Our goal is to repurpose drugs to block the growth of lung metastases, the lethal process in osteosarcoma. We therefore screened the NCI-panel of 114 FDA-approved oncology drugs to identify agents that potently reduce growth of osteosarcoma spheroids (sarcospheres). We first developed a system to routinely generate large numbers of highly-uniform spherical sarcospheres (1/well) with a 400um diameter, to most closely simulate micrometatases. Our primary drug screen (Z’-factor=0.70+0.10) utilized sarcospheres from three highly-metastatic human osteosarcoma cell lines (LM7, 143B, and MG63.3) in the presence and absence of MAP chemotherapeutics. Dose-response experiments with 13 of the most effective drugs confirmed initial results and allowed comparison with each drug's toxicity on normal human osteoblasts and normal small airway epithelial cells. Romidepsin, a HDAC inhibitor (HDACi), had the most favorable toxicity/efficacy ratios (TD₅₀/IC₅₀=57–580, depending on cell line). The only other HDACi in the panel of FDA-approved drugs (vorinostat) also ranked highly in the screen. Since newer HDACi's may have improved toxicity/efficacy ratios, we compared romidepsin and vorinostat with the three other HDACi's that are FDA-approved (belinostat, panobinostat, and valproic acid) plus one that is in clinical trials (entinostat). Romidepsin (C_max/IC₅₀=36–360) and belinostat (C_max/IC₅₀=14–20) reduced sarcosphere growth at clinically-achievable levels, in the presence or absence of MAP. Importantly, both romidepsin and belinostat were synergistic with MAP (BLISS scores=5–15). Propidium iodide staining showed that both romidepsin and MAP substantially induced cell death throughout the sarcospheres. Our results strongly support future studies to determine effects of romidepsin and belinostat on growth of lung metastases in vivo.

Objective

Dunkin Hartley guinea pigs, a commonly used animal model of osteoarthritis, were used to determine if high frequency ultrasound can ensure intra-articular injections are accurately positioned in the knee joint.

Introduction:

Recently there has been interest in an alternative method of aligning a total knee arthroplasty (TKA) referred to as kinematic alignment. The theoretical appeal of this method is that alignment of each patient's knee can be individualized through the use of preoperative imaging and computer software, with the goal of achieving pre-arthritic alignment through restoration of the axes of rotation of each particular knee. Clinical studies have evaluated the outcomes of this new alignment technique, but to date there have been no randomized controlled trials comparing kinematic alignment to mechanical alignment. This randomized controlled trial was conducted to compare kinematically aligned and mechanically aligned TKA outcomes of knee pain, function and motion at two years' post-op, along with a comparison of limb, knee, and implant alignment of the two methods.

Purpose

The coronoid and collateral ligaments are key elbow stabilizers. When repair of comminuted coronoid fractures is not possible, prosthetic replacement may restore elbow stability. A coronoid prosthesis has been designed with an extended tip in an effort to augment elbow stability in the setting of residual collateral ligament insufficiency. The purpose of this biomechanical study, therefore, was to compare an anatomic coronoid replacement with an extended tip implant both with and without ligament insufficiency.

Purpose

Limited information is available regarding the functional outcomes of radial head fractures managed with open reduction and internal fixation (ORIF). The purpose of this study was to determine the functional outcomes of radial head fractures treated with ORIF.

Purpose

Radial head implant over-lengthening, a common cause of capitellar wear and clinical failure, is difficult to diagnose using radiographs of the injured elbow. The purpose of this study was to determine if a novel measurement technique based on contralateral elbow radiographs, termed the RACER method, could be used to accurately estimate the magnitude of radial head implant over-lengthening. Part I of this study examined the side-to-side consistency of radiographic landmarks used in the measurement technique. Part II of this study validated the technique using simulated radial head implant over-lengthening in a cadaveric model.

Purpose

There have been a number of described techniques for sizing the diameter of radial head implants. All of these techniques, however, are dependent on measurements of the excised native radial head. When accurate sizing is not possible due to extensive comminution or due to a previous radial head excision, it has been postulated that the proximal radioulnar joint (PRUJ) may be used as an intraoperative landmark for correct sizing. The purpose of this study was to: 1) determine if the PRUJ could be used as a reliable landmark for radial head implant diameter sizing when the native radial head in unavailable, and (2) determine the reliability of measurements of the excised radial head.

Purpose

Current coronoid fracture classification systems are based on fragment size and configuration using plain radiographs and/or CT. During surgery, coronoid fracture fragments appear much larger than anticipated because cartilage is radiolucent and therefore not taken into account with preoperative imaging. The purpose of this study was to quantify the articular cartilage thickness of the coronoid process, with reference to coronoid fracture classifications.

