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Objective The aim of this study was to determine the biomechanical behaviour of a novel distraction–fusion system, consisting of an intervertebral distraction screw, pedicle locking screws and connecting rods, in the canine caudal cervical spine. Study Design Biomechanical study in cadaveric canine cervicothoracic (C3–T3) spines (n = 6). Cadaveric spines were harvested, stripped of musculature, mounted on a four-point bending jig, and tested using non-destructive four-point bending loads in extension (0–100 N), flexion (0–60 N) and lateral bending (0–40 N). Angular displacement was recorded from reflective optical trackers rigidly secured to C5, C6 and C7. Data for primary and coupled motions were collected from intact spines and following surgical stabilization (after ventral annulotomy and nucleotomy) with the new implant system. Results As compared with the intact spine, instrumentation significantly reduced motion at the operated level (C5-C6) with a concomitant non-significant increase at the adjacent level (C6-C7). Conclusion The combination of a locking pedicle screw-rod system and intervertebral spacer provides an alternative solution for surgical distraction–stabilization in the canine caudal cervical spine and supports the feasibility of using this new implant system in the management of disc-associated cervical spondylomyelopathy in dogs. The increase in motion at C6-C7 may suggest the potential for adjacent level effects and clinical trials should be designed to address this.

The use of extracorporeal shock wave therapy (ESWT) for the treatment of delayed or non-union of long bone fractures has been described in human patients with encouraging results. This case report describes the successful treatment of a mandibular fracture non-union with ESWT. To authors' knowledge, this is the first report of the clinical use of ESWT for the management of a non-union in a dog.

The Imaging in 2020 meeting convenes biannually to discuss innovations in medical imaging. The 2018 meeting, titled “Visualizing the Future of Healthcare with MR Imaging,” sought to encourage discussions of the future goals of MRI research, feature important discoveries, and foster scientific discourse between scientists from a variety of fields of expertise. Here, we highlight presented research and resulting discussions of the meeting.

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Diffuse idiopathic skeletal hyperostosis (DISH) is a disorder of unknown cause, in which new bone forms in soft tissues attached to the skeleton. Originally described in humans, in whom it is quite common, it is usually asymptomatic. New bone may completely bridge across joints, especially in the spine. However, it can be difficult to distinguish from diseases such as spondyloarthritis and spondylosis. With safer and increased use of radiography in diagnosis, the unfamiliar skeletal changes of asymptomatic DISH may now be coincidentally revealed during investigation of other disorders and result in misdiagnosis and unnecessary treatment. There have been case reports of its occurrence in great apes, but this is the first study to illustrate its appearances in a series of 11 skeletons of western and eastern lowland gorillas (Gorilla gorilla gorilla and Gorilla beringei graueri) from zoos in Europe and the United States. The study combines a review of available clinical and postmortem records with examination of the skeletons and radiologic investigation, such as computed tomography (CT). The results indicate that the disorder is probably common in older (>30 yr) captive gorillas, but that it is asymptomatic. It was not symptomatic during life in any of these animals. Several cases had unexpected features, such as extensive involvement of the thorax and extra-articular sacroiliac and tibiofibular joint fusions that are not typical in humans. By illustrating these skeletons, the study should aid differentiation of DISH from spondylosis (syn spondylosis deformans) and spondyloarhritis. It illustrates those features that are atypical of human DISH. CT scanning is valuable in such cases for examining diagnostically important areas such as sacroiliac joints. Increased awareness of DISH should help with understanding its cause, both in gorillas and humans.

Primary bone tumors or bone metastasis from solid tumors result in painful osteolytic, osteoblastic, or mixed osteolytic/osteoblastic lesions. These lesions compromise bone structure, increase the risk of pathologic fracture, and leave patients with limited treatment options. Primary bone tumors metastasize to distant organs, with some types capable of spreading to other skeletal sites. However, recent evidence suggests that with many solid tumors, cancer cells that have spread to bone may be the primary source of cells that ultimately metastasize to other organ systems. Most syngeneic or xenograft mouse models of primary bone tumors involve intra-osseous (orthotopic) injection of tumor cell suspensions. Some animal models of skeletal metastasis from solid tumors also depend on direct bone injection, while others attempt to recapitulate additional steps of the bone metastatic cascade by injecting cells intravascularly or into the organ of the primary tumor. However, none of these models develop bone metastasis reliably or with an incidence of 100%. In addition, direct intra-osseous injection of tumor cells has been shown to be associated with potential tumor embolization of the lung. These embolic tumor cells engraft but do not recapitulate the metastatic cascade. We reported a mouse model of osteosarcoma in which fresh or cryopreserved tumor fragments (consisting of tumor cells plus stroma) are implanted directly into the proximal tibia using a minimally invasive surgical technique. These animals developed reproducible engraftment, growth, and, over time, osteolysis and lung metastasis. This technique has the versatility to be used to model solid tumor bone metastasis and can readily employ grafts consisting of one or multiple cell types, genetically-modified cells, patient-derived xenografts, and/or labeled cells that can be tracked by optical or advanced imaging. Here, we demonstrate this technique, modeling primary bone tumors and bone metastasis using solid tumor graft implantation into bone.

Female physicians rarely choose spine surgery as their specialty. Although the specialty's nature and its associated lifestyle are potential barriers, gender-related issues may play an important part.To evaluate the gender discrimination among spine surgeons across Latin America.Cross-sectional survey.The participants in this study were 223 AO Spine Latin America (AOSLA) registered members who answered the web-based survey.Personal and professional demographics; gender-related objective and subjective experiences regarding career and personal life.A survey link containing a 24-item questionnaire was sent to the members' e-mails in September 2019. The survey was designed to evaluate the perception of gender discrimination by spine surgeons during their academic and professional lives.Out of 223 members who answered the survey, 196 (87.96%) were male and 27 (12.11%) female. Most were orthopedic surgeons (64.13%), ≥40 years of age (55.16%), and had20 years of experience (69.95%). Gender discrimination was more frequent among women than among men (66.67% vs. 1.02%), as did discouragement from becoming a spine surgeon, orthopedic surgeon, or neurosurgeon (81.48% vs. 0.51%). Females reported higher rates of sexual harassment (44.44% vs. 7.65%) and more often felt disadvantaged because of gender (55.56% vs. 2.55%). Working harder than men to achieve the same prestige and lack of female mentorship were the most common obstacles reported by women (55.56%). Residency/fellowship influenced the decision to postpone/avoid having children for 66.67% of women but only 37.75% of men. Creation of a Women's Committee in AO Spine was supported by 74.07% of women and 38.78% of men.Gender-based discrimination affects women more frequently than men in spine surgery. These experiences likely contribute to the low prevalence of female spine surgeons. Efforts to mitigate bias and support the professional development of women in neurosurgery, orthopedics and spine communities are encouraged.

