Autologous point-of-care stromal vascular fraction transplantation in dogs with advanced osteoarthritis of the knee and hip joints.

OBJECTIVE: The aim of the study was to assess lameness in dogs with advanced osteoarthritis of the hip and knee joints after a single autologous point-of-care transplantation of the Stromal Vascular Fraction (SVF) into the affected joint. MATERIALS AND METHODS: During a minilaparotomy, 10 g of falciform fat was removed from each patient for each joint to be treated. A modern and time-saving procedure (ARC TM System, InGeneron GmbH, Houston, USA) was used for the in-house preparation of the SVF, so that the isolated cells could be applied to the respective joint within 2 h after fat removal. In total, five knee joints of five patients and seven hip joints of four patients were treated. RESULTS: Improvement in lameness according to owner questionnaires was seen in 3 of 5 patients with knee joint arthritis and 2 of 4 patients with hip joint arthritis. Based on gait analysis, only one dog with gonarthrosis and one dog with coxarthrosis showed improvement up to a maximum of 3 months after surgery. CONCLUSION: This is the first case series on the treatment of osteoarthrosis of the knee or hip joint using point-of-care transplantation of the SVF. In individual cases, this method may represent a therapeutic approach for the treatment in dogs with advanced cox- or gonarthrosis, although only a short-term effect can be expected, which calls into question the effort and costs involved.

Experimental models of bone marrow lesions in ovine femoral condyles.

OBJECTIVE: To develop an in vivo experimental model for bone marrow lesions (BMLs) in ovine femorotibial joints. STUDY DESIGN: Randomized, prospective experimental study. ANIMALS: Eighteen healthy, skeletally-mature Dorper cross ewes. METHODS: One medial femoral condyle was penetrated with a 1.1 mm pin, and the contralateral medial femoral condyle was treated with transcutaneous extracorporeal shockwave (ESW) at 0.39 ± 0.04 mJ/mm2 . Clinical examination, magnetic resonance imaging (MRI), computed tomography (CT), and histopathological analyses were used to detect and characterize the development and progression of BMLs in the medial femoral condyle at 4, 8, and 12 weeks post-surgery. RESULTS: Pin penetration induced a BML detected on MRI within 2 weeks and lasted at least 12 weeks. BMLs were not observed in ESW-treated condyles. Histologically, BMLs were characterized by hemorrhage and inflammatory cellular infiltrate, and progressed to more dense fibrous tissue over time. Pathological changes were not observed in the articular cartilage overlying the region of BMLs. CONCLUSIONS: Direct, focal trauma to all layers of the osteochondral unit was sufficient to create an experimentally-induced BML which persisted for at least 90 days. The protocol used for ESW in this study did not induce BMLs. CLINICAL SIGNIFICANCE: Experimental induction of BMLs is possible and mimicked naturally occurring disease states. Volumetric imaging is a sensitive method for characterization of the dynamic nature of these lesions.

Positron emission tomography: a horse in the musculoskeletal imaging race.

Positron emission tomography (PET) has established itself as a pertinent tool in equine musculoskeletal imaging in the last few years. With the ability to provide functional information regarding both bone and soft tissues, PET has found several clinical applications in horses. PET is currently used in horses as an enhanced bone scan, providing high-resolution 3-dimensional information, in particular for imaging of the racehorse fetlock. Combined with CT and MRI, PET is particularly pertinent in horses for the assessment of subchondral bone and enthesis. The development of a dedicated PET scanner to image the distal limb of horses with standing sedation led to new applications, where PET is used as a first-line advanced imaging tool, in particular for foot, fetlock, and tarsal imaging. A complimentary clinical review of when to seek advanced imaging in equine athletes can be found in the companion Currents in One Health by Garrett in the July 2022 issue of the Journal of American Veterinary Medical Association. The clinical use of PET in human medicine remains mainly focused on oncological imaging; however, numerous small-scale clinical studies have demonstrated valuable applications for musculoskeletal imaging. These include assessment of foot and ankle pain, osteoarthritis of the knee and hip, osteoporosis, response to bisphosphonates, and chronic osteomyelitis. The use of musculoskeletal PET in dogs remains quite limited, but a few studies have recently been published and clinical interest is growing. The available research data and clinical applications between horses, humans, and dogs are currently quite disparate, but all suggest great promises for earlier and more accurate clinical diagnosis, as well as better understanding of pathophysiology and response to treatment. Translating knowledge from a species to another will undoubtedly help further growth of musculoskeletal PET.

