Procollagen type-III aminoterminal peptide in serum and synovial fluid of dogs with hip dysplasia and coxarthrosis

Hip dysplasia is an affection of the coxofemoral joint that progresses until stabilization is caused by fibrosis and osteoarthritic changes. This stabilization process can be examined by clinical and radiographic methods. The capability of evaluating the procollagen concentrations in liquids, such as serum and synovial fluid, has further offered the basis for an objective biochemical evaluation of the stabilization process. Our study was performed to evaluate whether determination of procollagen concentrations was suitable for the use in practice. The procollagen type-III aminoterminal peptide (P-III-NP) concentration was measured in serum and in synovial fluid from coxofemoral joints in 20 dogs. Dogs were grouped on the basis of evidence of dysplasia and osteoarthritic changes of the hip: (1) a control group of 6 dogs without clinical or radiographic signs of hip dysplasia, and (2) dysplastic group of 14 dogs, which was further grouped with respect to the coxofemoral joint laxity, as determined by the Ortolani test. Synovial fluid concentration of P-III-NP was significantly (P less than 0.05) higher in fluid from dysplastic joints than in fluid from normal joints. Serum concentrations of P-III-NP were significantly (P less than 0.05) higher in dogs in which results of the Ortolani test were positive.     

Comparison of arthroscopic and radiographic abnormalities in the hip joints of juvenile dogs with hip dysplasia

OBJECTIVE: To compare radiographic and arthroscopic abnormalities in juvenile dogs with clinically apparent hip dysplasia. DESIGN: Case series. ANIMALS: 52 dogs (70 hip joints) with clinical signs of hip dysplasia scheduled to undergo triple pelvic osteotomy. PROCEDURE: A ventrodorsal radiographic projection of the pelvis was evaluated by a radiologist unaware of clinical and arthroscopic findings, and radiographic osteoarthritic abnormalities were judged and scored as absent (0), mild (1), moderate (2), or severe (3). Arthroscopy was performed by a surgeon unaware of clinical and radiographic findings, and arthroscopic abnormalities were graded from 0 (normal) to 5 (exposed, eburnated subchondral bone). RESULTS: In 30 of the 70 (43%) hip joints, no radiographic osteoarthritic abnormalities were seen. Severe, full-thickness articular cartilage lesions (grade 4) of the femoral head or acetabulum were seen arthroscopically in 14 (20%) joints. Lesions > or = grade 2 were seen in 60 (86%) joints. Partial tearing of the ligament of the femoral head was present in 57 (81%) joints, and complete rupture was seen in 5 (7%). Radiographic abnormalities were seen in 13 of the 14 (93%; 95% confidence interval, 66% to 99.8%) joints with grade 4 arthroscopic abnormalities but in only 23 of the 46 (50%; 95% confidence interval, 35% to 65%) joints with grade 2 or 3 arthroscopic abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that radiography is not a sensitive method for identifying moderate cartilage lesions in juvenile dogs with hip dysplasia. If moderate cartilage lesions are an important prognostic indicator for the success of triple pelvic osteotomy, then methods other than radiography should be used to detect these lesions.     

Gelatinase activity in synovial fluid and synovium obtained from healthy and osteoarthritic joints of dogs

OBJECTIVE: To determine matrix metalloproteinase (MMP) activity in synovial fluid (SF) obtained from the joints of dogs with degenerative joint disease (DJD) secondary to various underlying conditions. SAMPLE POPULATION: 35 samples of SF obtained from 18 clinically normal (control) dogs and 34 samples of SF obtained from 17 dogs with DJD; dogs with DJD were from 2 populations (client-owned dogs and research dogs that had DJD secondary to the lysosomal storage disease mucopolysaccharidosis VII). PROCEDURE: MMP activity in samples of SF was semiquantitatively examined by use of gelatin or casein zymography. Western blot analysis was performed by use of antibodies for MMP-2 and MMP-9. In addition, in situ MMP activity was observed in sections of synovial membrane obtained from healthy and osteoarthritic joints. RESULTS: Samples of SF from osteoarthritic joints had higher MMP-2 activity and dramatically increased MMP-9 activity, compared with values for healthy joints. Substrate-overlay analyses indicated minimal gelatin-degrading activity in synoviocytes obtained from control dogs, whereas greater activity was seen in osteoarthritic synoviocytes, with additional activity in the underlying tissue. CONCLUSIONS AND CLINICAL RELEVANCE: Higher MMP-2 activity and dramatic increases in MMP-9 activity were associated with the osteoarthritic state, even though MMP-2 activity was detected in healthy joints. This study expands information on MMP production in SF of osteoarthritic joints in other species and documents the similarity of MMP activity patterns regardless of the cause of DJD.     

