H.A.W. Hazewinkel

The Dog as an Animal Model for Intervertebral Disc Degeneration

Study Design. Prospective observational and analytic study. Objective. To investigate whether spontaneous intervertebral disc degeneration (IVDD) occurring in both chondrodystrophic (CD) and nonchondrodystrophic dogs (NCD) can be used as a valid translational model for human IVDD research. Summary of Background Data. Different animal models are used in IVDD research, but in most of these models IVDD is induced manually or chemically rather than occurring spontaneously. Methods. A total of 184 intervertebral discs (IVDs) from 19 dogs of different breeds were used. The extent of IVDD was evaluated by macroscopic grading, histopathology, glycosaminoglycan content, and matrix metalloproteinase 2 activity. Canine data were compared with human IVD data acquired in this study or from the literature. Results. Gross pathology of IVDD in both dog types (CD and NCD) and humans showed many similarities, but the cartilaginous endplates were significantly thicker and the subchondral cortices significantly thinner in humans than in dogs. Notochordal cells were still present in the IVDs of adult NCD but were not seen in the CD breeds or in humans. Signs of degeneration were seen in young dogs of CD breeds (<1 year of age), whereas this was only seen in older dogs of NCD breeds (5–7 years of age). The relative glycosaminoglycan content and metalloproteinase 2 activity in canine IVDD were similar to those in humans: metalloproteinase 2 activity increased and glycosaminoglycan content decreased with increasing severity of IVDD. Conclusion. IVDD is similar in humans and dogs. Both CD and NCD breeds may therefore serve as models of spontaneous IVDD for human research. However, as with all animal models, it is important to recognize interspecies differences and, indeed, the intraspecies differences between CD and NCD breeds (early vs. late onset of IVDD, respectively) to develop an optimal canine model of human IVDD.

In early OA, thinning of the subchondral plate is directly related to cartilage damage: results from a canine ACLT-meniscectomy model

OBJECTIVE The pathogenesis of osteoarthritis (OA) includes cartilage degeneration, synovial inflammation, and bone changes. Slowly, the sequence and inter-relationship of these features is becoming clearer. Early models of OA suggest thinning of the subchondral plate in addition to trabecular bone changes. In the present study subchondral bone changes were studied in the canine anterior cruciate ligament transection (ACLT)-meniscectomy model. This model is characterized by intra-joint variability with respect to cartilage damage (predominantly medial) and loading (lateral unloading due to a shifted axis). METHODS In 13 Labrador dogs, OA was induced by transection of the anterior cruciate ligament and removal of the medial meniscus. Twelve weeks later, cartilage integrity was evaluated histologically using the modified Mankin score (0-11), and proteoglycan content was determined by Alcian Blue assay. Bone architecture of the tibia was quantified by micro-CT. RESULTS Cartilage damage was severe in the medial compartment (Mankin score +3.5, glycosaminoglycan (GAG) content -28%) and mild in the lateral compartment (Mankin score +1.6, GAG content -15%). Thinning and porosity of the subchondral plate were only present on the medial side (-21%, +87%, respectively). Interestingly, changes in trabecular bone structure did almost not occur in the medial compartment (volume fraction -7%) but were clear in the lateral compartment (-20%). CONCLUSION Thinning of the subchondral plate is a localized phenomenon related to cartilage degeneration while trabecular bone changes are related to mechanical (un)loading. The different mechanisms responsible for bone changes in OA should be taken in account when designing and interpreting studies interfering with bone turnover in the treatment of OA.

Cross-sectional study of the prevalence and clinical features of osteoarthritis in 100 cats

To assess clinical signs and relevance of osteoarthritis (OA) in cats, the radiographic prevalence of OA in the appendicular skeleton of 100 client-owned cats (≥ 6 years old) was assessed. Possible associations between radiographic OA, clinical locomotor system examination, and owner-perceived behavioural changes were evaluated. OA was most prevalent in the shoulders, elbows, hips and tarsal joints with 61% of cats having OA in at least one joint and 48% in more than one joint. Overall, clinical examination of the larger peripheral joints had the highest sensitivity and specificity for radiographic OA. Regression analysis showed age to be related to OA (P = 0.002), as were decreased mobility and grooming (P = 0.008), although there was a correlation with age. Finally, increased inappropriate elimination was associated with OA (P = 0.046). It was concluded that the prevalence of OA in cats is strikingly high and increases with age. OA in cats seems to be associated with behavioural changes.