Purpose

The coronoid process is an integral component for elbow stability. In the setting of a comminuted coronoid fracture, where repair is not possible, a prosthetic device may be beneficial in restoring elbow stability. The hypothesis of this in-vitro biomechanical study was that an anatomic coronoid prosthesis would restore stability to the coronoid deficient elbow.

Purpose

Capitellum hemiarthroplasty is an emerging concept. The current metallic capitellar implants have spherical surface shapes, but the native capitellum is not spherical. This study evaluated the effect of capitellar implant shape on the contact mechanics of the radiocapitellar joint when articulating with the native radial head.

Purpose of the study

Release of tight lateral structures is an integral part of balancing the valgus knee during knee replacement surgery. The posterolateral capsule is released through an inside-out technique. The common peroneal nerve is in close proximity to the capsule during this step. This study was undertaken to determine the distance of the nerve and the safe level for the posterolateral release.

Rapid prototyping (RP), especially useful in surgical specialities involving critical three-dimensional relationships, has recently become cheaper to access both in terms of file processing and commercially available printing resources.

One potential problem has been the accuracy of models generated. We performed computed tomography on a cadaveric human patella followed by data conversion using open source software through to selective-laser-sintering of a polyamide model, to allow comparative morphometric measurements (bone v. model) using vernier calipers. Statistical testing was with Student's t-test.

No significant differences in the dimensional measurements could be demonstrated. These data provide us with optimism as to the accuracy of the technology, and the feasibility of using RP cheaply to generate appropriate models for operative rehearsal of intricate orthopaedic procedures.

Hip resurfacing arthroplasty is an established and effective intervention for osteoarthritis of the hip in the young active patient, relying on the principle of femoral bone-stock preservation. A recognised mode of failure is neck thinning leading to radiological evidence of neck collapse and clinical failure.

We report on a series of these slow-neck-failure patients and highlight the increased incidence of this phenomenon in post-menopausal female patients. This is a single operator, single implant series; 172 cases were identified from databases at our institution. 76 were female, mean (SD) age 52 (7) years. 96 were male, mean (SD) age 51(12) years. 15 (8.7%) patients required revision. 12 (80%) were female, 9 (75%) of these were due to slow neck failure. In the men one patient developed ALVAL requiring removal of his bilateral hip resurfacings, the other failure mode was early femoral neck failure. Mean time to failure was 6 months in men and 37 months in women. This difference in failure rates is also seen in the NJR figures.

This review confirms the relatively high incidence of premature failure in post-menopausal females. NICE guidance in 2003, currently under review, stated that resurfacing is indicated in male patients up to 65 and female patients up to 60. As a result of this study we are currently advising post-menopausal patients that this risk of early failure may make total hip replacement a preferable option to resurfacing arthroplasty.

Introduction

Osteonecrosis (ON) is a disease that ultimately results in bone collapse. We investigated the correlation between SNPs and osteonecrosis.

Introduction

Osteonecrosis (ON) is one of the most debilitating skeletal disorders. Most patients with ON of the femoral head eventually require surgery, usually total hip arthroplasty, within a few years of disease onset. Previous reports have shown that alendronate reduces osteoclastic activity and reduces the incidence of femoral head collapse in osteonecrotic hips. A randomized study to examine the ability of alendronate to delay or prevent femoral head collapse was performed.

Purpose: Techniques to quantify soft-tissue forces in the upper extremity are not well described. Consequently, ligament forces of the elbow joint have not been reported. Knowledge of the magnitudes of tension of the primary valgus stabilizer, the anterior bundle of the medial collateral ligament (AMCL), would allow for an improved understanding of the load bourne by the ligament. The purpose of this in vitro study was to quantify the magnitude of tension in the native AMCL throughout flexion with the arm in the valgus orientation. We hypothesized that tension in the AMCL would increase with flexion.

Method: Five fresh-frozen cadaveric upper extremities (mean age 72 ± 10 years) were tested. To produce active muscle loading in a motion simulator, cables were affixed to the distal tendons of the brachialis, biceps brachii, triceps brachii, and brachioradialis and attached to actuators. The wrist was fixed in neutral flexion/extension and the forearm in neutral rotation. The arm was orientated in the valgus gravity-loaded position. A custom designed ligament load transducer was inserted into the AMCL. Active simulated flexion was achieved via computer-controlled actuation while passive elbow flexion was achieved by an investigator manually guiding the arm through flexion. Motion of the ulna relative to the humerus was measured using a tracking device.

Results: Both the active and passive motion pathways showed an increase in AMCL tension with increasing angles of elbow flexion (p < 0.05). There was no difference in AMCL tension levels between active and passive elbow flexion (p = 0.20). The mean maximum tension achieved was 97±33N and 94±40 N for active and passive testing respectively.