Additional kinematic variables to describe differences in the trot between clinically normal dogs and dogs with hip dysplasia

OBJECTIVE: To describe the abnormal gait of dogs with hip dysplasia by use of kinematic gait analysis. ANIMALS: 19 large-breed dogs with moderate to severe clinical and radiographic evidence of hip dysplasia and 10 clinically normal dogs (controls). PROCEDURE: Kinematic and force plate data were collected, and degree of coxofemoral joint abduction-adduction, mediolateral foot movement, distance between hind feet, maximum hind foot elevation, mediolateral pelvic movement, and coxofemoral joint angular acceleration were calculated. Essential Fourier coefficients were determined and used to reconstruct mean angular acceleration curves. Fourier coefficients and foot and pelvic movement data were compared between groups. RESULTS: Dogs with hip dysplasia had a greater degree of coxofemoral joint adduction and range of abduction-adduction and greater lateral pelvic movement, compared with controls. Foot movement variables did not differ significantly between groups. Coxofemoral joint angular acceleration was greater in the middle to end of the stance phase, whereas deceleration was greater in the late stance to early swing phase and middle to end of the swing phase in dogs with hip dysplasia, compared with controls. CONCLUSIONS AND CLINICAL RELEVANCE: Differences in degree of coxofemoral joint abduction-adduction, amount of mediolateral pelvic movement, and coxofemoral joint angular acceleration between clinically normal dogs and dogs with hip dysplasia may indicate a compensation in gait of affected dogs as a result of discomfort or biomechanical effects attributable to hip dysplasia and degenerative joint disease. Information gained from kinematic and kinetic gait analyses may be useful in evaluating treatments for hip dysplasia in dogs.     

Comparison of three radiographic methods for diagnosis of hip dysplasia in eight-month-old dogs.

OBJECTIVE: To compare the accuracy of the extended-hip radiographic (EHR) score, the distraction index (DI), and the dorsolateral subluxation (DLS) score for identifying hip dysplasia in dogs at 8 months of age. DESIGN: Cohort study ANIMALS: 129 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbreds. PROCEDURE: Radiography was performed when dogs were 8 months of age. Dogs were euthanatized at 8 to 36 months of age; hip dysplasia was diagnosed at the time of necropsy on the basis of results of a gross examination of the articular cartilage of the hip joints for signs of osteoarthritis. RESULTS: The EHR score, DI, and DLS score at 8 months of age were all significantly correlated with degree of cartilage degeneration at necropsy. Sensitivity and specificity of using EHR score at 8 months of age to diagnose hip dysplasia (scores > 3 were considered abnormal) were 38 and 96%, respectively; sensitivity and specificity of using DI (values > 0.7 were considered abnormal) were 50 and 89%; and sensitivity and specificity of using DLS score (scores < 55% were considered abnormal) were 83 and 84%. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that specificities of the 3 methods for diagnosing hip dysplasia in dogs at 8 months of age were similar. However, the DLS score had higher sensitivity, indicating that there were fewer false-negative results.     

Arthrogenic lameness of the fetlock: synovial fluid markers of inflammation and cartilage turnover in relation to clinical joint pain

REASONS FOR PERFORMING THE STUDY: Joint pain is one of the most common causes of lameness in the horse but its pathogenesis is poorly understood. OBJECTIVES: To investigate which synovial fluid markers may be related to the presence of clinically detectable joint pain in the horse. METHODS: Concentrations of structural (CPII, C2C, GAG) and inflammatory markers (PGE2, LTB4, CysLTs, bradykinin and substance P) were measured in fetlock joint fluid from 22 horses in which lameness was localised to the fetlock region by perineural anaesthesia. Levels of these markers were then compared in horses that responded (n = 15) to those that did not (n = 7) to subsequent intra-articular anaesthesia (IAA). RESULTS: Of all markers analysed, only substance P levels were significantly higher (P = 0.0358) in synovial fluid of horses that showed a positive response to IAA compared to those with a negative response to IAA. Notably, while PGE2 levels were found to be elevated in all 22 lame horses compared to sound controls (P = 0.0025), they were not related to the response to IAA. CONCLUSIONS: While levels of PGE2 are elevated in synovial fluid of lame horses that respond to perineural anaesthesia, only substance P is related to joint pain as detected by the response to intra-articular anaesthesia. POTENTIAL RELEVANCE: Substance P is associated with clinically detectable joint pain in the horse. Elevated levels of PGE2 in fetlock-lame horses, regardless of their response to IAA, indicate that either this mediator does not reflect intra-articular pain or that IAA might have limitations in differentiating between intra- and peri-articular sources of pain. Either way, a negative response to IAA may not exclude intra-articular pathology.     

