COMPARISON BETWEEN COMPUTED TOMOGRAPHIC ARTHROGRAPHY, RADIOGRAPHY, ULTRASONOGRAPHY, AND ARTHROSCOPY FOR THE DIAGNOSIS OF FEMOROTIBIAL JOINT DISEASE IN WESTERN PERFORMANCE HORSES.

The femorotibial joints are a common source of lameness in Western performance horses. The objective of this prospective study was to compare the radiography, ultrasonography, computed tomographic arthrography (CTA), and arthroscopy findings in horses with lameness localized to the femorotibial joints. Twenty-five stifles in 24 horses were included and were evaluated with all four of these diagnostic methods. Defects detected in femorotibial joint structures were compared between diagnostic methods using a McNemar's test to evaluate for disagreement. Cranial medial meniscotibial desmopathy was most detected on arthroscopy (in 14/25 cases) and was only detected on ultrasonography in three out of 11 (27.3%) arthroscopically observed cases, but was detected on CTA in nine out of 12 (75%) arthroscopically observed cases. Medial meniscal injury located on the craniolateral border was most detected on arthroscopy (n = 9) and was detected on CTA in five cases, but on ultrasonography in 0 cases. Detection of articular cartilage defects on the medial femoral condyle was most detected with arthroscopy (24/25, 96% cases) and was also detected on CTA in 12/20 (60%) cases with a significant disagreement identified between modalities (P = 0.02). Cranial and caudal cruciate ligament defects were detected on CTA in 6/22 (27.3%) and 7/19 (36.8%) cases, respectively, and with arthroscopy in 3/25 (12%) and 2/25 (8%) cases, respectively. The use of CTA detected more defects in the cruciate ligaments, proximal tibia, and ligament entheses than the other diagnostic methods, but was not reliable for detection of articular cartilage damage on the medial femoral condyle.

Radiofrequency Probe and Sharp Transection for Tenoscopic-Guided Desmotomy of the Accessory Ligament of the Superficial Digital Flexor Tendon.

OBJECTIVE: To compare intra and postoperative clinical features of desmotomy of the accessory ligament of the superficial digital flexor tendon (ALSDFT) using the Saber radiofrequency (SaberRF) electrosurgical probe versus sharp transection with a tenotomy knife. STUDY DESIGN: Randomized, controlled, blocked (horse) design. ANIMALS: Adult horses (n = 6). METHODS: Each horse received bilateral, tenoscopic-guided ALSDFT desmotomy with a SaberRF and tenotomy knife, randomly assigned to left, or right limb. The desmotomy duration and intraoperative hemorrhage grades were recorded. Postoperatively, the grades for surgical incision, carpal sheath effusion, carpal range of motion, flexion pain, and lameness were recorded. Light microscopy using hematoxylin and eosin, and viability staining were performed on the ALSDFT, flexor carpi radialis tendon, radial head of the deep digital flexor tendon, and the deep digital flexor tendon. Variables were compared between desmotomy methods with a paired t-test, Wilcoxon signed rank test, or a repeated measures mixed model. Statistical significance was set at P < .05. RESULTS: Desmotomy of the ALSDFT was completed in all horses. Only mild hemorrhage was observed and not different between methods (SaberRF 2/5 limbs; tenotomy knife 5/6 limbs, P = .078). Carpal sheath effusion was greater for SaberRF at Day 1 (P = .019) but not different from tenotomy knife at any later time. There was no significant difference between methods for viability staining or other measured outcomes. CONCLUSIONS: Tenoscopic-guided ALSDFT desmotomy with the SaberRF probe showed no difference in measured outcomes to sharp transection with a tenotomy knife and minimal collateral tissue damage was observed.

Fasting horses perioperatively decreases manure production and increases time to manure output postoperatively: a controlled randomized trial.