Objective To determine the biomechanical behavior of a novel distraction-stabilization system, consisting of an intervertebral distraction bolt, polyaxial screws, and connecting rods, in the canine lumbosacral spine. Study design Biomechanical study. Sample population Cadaveric canine lumbosacral spines (L4-Cd3) (N = 8). Methods Cadaveric lumbosacral spines were harvested, stripped of musculature, mounted on a 4-point bending jig, and tested in extension, flexion, and lateral bending using nondestructive compressive axial loads (0-150 N). Angular displacement was recorded from reflective optical trackers rigidly secured to L6, L7, and S1. Data for primary and coupled motion were collected from intact spines, after destabilization at L7-S1, and following surgical stabilization with the new implant system. Results As compared with the intact spine, laminectomy resulted in a modest increase in angular displacement at L6-L7 and a marked increase at L7-S1. Instrumentation significantly reduced motion at the operated level (L7-S1) with a concomitant increase at the adjacent level (L6-L7). Conclusion The combination of a polyaxial pedicle screw-rod system and intervertebral spacer provides a versatile solution of surgical stabilization of the lumbosacral joint following surgical decompression in the canine lumbosacral spine. The increase in motion at L6-L7 may suggest the potential for adjacent level effects and clinical trials should be designed to address this question. Clinical relevance These results support the feasibility of using this new implant system for the management of degenerative lumbosacral disease in dogs. The increase in motion at L6-L7 may suggest the potential for adjacent level effects and clinical trials should be designed to address this question.

The use of animals in research is under increasing scrutiny from the general public, funding agencies and regulatory authorities. Our ability to continue to perform in-vivo studies in laboratory animals will be critically determined by how researchers respond to this new reality. This Perspectives article summarizes recent and ongoing initiatives within ORS and allied organizations to ensure that musculoskeletal research is performed to the highest ethical standards. It goes on to present an overview of the practical application of the 3Rs (reduction, refinement and replacement) into experimental design and execution, and discusses recent guidance with regard to improvements in the way in which animal data are reported in publications. The overarching goal of this review is to challenge the status quo, to highlight the absolute interdependence between animal welfare and rigorous science, and to provide practical recommendations and resources to allow clinicians and scientists to optimize the ways in which they undertake preclinical studies involving animals. This article is protected by copyright. All rights reserved

OBJECTIVE: To assess technical feasibility and mechanical properties of 3 locking plate designs (Zero-P, Zero-P VA, and Uniplate 2) for use in the canine cervical spine. STUDY DESIGN: Prospective ex vivo study. ANIMALS: Cadaver cervical spines from skeletally mature large breed dogs (n = 18). METHODS: Specimens were screened using radiography and allocated into balanced groups based on bone density. Stiffness of intact C4-C5 vertebral motion units was measured in extension, flexion, and lateral bending using nondestructive 4-point bend testing. Uniplate 2 was then implanted at C4-C5 and mechanical testing was repeated. Mechanical test data were compared against those from 6 spines implanted with monocortical screws, an allograft ring spacer, and PMMA. RESULTS: The Zero-P and Zero-P VA systems could not be surgically implanted due to anatomical constraints in the vertebral column sizes of the canine cervical spines used in this study. Fixation with Uniplate 2 or with screws/PMMA significantly increased stiffness of the C4-C5 vertebral motion units compared to unaltered specimens (P

OBJECTIVE: To evaluate the safety and efficacy of an intra-articular injection of autologous protein solution (APS) for treatment of canine osteoarthritis (OA). STUDY DESIGN: Prospective, randomized, blinded, placebo-controlled pilot clinical trial. ANIMALS: Client-owned dogs with single limb lameness because of OA in a stifle or elbow joint (n=21). METHODS: Lame dogs, confirmed with OA by physical and lameness examination and imaging, were randomly assigned to control or treatment groups. Owners, blinded to treatment, scored pain (University of Pennsylvania Canine Brief Pain Inventory) and lameness severity (Hudson Visual Analogue Scale [HVAS]). Weight-bearing was assessed by kinetic gait analysis. Dogs were injected intra-articularly with APS (treatment group) or saline solution (control group). Evaluations were performed before injection, and 2 and 12 weeks post-injection. RESULTS: Compared to pretreatment values, APS treatment data showed a significant improvement in week 12 pain scores (improved 25.6% over baseline), lameness scores (improved 15% over baseline) and peak vertical force (PVF; N/kg; increased 14.9% of baseline), as well as vertical impulse (Ns/kg) and PVF normalized to stance time (N/kg/s). Control group dogs improved at week 2 in owner assigned indices, but not force plate values and had no significant improvement in scores or force plate values from pretreatment values at 12 weeks. CONCLUSION: APS injection reduced pain and lameness scores and increased weight-bearing associated with the OA-affected joint in dogs at 12 weeks providing preliminary evidence that APS therapy may be beneficial in the treatment of OA in dogs and supporting pursuit of additional studies.

Objective The goal of this study was to determine whether computer-assisted surgical navigation improves the accuracy of tibial component alignment in canine total knee replacement (TKR). Study Design Retrospective radiographic review and prospective ex vivo study. Sample Population Canine TKR radiographs (n = 17 sets) and canine cadaveric stifles (n = 12). Methods Radiographs from TKR surgical workshops were reviewed to determine the incidence and magnitude of tibial component malalignment. Tibial component alignment was compared after either standard (“surgeon-guided”) component placement or computer-assisted (“navigation-guided”) placement. Results were compared against the current recommendations of a neutral (0° varus–valgus) ostectomy in the frontal plane and 6° of caudal slope in the sagittal plane. A prospective cadaveric study was then undertaken by performing TKR in 12 canine stifle joints. Results Malalignment of >3° in the frontal and sagittal planes was identified in 12% and 24% of the radiographs from the retrospective review, respectively. Surgical navigation reduced both the mean error (P = .007) and the variability in frontal plane alignment (P

OBJECTIVES: To determine whether administration of local anaesthetic at the site of skin incision during open lacrimal drainage surgery under general anaesthesia alters the total dosage of anaesthetic drugs required during total intravenous anaesthesia (TIVA), and whether it alters postoperative pain and recovery. STUDY DESIGN: Masked comparison of a randomized, two-group interventional study. PATIENTS AND METHODS: Patients undergoing unilateral external dacryocystorhinostomy under total intravenous general anaesthesia were recruited from the lacrimal service at Moorfields Eye Hospital between September 2012 and February 2014. The patients were randomised to receive, after induction and stabilisation of general anaesthesia, infiltration of the ipsilateral paranasal tissues with 2.5 ml of 0.5% bupivacaine with 1:100000 epinephrine (“treatment” group), or a sham injection (“control” group); the infiltration was performed about 7 min prior to the skin incision. The infusion rates for propofol and remifentanil were adjusted to maintain a steady intra-operative mean blood pressure of 55–70 mmHg and BIS score of 40–60%. The time taken for extubation of the patient after cessation of TIVA was recorded, and postoperative pain scores (on a Likert scale from 0–10) were taken at regular intervals after extubation. The average intra-operative mean blood pressures, total drug usage, extubation time and pain scores for each of the two groups were compared using two-tail Student's t-testing and Wilcoxon rank sum testing. RESULTS: There were 12 patients (7 female; 58%) in the treatment group and 11 (7 female; 64%) in the control group, with similar average age at surgery (59 years treatment, 53 years control; p = 0.38) The average operative time was 45 min in the treatment group (median 42, range 30–55) and 47 min (median 45; range 37–61) in the control group (p = 0.52). The mean dosage of propofol required to maintain satisfactory GA was significantly less in the “treatment” group (89.8 mcg/kg/min) as compared to the “control” group (mean 126 mcg/kg/min) (p = 0.0007). Likewise, remifentanil dosage was significantly less in the “treatment” group (100 ng/kg/min) as compared to controls (259 ng/kg/min) (p = 0.00007). The mean non-invasive blood pressure was consistently lower during surgery in the “treated” group, and showed less intra-operative variation. After surgery, the patients receiving LA had a significantly shorter extubation time (mean time 6.0 min in “treated” group, 12.1 min in “controls”; P