Evaluation of multiple radiographic predictors of cartilage lesions in the hip joints of eight-month-old dogs

OBJECTIVE: To determine the radiographic methods that best predict the development of osteoarthritis in the hip joints of a cohort of dogs with hip dysplasia and unaffected dogs. ANIMALS: 205 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbred dogs. PROCEDURE: Pelvic radiography was performed when the dogs were 8 months old. Ventrodorsal extended-hip, distraction, and dorsolateral subluxation (DLS) radiographs were obtained. An Orthopedic Foundation for Animals-like hip score, distraction index, dorsolateral subluxation score, and Norberg angle were derived from examination of radiographs. Osteoarthritis was diagnosed at the time of necropsy in dogs > or = 8 months of age on the basis of detection of articular cartilage lesions. Multiple logistic regression was used to determine the radiographic technique or techniques that best predicted development of osteoarthritis. RESULTS: A combination of 2 radiographic methods was better than any single method in predicting a cartilage lesion or a normal joint, but adding a third radiographic method did not improve that prediction. A combination of the DLS score and Norberg angle best predicted osteoarthritis of the hip joint or an unaffected hip joint. All models that excluded the DLS score were inferior to those that included it. CONCLUSIONS AND CLINICAL RELEVANCE: A combination of the DLS score and Norberg angle was the best predictor of radiographic measures in 8-month-old dogs to determine whether a dog would have normal or osteoarthritic hip joints.     

Estimation of genetic population variables for six radiographic criteria of hip dysplasia in a colony of Labrador Retrievers

OBJECTIVE: To estimate genetic population variables for 6 radiographic criteria of canine hip dysplasia (CHD). ANIMALS: 664 full- and half-siblings from a colony of Labrador Retrievers. PROCEDURE: Heritability estimates and genetic correlations were calculated for 6 radiographic criteria of CHD. Two evaluation protocols were compared: the grade of the most severely affected hip joint and the sum of the scores for both hip joints. The predictive performance of estimated breeding values was also evaluated. RESULTS: The overall prevalence of CHD (Federation Cynologique Internationale grades C, D, and E) was 29.6%. Median age at radiographic examination was 377 days. Heritability for the total CHD grade, Norberg angle (NA), coverage of the femoral head (COV), craniodorsal acetabular rim (ACR), subchondral bone sclerosis (SUBCH), shape of the femoral head and neck (FHN), and osteoarthritic changes at the insertion site of the joint capsule (JC) was estimated as follows: 0.44, 0.43, 0.46, 0.37, 0.32, 0.21, and 0.05, respectively. Heritability estimates were slightly higher for the sum of the scores for both hip joints. If NA and COV were included as fixed effects in the model for the dependent variables ACR, SUBCH, FHN, and JC , then heritability of these traits significantly decreased (0.08 to 0.15). High scores of NA and COV lead to a significant increase of the scores of the remaining criteria. CONCLUSIONS AND CLINICAL RELEVANCE: Canine hip dysplasia is heritable to a moderate degree. Signs of subluxation revealed the highest heritability estimates. The criteria ACR, SUBCH, FHN, and JC were strongly influenced by NA and COV.     

Cellular composition of bronchial brushings obtained from healthy dogs and dogs with chronic cough and cytologic composition of bronchoalveolar lavage fluid obtained from dogs with chronic cough

OBJECTIVE: To determine whether bronchial brushings from dogs with chronic cough have increased numbers of goblet cells and WBCs, compared with numbers for healthy dogs, or have differing WBC populations, compared with populations in bronchoalveolar lavage (BAL) fluid obtained from dogs with chronic cough. ANIMALS: 9 healthy dogs and 10 dogs with chronic cough. PROCEDURE: Specimens were collected by use of bronchoscopy. Cellular composition was determined for brushings, and results from dogs with chronic cough were compared with those from healthy dogs. Cellular composition of brushings was compared with composition of BAL obtained from dogs with chronic cough. RESULTS: Brushings from healthy dogs contained a median of 2.9 x 10(6) epithelial cells, comprising 100% epithelial cells (96% ciliated, 3% goblet, and 1% other) and no WBCs. Brushings from dogs with chronic cough had 4.5 x 10(6) epithelial cells, comprising 93% epithelial cells (86% ciliated, 2% goblet, and 12% other). Dogs with chronic cough had significantly greater percentages of WBCs (7%) and neutrophils (6%), compared with values for healthy dogs. Five dogs with chronic cough had no neutrophilic inflammation evident in BAL, but 4 of these had evidence of neutrophilic inflammation in brushings. CONCLUSIONS AND CLINICAL RELEVANCE: Neutrophils, but not goblet cells, were increased in brushings from dogs with chronic cough. Analysis of bronchial brushings provides information about airway inflammation that differs from that found by examination of BAL in some dogs with chronic cough and is a more sensitive indicator of airway inflammation than cytologic examination of BAL in these dogs.     