OBJECTIVE: To compare 3 perioperative feeding regimens and their effect on anesthetic complications, manure output, and colic proportion in healthy horses. METHODS: 45 horses presenting for elective orthopedic procedures were randomly assigned to 1 of 3 groups: not fasted (NF; continuous access to hay perioperatively), fasted muzzled (FM; 10-hour preoperative fast with slow refeeding postoperatively and muzzle placement), or fasted not muzzled (FNM; same as FM without muzzle placement). Anesthetic protocol was standardized. Outcomes compared between groups included anesthesia time, arterial oxygenation, duration of hypotension, perioperative manure output, time to first passage of manure postoperatively, pain scores, and colic proportion. Comparisons were made with a mixed model and Fisher exact test with statistical significance considered at P ≤ .05. RESULTS: No differences were seen in pain scores, oxygenation, hypotension, or colic between groups. Groups FM and FNM had a significantly greater mean reduction in postoperative manure weight (-81% and -70%; P = .003) and number of manure piles (-63% and -55%; P = .005) compared to group NF (-39% and -22%; P < .001; weight and piles, respectively). Mean ± SD minutes to passage of manure postoperatively was significantly shorter in group NF (238 ± 13 minutes) than groups FM (502 ± 174 minutes; P < .001) and FNM (444 ± 171 minutes; P = .003). CLINICAL RELEVANCE: Horses with continuous access to hay prior to and following recovery from anesthesia passed more manure and passed manure sooner after surgery than their fasted counterparts without detrimental effect on anesthetic parameters and postoperative complications. Continuous access to hay perioperatively supports manure production in healthy horses without increase in anesthetic complications.

A polymer network architecture provides superior cushioning and lubrication of soft tissue compared to a linear architecture.

We report the relationships between linear vs. network polymer architecture and biomechanical outcomes including lubrication and cushioning when the polymers are applied to the surface of articulating knee cartilage. Aqueous formulations of the bioinspired polymer poly(2-methacryloyloxylethyl phosphorylcholine) (pMPC) exhibit tuneable rheological properties, with network pMPC exhibiting increased elasticity and viscosity compared to linear pMPC. Application of a polymer network, compared to a linear one, to articulating tissue surfaces reduces friction, lessens tissue strain, minimizes wear, and protects tissue - thereby improving overall tissue performance. Administration of the network pMPC to the middle carpal joint of skeletally mature horses elicits a safe response similar to saline as monitored over a 70 day period.

Forelimb muscle activity during equine locomotion.

Few quantitative data exist to describe the activity of the distal muscles of the equine forelimb during locomotion, and there is an incomplete understanding of the functional roles of the majority of the forelimb muscles. Based on morphology alone it would appear that the larger proximal muscles perform the majority of work in the forelimb, whereas the smaller distal muscles fulfil supplementary roles such as stabilizing the joints and positioning the limb for impact with the ground. We measured the timing and amplitude of the electromyographic activity of the intrinsic muscles of the forelimb in relation to the phase of gait (stance versus swing) and the torque demand placed on each joint during walking, trotting and cantering. We found that all forelimb muscles, except the extensor carpi radialis (ECR), were activated just prior to hoof-strike and deactivated during stance. Only the ECR was activated during swing. The amplitudes of muscle activation typically increased as gait speed increased. However, the amplitudes of muscle activation were not proportional to the net joint torques, indicating that passive structures may also contribute significantly to torque generation. Our results suggest that the smaller distal muscles help to stabilize the forelimb in early stance, in preparation for the passive structures (tendons and ligaments) to be stretched. The distal forelimb muscles remain active throughout stance only during canter, when the net torques acting about the distal forelimb joints are highest. The larger proximal muscles activate in a complex coordination to position and stabilize the shoulder and elbow joints during ground contact.

Quantitative Evaluation of Equine Articular Cartilage Using Cationic Contrast-Enhanced Computed Tomography.