Intervertebral disc degeneration in the dog. Part 2: Chondrodystrophic and non-chondrodystrophic breeds

Dogs can be grouped into two distinct types of breed based on the predisposition to chondrodystrophy, namely, non-chondrodystrophic (NCD) and chondrodystrophic (CD). In addition to a different process of endochondral ossification, NCD and CD breeds have different characteristics of intravertebral disc (IVD) degeneration and IVD degenerative diseases. The anatomy, physiology, histopathology, and biochemical and biomechanical characteristics of the healthy and degenerated IVD are discussed in the first part of this two-part review. This second part describes the similarities and differences in the histopathological and biochemical characteristics of IVD degeneration in CD and NCD canine breeds and discusses relevant aetiological factors of IVD degeneration.

Age-related plasma concentrations of growth hormone (GH) and insulin-like growth factor I(IGF-I) in great dane pups fed different dietary levels of protein

During a 20-week study, 17 Great Dane dogs, 7 weeks of age, were used to study the influence of 3 isoenergetic diets differing in dietary protein levels (i.e., 31.6%, 23.1%, and 14.6% on a dry matter basis) on body weight, growth in length, and age-related plasma GH and IGF levels. Significant differences occurred in weekly body weight gain of the high- and low- protein groups only in the fourth week of the study. There was a significant decrease in mean basal plasma GH values with time from 14.8 +/- 2.2, 13.7 +/- 2.2, and 14.3 +/- 2.2 micrograms/l in the second week to 2.3 +/- 1, 0.7 +/- 0.4, and 1.8 +/- 0.7 microgram/l in the last week of the study for the high-, normal- and low-protein groups, respectively. Differences among groups were not significant. There was a positive correlation between the decrease in weekly body weight gain and plasma GH concentration in all 3 groups. IGF-I concentrations in plasma did not change consistently with age and were not correlated with plasma GH values. Significant differences in plasma IGF-I concentrations were found between groups at 15 weeks of age. Preliminary results of measurements of IGF receptors in the membranes of growth plate cartilage of long bones of 5 dogs revealed that homologous displacement of 125I-labeled IGF-I binding resulted in similar curves. A single binding site for IGF-I was assumed. The large number of type II IGF receptors in 7 dogs suggests a key role for IGF-II in postnatal skeletal growth. The results of this study demonstrate for the first time that in Great Dane pups basal GH concentrations in plasma decrease between 7 and 27 weeks of age, parallel to the decrease in growth velocity, whereas the plasma IGF-I concentrations remain relatively high and unchanged. The slight but statistically significant effects of low-protein feeding on growth velocity and circulating concentrations of IGF-I indicate that a diet containing 14.6% protein on a dry matter basis (13% protein as metabolizable energy) is marginal for growing Great Dane pups between 7 and 17 weeks of age.

Calcium metabolism in great dane dogs fed diets with various calcium and phosphorus levels

The influence of dietary calcium on calcium metabolism was investigated in growing dogs that reach an adult body weight similar to that of humans. Seven groups of dogs (n greater than or equal to 5) were raised on a diet with a composition meeting the National Research Council (NRC) requirements (1974), but differing in calcium content, with or without a constant ratio to phosphorus. Control dogs fed 1.1% calcium and 0.9% phosphorus (all on a dry matter basis) were fed ad libitum (n = 10) or in restricted amounts (n = 6); dogs fed high calcium (3.3%) diets received either 0.9% phosphorus (n = 6) or 3.0% phosphorus (n = 6); dogs fed low calcium (0.55%) diets received either 0.9% phosphorus (n = 5 + 6) or 0.5% phosphorus (n = 8). Food intake, circulating total calcium and inorganic phosphorus concentrations and calcium metabolism, with 45Ca kinetics, were studied at 8, 14, 20 and 26 wk of age. Except for the difference in food intake in two groups at 14 wk (i.e., 0.55% calcium-0.9% phosphorus higher and 3.3% calcium-0.9% phosphorus lower, respectively, than the controls) no differences were noticed during the rest of the study. The mean plasma calcium concentrations did not differ between groups during the studies, whereas that of inorganic phosphorus revealed temporal aberrations in two groups. An absorption coefficient alpha of 45-66% was found for the control group. High and low calcium diets gave rise to values of 23-43% and 70-97%, respectively, for alpha irrespective of the phosphorus content of the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Intervertebral disc degeneration in the dog. Part 1: Anatomy and physiology of the intervertebral disc and characteristics of intervertebral disc degeneration

Intervertebral disc (IVD) degeneration is common in dogs and can give rise to a number of diseases, such as IVD herniation, cervical spondylomyelopathy, and degenerative lumbosacral stenosis. Although there have been many reports and reviews on the clinical aspects of canine IVD disease, few reports have discussed and reviewed the process of IVD degeneration. In this first part of a two-part review, the anatomy, physiology, histopathology, and biochemical and biomechanical characteristics of the healthy and degenerated IVD are described. In Part 2, the aspects of IVD degeneration in chondrodystrophic and non-chondrodystrophic dog breeds are discussed in depth.