Objectives Various materials are used to construct splints for mid-diaphyseal tibial fracture stabilization. The objective of this study was to compare construct stiffness and inter-fragmentary bone motion when fibreglass (FG) or thermoplastic (TP) splints are applied to either the lateral or cranial aspect of the tibia in a mid-diaphyseal fracture model. Methods A coaptation bandage was applied to eight cadaveric canine pelvic limbs, with a custom-formed splint made of either FG or TP material applied to either the lateral or cranial aspect of the osteotomized tibia. Four-point bending tests were performed to evaluate construct stiffness and inter-fragmentary motion in both frontal and sagittal planes. Results For a given material, FG or TP, construct stiffness was not affected by splint location. Construct stiffness was significantly greater with cranial FG splints than with cranial TP splints (p Clinical Significance FG produces a stiffer construct, but the difference is not reflected in a reduction in inter-fragmentary motion. For lateral splints, FG splints are associated with reduced inter-fragmentary motion as compared with TP and may therefore have slight superiority for this application.

STUDY DESIGN: Prospective study. OBJECTIVE: To identify proteins with differential expression in the cerebrospinal fluid (CSF) from 15 clinically normal (control) dogs and 15 dogs with cervical spondylomyelopathy (CSM). SUMMARY OF BACKGROUND DATA: Canine CSM is a spontaneous, chronic, compressive cervical myelopathy similar to human cervical spondylotic myelopathy. There is a limited knowledge of the molecular mechanisms underlying these conditions. Differentially expressed CSF proteins may contribute with novel information about the disease pathogenesis in both dogs and humans. METHODS: Protein separation was performed with 2-dimensional electrophoresis. A Student t test was used to detect significant differences between groups (P < 0.05). Three comparisons were made: (1) control versus CSM-affected dogs, (2) control versus non-corticosteroid-treated CSM-affected dogs, and (3) non-corticosteroid-treated CSM-affected versus corticosteroid-treated CSM-affected dogs. Protein spots exhibiting at least a statistically significant 1.25-fold change between groups were selected for subsequent identification with capillary-liquid chromatography tandem mass spectrometry. RESULTS: A total of 96 spots had a significant average change of at least 1.25-fold in 1 of the 3 comparisons. Compared with the CSF of control dogs, CSM-affected dogs demonstrated increased CSF expression of 8 proteins including vitamin D-binding protein, gelsolin, creatine kinase B-type, angiotensinogen, α-2-HS-glycoprotein, SPARC (secreted protein, acidic, rich in cysteine), calsyntenin-1, and complement C3, and decreased expression of pigment epithelium-derived factor, prostaglandin-H2 D-isomerase, apolipoprotein E, and clusterin. In the CSF of CSM-affected dogs, corticosteroid treatment increased the expression of haptoglobin, transthyretin isoform 2, cystatin C-like, apolipoprotein E, and clusterin, and decreased the expression of angiotensinogen, α-2-HS-glycoprotein, and gelsolin. CONCLUSION: Many of the differentially expressed proteins are associated with damaged neural tissue, bone turnover, and/or compromised blood-spinal cord barrier. The knowledge of the protein changes that occur in CSM and upon corticosteroid treatment of CSM-affected patients will aid in further understanding the pathomechanisms underlying this disease. LEVEL OF EVIDENCE: N/A.

Objective To describe the magnetic resonance imaging (MRI), arthroscopic, and histopathologic changes in dogs with medial coronoid disease and to identify potential relationships between these findings. Study Design Retrospective case series. Sample Population Twenty-five diseased medial coronoid processes (MCP) were collected from 19 dogs with a confirmed diagnosis of medial coronoid disease that were surgically treated by subtotal coronoid ostectomy. A reference group of normal MCP was collected from 9 dogs euthanatized for reasons unrelated to elbow disease. Methods MCP specimens were evaluated by MRI using a novel grading scheme (all dogs), arthroscopy using a modified Outerbridge scheme (affected dogs only) and histopathology (all dogs). Results The common histopathologic findings were subchondral microfractures, subchondral microfractures continuous with cartilaginous fissures, moderate to severe hypercellularity of the marrow space, trabecular bone necrosis, and articular cartilage degeneration. The severity of cartilage disease in the MCP was moderate to severe in most specimens, even in cases with minimal arthroscopic pathology. Three distinct patterns of bone marrow lesion (BML) were identified adjacent to the MCP, but there was no correlation between BML pattern and either histopathologic or arthroscopic findings. There was moderate correlation between modified Outerbridge scores and MRI scores. No correlation was identified between the histopathologic changes and either MRI or arthroscopic scores. Conclusion There was no significant correlation between the clinical scores and histopathologic changes. Ongoing improvements in the resolution of noninvasive imaging techniques will likely improve description and understanding of the MCP disease in dogs.

Although magnetic resonance imaging (MRI) has been increasingly used as a diagnostic tool for cervical spine injuries in canines, a comprehensive normal MRI anatomy of the canine cervical spine muscles is lacking. Therefore, the purpose of this study was to build a magnetic resonance imaging atlas of the normal cross sectional anatomy of the muscles of the canine cervical spine. MRI scans were performed on a canine cadaver using a combination of T1 and T2-weighted images in the transverse, sagittal and dorsal planes acquired at a slice thickness of 1 mm. Muscle contours were traced manually in each slice, using local osseous structures as reference points for muscle identification. Twenty-two muscles were traced in 401 slices in the cervical region. A three dimensional surface model of all the contoured muscles was created to illustrate the complex geometrical arrangement of canine neck muscles. The cross-sectional area of the muscles was measured at the mid-level of each vertebra. The accuracy of the location of the mapped muscles was verified by comparing the sagittal view of the 3D model of muscles with still photographs obtained from anatomic canine cadaver dissection. We believe that this information will provide a unique and valuable resource for veterinary researchers, clinicians and surgeons who wish to evaluate MRI images of the cervical spine. It will also serve as the foundation for ongoing work to develop a computational model of the canine cervical spine in which anatomical information is combined with electromyographic, kinematic and kinetic data.