Intra-articular Injectates: What to Use and Why.

Intra-articular injections are a nonsurgical treatment modality that can be used to manage osteoarthritis, naturally occurring or surgically induced acute synovitis, and intra-articular ligamentous or tendon injury. This option may be assistive for patients in which other conservative modalities are ineffective, or in conjunction with other forms of treatment. It may also be used as the primary treatment. Injectates labeled for use in companion animal joints include corticosteroids and viscosupplements. Additional injectates, that are not specifically approved for use in companion animals are but are reported in the literature, include orthobiologics and a radioisotope of Tin-117m.

Animal models of osteoarthritis: characterization of a model induced by Mono-Iodo-Acetate injected in rabbits.

Knee Osteoarthritis is a considerable public health concern, both in terms of life quality and treatment financial impacts. To investigate this disease, animal models are deemed a promising alternative. In fact, although a perfect model is generally farfetched, the creation of models that simulate human disease as accurately as possible remains an important research stake. This study aims to highlight the usefulness of the model induced by injected Mono-Iodo-Acetate and to standardize it for the rabbit species. Osteoarthritis was induced by an infra-patellar injection of 0.2 ml of an MIA solution in the left knee of 24 female New Zealand rabbits. The right knee served as a control by receiving an injection of physiological serum. The rabbits were divided into 4 groups of 6 individuals each according to the dose of MIA received per knee. All rabbits were euthanized 30 days after the injection. After sacrifice, the knees were carefully dissected and macroscopic and microscopic scores of cartilage, meniscal and synovial lesions were attributed to each group. Our study followed the laboratory animal care and management guideline published in 2017 by the Canadian Council of Animal Care. The control knees of all rabbits showed no macroscopic or microscopic lesions. The macroscopic lesions: osteophytes, meniscal lesions, fibrillation and erosion of the cartilage and microscopic lesions: disorganization of the chondrocytes, decrease in proteoglycans and synovial inflammation clinically diagnosed in human pathology were all detected and were similarly reproducible among the knees of the same group. Through this work, we highlighted the merits of the arthritis model induced by MIA, namely its simulation of several aspects of human pathology. Further advantages are low cost, speed, reproducibility. This model notably avoids delicate and risky surgical operations.

Assessment of DNA Methylation Patterns in the Bone and Cartilage of a Nonhuman Primate Model of Osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) affects humans and several other animals. Thus, the mechanisms underlying this disorder, such as specific skeletal tissue DNA methylation patterns, may be evolutionary conserved. However, associations between methylation and OA have not been readily studied in nonhuman animals. Baboons serve as important models of disease and develop OA at rates similar to those in humans. Therefore, this study investigated the associations between methylation and OA in baboons to advance the evolutionary understanding of OA. DESIGN: Trabecular bone and cartilage was collected from the medial condyles of adult female baboon femora, 5 with and 5 without knee OA. The Infinium HumanMethylation450 BeadChip (450K array) was used to identify DNA methylation patterns in these tissues. RESULTS: Approximately 44% of the 450K array probes reliably align to the baboon genome, contain a CpG site of interest, and maintain a wide distribution throughout the genome. Of the 2 filtering methods tested, both identified significantly differentially methylated positions (DMPs) between healthy and OA individuals in cartilage tissues, and some of these patterns overlap with those previously identified in humans. Conversely, no DMPs were found between tissue types or between disease states in bone tissues. CONCLUSIONS: Overall, the 450K array can be used to measure genome-wide DNA methylation in baboon tissues and identify significant associations with complex traits. The results of this study indicate that some DNA methylation patterns associated with OA are evolutionarily conserved, while others are not. This warrants further investigation in a larger and more phylogenetically diverse sample set.

Fib3-3 as a Biomarker for Osteoarthritis in a Rat Model with Metabolic Dysregulation.