OBJECTIVE: To investigate the diffusion trajectory of a cationic contrast medium (CA4+) into equine articular cartilage, and to assess normal and degenerative equine articular cartilage using cationic contrast-enhanced computed tomography (CECT). DESIGN: In the first experiment (Exp1), equine osteochondral specimens were serially imaged with cationic CECT to establish the diffusion time constant and time to reach equilibrium in healthy articular cartilage. In a separate experiment (Exp2), articular cartilage defects were created on the femoral trochlea (defect joint) in a juvenile horse, while the opposite joint was a sham-operated control. After 7 weeks, osteochondral biopsies were collected throughout the articular surfaces of both joints. Biopsies were analyzed for cationic CECT attenuation, glycosaminoglycan (GAG) content, mechanical stiffness (Eeq), and histology. Imaging, biochemical and mechanical data were compared between defect and control joints. RESULTS: Exp1: The mean diffusion time constant was longer for medial condyle cartilage (3.05 ± 0.1 hours) than lateral condyle cartilage (1.54 ± 0.3 hours, P = 0.04). Exp2: Cationic CECT attenuation was lower in the defect joint than the control joint (P = 0.005) and also varied by anatomic location (P = 0.045). Mean cationic CECT attenuation from the lateral trochlear ridge was lower in the defect joint than in the control joint (2223 ± 329 HU and 2667 ± 540 HU, respectively; P = 0.02). Cationic CECT attenuation was strongly correlated with both GAG (ρ = 0.79, P < 0.0001) and Eeq (ρ = 0.61, P < 0.0001). CONCLUSIONS: The equilibration time of CA4+ into equine articular cartilage is affected by tissue volume. Quantitative cationic CECT imaging reflects the biochemical, biomechanical and histological state of normal and degenerative equine articular cartilage.

Cationic contrast-enhanced computed tomography distinguishes between reparative, degenerative, and healthy equine articular cartilage.

Cationic contrast-enhanced computed tomography (CECT) is a quantitative imaging technique that characterizes articular cartilage, though its efficacy in differentiating repair tissue from other disease states is undetermined. We hypothesized that cationic CECT attenuation will distinguish between reparative, degenerative, and healthy equine articular cartilage and will reflect biochemical, mechanical, and histologic properties. Chondral defects were created in vivo on equine femoropatellar joint surfaces. Within defects, calcified cartilage was retained (Repair 1) or removed (Repair 2). At sacrifice, plugs were collected from within defects, and at locations bordering (adjacent site) and remote to defects along with site-matched controls. Articular cartilage was analyzed via CECT using CA4+ to assess glycosaminoglycan (GAG) content, compressive modulus (E eq ), and International Cartilage Repair Society (ICRS) II histologic score. Comparisons of variables were made between sites using mixed model analysis and between variables with correlations. Cationic CECT attenuation was significantly lower in Repair 1 (1478 ± 333 Hounsfield units [HUs]), Repair 2 (1229 ± 191 HUs), and adjacent (2139 ± 336 HUs) sites when compared with site-matched controls (2587 ± 298, 2505 ± 184, and 2563 ± 538 HUs, respectively; all p < .0001). Cationic CECT attenuation was significantly higher at remote sites (2928 ± 420 HUs) compared with Repair 1, Repair 2, and adjacent sites (all p < .0001). Cationic CECT attenuation correlated with ICRS II score (r = .79), GAG (r = .76), and E eq (r = .71; all p < .0001). Cationic CECT distinguishes between reparative, degenerative, and healthy articular cartilage and highly correlates with biochemical, mechanical, and histological tissue properties.

Relationship between muscle forces, joint loading and utilization of elastic strain energy in equine locomotion.