Basic science studies remain a critically important part of the knowledge-discovery process in musculoskeletal patient care. This article highlights several of the key advances in orthopaedic basic science over the past year. It should be noted that some topics of tremendous basic science interest, most notably orthopaedic infection and neoplasia, are not covered in detail in this article because they have been the focus of previous Specialty Update articles in The Journal 1 , 2 . ### A Joint as an Organ It is now widely accepted that a joint is best considered an organ, rather than a simple tissue, and that osteoarthritis (OA) represents a spectrum of pathologies affecting several of the core structures that make up the joint. Early understanding of OA focused on the changes that were grossly evident on joint inspection, including cartilage degradation, subchondral bone sclerosis, synovial inflammation, and osteophyte formation. More recently, this picture has been expanded to include the contributions of local changes in peri-articular muscles, nerves, and intra-articular structures such as the fat pad. This expanded understanding of the complexity of joint structure and function3 should facilitate the development of more robust and productive in vitro models for studying joint disease and its management. It will also drive the development of more effective regenerative strategies that target multiple aspects of organ function, rather than focusing on cartilage repair/regeneration alone. ### Posttraumatic OA The majority of preclinical, induced (i.e., nonnatural) models of OA involve the creation of traumatic instability within the joint. Although this may limit the translational relevance of studies performed with these models, particularly with regard to the efficacy of pharmacological or biological therapies, it has facilitated notable recent advances in our understanding of the effects of trauma on function of the joint organ. Blaker et al. reported on the use of mouse models of posttraumatic OA (PTOA) and …

Objective—To determine efficacy of a single intra-articular injection of an autologous platelet concentrate for treatment of osteoarthritis in dogs. Design—Randomized, controlled, 2-center clinical trial. Animals—20 client-owned dogs with osteoarthritis involving a single joint. Procedures—Dogs were randomly assigned to a treatment or control group. In all dogs, severity of lameness and pain was scored by owners with the Hudson visual analog scale and the University of Pennsylvania Canine Brief Pain Inventory, respectively, and peak vertical force (PVF) was determined with a force platform. Dogs in the treatment group were then sedated, and a blood sample (55 mL) was obtained. Platelets were recovered by means of a point-of-use filter and injected intra-articularly within 30 minutes. Control dogs were sedated and given an intra-articular injection of saline (0.9% NaCl) solution. Assessments were repeated 12 weeks after injection of platelets or saline solution. Results—Dogs weighed between 18.3 and 63.9 kg (40.3 and 140.6 lb) and ranged from 1.5 to 8 years old. For control dogs, lameness scores, pain scores, and PVF at week 12 were not significantly different from pretreatment values. In contrast, for dogs that received platelet injections, lameness scores (55% decrease in median score), pain scores (53% decrease in median score), and PVF (12% increase in mean PVF) were significantly improved after 12 weeks, compared with pretreatment values. Conclusions and Clinical Relevance—Results suggested that a single intra-articular injection of autologous platelets resulted in significant improvements at 12 weeks in dogs with osteoarthritis involving a single joint.

OBJECTIVE To compare biomechanical stiffness of cadaveric canine cervical spine constructs stabilized with bicortical stainless steel pins and polymethylmethacrylate (PMMA), monocortical stainless steel screws with PMMA, or monocortical titanium screws with PMMA. STUDY DESIGN Biomechanical cadaver study. ANIMALS Eighteen canine cervical vertebral columns (C2-C7) were collected from skeletally mature dogs (weighing 22-32 kg). METHODS Specimens were radiographed and examined by dual energy X-ray absorptiometry. Stiffness of the unaltered C4-C5 intervertebral motion unit was measured in extension, flexion and lateral bending using non-destructive 4-point bend testing. Specimens were then stabilized by (1) bicortical stainless steel pins/PMMA, (2) monocortical stainless steel screws/PMMA, or (3) monocortical titanium screws/PMMA. Mechanical testing was repeated and stiffness data from unaltered specimens and the 3 treatment groups were compared. RESULTS All 3 surgical methods significantly increased stiffness of the C4-C5 motion unit compared with the unaltered specimen (P

Summary Objectives: To evaluate the in vitro anti -bacterial activity of a silver-impregnated coating against a biofilm-forming strain of methicillin-resistant Staphylococcus pseud -intermedius (MRSP). Methods: A clinical MRSP isolate sourced from a failed canine knee implant was evaluated for biofilm production and used in the present study. Using a standard test method and a clinically approved titanium substrate, the antimicrobial activity of a novel silver plasma coating was determined at two times: five minutes after inoculation of the specimens (T0) and after 24 hours of incubation (T24). Scanning electron microscopy was used to evaluate the biofilm formation on specimens. Results: The tested clinical MRSP isolate was classified as a strong biofilm producer. The silver coating significantly reduced the MRSP growth more than four log steps compared to the non-coated specimens and showed more than 99.98% reduction in the number of colony forming units after 24 hours. Scanning electron microscopy images revealed that silver-coated surfaces did not manifest detectable biofilm, while biofilm formation was readily observed on the control specimens. Clinical significance: The silver coating exhibited excellent activity against the multi-drug resistant biofilm-forming MRSP isolate. The next stage of this work will involve testing in an animal model of orthopaedic infection. Positive results from animal studies would support the introduction of the silver plasma coating as a new strategy for preventing implant contamination, biofilm formation, and surgical infection in dogs undergoing orthopaedic surgery.Supplementary Material for this paper is available online at: http://dx.doi.org/10.3415/VCOT-15-08-0134

Approximately 2 million patients in the United States annually undergo total joint arthroplasty with reaming and placement of intramedullary nails, resulting in extravasation of bone marrow and fat into the circulatory system and potentially causing fat embolism syndrome. Acute and chronic changes in mental status documented after these procedures may be related to embolic events. The Reamer/Irrigator/Aspirator (RIA) device has been shown to decrease intramedullary pressure during reaming. We hypothesized that the use of the RIA in a canine model would reduce the number of microemboli detected in the carotid artery and brain compared with nailing either with or without reaming.Twenty-four large canines underwent unreamed nailing (UR), sequentially reamed nailing (SR), or RIA-reamed nailing (RIA) of bilateral femora (eight dogs per group). During reaming and nailing, the number and size of microemboli transiting the carotid artery were recorded. After euthanasia, the brain was harvested for immunostaining and measurement of microinfarction volumes.Total embolic load passing through the carotid artery was 0.049 cc (UR), 0.045 cc (SR), and 0.013 cc (RIA). The number and size of microemboli in the UR and SR groups were similar; however, the RIA group had significantly fewer larger-sized (200-μm) emboli (p = 0.03). Pathologic examination of the brain confirmed particulate emboli, and histologic analyses demonstrated upregulation of stress-related proteins in all groups, with fewer emboli and less evidence of stress for RIA reaming.RIA reaming decreased microemboli compared with traditional reaming and unreamed nailing, suggesting that intramedullary pressure and heat are important variables. The documented embolic events and brain stress may help to explain subtle neurobehavioral symptoms commonly seen in patients after undergoing long-bone reaming procedures.RIA reaming decreased cranial embolic events and may have an ameliorating effect on postoperative neurologic sequelae.

This review describes recent research efforts focused on increasing the specificity of contrast agents for proton magnetic resonance imaging (MRI). Contrast agents play an indispensable role in MRI by enhancing the inherent contrast of images; however, the non-specific nature of current clinical contrast agents limits their usefulness. This limitation can be addressed by conjugating contrast agents or contrast-agent-loaded carriers—including polymers, nanoparticles, dendrimers, and liposomes—to molecules that bind to biological sites of interest. An alternative approach to conjugation is synthetically mimicking biological structures with metal complexes that are also contrast agents. In this review, we describe the advantages and limitations of these two targeting strategies with respect to translation from in vitro to in vivo imaging while focusing on advances from the last ten years.