OBJECTIVE: Fibulin-3 is a glycoprotein highly expressed in osteoarthritic cartilage and inhibits angiogenesis and chondrocyte differentiation. Recent studies have indicated that fibulin-3 has potential value as a biomarker in osteoarthritis. The aim of the present study is to examine the role of 3 fibulin-3 peptides (Fib3-1, Fib3-2, and Fib3-3) and a type II collagen degradation product in a rat osteoarthritis model with systemic metabolic alterations combined with local cartilage damage. DESIGN: Forty, 12-week-old male, Wistar rats were randomly divided over 2 groups: a standard or a high-fat diet inducing metabolic dysregulation. After 12 weeks, articular cartilage damage was induced on the femoral condyles (groove model), in 1 knee joint in 14 rats of each diet group. At endpoint, blood was collected and serum was isolated. Enzyme-linked immunosorbent assay on all selected fibulin-3 fragments was performed from serum samples in addition to immunohistochemical analysis for Fib3-3. RESULTS: Serum concentrations of Fib3-3 were increased by 29.9%, when cartilage damage was induced in addition to a high-fat diet. Fib3-3 was also associated with an increased histological total joint degeneration (r = 0.435) and cartilage degeneration (r = 0.435). Immunostainings demonstrated increased Fib3-3 in the superficial cartilage of animals with high-fat diet and/or cartilage damage. CONCLUSIONS: In the rat groove model combined with high-fat diet-induced metabolic dysregulation an increased Fib3-3 concentration was observed systemically, which is associated with local joint degeneration. This suggests that systemic Fib3-3 concentrations can indicate the status of joint degeneration and function as a biomarker in osteoarthritis.

Pharmacokinetic Profile of Intra-articular Fluticasone Propionate Microparticles in Beagle Dog Knees.

OBJECTIVE: The objective of this pilot study was to determine time point(s) at which maximum concentration of fluticasone propionate (Cmax) occurs in synovial fluid and plasma in Beagle dog knees after intra-articular injection of EP-104IAR. DESIGN: EP-104IAR is composed of fluticasone propionate drug crystals coated with heat-treated polyvinyl alcohol (PVA) to result in extended release properties. Thirty-two Beagle dogs had an injection of EP-104IAR into the knee joint at 2 different dose levels (0.6 mg and 12 mg). Outcome measures included plasma, synovial fluid, and articular cartilage fluticasone propionate concentrations as well as histological analysis of cartilage and synovium at a variety of time points up to 58 days postdosing. RESULTS: Intra-articular administration of 0.6 and 12 mg EP-104IAR was well tolerated. Early minor abnormalities found on microscopy resolved by the end of the study. There were no quantifiable concentrations of fluticasone propionate in plasma of animals administered 0.6 mg at any of the sampling time points. Highest concentrations in plasma following 12 mg administration occurred 1 day postdose and declined with a half-life of approximately 45 days. Highest concentrations of fluticasone propionate in synovial fluid and cartilage generally occurred 5 days postdose in both dose groups and declined with a half-life of approximately 11 to 14 days. CONCLUSIONS: EP-104IAR is capable of providing a safe and prolonged local exposure to a corticosteroid in the synovial joint while minimizing systemic exposure, with peak exposures occurring within a matter of days after dosing before declining in all tissues in a predictable manner.

Characterization of endocannabinoids and related acylethanolamides in the synovial fluid of dogs with osteoarthritis: a pilot study.

BACKGROUND: Cannabis-based drugs have been shown to be effective in inflammatory diseases. A number of endocannabinoids including N- arachidonoylethanolamide (anandamide, AEA) and 2-arachidonyl glycerol (2-AG) with activity at the cannabinoid receptors (CBR) CBR1 and CBR2, have been identified. Other structurally related endogenous fatty acid compounds such as oleoylethanolamide (OEA) and palmitoyl ethanolamide (PEA) have been identified in biological tissues. These compounds do not bind to CBR but might be involved in facilitating the actions of directly acting endocannabinoids and thus are commonly termed "entourage" compounds due to their ability to modulate the endocannabinoid system. The aim of this study was to evaluate the presence of endocannabinoids and entourage compounds in the synovial fluid of dogs with osteoarthritis subjected to arthrotomy of the knee joint. Cytokines and cytology were studied as well. RESULTS: AEA, 2-AG, OEA and PEA were all present in the synovial fluid of arthritic knees and in the contralateral joints; in addition, a significant increase of OEA and 2AG levels were noted in SF from OA knees when compared to the contralateral joints. CONCLUSION: The identification and quantification of endocannabinoids and entourage compounds levels in synovial fluids from dogs with OA of the knee is reported for the first time. Our data are instrumental for future studies involving a greater number of dogs. Cannabinoids represent an emerging and innovative pharmacological tool for the treatment of OA and further studies are warranted to evaluate the effectiveness of cannabinoids in veterinary medicine.