Storage and utilization of strain energy in the elastic tissues of the distal forelimb of the horse is thought to contribute to the excellent locomotory efficiency of the animal. However, the structures that facilitate elastic energy storage may also be exposed to dangerously high forces, especially at the fastest galloping speeds. In the present study, experimental gait data were combined with a musculoskeletal model of the distal forelimb of the horse to determine muscle and joint contact loading and muscle-tendon work during the stance phase of walking, trotting and galloping. The flexor tendons spanning the metacarpophalangeal (MCP) joint - specifically, the superficial digital flexor (SDF), interosseus muscle (IM) and deep digital flexor (DDF) - experienced the highest forces. Peak forces normalized to body mass for the SDF were 7.3±2.1, 14.0±2.5 and 16.7±1.1 N kg(-1) in walking, trotting and galloping, respectively. The contact forces transmitted by the MCP joint were higher than those acting at any other joint in the distal forelimb, reaching 20.6±2.8, 40.6±5.6 and 45.9±0.9 N kg(-1) in walking, trotting and galloping, respectively. The tendons of the distal forelimb (primarily SDF and IM) contributed between 69 and 90% of the total work done by the muscles and tendons, depending on the type of gait. The tendons and joints that facilitate storage of elastic strain energy in the distal forelimb also experienced the highest loads, which may explain the high frequency of injuries observed at these sites.

Effects of early exercise on metacarpophalangeal joints in horses.

OBJECTIVE: To determine the effects of exercise at an early age on tissues in the metacarpophalangeal joints of horses. ANIMALS: Twelve 18-month-old horses. PROCEDURES: All horses were pasture reared, but 6 horses had additional exercise starting at 3 weeks of age until 18 months of age. At that time, computed tomography, articular cartilage metabolism evaluation, and histologic assessments of synovial membrane, articular cartilage, and subchondral bone were performed. RESULTS: Exercised horses had fewer gross lesions, less articular cartilage matrix staining in the dorsal aspect of the condyle, greater bone fraction in the dorsolateral aspect of the condyle, and higher bone formation rate, compared with nonexercised horses. CONCLUSIONS AND CLINICAL RELEVANCE: Exercise at a young age may be protective to joints, although more research is needed to characterize changes in articular cartilage matrix. Results suggested that exercise can be safely imposed at an early age.

Evaluation of polysulfated glycosaminoglycan or sodium hyaluronan administered intra-articularly for treatment of horses with experimentally induced osteoarthritis.

OBJECTIVE: To assess clinical, biochemical, and histologic effects of polysulfated glycosaminoglycan (PSGAG) or sodium hyaluronan administered intra-articularly in treatment of horses with experimentally induced osteoarthritis. ANIMALS: 24 horses. PROCEDURES: Osteoarthritis was induced arthroscopically in 1 middle carpal joint of all horses. Eight horses received hyaluronan (20 mg) and amikacin (125 mg) intra-articularly on study days 14, 21, and 28. Eight horses received PSGAG (250 mg) and amikacin (125 mg) intra-articularly on study days 14, 21, and 28. Eight control horses received 2 mL of saline (0.9% NaCl) solution and amikacin (125 mg) intra-articularly on study days 14, 21, and 28. Clinical, radiographic, synovial fluid analysis, gross, histologic, histochemical, and biochemical findings were evaluated. RESULTS: No adverse treatment-related events were detected. Induced osteoarthritis caused a substantial change in lameness, response to flexion, joint effusion, and radiographic findings, and of these, synovial fluid effusion was reduced with PSGAG, compared with control horses. No changes in clinical signs were seen with PSGAG or hyaluronan, compared with control horses. Histologically, the degree of synovial membrane vascularity and subintimal fibrosis was significantly reduced with PSGAG treatment, compared with controls. Histologically, significantly less fibrillation was seen with hyaluronan treatment, compared with controls. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that PSGAG and hyaluronan had beneficial disease-modifying effects and are viable therapeutic options for osteoarthritis in horses.

Evaluation of topically administered diclofenac liposomal cream for treatment of horses with experimentally induced osteoarthritis.

