are emerging. This suggests that the pharmacological targeting of this system may also influence skeletal mass and integrity. Methods. Osteoblast progenitor cells were cultured with therapeutic doses of aprotinin and aminocaproic acid. The effect of the antifibrinolytics on osteoblast development was determined by measuring cellular viability and proliferation, quantification of matrix mineralization, and genetic analysis of osteoblast differentiation markers. Protease inhibition profiles of the antifibrinolytics were determined by amidolytic chromogenic assays. Results. Therapeutic concentrations of aprotinin dose-dependently inhibited plasmins proteolytic activity, stimulated osteoblast proliferation, and inhibited osteoblast differentiation and matrix mineralization. Aprotinin inhibition of osteoblast differentiation and matrix mineralization could be recovered by removing aprotinin from culture or stimulating cells with bone morphogenetic protein-2 or plasmin. Conversely, aminocaproic acid inhibited plasmins proteolytic activity significantly less than aprotinin and had no effect on osteoblast proliferation, differentiation, or matrix mineralization in its therapeutic range. Conclusion. These findings demonstrate that the antifibrinolytics have drastically different effects on osteoblasts due in part to different efficacies of protease inhibition. Further, this work suggests that the fibrinolytic proteases and their inhibitors have great potential to regulate bone by affecting the processes that control osteoblast growth and differentiation.

Medial Approach for Drainage of the Obturator Musculature in Children

Background: In a recent study designed to determine the anatomic location of infection in children presenting with acute hip pain, fever, and elevated inflammatory markers, we demonstrated the incidence of infection of the musculature surrounding the hip to be greater than twice that of septic arthritis. Importantly, the obturator musculature was infected in >60% of cases. Situated deep in the pelvis, surrounding the obturator foramen, debridement of these muscles and placement of a drain traditionally requires an extensive ilioinguinal or Pfannenstiel approach, placing significant risk to the surrounding neurovascular structures. We hypothesized that the obturator internus and externus could be successfully debrided using a limited medial approach. Methods: An IRB-approved prospective study of children (0 to 18 y) evaluated in the pediatric emergency department by an orthopaedic surgeon to rule out septic hip arthritis at a tertiary care children’s hospital (July 1, 2010 to June 30, 2012) was conducted. Infected obturator musculature was identified and confirmed using magnetic resonance imaging. Cadaveric dissection was performed comparing the ilioinguinal, Pfannenstiel, and proposed minimally invasive medial approach. The proposed approach was utilized to debride and place drains in 7 consecutive patients. Results: Anatomic information gained from magnetic resonance images of patients with abscess within the obturator musculature, and from the results of cadaveric studies, allowed for planning of a novel surgical approach. We found that through the surgical approach used to perform an osteotomy of the ischium (Tonnis) the obturator externus could be debrided through the adductor brevis and the obturator internus could be debrided through the obturator foramen. Using our medial approach, resolution of symptoms in all children who underwent surgical drainage resulted without complication. Conclusions: Our medial approach can safely access the obturator musculature for abscess decompression and drain placement with successful results. Advantages to this approach include: lower risk to neurovascular structures within the pelvis, less soft tissue trauma, and similarity to current techniques used for adductor lengthening, medial reduction of the dislocated hip, and osteotomy of the ischium. Level of Evidence: Level II.