Obesity, Exercise and Orthopedic Disease.

Osteoarthritis is common among aging canine and feline patients. The incidence and severity of clinical lameness are closely correlated to body condition in overweight and obese patients. Excessive adiposity may result in incongruous and excessive mechanical loading that worsens clinical signs in affected patients. Data suggest a potential link between adipokines, obesity-related inflammation, and a worsening of the underlying pathology. Similarly, abnormal physical stress and generalized systemic inflammation propagated by obesity contribute to neurologic signs associated with intervertebral disc disease. Weight loss and exercise are critical to ameliorating the pain and impaired mobility of affected animals.

Effects of one-time and two-time intra-articular injection of hyaluronic acid sodium salt after joint surgery in dogs.

Thirty-one dogs with patellar luxation (grades 2 and 3) were categorized into three groups. Group 1 (G.1; n = 12) had sodium hyaluronate (SHA) intra-articularly injected into the stifle joint that received surgery. Group 2 (G.2; n = 10) received SHA twice: first after surgery and then 1 week later. Group 3 (G.3; n = 9) served as a control, without injection. Blood was collected before injection and then once a week for 4 weeks after injection for evaluation of chondroitin sulfate (CS-WF6) and hyaluronan (HA). The results revealed significantly (p < 0.05) improved clinical scores by the end of week 4 in G.1 and G.2 relative to G.3; however, there was no significant difference between G.1 and G.2. There was a significant decrease (p < 0.05) in serum CS-WF6 levels beginning at week 2 in G.1 and G.2. At weeks 3 and 4, serum HA in G.1 and G.2 differed from that in G.3 (p < 0.05). No significant difference (p > 0.05) was observed in serum biomarkers between G.1 and G.2. In conclusion, intra-articular injection with SHA after joint surgery may improve homeostasis of the joint, retarding the process of OA.

Unravelling the relationship between age, nociception and joint destruction in naturally occurring osteoarthritis of Dunkin Hartley guinea pigs.

Osteoarthritis (OA) is a debilitating and painful disease, the incidence of which increases with advancing age. One of the confounding aspects of OA is that there is a disconnect between the severity of joint degeneration and the intensity of pain reported. This study examined the relationship between age, joint nociception, and joint pathology in an animal model of naturally occurring OA. Dunkin Hartley guinea pigs were grouped according to age: young (2-5 months) and senescent (17-37 months). Joint nociception was objectively measured in these animals by recording electrophysiologically from knee joint primary afferents in response to non-noxious and noxious movements of the knee. Joint pathology in the same knees was then determined by histomorphology and micro-computerized tomography (micro-CT). A principal components analysis was carried out on the data to determine if any correlation exists between each of the measured variables. In aged guinea pigs, 33% of joint mechanosensory nerves were spontaneously active, whereas young animals showed no such neural activity at rest. The frequency of afferent firing evoked by noxious movements was greater in old guinea pigs. Micro-CT and histopathological determination of OA positively correlated with age; however, there was no significant correlation between the severity of joint degeneration and nociception. In the Dunkin Hartley model of inveterate OA, the level of joint pathology correlates well with increasing age. This study also provides the first objective evidence that there is no correlation between joint nociception and articular damage, thereby corroborating the clinical observation that pain is a poor predictor of OA severity.

Osteophytosis, subchondral bone sclerosis, joint effusion and soft tissue thickening in canine experimental stifle osteoarthritis: comparison between 1.5 T magnetic resonance imaging and computed radiography.