OBJECTIVE: To assess the clinical, biochemical, and histologic effects of topically administered diclofenac liposomal cream (DLC) in the treatment of horses with experimentally induced osteoarthritis. ANIMALS: 24 horses. PROCEDURES: Osteoarthritis was induced arthroscopically in 1 middle carpal joint of all horses. Eight horses treated with DLC were given 7.3 g twice daily via topical application. Eight horses treated with phenylbutazone were given 2 g orally once daily. Eight control horses received no treatment. Evaluations included clinical, radiographic, magnetic resonance imaging, synovial fluid, gross, and histologic examinations as well as histochemical and biochemical analyses. RESULTS: No adverse treatment-related events were detected. Horses that were treated with DLC or phenylbutazone had significant clinical improvement of lameness, unlike the control horses. Treatment with DLC induced significant improvement in staining and total articular glycosaminoglycan content, compared with no treatment. Treatment with phenylbutazone induced significant reduction in synovial fluid prostaglandin E2 concentration, compared with DLC and no treatment. Treatment with DLC induced significantly less radial carpal bone sclerosis and overall gross cartilage erosion, compared with phenylbutazone. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that DLC had both clinical sign-modifying and disease-modifying effects. Only clinical sign-modifying effects were detected in association with phenylbutazone administration. Treatment with DLC had significant beneficial effects, compared with phenylbutazone, and no detrimental effects. Results suggested that DLC is a viable therapeutic option for horses with osteoarthritis.

Influence of early conditioning exercise on the development of gross cartilage defects and swelling behavior of cartilage extracellular matrix in the equine midcarpal joint.

OBJECTIVE: To investigate the influence of early conditioning exercise on the development of gross cartilage defects and swelling behavior of cartilage extracellular matrix (ECM) in the midcarpal joint of horses. ANIMALS: 12 Thoroughbreds. PROCEDURES: 6 horses underwent early conditioning exercise from birth to 18 months of age (CONDEX group), and 6 horses were used as control animals (PASTEX group). The horses were euthanized at 18 months of age, and the midcarpal joints were harvested. Gross defects of the cartilage surface were classified and mapped. Opposing surfaces of the third and radial carpal bones were used to quantify swelling behavior of the cartilage ECM. RESULTS: A wide range of gross defects was detected in the cartilage on the opposing surfaces of the bones of the midcarpal joint; however, there was no significant difference between the CONDEX and PASTEX groups. Similarly, no significant difference in swelling behavior of the cartilage ECM was evident between the CONDEX and PASTEX groups. CONCLUSIONS AND CLINICAL RELEVANCE: In the study reported here, we did not detect negative influences of early conditioning exercise on the prevalence of gross defects in cartilage of the midcarpal joint or the quality of the cartilage ECM as defined by swelling behavior. These results suggested that early conditioning exercise may be used without negative consequences for the midcarpal joint and the cartilage ECM of the third and radial carpal bones.

Contrast-Enhanced Computed Tomography Scoring System for Distinguishing Early Osteoarthritis Disease States: A Feasibility Study.

Early detection of osteoarthritis (OA) remains a diagnostic challenge owing to insensitive diagnostic techniques currently available. Herein a new semiquantitative scoring system, based upon contrast-enhanced computed tomographic (CECT) imaging, is described for further refinement of early OA disease staging. Trochlear ridge cartilage defects were surgically created in the femoropatellar joint of an adult horse (ACUC approved protocols). Seven weeks post-surgery, CECT imaging was performed on a clinical scanner after intra-articular injection of a cationic iodinated contrast agent, CA4+, into both injured and control femoropatellar joint compartments. The femoral cartilage surface was densely biopsied, and specimens were assessed for visual (Outerbridge score), functional (equilibrium compressive modulus), and biochemical (glycosaminoglycan content) measures of cartilage quality. Cartilage CECT attenuation was compared with cartilage quality measures using receiver operating characteristic curve analysis to establish attenuation thresholds for distinguishing among cartilage quality levels. CECT imaging identifies macroscopically damaged cartilage regions and in morphologically identical tissue provides moderately sensitive and specific semiquantitative segregation of cartilage quality based upon CECT attenuation, reflecting both glycosaminoglycan content and compressive stiffness of cartilage area under the curve (AUC = 0.83 [95% confidence interval [CI]: 0.72-0.93] for distinguishing poor quality and AUC = 0.76 [95% CI: 0.65-0.90] for distinguishing healthy quality cartilage). A semiquantitative 6-point scoring system-the Osteoarthritis Attenuation and Morphological Assessment (OAMA) score-is proposed as a tool for assessing cartilage quality from CECT images. The OAMA scoring system expands the current disease staging capability of early OA by inclusion of morphological, biochemical, and biomechanical assessments. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2138-2148, 2019.