Association between radiographic assessment of hip status and subsequent incidence of veterinary care and mortality related to hip dysplasia in insured Swedish dogs

Our objective was to evaluate the association between grading of hip status as assessed by radiographic examination (hip screening) and subsequent incidence of veterinary care and mortality related to hip dysplasia (HD) in five breeds of insured dogs in Sweden. Screening results for hip status from the Swedish Kennel Club and data on veterinary care and mortality from the insurance company Agria were merged based on the registration number of the dog. Dogs of five breeds (Bernese Mountain Dogs, German Shepherds, Golden Retrievers, Labrador Retrievers, and Rottweilers) screened during 1995–2004 and covered by an insurance plan for veterinary care or life at the time of screening were included. The study populations included between 1667 and 10,663 dogs per breed. Breed-specific multivariable Cox proportional-hazards analyses were performed to evaluate the impact of radiographic hip status on time from hip screening to first HD-related veterinary and life claim, respectively. The effects of gender, birth season, and a time-varying covariate of year were also studied. Additional analyses, on the five breeds combined, were performed to investigate the effects of hip status, breed, and the interaction between hip status and breed. The effect of hip status was highly significant (P < 0.001) for both life and veterinary claims related to HD in all five breeds with increased hazard ratio (HR) for deteriorating hip status. Dogs with moderate or severe hip status at screening had a markedly increased hazard of HD-related veterinary care and mortality compared with dogs assessed as free or mild. The time-varying covariate of year showed a significantly higher HR in the last time period for German Shepherds and Labrador Retrievers in the analyses of veterinary claims. In the analyses on all five breeds, German Shepherds had the highest HR for both veterinary care and mortality related to HD, followed by Bernese Mountain Dogs. Golden and Labrador Retrievers had the lowest HR. The effect of hip status on the hazard was the same irrespective of breed. However, as a consequence of differences between breeds in overall risk, the predictive ability of screening results for subsequent incidence of HD-related problems for individual dogs was breed-dependent. Based on the strong association between radiographic hip status and incidence of HD-related veterinary care and mortality, and the previously reported moderate heritability of hip status, we conclude that selection based on screening results for hip status can be expected to reduce the risk of HD-related clinical problems.     

Recombinant equine growth hormone administration: effects on synovial fluid biomarkers and cartilage metabolism in horses

REASONS FOR PERFORMING STUDY: Recombinant equine growth hormone (reGH) has recently been evaluated for effects on body condition and wound healing. It has the potential to influence articular cartilage via stimulation of IGF-1. OBJECTIVES: To investigate effects of administration on synovial joint metabolism. METHODS: Six mature horses were given 20 microg/kg bwt reGH daily for 8 weeks by i.m. injection. Three control horses were injected with sterile water. Serum and synovial fluid samples were collected at 6, 8, 11 and 16 weeks for GH and IGF-1 assays. Articular cartilage harvested at week 16 was evaluated by Western analysis using monoclonal antibodies BC-13, BC-4, 8-A-4 and CH-3. RESULTS: Concentrations of IGF-1 in serum and synovial fluid were significantly elevated (P < 0.05) at 6 and 8 weeks in the reGH group. Glycosaminoglycan concentrations in synovial fluid were significantly less than controls at these time points, suggesting that reGH may modulate proteoglycan metabolism in articular cartilage. In the reGH group, there were not any alterations in synovial fluid content of 3B3(-) epitope or aggrecan metabolite, or in aggrecan or link protein catabolites retained within cartilage, that might be expected with development of osteoarthritis. CONCLUSIONS: Intramuscular administration of reGH may be a more efficient means of delivery of IGF-1 to joints for cartilage resurfacing initiatives. POTENTIAL RELEVANCE: We found no alterations in cartilage metabolism indicative of development of osteoarthritis.     