OBJECTIVE: To compare use of 1.5 T magnetic resonance imaging (MRI) and computed radiography (CR) for morphologic and temporal evaluation of osteophytosis, subchondral sclerosis, joint effusion, and synovial thickening in experimentally induced canine stifle osteoarthritis (OA). STUDY DESIGN: Prospective study. ANIMALS: Dogs (n=8). METHODS: CR (mediolateral and caudocranial projections) and MRI (dorsal 3D T1-weighted gradient echo, sagittal 3D SPGR and T2-weighted fast spin echo with fat saturation) were performed at baseline (n=8) and at week 4 (n=5), week 8 (n=8), and week 26 (n=5) after cranial cruciate ligament transection. Osteophytosis, subchondral bone sclerosis, and joint effusion were scored on CR and MRI, and synovial thickening on MRI. RESULTS: MRI was more sensitive than CR for detection of osteophytosis and could better discriminate joint effusion from soft tissue thickening, although scores for these variables strongly correlated between modalities (rho=0.94 [osteophytosis] and 0.80 [effusion]; P<.001). Scores for subchondral bone sclerosis also correlated (rho=0.54, P<.004), although this variable may have been over interpreted on CR. Joint effusion and synovial thickening peaked at week 8, before partially regressing at week 26. Conversely, osteophytosis and sclerosis progressed semi-linearly over 26 weeks. CONCLUSION: MRI is more sensitive than radiography in assessing onset and progression of osteophytosis in canine experimental stifle OA and provides enhanced discrimination between joint effusion and synovial thickening. CLINICAL RELEVANCE: MRI is as a more powerful imaging modality that should be increasingly used in animals to assess the joint related effects of disease-modifying OA drugs.

Comparison of trot kinetics between dogs with stifle or hip arthrosis.

The purposes of this study were: 1) to describe and compare the trotting gait of normal and lame dogs secondary to stifle (GONOA) or hip (COXOA) osteoarthritis (OA) using multiple ground reaction forces (GRF) parameters, and 2) to pinpoint any characteristic in gait profile ('signatures') which could help to discriminate a lameness secondary to GONOA or COXOA. Fifty-one large breed dogs with OA (19 GONOA, 32 COXOA) and 22 normal dogs were included in the study. The vertical and cranio-caudal (braking-propelling) GRF were collected. The total stance time, and for each orthogonal vector, the peak force, impulse, time to peak, and the rate of limb loading were recorded. Vertical and craniocaudal forces were found to be significantly decreased in both OA groups compared to normal dogs. Vertical, cranial and caudal limb loading were also most often lower for both OA groups. In addition, the vertical and cranial forces were significantly lower in dogs with GONOA compared to COXOA and normal dogs. This study has demonstrated that, at a trotting gait, OA dogs secondary to GONOA and COXOA load their affected limb, brake and propel earlier during the stance phase, but generally with less magnitude than normal dogs. Dogs affected by GONOA also present more severe gait alterations than dogs with COXOA. The vertical and braking specific GRF alterations described may be kinetic 'signatures' linked more to lame dogs secondary to GONOA versus COXOA. Finally, this study has also provided useful baseline GRF data for further clinical and research investigations.

Alterações radiográficas e ultra-sonográficas iniciais em osteoartrite experimental eqüina / Early radiographic and ultrasonographic changes in equine experimental osteoarthritis

Avaliaram-se oito articulações metacarpofalangeanas (MCF) de eqüinos adultos pelos exames radiográfico e ultra-sonográfico após indução cirúrgica de uma instabilidade articular, para mimetizar as alterações iniciais da osteoartrite (OA) naturalmente adquirida. Foram mensurados a circunferência articular, a amplitude do movimento articular e o grau de claudicação dos membros torácicos (avaliação clínica). Dez dias após a intervenção cirúrgica os animais foram exercitados em um andador por um período de 60 dias. Os exames radiográfico e ultra-sonográfico foram realizados antes da intervenção cirúrgica e após 25, 40 e 70 dias, e a avaliação clínica, semanalmente, durante todo o período experimental. Observaram-se alterações ultra-sonográficas aos 25 dias após a instabilidade articular, enquanto as alterações radiográficas somente foram visualizadas aos 40 dias. Houve aumento significativo (P<0,05) da circunferência articular da articulação MCF operada (25,75cm± 1,1) a partir do sétimo dia, em relação à articulação controle (24,88cm± 1,0) e diminuição da amplitude do movimento da articulação operada (96,38º± 10,7) a partir do 25º dia, em relação ao seu valor basal (109,24º± 10,3) e em relação ao controle (108,75º± 8,3). O grau de claudicação aumentou significativamente (P<0,05) durante o período do estudo, com valor médio do escore de 1,5 para o membro operado em relação ao membro contralateral. Em conclusão, os sinais iniciais da OA cirurgicamente induzida foram melhor e mais precocemente detectados pela ultra-sonografia quando comparado ao exame radiografico. As mensurações da circunferência articular e da amplitude do movimento articular são úteis na avaliação das doenças articulares.