Evaluation of increased subchondral bone density in areas of contact in the metacarpophalangeal joint during joint loading in horses.

OBJECTIVE: To quantitatively evaluate contact area under 2 loads and subjectively compare contact areas with subchondral bone (SCB) density patterns in intact metacarpophalangeal joints of horses. SAMPLE POPULATION: 6 forelimbs from horses without musculoskeletal disease. PROCEDURES: Computed tomographic scans of intact metacarpophalangeal joints were analyzed to obtain SCB density measurements. Each limb was loaded on a materials testing system to 150 degrees and 120 degrees extension in the metacarpophalangeal joint, and the joint was stained via intra-articular injection with safranin-O or toluidine blue, respectively. Each joint was disarticulated, and the surface area was digitized. Total articular surface area, contact area, and percentage contact area at each angle were calculated for the distal third metacarpal condyles, the proximal phalanx, and the proximal sesamoid bones. RESULTS: Contact area on the third metacarpal condyles, proximal sesamoid bones, and the proximal phalanx significantly increased with increased load. Areas of contact subjectively appeared to have a higher density on computed tomographic scans. CONCLUSIONS AND CLINICAL RELEVANCE: Areas consistently in contact under higher load were associated with increased SCB density. This supports the idea that the SCB adapts to the load applied to it. As load increased, contact area also increased, suggesting that areas not normally loaded may have a high degree of stress during impact loading. Quantifying how contact in the joint changes under different loading conditions and the adaptation of the bone to this change in normal and abnormal joints may provide insight into the pathogenesis of osteochondral disease.

Biomechanical and histologic evaluation of the effects of underwater treadmill exercise on horses with experimentally induced osteoarthritis of the middle carpal joint.

OBJECTIVE To evaluate the effects of exercise in an underwater treadmill (UWT) on forelimb biomechanics and articular histologic outcomes in horses with experimentally induced osteoarthritis of the middle carpal joint. ANIMALS 16 horses. PROCEDURES An osteochondral fragment was induced arthroscopically (day 0) in 1 middle carpal joint of each horse. Beginning on day 15, horses were assigned to exercise in a UWT or in the UWT without water (simulating controlled hand walking) at the same speed, frequency, and duration. Thoracic and pelvic limb ground reaction forces, thoracic limb kinematics, and electromyographic results for select thoracic limb muscles acting on the carpi were collected on days -7 (baseline), 14, 42, and 70. Weekly evaluations included clinical assessments of lameness, response to carpal joint flexion, and goniometric measurements of thoracic limb articulations. At study conclusion, articular cartilage and synovial membrane from the middle carpal joints was histologically examined. RESULTS Exercise in a UWT significantly reduced synovial membrane inflammation and resulted in significant clinical improvements with regard to symmetric thoracic limb loading, uniform activation patterns of select thoracic limb muscles, and return to baseline values for carpal joint flexion, compared with results for horses with simulated hand walking. CONCLUSIONS AND CLINICAL RELEVANCE Overall improvements in thoracic limb function, joint range of motion, and synovial membrane integrity indicated that exercise in a UWT was a potentially viable therapeutic option for the management of carpal joint osteoarthritis in horses.

Evaluation of subchondral bone mineral density associated with articular cartilage structure and integrity in healthy equine joints with different functional demands.

