Ch 58 Pathogenesis of HD Flashcards

Question

What nutritional factors may play a role in HD?

Answer 1

- High dietary Ca and excessive VitD (delayed endochondral ossification ans skeletal remodeling) - High density anion gap diet (increased osmolality in synovial fluid and increased volume) No dietary deficiencies have been shown to “cause” hip dysplasia, but dietary excesses have been found to contribute

Answer 2

genetic and an environmental basis to explain the observed variation in expressed phenotype - gender-matched cohorts of Labrador Retriever littermates, food restriction (i.e., an environmental influence) to maintain a lean body mass was shown to have a profound effect on delaying the onset and lowering the severity of hip dysplasia - injectable polysulfated glycosaminoglycan (Adequate longitudinal trials imposing these strategies in cohorts of puppies matched for osteoarthritis susceptibility have not been carried out)

Answer 3

Give to puppies from dysplastic parents as twice weekly injections from 6wk to 8mo reduced subluxation scores and reduced histopath evidence of arthritis at 8mo

Answer 4

* mechanoreceptors in joint capsule and fibrous constraints * constantly transmitting information to the brain and surrounding tissue re position, movement, and loading. * increased synovial fluid volume might lead to destructive joint forces * Two protective mechanisms to limit subluxation: * 1. SF volume is fixed and minimal > low intracapsular pressure (P) limits translation when joint tends to subluxate during the swing phase. * 2. active factor, a feedback loop triggered by capsular stretching. With lower synovial fluid volume, critical pressure differentials would occur earlier in the subluxation process, causing the capsule to invaginate, thereby stretching it and its associated mechanorecepters. * mechanorecepter activation> periarticular muscles recruited to position the femoral head closer to the acetabulum > larger loads/ weight bearing results in little abrupt reduction. * With increasing synovial fluid volume> protective mechanisms are triggered later during the subluxation of swing phase (i.e., it takes greater subluxation of the femoral head to trigger stretching of the capsular mechanoreceptors). * severe laxity> protective mechanisms fail to be recruited before foot strike> lead to catastrophic hip reduction at foot strike

Answer 5

Panosteitis OCD HOD CCLR LS stenosis Neoplasia

Answer 6

* Wide or narrow based stance * Hips or spinal sway * Stiff, short-strided * shifting weight to thoracic limbs by extending stifle and tarsocrural joints * Bunny-hopping

Answer 7

- large and giant breeds, such as GSD, Rottweilers, Labrador, Golden Retrievers - clinical signs can be divided into two forms. In the juvenile or severe form, dogs are typically presented between 5 and 12 months of age (result of extreme joint laxity, pain dt stretch lig/capsule + microfracture) - capsular strain and inflammation induced by joint laxity cause periarticular fibrosis. This phase of the disease is often associated with reduction or even elimination of clinical signs - chronic form of canine hip dysplasia has highly variable onset (dt OA)

Answer 8

- complete general physical exam> rule out other disease and to determine patient for sedation/GA. - Orthopedic and neurologic examinations - 32% of dogs referred for hip dysplasia had CCLR - Extreme subluxation may result in a low and wide pelvic limb posture - atrophied pelvic limb musculature, reduce ROM, apin extension - young dogs > Bardens, Barlow, and Ortolani (subjective tests) Bardens method - direct lateral force is applied with one hand lifting the femur, without abduction, and the other hand on the greater trochanter> movement more than 1/2 inch suggests laxity ortolani - positive Ortolani sign > joint laxity, NOT definitively shown to be a predictor of development of clinical signs or osteoarthritis - In the mature dog a positive Ortolani sign or Bardens test is rarely palpated, most likely because of the presence of periarticular fibrosis, remodeling of the dorsal acetabular rim, or the presence of a shallow acetabulum.

Answer 9

50% | Ortolani: limb abducted, proximal force, reduction of the femoral head

Answer 10

- Radiography is the principal diagnostic modality used - ultrasonography,(CT), (MRI) > none shown to have improved diagnostic or prognostic utility - Radiographic signs of osteoarthritis denote a definitive diagnosis of canine hip dysplasia but such signs are strongly influenced by the age - at 6 months of age, only 16% to 32% of the dogs examined were correctly diagnosed as dysplastic; at 1 year of age, correct diagnosis increased to 63% to 69%; and at 2 years of age, 92% to 95% (BUT these dogs not followed beyond 5yrs)