Molecules containing multiple lanthanide ions have unique potential in applications for medical imaging including the areas of magnetic resonance imaging (MRI) and fluoresence imaging. The study of multilanthanide complexes as contrast agents for MRI and as biologically responsive fluorescent probes has resulted in an improved understanding of the structural characteristics that govern the behavior of these complexes. This review will survey the last five years of progress in multinuclear lanthanide complexes with a specific focus on the structural parameters that impact potential medical imaging applications. The patents cited in this review are from the last five years and describe contrast agents that contain multiple lanthanide ions.

Cementless fixation for the tibial component in total knee arthroplasty (TKA) remains problematic. Peri-Apatite (PA), a solution-deposited hydroxyapatite, is under investigation as an option for improving the fixation of cementless tibial components. In this study, radiostereometric analysis was used to document implant migration in 48 dogs that underwent TKA with cementless, PA-coated, or cemented tibial components. Migration at 12 weeks was similar in the 2 groups. At 12 months, there was greater migration in the PA-coated group, but the difference between the 2 groups was below the threshold considered clinically significant. In this canine TKA model, cementless fixation with PA performed less well than did cemented fixation, but not to a degree that would make a clinical difference in the short term.

Background: Unloading treatments for osteoarthritis of the knee, such as valgus braces, have been shown to reduce medial joint-loading and pain. The purpose of this preclinical study was to investigate the tissue response to an extracapsular implantable device (KineSpring System; Moximed, Hayward, California) that is designed to reduce loading across the medial compartment of the knee. Methods: Eleven sheep were implanted with the KineSpring System, consisting of bases secured to the medial femoral and tibial cortices with bone screws and also consisting of a joint-spanning load-absorber composed of a piston and spring assembly inside a polymeric sheath. In nine sheep, titanium alloy washers with either an uncoated or a plasma-sprayed titanium-hydroxyapatite (TPS-HA) coated undersurface were fixed with screws to the contralateral femur and tibia to investigate the effects of surface treatment on extracortical bone apposition. The functionality of the KineSpring System was assessed by fluoroscopy, tissue response was determined by gross and microscopic histology, and implant fixation was determined by radiography, microradiography, and histomorphometry at four, twelve, twenty-six, and fifty-two weeks. Results: The function of the KineSpring System was confirmed in all sheep. Seventeen of eighteen TPS-HA coated bases and thirty-six of thirty-six washers had stable bone fixation; one coated base was loose with evidence of infection. At four weeks, there was an early, expected inflammatory response, but this response resolved by twelve weeks and a pseudosynovial membrane formed around the sheath. Bone apposition increased over time for the TPS-HA coated bases and for uncoated washers (p < 0.05). There was good apposition of the TPS-HA coated washers even at early time points, with no subsequent increase in apposition over time. Conclusions: The KineSpring System demonstrated safety in a simulated use model for periods of up to fifty-two weeks. Screws result in stable implant fixation and TPS-HA coating allows for early and long-lasting cortical bone apposition and integration. Clinical Relevance: This implant warrants further investigation as a means of reducing medial compartment loading and pain in patients with osteoarthritis of the knee.

Extensive periosteal stripping (PS) is a risk factor for post-radiation pathologic fracture following surgery for extremity soft tissue tumors. The purpose of this study was to determine the effects of PS on bone structure and mechanical properties. Thirty-one skeletally mature mice underwent PS, with circumferential removal of periosteum from an 8-mm segment of the mid-diaphysis of the left femur. Thirty-one control mice underwent sham surgery in which the femur was isolated without manipulation of the periosteum. At 2, 6, 12, or 26 weeks following surgery, the left femora were examined by micro-CT to quantify cortical thickness (CtTh), cross-sectional area (CSA), bone volume (BV), and polar moment of inertia (PMI). Three-point mechanical bend testing was performed and peak load, stiffness, and energy to failure were determined. PS resulted in significantly decreased CtTh, CSA, BV, and PMI at all time points. Peak load, stiffness, and energy to failure were significantly reduced at 2, 6, and 12 weeks. There were no significant differences in mechanical properties at 26 weeks. In this mouse model, extensive circumferential PS resulted in sustained changes in bone structure that were still evident after 6 months, accompanied by reductions in bone strength that persisted for at least 3 months.

Graphene's single atomic layer of sp(2) carbon has recently garnered much attention for its potential use in electronic applications. Here, we report a memory application for graphene, which we call graphene flash memory (GFM). GFM has the potential to exceed the performance of current flash memory technology by utilizing the intrinsic properties of graphene, such as high density of states, high work function, and low dimensionality. To this end, we have grown large-area graphene sheets by chemical vapor deposition and integrated them into a floating gate structure. GFM displays a wide memory window of ∼6 V at significantly low program/erase voltages of ±7 V. GFM also shows a long retention time of more than 10 years at room temperature. Additionally, simulations suggest that GFM suffers very little from cell-to-cell interference, potentially enabling scaling down far beyond current state-of-the-art flash memory devices.

Objective: To define the kinematic motion patterns of the canine cervical spine, with a particular emphasis on identifying differences between the cranial (C2–C4) and caudal (C5–C7) segments, and to determine the significance of coupled motions (CM) in the canine cervical spine. Study Design: Cadaveric biomechanical study. Sample Population: Cervical spines of 8 Foxhounds. Methods: Spinal specimens were considered free of pathology based on radiographic, computed tomography, and magnetic resonance imaging examinations. All musculature was removed without damaging ligaments or joint capsules. Spines were mounted in a customized pure-moment spine testing jig, and data were collected using an optoelectronic motion capture system. Range of motion, neutral zone and CM in flexion/extension, left/right lateral bending and left/right axial rotation were established. Data were analyzed using mixed-effects maximum likelihood regression models. Results: Total flexion/extension did not change across the 4 levels. There was no difference between flexion and extension, and no CM was identified. Lateral bending was not different across levels, but tended to be greater in the cranial spine. Axial rotation was ∼2.6 times greater in the caudal segments. Lateral bending and axial rotation were coupled. Conclusions: Kinematics of the cranial and caudal cervical spine differed markedly with greater mobility in the caudal cervical spine.