Eight metacarpophalangeal joints (MCP) of mature horses were evaluated by radiographic and ultrasonographic exams after surgically instability-induced that mimics the early changes of naturally acquired osteoarthritis (OA). Joint circunference, range of motion and lameness score were measured (clinical evaluation). Ten days after surgically joint instability the animals were walked on a horse walker by a 60-day period. Radiography and ultrasonography were taken immediately before desmotomy and 25, 40 and 70 days after surgery. Clinical evaluation was performed at each 7-day intervals. Ultrasonographic changes were observed on day 25 after articular instability while radiographic changes were only visualized on day 40. Joint circunference was significantly higher (P<0.05) in OA joints (25.75cm± 1.1) on day 7 as compared with contralateral joints (24.88cm± 1.0) and a range of motion was significantly less (P<0.05) in OA joints (96.38º± 10.7), on day 25, compared with basal value (109.24º± 10.3) and contralateral joint (108.75º± 8.3). Lameness score significantly increased (P<0.05) over time with mean score 1.5 for the 70-day study period. In conclusion, changes of induced OA joint were earlier and better detected by ultrasonography than by radiography. The measure of joint circunference and range of motion are useful in joint disease evaluation.

Evaluation of pentosan polysulfate sodium in the postoperative recovery from cranial cruciate injury in dogs: a randomized, placebo-controlled clinical trial.

OBJECTIVE: To evaluate the efficacy of pentosan polysulfate (PPS) for improving the recovery period and mitigate the progression of osteoarthritis (OA) of the canine stifle after extracapsular stabilization of cranial cruciate ligament (CCL) injuries. STUDY DESIGN: Randomized, blinded, placebo-controlled clinical trial. ANIMALS: Dogs (n=40) with unilateral CCL instability. METHODS: Each dog had an extracapsular stabilization of the stifle with or without partial meniscectomy. Dogs were divided into 4 groups based on preoperative radiographic assessment and whether a partial meniscectomy was performed. Dogs were randomly assigned to either (3 mg/kg) PPS or placebo treatment in each group, and then injected subcutaneously weekly for 4 weeks. Lameness, radiographic changes, biological marker concentration in blood and urine, and ground reaction forces (GRFs) were collected preoperatively, and at 6, 12, 24, and 48 weeks. Data were analyzed within and between groups using repeated measures ANOVA; P<.05 was considered significant. RESULTS: No adverse reactions to PPS were reported. Thirty-nine dogs completed a minimum of 24-weeks follow-up and 33 dogs completed 48 weeks. All dogs clinically improved after surgery without differences in lameness score, vertical GRFs, or radiographic progression. Grouped and evaluated only by initial radiographic score, PPS-treated dogs improved significantly faster in braking GRFs than placebo-treated dogs. In dogs with partial meniscectomies, urine deoxypyridinoline, and serum carboxy-propeptide of type II collagen were significantly increased at 6 weeks in placebo-treated dogs compared with PPS-treated dogs. CONCLUSIONS: PPS administered after stabilization of the cruciate deficient stifle may prove to be a useful adjunctive treatment option, although further studies are necessary to substantiate this claim.

Nitrite and nitrotyrosine concentrations in articular cartilage, subchondral bone, and trabecular bone of normal juvenile, normal adult, and osteoarthritic adult equine metacarpophalangeal joints.