OBJECTIVE: To determine and correlate subchondral bone mineral density and overlying cartilage structure and tensile integrity in mature healthy equine stifle (low magnitude loading) and metacarpophalangeal (high magnitude loading) joints. ANIMALS: 8 healthy horses, 2 to 3 years of age. PROCEDURE: Osteochondral samples were acquired from the medial femoral condyle (FC) and medial trochlear ridge (TR) of the stifle joint and from the dorsal (MC3D) and palmar (MC3P) aspects of the distal medial third metacarpal condyles of the metacarpophalangeal joint. Articular cartilage surface fibrillation (evaluated via India ink staining) and tensile biomechanical properties were determined. The volumetric bone mineral density (vBMD) of the underlying subchondral plate was assessed via dual-energy x-ray absorptiometry. RESULTS: Cartilage staining (fibrillation), tensile moduli, tensile strength, and vBMD were greater in the MC3D and MC3P locations, compared with the FC and TR locations, whereas tensile strain at failure was less in MC3D and MC3P locations than FC and TR locations. Cartilage tensile moduli correlated positively with vBMD, whereas cartilage staining and tensile strain at failure correlated negatively with vBMD. CONCLUSIONS AND CLINICAL RELEVANCE: In areas of high joint loading, the subchondral bone had high vBMD and the articular cartilage surface layer had high tensile stiffness but signs of structural wear (fibrillation and low failure strain). The site-dependent variations and relationships in this study support the concept that articular cartilage and subchondral bone normally adapt to physiologic loading in a coordinated way.

Evaluation of Ad-BMP-2 for enhancing fracture healing in an infected defect fracture rabbit model.

The objective of this study was to evaluate the use of adenoviral transfer of the BMP-2 gene (Ad-BMP-2) for enhancing healing in an infected defect fracture model. A femoral defect stabilized with plates and screws was surgically created in sixty-four skeletally mature New Zealand white rabbits. Experimental groups were: (1) non-infected Ad-luciferase (Ad-LUC, NONLUC), (2) non-infected Ad-BMP-2 (NONBMP), (3) infected Ad-LUC (INFLUC), and (4) infected Ad-BMP-2 (INFBMP). A sclerosing agent was applied to the ends of the bone at surgery to facilitate the development of osteomyelitis. Fracture healing was evaluated radiographically and histologically. Data were analyzed using an ANOVA, with statistical significance set as p<0.05. Rabbits in the non-infected and infected groups that were treated with Ad-BMP-2 had earlier initial- and bridging-callus formation, and a higher overall external callus grade compared to rabbits in the Ad-LUC groups. Rabbits in the Ad-LUC groups had more defect ossification compared to rabbits in the Ad-BMP-2 groups. There was a trend for rabbits in the Ad-BMP-2 group that were euthanized at 2 and 4 weeks after surgery to have more bone and cartilage compared to rabbits in the Ad-LUC group. The results of this study suggest that Ad-BMP-2 enhances the early stages of healing in an infected defect fracture. The results of our study were not as favorable as those reported in previous studies because animals healed by a large bridging callus and not by defect ossification. This could have been a result of the sclerosing agent, which may have damaged the cells in the defect.

Evaluation of serum biochemical markers of bone metabolism for early diagnosis of nonunion and infected nonunion fractures in rabbits.

OBJECTIVE: To evaluate the use of serum concentrations of biochemical markers of bone metabolism (osteocalcin [OC], bone-specific alkaline phosphatase [BS-ALP], and deoxypyridinoline [DPYR]) to compare healing in infected versus noninfected fractures and in fractures with normal repair versus delayed (nonunion) repair in rabbits. ANIMALS: 32 female 9- to 10-month-old New Zealand White rabbits. PROCEDURE: A femoral fracture defect was made in each rabbit. Rabbits were assigned to the following groups: the bone morphogenetic-2 gene treatment group with either noninfected nonunion or infected (ie, inoculation of defects with Staphylococcus aureus) nonunion fractures or the luciferase (control) gene treatment group with either noninfected nonunion or infected nonunion fractures. Serum samples were obtained before surgery (time 0) and 4, 8, 12, and 16 weeks after surgery. Callus formation and lysis grades were evaluated radiographically at 16 weeks. RESULTS: Serum OC and BS-ALP concentrations decreased from time 0 at 4 weeks, peaked at 8 weeks, and then decreased. Serum DPYR concentration peaked at 4 weeks and then decreased, independent of gene treatment group or fracture infection status. Compared with rabbits with noninfected fractures, those with infected fractures had lower serum OC and BS-ALP concentrations at 4 weeks, higher serum OC concentrations at 16 weeks, and higher serum DPYR concentrations at 4, 8, and 16 weeks. Combined serum OC, BS-ALP, and DPYR concentrations provided an accuracy of 96% for prediction of fracture infection status at 4 weeks. CONCLUSIONS AND CLINICAL RELEVANCE: Measurement of multiple serum biochemical markers of bone metabolism could be useful for clinical evaluation of fracture healing and early diagnosis of osteomyelitis.