Maintenance ensures the reliability of the equipment to meet operation's demands. Operations ensure the production of sufficient and high quality product. Engineering designs and installs equipment that minimizes risk. Safety ensures that the engineering and administrative controls are in place to minimize that risk. This article presents a concept that combines these reliability and safety efforts, such that the maintenance, operations, engineering and safety groups speak the same language to minimize the overall business risk. This proposed approach combines existing plant reliability efforts with several Process Safety Management elements. The basic steps include identifying safety-critical equipment, ensuring accurate and up-to-date Process Safety Information (PSI), establishing the mechanical integrity (MI) Program, establishing Planned Maintenance (PM) programs, and creating equipment-specific maintenance procedures. The resultant mechanical integrity quality assurance (MI QA) program combines equipment reliability and operational integrity efforts to ensure that the equipment is properly designed (via PSI), fabricated as designed (via PSI and MI), and installed as designed (via Pre-Start-up Safety Reviews). The MI QA program also ensures that the equipment is operated and maintained as designed by trained personnel. Some benefits include being able to: (1) share and document best MI and PM practices between different sites; (2) focus limited PM-related resources on the process safety-critical equipment; and (3) help monitor the essential reliability efforts to ensure continued safe operation. © 2011 American Institute of Chemical Engineers Process Saf Prog, 2011

Objective: To determine whether the fatigue properties of an interlocking nail (ILN) construct are influenced by metaphyseal or diaphyseal location of the locking bolt. Study Design: Ex vivo mechanical investigation. Sample Population: Adult canine femora (n=19 pairs). Methods: Femora were implanted with a 6-mm diameter ILN. In 1 femur, the ILN was locked with a 2.7 mm bolt placed in the diaphysis; the ILN in the contralateral femur was locked with a bolt placed in the metaphysis. Constructs were tested to failure in axial loading (9 pairs) or torsion (10 pairs), with failure defined as displacement>2 mm or a total of 500,000 cycles for axial loading, and rotation>45° for torsional loading. Outcome measures included initial construct stiffness, number of cycles to failure, peak load, and peak torque. After testing, microradiography and histology were used to determine the location and nature of construct failure. Results: Metaphyseal bolts failed at higher axial loads than diaphyseal bolts (P=.03), with bolt failure because of bending at the nail-bolt interface. All of the metaphyseal bolt constructs survived torsional testing whereas 9 of 10 diaphyseal bolt constructs failed catastrophically because of spiral fracture through the adjacent cortical bone. Conclusions: Placement of a locking bolt in metaphyseal bone extends fatigue life under axial loading and decreases the incidence of catastrophic failure under torsional loading.

Background The specific aim of this study was to determine the whether a novel, hydrogel-coated polyester mesh (Scout) can be used to reduce the incidence and severity of adhesion formation in vivo. Methods An established rat model of post-surgical adhesion formation was used in which adhesions are generated through surgical trauma to the surfaces of the cecum and the adjacent abdominal wall. Thirty-seven rats were randomly allocated either to a control group (no intervention; n = 14 rats) or to one of two treatment groups in which the abraded surfaces were separated with either the Scout material (n = 11 rats) or an FDA-approved form of expanded polytetrafluorethylene (PTFE) (PRECLUDE Vessel Guard; n = 12 rats). Animals were euthanized 7 d after surgery and gross necropsy examinations were performed. Mechanical testing was used to measure the strength of any adhesions that were identified, and histology was used to characterize within the adhesion tissue and on the surface(s) of the barrier materials. Results Five animals were excluded because of surgical failure (1 control; 2 PRECLUDE Vessel Guard; 2 Scout). Adhesions were seen in 10 of 13 control animals (77%). There were no adhesions in any of the animals treated with either PRECLUDE Vessel Guard or Scout material. Histology demonstrated mild cellular adhesion to both the PRECLUDE Vessel Guard and the Scout material. Although there was a sub-acute to chronic inflammatory response to the surgical trauma, there was no evidence of delamination, shearing, or degradation of either the Scout material or PRECLUDE Vessel Guard. Conclusions The hydrogel-coated Scout material was as effective as the approved predicate material in this model. Both materials were well tolerated. Further testing of the Scout material is now warranted.

Background: Dogs have a high prevalence of disc-associated cervical spinal cord disorders. Despite this, there are no descriptions of the micromorphometry or cellular characteristics of canine cervical intervertebral discs. Hypothesis/Objectives: To compare micromorphometric and cellular characteristics at 4 disc regions (outer annulus [OA], inner annulus [IA], transitional zone [TZ], nucleus pulposus [NP]). We hypothesized that measurements would differ between chondrodystrophic (CH) and nonchondrodystrophic (NCH) dogs. Animals: Six CH dogs and 6 NCH dogs, under 3 years old. Methods: Histologic sections of all cervical discs from each dog were examined. Micromorphometric variables included relative ratio of ventral to dorsal annulus fibrosus (AF), number and mean width of AF fibers, and relative percentage of NP. Cellular variables included cell density, morphology, and grouping. Results: The NP from CH dogs was smaller, more rounded, and more dorsally located compared with that from NCH dogs. The NP occupied a greater proportion of the disc in NCH dogs compared with CH dogs (27.7 versus 15.8%; P < .001). The ratio of ventral to dorsal AF was approximately 3 : 1 in the CH group and 2 : 1 in the NCH group. Cellular variables were region dependent. Cell density was 2.4-fold higher in the OA compared with the NP. Approximately 50 of NP cells and 4.5% of OA cells occurred in groups. Conclusions and Clinical Importance: Micromorphometric variables differed by CH status. Cellular variables differed by disc region. Our findings potentially can explain the high incidence of intervertebral disc extrusions in CH dogs compared with NCH dogs.

Many patients with symptomatic bone metastases receive radiation therapy, even though radiation is known to have potential adverse effects on bone. We hypothesized that the concurrent use of a bisphosphonate drug (zoledronic acid, ZA) or a combination of ZA plus an anabolic agent (parathyroid hormone, PTH) would lead to improvements in the microarchitecture and mechanical properties of irradiated bone. Human breast cancer cells were injected into the distal femur of 56 female nude mice, which were then divided into four groups: no treatment (0 Gy), radiation administered 4 weeks postinjection (20 Gy), radiation plus ZA (12.5 microg/kg weekly from weeks 4 to 12) (20 Gy + ZA), and radiation followed by ZA (25 microg/kg weekly from weeks 4 to 8) and PTH(1-34) (100 microg microg/kg daily from weeks 8 to 12) (20 Gy + ZA + PTH). Left limbs served as normal control bones. Bone loss over the 12-week study was tracked with serial radiography and bone densitometry. At the end of the study, micro-computed tomography and mechanical testing were used to quantify bone microarchitecture and bone strength. Radiation alone failed to prevent tumor-induced decreases in bone mineral density (BMD), trabecular bone volume, and bone strength. Treatment with 20 Gy + ZA or 20 Gy + ZA + PTH as adjuncts to radiation was effective at preserving trabecular bone architecture and bone strength at normal levels. ZA reduced the risk of mechanical fragility following irradiation of a lytic bone lesion. Supplemental use of PTH did not result in further increases in bone strength but was associated with significant increases in BMD and bone mass, suggesting that it may be beneficial in enhancing bone architecture following radiation therapy.

OBJECTIVE To characterize and compare gait variables in Doberman Pinschers with and without cervical spondylomyelopathy (CSM). ANIMALS 18 Doberman Pinschers (9 clinically normal dogs and 9 CSM-affected dogs). PROCEDURES A neurologic examination was performed on all dogs. The diagnosis of CSM was confirmed with MRI. Temporospatial and kinetic gait variables were measured by use of a pressure-sensitive walkway. Temporospatial variables evaluated included stance phase duration, swing phase duration, gait cycle duration, stride length, and gait velocity. Kinetic variables evaluated included peak vertical force and vertical impulse. Random-effects linear regression was used to determine the difference between CSM-affected and clinically normal dogs for each of the 7 variables. RESULTS Values for temporospatial variables were significantly smaller in the thoracic limbs of CSM-affected dogs, compared with values for the thoracic limbs of clinically normal dogs. For the kinetic variables, peak vertical force was significantly higher in the thoracic limbs than the pelvic limbs for all dogs. Vertical impulse values were higher in the thoracic limbs than the pelvic limbs. There were significant differences in mean vertical impulse between the thoracic and pelvic limbs for both groups. CONCLUSIONS AND CLINICAL RELEVANCE In this study, significant differences in temporospatial variables were identified between the thoracic limbs of clinically normal and CSM-affected dogs, with the values being smaller for the CSM-affected dogs than for the clinically normal dogs. A pressure-sensitive walkway may provide a valid, practical option for rapid, objective assessment of gait and response to treatment in dogs with CSM.