Conclusion: AMCL tension levels were observed to increase with elbow flexion, indicating that other structures (such as the joint capsule and the shape of the articulation) are likely more responsible for joint stability near full extension, and that the AMCL is recruited at increased angles of elbow flexion. With respect to load magnitudes, Regan et al. found the maximum load to failure of the AMCL was 261 N, while Armstrong et al. reported a failure load of 143 N in cyclic testing. The maximum AMCL tension level observed in this study was 160 N. Failure of the AMCL was not observed, which may be due to differences in specimen size, age, or the method of load application. In summary, this in vitro cadaveric study has provided a new understanding of the magnitudes of AMCL tension through the arc of elbow flexion, and this has important implications with respect to the desired target strength of repair and reconstruction techniques. These findings will also assist in the development and validation of computational models of the elbow.

Purpose: Most displaced olecranon fractures can be treated with ORIF. However with severe comminution or bone loss, excision of the fragments and repair of the triceps to the ulna is recommended. The triceps can be reattached to either the anterior or posterior aspect of the ulna. The purpose of this in-vitro study was to determine the effect of triceps repair technique on elbow laxity and extension strength in the setting of olecranon deficiency.

Method: Eight unpreserved cadaveric arms were used (age 75 ± 11 years). Surface models were generated from CT images and sequential olecranon resections in 25% increments were performed using real-time navigation. Muscle tendons (biceps, brachialis, brachioradialis and triceps) were sutured to actuators of an elbow motion simulator, which produced active extension. A tracking system recorded kinematics in the varus and valgus positions. A triceps advancement was performed using either an anterior or posterior repair to the remaining olecranon in random order. Triceps extension strength was measured in the dependent position with the elbow flexed 90° using a force transducer located at the distal ulnar styloid, while triceps tension was increased from 25–200 N. Outcome variables included maximum varus-valgus elbow laxity and triceps extension strength. Two-way repeated measures ANOVAs were performed for laxity comparing resection level and repair method. Three-way repeated measures ANOVAs were performed for triceps extension strength comparing triceps tension, resection level and repair method. Significance was set at p < 0.05.

Results: Progressive olecranon resection increased elbow laxity (p < 0.001). Although the posterior repair produced slightly greater laxity for all but the 50% resection, this difference was not significant (p = 0.2). The posterior repair provided greater extension strength than the anterior repair at all applied triceps tensions and for all olecranon resections (p = 0.01). The initial 0% resection reduced extension strength for both repairs (p < 0.01), however, there was no effect of progressive olecranon resections (p = 0.09).

Conclusion: There was no significant difference in laxity between the anterior and posterior repairs. Thus even for large olecranon resections, the technique of triceps repair does not have significant influence on joint stability. Extension strength was not reduced by progressive olecranon resections, perhaps due to wrapping of the triceps tendon around the trochlea putting it in-line with the ulna and giving it a constant moment arm. Triceps extension strength was higher for the posterior repair. This is likely due to the greater distance and hence moment arm of the posterior repair to the joint rotation center. Conversely, the anterior repair brings the triceps insertion closer to the joint center, reducing the moment arm. Since there was no significant difference in laxity between the repairs, the authors favour the posterior repair due to its significantly higher triceps extension strength.

Purpose: This in-vitro study examined the effect of simulated Colles fractures on load transmitted to the distal ulna, using an in-line load cell. Our hypothesis was distal radial fracture malposition will increase distal radial ulnar joint (DRUJ) load relative to the native position of the radius.

Method: Eight fresh frozen upper-extremities were mounted in a motion simulator which enabled active forearm rotation. An osteotomy was performed just proximal to the distal radioulnar joint, and a 3-degree of freedom modular appliance was implanted which simulated Colles type distal radial fracture deformities. This device allowed for accurate adjustment of dorsal angulation and translation (0, 10, 20 and 30 degrees dorsal angulation and 0, 5 and 10mm dorsal translation both isolated and in combination). A 6-DOF load cell was inserted in the distal ulna 1.5 cm proximal to the ulnar head to quantify DRUJ joint forces. Distal ulnar loading was measured following simulated distal radial deformities with both an intact and sectioned triangular fibrocartilage complex (TFCC).

Results: The maximum resultant transverse distal ulnar load occurred during active forearm pronation and supination. Increasing magnitudes of dorsal angulation and translation of the distal radius increased loading in the distal ulna. For pronation with the ligaments intact, the transverse resultant load for the non-fracture, native positioning was significantly lower (p< 0.05) than the majority of malpositioned cases except for the translations only (not combined with angulation). However, all fracture orientations for supination had an increased effect on the resultant loading (p< 0.05) when ligaments were intact. Greater forces were measured in the distal ulna when the TFCC intact relative to TFCC sectioning. Sectioning the TFCC eliminated the effect of fracture malposition for both pronation and supination. The range of maximum transverse force for intact pronation and supination was between 118& #61617;34N and 130& #61617;39N, respectively. Similarly, for sectioned pronation and supination, the maximum transverse forces were and 93& #61617;40N and 89& #61617;24N, respectively.