Prevalence and co-occurrence of hip dysplasia and elbow dysplasia in Dutch pure-bred dogs

Hip as well as elbow dysplasia (HD, ED) are developmental disorders leading to malformation of their respective joints. For a long time both disorders have been scored and targeted for improvement using selective breeding in several Dutch dog populations. In this paper all scores for both HD and ED, given to pure bred dogs in the Netherlands from 2002 to 2010, were analyzed. Heritabilities and correlations between HD and ED were calculated for the 4 most frequently scored breeds. Heritabilities ranged from 0.0 to 0.37 for HD related traits (FCI-score, osteoarthritis, congruity, shape and laxity (Norberg angle); FCI: Fédération Cynologique Internationale) and from 0.0 to 0.39 for ED related traits (IEWG score, osteoarthritis, sclerosis and indentation; IEWG: International Elbow Working Group). HD related traits showed high genetic and residual correlations among each other but were only to a minor extent correlated with ED related traits, which also showed high correlations among each other. Genetic correlations were higher than residual correlations. Phenotypic and genetic trends since 2001 for the four most scored breeds were slightly positive but decreasing over time, indicating that selection over the past decade has not been effective.     

Plasma and synovial fluid lysozyme activity in horses with experimental cartilage defects

Cartilaginous defects were created in the radiocarpal joints of 12 horses. Synovial fluid cytologic features, lysozyme activity, and beta-glucuronidase activity were monitored for 16 days. A comparison was made of plasma lysozyme and beta-glucuronidase activity and of synovial fluid lysozyme, beta-glucuronidase, and leukocyte concentrations. Plasma lysozyme was found to be independent of synovial fluid lysozyme activity. Synovial fluid lysozyme was significantly increased (P less than 0.001) in all joints with surgically induced defects (group I) compared with controls (arthrocentesis done; group III). However, there was no significant difference in lysozyme activity in group I joints and sham-operated controls (cartilage exposed only; group II). Increased lysozyme concentration was found to be positively correlated with increased numbers of leukocytes in the synovial fluid. Parallel changes were noted in synovial fluid beta-glucuronidase activity, indicating that much of the observed synovial fluid lysozyme activity was of lysosomal origin and not from cartilage destruction. Lysozyme activity in synovial fluid was found to be a very sensitive indicator of acute joint injury or inflammation (or both).     

Prevalence of hip dysplasia according to official radiographic screening, among 31 breeds of dogs in France.

In order to determine the prevalence of hip dysplasia (HD) from radiographs that were submitted for authorative grading, and its changes over the time in 31 breeds of dogs in France, a 14 year-retrospective study was conducted. Significant differences were observed between breeds, with HD prevalence ranging from 59.7% (Cane Corso) to 3.9% (Siberian Husky). When comparing the 1993-1999 with the 2000-2006 period in 15 breeds, a significant decrease in HD prevalence was detected in Berger Picard, Bernese Mountain dog, Briard, Gordon Setter, White Swiss Sheepdog and Rottweiler. Modifications observed in the other breeds were not statistically significant.     

Delayed ossification of the femoral head in dogs with hip dysplasia

In humans, delayed ossification of the caput femoris is often seen associated with hip dysplasia in babies. This phenomenon may possibly exist in dogs. In this study, the radiographic appearance of the caput femoris of 13 German shepherd dogs was examined. The dogs underwent pelvic radiography at the age of 14 to 15 days, six weeks, and 12 months. A significant relationship was shown between hip dysplasia and the late appearance of the epiphysis of the caput femoris (P=0–02). At the age of 14 to 15 days it was not possible to see both epiphyses in 54 per cent of the dogs. All of these dogs had hip dysplasia when they were 12 months old. This was in contrast to the six dogs which had both epiphyses visible when they were 14 to 15 days old. At 12 months of age, four of these dogs (67 per cent) did not show any sign of hip dysplasia.     

Retrospective evaluation of the long-term outcome of non-surgical management of 74 dogs with clinical hip dysplasia

The long-term outcome for dogs treated non-surgically for clinical signs of canine hip dysplasia were evaluated retrospectively; 74 dogs were evaluated by a postal questionnaire sent to their owners, and 24 of these were also evaluated by a veterinary clinical examination. A total of 11 outcome variables were evaluated. Depending on the variable assessed, between 31 (41.9 per cent) and 49 (66.2 per cent) of the dogs remained clinically affected according to their owner's assessment, and between 17 (70.8 per cent) and 23 (95.8 per cent) of the 24 dogs had abnormalities attributed to hip osteoarthritis according to the veterinary assessment. Orthopaedic abnormalities other than hip dysplasia affected 17 of the 24 dogs. Long-term medications had been prescribed for the treatment of clinical signs associated with hip dysplasia in 41 of the 74 dogs.