Ewing's sarcoma of bone is a primary childhood malignancy of bone that is treated with X-radiation therapy in combination with surgical excision and chemotherapy. To better study Ewing's sarcoma of bone we developed a novel model of primary Ewing's sarcoma of bone and then treated animals with X-radiation therapy. We identified that uncontrolled tumor resulted in lytic bone destruction while X-radiation therapy decreased lytic bone destruction and increased limb-length asymmetry, a common, crippling complication of X-radiation therapy. Osteoclasts were indentified adjacent to the tumor, however, we were unable to detect RANK-ligand in the Ewing's tumor cells in vitro, which lead us to investigate alternate mechanisms for osteoclast formation. Ewing's sarcoma tumor cells and archival Ewing's sarcoma of bone tumor biopsy samples were shown to express MCSF, which could promote osteoclast formation. Increased monocyte numbers were detected in peripheral blood and spleen in animals with untreated Ewing's sarcoma tumor while monocyte number in animals treated with x-radiation had normal numbers of monocytes. Our data suggest that our Ewing's sarcoma of bone model will be useful in the study Ewing's sarcoma tumor progression in parallel with the effects of chemotherapy and X-radiation therapy.

Eu(II)-containing materials have unique luminescence, redox, and magnetic properties that have potential applications in optoelectronics, sensors, and imaging. Here, we report the synthesis and characterization of Eu(II)-containing aza-222 cryptate that displays yellow luminescence and a quantum yield of 26% in aqueous media. The crystal structure reveals a staggered hula-hoop geometry. Both solid-state and solution-phase data are presented that indicate that the high quantum yield is a result of the absence of OH oscillators in the inner sphere of the complex. We expect that Eu(II)-containing aza-222 cryptate is a step toward Eu(II)-containing luminescent materials that can be used in a variety of applications including biological imaging.

Pathological fracture is a devastating complication of osteolytic bone metastases. The progression of osteolysis and its effect on bone fracture risk are poorly understood. The goal of this study was to determine the temporal changes in bone strength following tumor inoculation in a preclinical model of tumor osteolysis. In addition, a predictive model was developed between non-invasive radiographic measures and bone strength. The right femora of female nude mice were injected with breast cancer cells; the left limb served as a sham-operated control. Radiographs and DEXA scans were obtained at the time of surgery and at 3, 6, and 9 weeks. Groups of mice were euthanized at each time point for mechanical assessment. Micro-CT analysis was performed on a sub-set of mice with advanced state disease to quantify bone loss. Radiographs documented an increase in tumor osteolysis over time, with 58% of the mice showing signs of osteolysis at 3 weeks, 75% at 6 weeks, and 81% at 9 weeks. BMD measurements revealed a 21.6% increase from baseline in the controls whereas tumor-injected femora failed to increase in BMD over the same time course. Tumor-bearing limbs exhibited statistically significant decreases in torque at failure (86%), energy to failure (88%), and initial stiffness (94%) compared to the controls. Both lysis scores and BMD measurements proved to be modest predictors of mechanical strength, accounting for approximately 73% and 41% of variation in torque at failure, respectively. Micro-CT analysis revealed decreases in both total bone volume in the distal femur (31%) and metaphyseal fractional trabecular bone (89%). We have shown that non-invasive radiographic techniques provide a useful tool for monitoring the progression of tumor osteolysis and for predicting the mechanical strength of tumor-bearing bones in this model. By integrating non-invasive measures of tumor osteolysis and fracture risk, we have validated a clinically relevant platform for evaluating new therapeutic approaches for preserving and/or restoring bone affected by metastatic disease.

The principles and indications for primary external dacryocystorhinostomy are outlined, together with a description of a safe and reliable technique that can be used under local or general anaesthesia; the description includes practical details for both the anaesthesia and the surgery. The postoperative management of patients and the complications of the surgery are also presented.

Bone metastasis is a common untreatable complication associated with prostate cancer. Metastatic cells seed in skeletal sites under active turnover containing dense marrow cellularity. We hypothesized that differences in these skeletal-specific processes are among the critical factors that facilitate the preferential localization of metastatic prostate cancer in bone. To test this, athymic mice were administered PTH to induce bone turnover and increase marrow cellularity daily 1 wk before and after intracardiac inoculation of luciferase-tagged PC-3 cells. Tumor localization was monitored by bioluminescence imaging weekly for 5 wk. At the time of tumor inoculation, PTH-treated mice demonstrated significant increases in serum levels of bone turnover markers such as osteocalcin and tartrate-resistant acid phosphatase 5b and in the number of tartrate-resistant acid phosphatase-positive osteoclasts per millimeter of bone when compared with the other groups. Likewise, PTH treatment stimulated a qualitative increase in marrow cellular proliferation as determined by 5-bromo-2'-deoxyuridine immunostaining. Skeletal metastases formed in the hind limb and craniofacial regions of young mice with no difference between groups. In adult mice, however, bioluminescent signals in the hind limb and craniofacial regions were 3-fold higher in PTH-treated mice vs. controls. Fluorochrome labeling revealed increased bone formation activity in trabecular bone adjacent to tumors. When zoledronic acid, a nitrogen-containing bisphosphonate that inhibits osteoclast-mediated bone resorption, was administered concurrently with PTH, a significant reduction in the incidence of bone tumors was observed. Overall, these studies provide new evidence that skeletal sites rich in marrow cellularity under active turnover offer a more congenial microenvironment to facilitate cancer localization in the skeleton.

At therapeutic levels in pediatric patients, radiation causes damage to the growth plate and contributes to growth deformity and fractures. The purpose of this project was to examine the effects of x-ray irradiation on regional bone mineral density (BMD) and osteoclast histology of rat bone with and without radioprotectant amifostine (AMF) pretreatment. Seventy-two weanling rats had their right knee irradiated with single fraction 17.5 Gy, whereas the left leg was used as an internal control. Twelve animals were euthanized at each of 6 time periods (0.5-6 wk) after irradiation, half having received 100 mg/kg amifostine. BMD (g/cm3) was determined for both the right and left femurs using peripheral quantitative computed tomography (CT) (pQCT). Tibial sections were stained for osteoclasts/chondroclasts with tartrate-resistant acid phosphatase. Statistically significant increases in BMD within the radiation field were seen in the treatment groups' right irradiated legs over the control unirradiated left legs at all time points from 0.5 through 6 weeks. Anatomically, a peak in BMD occurs in the region immediately adjacent to the chondro-osseous junction at 2 weeks after irradiation and then moves proximally within the adjacent metaphysis after 3 weeks. Corresponding to these findings, histologically a 2-week nadir occurs after irradiation in osteoclasts/chondroclast numbers adjacent to the chondro-osseous junction with a 71.9% decrease compared with controls (p