Incidence of intervertebral disk degeneration–related diseases and associated mortality rates in dogs

OBJECTIVE To determine the incidence and distribution of intervertebral disk (IVD) degeneration-related diseases in a large population of dogs of various breeds, ages, and sexes and to determine mortality rates among dogs with these diseases. DESIGN Epidemiological study. SAMPLE Insurance data for dogs with veterinary health-care and life insurance coverage (n = 665,249 and 552,120, respectively). PROCEDURES Insurance claim records of 1 company in Sweden were searched to identify dogs with IVD degeneration-related diseases; incidence and mortality rates were determined for affected dogs < 12 years old and < 10 years old, respectively. Only the first paid IVD degeneration-related claim for a dog was included in incidence rate calculations. RESULTS The incidence rate of IVD degeneration-related diseases was 27.8 (95% confidence interval [CI], 27.2 to 28.4) occurrences/10,000 dog-years at risk (DYAR), indicating that approximately 0.3% of dogs/y in this population were affected. Miniature Dachshund was the most highly represented breed, followed by Standard Dachshund and Doberman Pinscher (237.1 [95% CI, 212.9 to 261.4], 141.5 [95% CI, 135.5 to 147.4], and 88.6 [95% CI, 72.1 to 105.2] occurrences/10,000 DYAR, respectively). The incidence rate of IVD degeneration-related disease was greater in male than in female dogs and increased with age. Overall mortality rate attributed to IVD degeneration-related diseases was 9.4 (95% CI, 8.9 to 9.8) deaths/10,000 DYAR and was greater in males than in females. CONCLUSIONS AND CLINICAL RELEVANCE Differences in incidence rates among various breeds suggested a genetic involvement. Knowledge of the distribution of IVD degeneration-related diseases among dogs of various breeds and ages may facilitate early diagnosis and preemptive treatments in patients at risk for developing these diseases.

Effect of diets with different calcium and phosphorus contents on the skeletal development and blood chemistry of growing great danes

The skeletal development of three groups of great dane dogs, fed a diet composed according to the published nutritional requirements for dogs (controls) or with increased calcium or calcium and phosphorus content, was examined radiographically, histologically and biochemically. The diets were fed from the time the dogs first began eating food in addition to their dams milk, until they were 17 weeks old. Thereafter, the calcium and phosphorus intakes of the dogs in the high calcium groups were normalised for a further 10 weeks. The dogs fed the high calcium diet without a proportionally high phosphorus intake became hypercalcaemic and hypophosphataemic, and had severe disturbances in skeletal development, growth, and mineralisation which were typical for rickets. After their calcium intake was normalised the lesions of rickets resolved but osteochondrotic lesions became apparent. The dogs fed the high calcium and phosphorus diet became slightly hypophosphataemic, their growth was retarded, and they had disturbances in skeletal development resembling osteochondrosis, which had only partly resolved after 10 weeks on the normal calcium and phosphorus diet.

Evaluation of intervertebral disk degeneration in chondrodystrophic and nonchondrodystrophic dogs by use of Pfirrmann grading of images obtained with low-field magnetic resonance imaging

OBJECTIVE To assess whether the Pfirrmann system for grading lumbar intervertebral disk (IVD) degeneration in humans can also be used in dogs. ANIMALS 202 dogs. PROCEDURES Magnetic resonance imaging was used to obtain images of vertebral segments from dogs, which were reviewed separately by 3 observers who graded the extent of degeneration in each visible IVD by use of the Pfirrmann classification system used for grading lumbar IVD degeneration in humans. Grading was validated against 2 factors associated with the extent of disk degeneration: type of dog (chondrodystrophic or nonchondrodystrophic breeds) and age. RESULTS Interobserver and intraobserver agreement for Pfirrmann grading of IVD degeneration were good (κ scores, 0.81 to 0.93). An increase in the extent of disk degeneration was positively correlated with increases in age and with chondrodystrophic breed. CONCLUSIONS AND CLINICAL RELEVANCE The Pfirrmann system was reliably used to grade IVD degeneration in dogs of various breeds and ages. An increase in the extent of IVD degeneration was positively correlated with increases in age and with chondrodystrophic-type dogs.