OBJECTIVE: Osteoarthritis (OA) is a chronic debilitating joint disorder in which the importance of inflammation is increasingly recognized. In advanced cases, both the articular cartilage and the underlying bony layers are affected, but the exact sequence of events and their localization in the initial phase of pathogenesis remain uncertain. We measured nitric oxide (NO) end products in tissue layers that constitute the bearing surface of the joint, as possible indicators of physiological and pathological processes. METHODS: Nitrite as a measure for NO and nitrotyrosine was measured in articular cartilage, subchondral bone, and the underlying trabecular bone of the proximal articular surface of the first phalanx of healthy mature horses (n = 15; age range 5-18 yrs), mature horses affected by OA (n = 15; age range 8-22 yrs), and unaffected juvenile horses (n = 13; age range 6 months-4 yrs). Data were correlated with cartilage damage, as quantified by the Cartilage Degeneration Index. RESULTS: In all 3 layers the nitrite concentration was higher in OA joints (cartilage, p < 0.001; subchondral and trabecular bone, p < 0.05). The concentration of nitrite was significantly higher in cartilage and subchondral bone of juvenile horses compared with mature horses (p < 0.001). Nitrotyrosine concentrations were significantly higher in subchondral bone of OA horses compared with healthy controls (p < 0.001), but significantly lower in trabecular bone of juvenile horses (p < 0.01). CONCLUSION: The similarities observed over the 3 tissue layers support the concept of the bearing surface of the joint as a functional entity. Nitrite concentration seems to be a good indicator of tissue metabolic activity, but cannot discriminate between physiological (juvenile animals) and pathological (OA cases) processes. The increased nitrotyrosine levels in subchondral bone of OA-affected animals suggest that this layer is important in early or moderate OA, and implies a role of oxidative stress in the development of the disease.

The evaluation of extracorporeal shockwave therapy in naturally occurring osteoarthritis of the stifle joint in dogs.

Extracorporeal shockwave therapy (ESWT) has expanded from the original uses of human urinary calculi treatment to veterinary orthopaedic applications. This paper investigates the feasibility and efficacy of treating dogs with osteoarthritis of the stifle joint with ESWT. In this study, dogs with persistent stifle lameness despite previous surgical or medical treatment were either treated with ESWT or served as untreated controls. The more lame rear limb of each dog was determined by force platform analysis. The range of motion (ROM) of the stifle joints was assessed by goniometry. Force platform gait analysis and goniometry were performed on both groups for four visits at three-week intervals and a final examination four weeks later. Shock wave therapy was performed three times on the treated dogs, once at each of the first three examinations. A placebo treatment consisting of clipping and wetting the hair was performed on the control dogs. The vertical forces were evaluated for objective analysis of treatment response. For peak vertical force (PVF), four of seven treated dogs improved, while only one of five of control dogs improved. The PVF for the within group analysis did not show any significant change for the treated group, however, the control group has a significant decrease (p = 0.05) in PVF consistent with an increase in lameness. The range of motion (ROM) of the stifle joint improved in five of seven treated dogs and three of five controls. Dogs in the treated group had a trend toward increased ROM (p = 0.07) and a 'positive slope' when compared to dogs in the control group which did not have a significant change (p = 0.78) and had a negative slope indicating the dogs were developing a decrease in ROM. The subjective data provided by client questionnaire did not show significant difference between groups.

Examination of synovial fluid and serum following intravenous injections of hyaluronan for the treatment of osteoarthritis in dogs.

A randomized, blinded, prospective clinical trial was performed to determine the effects of intravenous (i.v.) administration of hyaluronan sodium (HA) on serum glycosaminoglycans (GAG) concentrations, synovial fluid (SF) hyaluronan concentrations and viscosity in dogs treated for unilateral rupture of the cranial cruciate ligament. Twenty-two dogs undergoing tibial plateau leveling osteotomy were used in this study. Synovial fluid from both stifles and serum were collected prior to surgery and at 2, 4, and 8 weeks following surgery. Dogs received either 1.0 ml (10 mg) of sodium hyaluronate (treatment group 1; n = 10) or equal volume of 0.9% NaCl (treatment group 2; n = 12), i.v. immediately, 2 and 4 weeks following surgery. Synovial fluid viscosity was evaluated using a magnetically driven, acoustically tracked, translating-ball rheometer. Synovial fluid HA disaccharide content was measured by fluorophore-assisted carbohydrate electrophoresis. Serum GAG concentrations were measured by alcian blue spectrophotometric assay. Data were analyzed using a Wilcoxon sign rank test (p < 0.05). Mean +/- SD viscosity (cP) was significantly higher (p = 0.011) in SF obtained from the intact stifle (450 +/- 604.1) than injured (54.8 +/- 60.8) prior to surgery. Mean +/- SD HA concentrations (ug/ml) were significantly higher (p = 0.02) in synovial fluid obtained from the injured stifles (281.4 +/- 145.9) than intact stifles (141.6 +/- 132.5). No significant difference was noted within or between treatment groups in SF viscosity, HA concentrations, or serum GAG concentrations at any time following surgery. Stifles with cranial cruciate ligament insufficiency had significant alterations in SF viscosity and HA concentrations.