Conclusion: Malpositioning of distal radial fractures in dorsal translation and angulation was found to increase forces in the distal ulna, which may be an important source of residual pain following malunion of Colles fractures. Healing of the distal radius in an anatomic position resulted in the least forces. Sectioning the TFCC released the tethering effect of the radius on the ulna, decreasing DRUJ force. This is the first study of its kind to attempt to quantify the forces at the DRUJ as a result of Colles fractures, and these early findings provide important baseline information related to the biomechanics of the DRUJ.

Purpose: The identification of anatomical landmarks is an important aspect of joint surgery, to ensure proper placement and alignment for implants and other reconstructive procedures. At the elbow, the center of the capitellum (derived via a digitization of the surface and subsequent sphere fitting) has been well established as a key landmark to identify the axis of rotation of the joint. For some cases, and in particular minimally invasive surgery, only small regions of the capitellum may be exposed which may lead to errors in determining the centre. The purpose of this study was to identify the optimal location of digitizations of the capitellum.

Method: Twenty-five fresh frozen cadaveric distal humeri (19 left, 6 right) were studied. Using an x-ray computed tomography scanner, volumetric images of each specimen were acquired and used to reconstruct a 3-dimensional digital model of the specimen using the Visualization Toolkit (VTK). A sphere-fit algorithm was used to determine the centre of the spherical capitellum based on manually chosen (digitized) points across the 3D capitellar surface. The true geometric centre was located by digitizing points across the entire capitellar surface. Three sub-regions of the capitellum, commensurate with typical surgical approaches with minimal dissection, were then digitized. These were superior anterior lateral (SAL), inferior anterior lateral (IAL) and a combination of these two regions. These regions were compared to the true center using a 1-way Repeated Measures ANOVA with significance set to p = 0.05.

Results: Digitizations of only SAL and IAL sub-regions resulted in the largest differences relative to the true centre: SAL = 3.9±3.4 mm, IAL = 4.2±3.4 mm, (p < 0.0005). There was no difference between SAL and IAL (p = 1.0). Digitization of the combined SAL + IAL regions, while significantly different from the entire capitellum, resulted in the smallest mean difference of 0.87±0.84 mm.

Conclusion: These data show that the region of digitization affects the accuracy of predicting the capitellum centre. In a previous study by our group, we showed that an accurate determination of the centre of a sphere can be achieved with a small surface area of digitization. In the current study, the large errors that occurred when a small surface was digitized (i.e. SAL and IAL alone), are in all likelihood, due the non-spherical nature of the capitellum. In summary, while the most precise method in locating the true centre is to digitize the entire capitellar surface where possible, an alternative approach is to digitize both the superior and inferior anterior lateral regions.

Purpose: The purpose of this study was to determine the effect of serial olecranon resections on elbow stability.

Method: Eight fresh, previously frozen cadaveric arms underwent CT scanning. The specimens were mounted in an in-vitro motion simulator, and kinematic data was obtained using an electromagnetic tracking system. Simulated active and passive flexion was produced with servo-motors and pneumatic pistons attached to specific muscles. Flexion was studied in the dependent, horizontal, varus, and valgus positions. Custom computer navigation software was utilized to guide serial resection of the olecranon in 12.5% increments. A triceps advancement repair was performed following each resection.

Results: Serial olecranon resections resulted in a significant increase in valgus-varus (V-V) laxity for both passive (p< 0.001) and active (p=0.04) flexion. For passive motion this increase reached statistical significance following the 12.5% resection. This corresponded to an increase in V-V laxity of 1.4 ± 0.1o and a total laxity of 7.5 ± 1.0o. For active flexion this increase reached significance following the 62.5% resection. This corresponded to an increase in V-V laxity of 5.6 ± 1.1o and a total laxity of 11.2 ± 1.5. There was no significant effect of sequential olecranon excision on elbow kinematics or stability with the elbow in the vertical or horizontal positions. The elbows became grossly unstable after resection of greater than 75% of the olecranon.

Conclusion: A progressive increase in the varus-valgus laxity of the elbow was seen with sequential excision of the olecranon. Laxity of the elbow was increased with excision of 75% of the olecranon, likely due to the loss of the bony congruity and attachment site of the posterior band of the medial collateral ligament. Gross instability resulted when 87.5% or greater was removed, likely due to damage to the anterior band of the medial collateral ligament as it inserts on the sublime tubercle of the ulna. Rehabilitation of the elbow with the arm in the dependant position should be considered following excision of the olecranon; varus and valgus orientations should be avoided. The contribution of the olecranon to elbow stability may be even more important in patients with associated ligament injuries or fractures of the elbow.