Answer 11

VD rads: dorsal recumbency, pelvic limbs pulled into extension with femora parallel and slightly pronated (internally rotated), patella superimposed over the trochlear groove - reported to be an insensitive diagnostic tool, having poor precision and poor predictive accuracy for the diagnosis - windup of the joint capsule > masking observable joint laxity ,factor contributing to the high rate of false-negative diagnoses Hip dysplasia dx: - Hip joint laxity, subjectively or objectively interpreted as subluxation - radiographic presence of osteoarthritis (4) radiographic signs of osteoarthritis lags behind the early in vivo structural changes associated with osteoarthritis. Early changes typical of osteoarthritis can, however, be found on arthroscopy - Orthopedic Foundation for Animals (OFA) decided to limit the earliest age of hip screening in the United States to dogs 2 years of age - hip-extended screening Australian systems, specify dogs 1 year of age or older - evaluating hips at 1 year of age versus 2 years of age is associated with a minimum error in diagnosis of 30%

Answer 12

Femoral periarticular osteophyte formation Subchondral sclerosis of the craniodorsal aspect of the acetabulum Osteophytes on the cranial or caudal acetabular margin Joint remodeling from chronic wear

Answer 13

Femoral periarticular osteophyte formation - caudolateral curvilinear osteophyte (CCO) (“Morgans line) - circumferential femoral head osteophyte (CFHO) - “puppy line” - gone by 18m, dont confuse with CCO (shorter, more subtle) A; CFHO B; CCO C; puppy line | predict later development of well-accepted radiographic signs of OA

Answer 14

hip-extended radiographs of dogs at least 12 months of age. - eight of nine radiographic features (both subjective and objective) scored on a scale from 0 to 6, and one feature scored from 0 to 5 (0 being ideal) - Scores are added for a maximum (worst) subtotal score of 53 per hip joint and a maximum total score for both hip joints of 106. - (2) provide estimations of laxity, degree of subluxation, and Norberg angle - (7) features evaluate for OA - keep records of mean and median scores for each breed - film submission is voluntary, and breeding thresholds are not enforced - no requirement for later film evaluation - Predictive accuracy reported to be low - high rate of false-negative diagnoses hinders further genetic progress toward eliminating canine hip dysplasia - Most abnormal hip radiographs do not get submitted to the OFA, but half of the normal hip radiographs also do not get submitted.

Answer 15

- **Voluntary** film submission forming a large prescreening bias - Not required to be evaluated **later in life** Selection bias makes it impossible to arrive at accurate disease prevalence figures or to assess the rate of improvement data suggest that dogs carrying the genes (susceptibility) for canine hip dysplasia, falsely diagnosed as “normal,” are routinely returned to the gene pool for breeding purposes based on OFA scores | Orthopedic Foundation for Animals

Answer 16

VD extended (for comparison) Compression (shows congruency and true depth of hip joint) Distraction (quantification of the relative degree of femoral head displacement)

Answer 17

- distraction device acts as a fulcrum at the level of the proximal femur, serving to lateralize the femoral heads when the practitioner exerts a small adduction force - degree of femoral head displacement from the acetabulum by means of a distraction index, ranges from 0 to >1, with 0= full congruency and 1= complete luxation - veterinarian performing the procedure receive special training - DI = distance between the center of the femoral head and the center of curvature of the acetabulum divided by the radius of the femoral head - avoid selection bias in the database, it is mandatory for all PennHIP evaluations to be submitted - can be performed with documented accuracy as early as 16 weeks of age - PennHIP report: DI of each hip with stratified risk for developing OA, subjective OA assessment, and a laxity ranking relative to breed average - PennHIP is a continuous scale, though with OA are recomemended to not breed

Answer 18

- ability to assess the “risk” of a young dog developing the osteoarthritis - Dogs having the tightest hip joints (DI < 0.30) have a very low likelihood - Such predictive information is vital for the selection of service dogs - breeders can use the information to select appropriate breeding candidates to make genetic changes toward better hip phenotype - vets can discuss strategies in young dogs with pet owners on the prospect of osteoarthritis later in life (minimise OA) - predictive medicine> risk assessment followed by prescribed strategies for risk reduction by implement evidence-based preventive measures, such as caloric restriction, early in life