Use of scintigraphy for assessment of fracture healing and early diagnosis of osteomyelitis following fracture repair in rabbits.

OBJECTIVE: To evaluate use of technetium Tc 99m disodium hydroxymethylene diphosphonate (99m-Tc-HDP) for assessing fracture healing and 99m-Tc-HDP and technetium Tc 99m ciprofloxacin (99m-Tc-CIPRO) for early diagnosis of osteomyelitis in rabbits. ANIMALS: 32 skeletally mature New Zealand White rabbits. PROCEDURE: A femoral fracture defect stabilized with bone plates and cortical screws was used. Scintigraphy was performed 4, 8, 12, and 16 weeks after surgery. The 99m-Tc-CIPRO scan was performed 48 hours after the 99m-Tc-HDP scan. The uptake ratio of the experimental limb to the normal limb was calculated by use of multiple regions of interest. Results of radiography performed to determine external callus and lysis grade and percentage defect ossification at 16 weeks were compared with scintigraphy results. RESULTS: Infected fractures had a higher uptake ratio for 99m-Tc-HDP and 99m-Tc-CIPRO than noninfected fractures. Infected fractures could be differentiated from noninfected fractures late in healing by use of 99m-Tc-HDP. Although 99m-Tc-CIPRO was better than 99m-Tc-HDP for identifying infection, there was a high incidence of false positive and negative results with 99m-Tc-CIPRO. There was an association between 99m-Tc-HDP uptake ratio and callus formation and a good correlation between 99m-Tc-HDP uptake ratio and defect ossification after 4 weeks. CONCLUSIONS AND CLINICAL RELEVANCE: 99m-Tc-HDP and 99m-Tc-CIPRO may be useful for diagnosing osteomyelitis late in fracture healing; however, false positive and false negative results occur. Technetium Tc 99m disodium hydroxymethylene diphosphonate may be useful for evaluating fracture healing.

Evaluation of a subject-specific finite-element model of the equine metacarpophalangeal joint under physiological load.

The equine metacarpophalangeal (MCP) joint is frequently injured, especially by racehorses in training. Most injuries result from repetitive loading of the subchondral bone and articular cartilage rather than from acute events. The likelihood of injury is multi-factorial but the magnitude of mechanical loading and the number of loading cycles are believed to play an important role. Therefore, an important step in understanding injury is to determine the distribution of load across the articular surface during normal locomotion. A subject-specific finite-element model of the MCP joint was developed (including deformable cartilage, elastic ligaments, muscle forces and rigid representations of bone), evaluated against measurements obtained from cadaver experiments, and then loaded using data from gait experiments. The sensitivity of the model to force inputs, cartilage stiffness, and cartilage geometry was studied. The FE model predicted MCP joint torque and sesamoid bone flexion angles within 5% of experimental measurements. Muscle-tendon forces, joint loads and cartilage stresses all increased as locomotion speed increased from walking to trotting and finally cantering. Perturbations to muscle-tendon forces resulted in small changes in articular cartilage stresses, whereas variations in joint torque, cartilage geometry and stiffness produced much larger effects. Non-subject-specific cartilage geometry changed the magnitude and distribution of pressure and the von Mises stress markedly. The mean and peak cartilage stresses generally increased with an increase in cartilage stiffness. Areas of peak stress correlated qualitatively with sites of common injury, suggesting that further modelling work may elucidate the types of loading that precede joint injury and may assist in the development of techniques for injury mitigation.