Background context: The anterior cervical ligament is routinely excised during cervical interbody fusion. Loss of this ligament may predispose to instability at the fusion site. Anterior plating restores stability but leads to a risk of stress shielding. An alternative approach would be to use a less rigid fixation system that would provide anterior support while allowing micromotion that could enhance bone healing within the fusion site. Purpose: To determine whether augmentation of an interbody fusion with a synthetic ligament en- hances fusion. Study design: Prospective randomized study in a large animal model of cervical fusion. Outcome measures: The primary outcome was evidence of interbody fusion, as determined by radi- ography, computed tomography (CT), histology and biomechanical testing. Methods: Twelve skeletally mature sheep underwent single level (C2-3) anterior discectomy and interbody fusion using fresh frozen allograft. In six animals, the fusion was augmented with a braided polyethylene device rigidly fixed to C2 and C3 with screws. Sheep were euthanized 12 weeks postoperatively. Specimens were radiographed and then examined by CT. Six fusion sites (three control, three augmented) were used for nondestructive biomechanical testing to assess the stability of the fusion site. The remaining specimens were processed for undecalcified histology. Results: As determined by radiography, the augmented group had 83% solid union as compared with 67% in the control group ( p � .05). There was no difference regarding bone graft dislodgment between the two groups. The extension stiffness of the augmented group was significantly higher ( p � .05) than that of controls, but there was no significant difference between the two groups in flex- ion stiffness. There was no significant difference in bone formation in the two groups as determined by CT and histology, although there was a trend for increased endochondral ossification in the aug- mented repairs. There was no evidence of significant adverse tissue reactions to the ligament. Conclusions: Use of a synthetic ligament was associated with a moderate increase in fusion rate and a statistically significant increase in fusion site stiffness in extension. The use of an augmentation device, such as this synthetic ligament, may be beneficial in cervical fusion, especially when multi- level surgery is being contemplated.

Background context: Mechanical forces have been considered responsible for stress shielding an arthrodesis, but the biology of a developing lumbar fusion has not been well characterized. Purpose: A large animal model was used to test the hypothesis that mechanical forces modify the biological processes involved in a developing bony fusion. Study design: Lumbar fusion was performed in an ovine model using custom instrumentation that permitted a controlled degree of anterior-posterior translation after surgery. Fusion sites were evaluated by radiography, microradiography, histology and histomorphometry at time points that corresponded with predicted early and later stages of bone healing. Methods: Fourteen skeletally mature ewes underwent lumbar spinal fusion under general anesthesia. In the control (stable) group, the spine was rigidly fixed with a cage anteriorly and pedicle screws posteriorly. In the experimental (unstable) group, the spine was destabilized by an annulectomy (with no anterior implant) and custom pedicle screws that allowed 2 mm of anterior-posterior translation. Animals were euthanized 6 and 12 weeks after surgery. Results: Radiographs confirmed that the fusion mass had not fully consolidated at either time point. Microradiographs revealed a trend toward increased bone formation at 6 weeks in the stable case as compared with the unstable, but by 12 weeks, this trend had reversed (p=.03). Intramembranous bone formation was the primary mechanism of healing near the transverse process in animals with both stable and unstable fixation. In the area between the two transverse processes, new bone formation occurred primarily through endochondral ossification. At 12 weeks, the stable case had significantly more cartilage formed (p=.023) but less newly formed bone (p=.07) as compared with the quantitatively unstable. Conclusions: This clinically realistic animal model allowed characterization of the biology of the developing arthrodesis before fusion. Under stable or unstable conditions, endochondral ossification was the predominant mechanism of new bone formation within the intertransverse process region. This finding, which contrasts with previous reports from small animal models of spine fusion, may reflect a difference in biology that results from the increased size of the intertransverse space in sheep as compared with small animals. Interestingly, mechanical instability increased the formation of new bone within this region, but not at the transverse process. Endochondral ossification therefore appears to respond to mechanical factors in the fusion site. The ovine model shows promise as an alternative to the rabbit model and may provide a more stringent test for potential new surgical and nonsurgical strategies for spine fusion.

Serum and urinary assays of bone markers provide a noninvasive alternative to bone biopsy in the study of bone metabolism in humans. Many of the commercial assays that were originally developed for use in humans have been shown to cross-react in dogs, and it should therefore be possible to use these assays to study bone remodeling in dogs. The interpretation of bone marker data in humans is hampered by extensive inter- and intra-subject variability. The specific aim of this study was therefore to determine the extent of biological variability in bone markers in dogs. Serum and urine samples were collected every 4 hours over a 24-hour period (short-term study), and every week over a 12-week period (long-term study). Serum bone-specific alkaline phosphatase (BALP) and urinary deoxypyridinoline (Dpd) and N-terminal telopeptide of collagen (NTx) were measured with commercial enzyme immunoassays. Serum osteocalcin (OC) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP) were measured with commercial radioimmunoassays. In the short-term study, statistically significant diurnal rhythms were identified for OC, BALP, ICTP, and Dpd. No clear rhythm was evident for NTx. There was no evidence of statistically significant long-term variability in marker excretion over the 12 weeks. Our findings confirm the utility of these assays in dogs. However, as in humans, care must be taken to ensure that specimens are collected at a consistent time of day. Moreover, given the inherent variability in marker excretion in individual animals, the most appropriate use for these assays is as a screening tool for cohort studies, rather than as a diagnostic or prognostic tool in the individual animal.

Purpose A large animal model is desired for preclinical studies aimed at reconstructing severe mandibular skeletal defects using tissue engineering techniques. To identify the size and location requirements for a mandibular critical-size bone defect in growing pigs, the present study investigated the spontaneous healing of surgically created mandibular defects. Materials and Methods Six 4-month-old domestic pigs were used. In pigs 1 and 2, a 3-, 5-, or 7-cm 3 subperiosteal mandibular defect was created. In pigs 3 to 6, 3- to 5-cm 3 bilateral defects were randomly created at the anterior (apical to the molars) and posterior (mandibular angle) mandibular regions. Spontaneous healing of these defects was assessed by serial computed tomography scans (postoperative week 1, 6, and 12) and histologic analyses. Results In pigs 1 and 2, regardless of defect size, the anterior, but not posterior, defects had largely healed. Systematic analyses of pigs 3 to 6 revealed, first, the extent of defect regeneration from spontaneous healing was significantly less in the posterior than in the anterior defects, with about two thirds and one third of the original defect volume remaining, respectively. Second, histologically, the posterior defects had considerably less regeneration and more evident tapering of the new bone than did the anterior defects. Finally, the buccal periosteum had completely regenerated in the anterior defects, but had only partially done so in the posterior defects. Also, the buccal surface contour was moderately concave in the anterior defects, but it was severely concave in the posterior defects. Conclusions Despite robust spontaneous healing of mandibular defects in growing pigs, 5-cm 3 defects in the mandibular angle region without buccal periosteum would be a reasonable critical-size defect model relevant to mandibular defects in adolescent humans.