Answer 19

The anesthetized animal is placed in a kneeling, sternal recumbency, with femora adducted and stifle joints flexed - forced to subluxate in a dorsolateral direction, and the degree of subluxation is quantified by assessment of the percentage of femoral head coverage (increase risk OA if % of femoral head coverage ≥ 56) - strong correlation between distraction index and dorsolateral subluxation score - No longitudinal studies linking DLS score to the development of radiographic OA been performed (i.e no life span study like for DI) - study DLS vs DI: 23% of dogs predicted to be unsusceptible to OA by the DLS had radiographic evidence of OA > Such dogs would be false-negative diagnoses. - resolved lateralization force in the DLS test. The cartilage contact tangent becomes more vertical with progressive lateralization of the femoral head. This results in a decrease in the resolved lateralization force, meaning that femoral head displacement in the DLS test is strongly influenced by remodeling of the craniodorsal rim of the acetabulum - hip is more extended and more adducted than the position of maximum laxity (estimated reduction of ~30% compared with neutral positioning) - no clinical or diagnostic advantages over PennHIP.

Answer 20

- Flückiger et al. - quantifies hip joint laxity radiographically by using a dorsally directed force that causes dorsolateral displacement of the femoral heads - dog in dorsal recumbency - hip position is approximately the same as DLS - subluxation index: using circle gauges laid over the structures of the femoral head and acetabulum. - No follow-up studies beyond 1 year of age have been published

Answer 21

- prospective analyses of the diagnostic sensitivity and specificity of these methods as a function of long-term (greater than 2 years) outcome measures have not been done - Ortolani in 1937 and Barlow in 1962 adapted from kids - some surgeons may use the angles of subluxation and reduction of the hip joint, derived from Ortolani palpation, as indications for surgery - Gatineau et al: reduction angle a predictor of radiographic OA at 2 years of age > early useful tool in planning preventive surgery. study, however, failed to recognize that hip osteoarthritis can develop long after 2 - STUDY: compare to DI, norberg and extnded. - 95 dogs having normal hip joints by hip-extended score, 59% had a positive Ortolani sign; thus the absence of subluxation on the hip-extended radiograph did not accurately represent the underlying palpable laxity. - distraction index was strongly correlated with Ortolani palpation for dogs without radiographic signs of osteoarthritis; the presence of osteoarthritis weakened the correlation - > 50% of dogs without an Ortolani sign, had laxity indicating susceptibility to osteoarthritis (DI ≥ 0.30). Therefore a negative Ortolani sign is not always indicative of a tight hip joint.

Answer 22

ultrasonography is used as a screening tool in human babies, has been found to have a high rate of false-positive diagnoses, - Dynamic ultrasonography between 8 and 16 weeks appears to permit joint laxity assessment, but the subjectivity of scoring leads to imprecision - Femoral head ossification, occurring at approximately 8 weeks of age, precludes ultrasonographic assessment of acetabular morphology or cartilage integrity later in life

Answer 23

MRI was used to demonstrate a relationship between joint laxity, as measured by distraction index in 7- to 9-week-old puppies, and the synovial fluid volume index; however, a poor association was seen between hip joint laxity at 7 to 9 weeks compared with laxity measured later in life, - At 16 weeks of age, a combination of radiographic distraction index with the CT-determined center-edge angle was found to be most strongly associated with later development of hip osteoarthritis at 2 years of age (BUT evidence of OA at 2 years of age is not a definitive gold standard for hip dysplasia)

Answer 24

- Increased hip extension at end of stance phase - Increased femorotibial flexion through stance and early swing phase - Coxofemoral deceleration early in stance phase - Increased stride length with decreased peak vertical force immature dogs (16 weeks) with moderate passive hip joint laxity and no hip osteoarthritis, no relationship between distraction index and joint kinematics was noted. dogs with radiographic evidence of hip osteoarthritis were compared to those without, no difference in ground reaction force was noted, but significant differences in joint kinematics were observed.

Answer 25

Two principal strategies 1. genetic control: aimed at **reducing prevalence** in future generations by optimally selecting breeding dogs that are free of susceptibility 2. prevent, delay, or mitigate the expression in susceptible dogs in the current generation. predictive medicine (apply evidence-based methods to lower disease risk or reduce disease progression) ideal hip screening/diagnostic test

Answer 26

holy grail = discovering the totality of genes that can explain all of the phenotypic variation associated with expression of the disease. 1) seven–single nucleotide polymorphism test > specific to one breed and related more to severity genes than to causal ones. using only a well-defined phenotype, a known pedigree structure 2) principles of quantitative genetics 3) characteristics of the ideal hip screening tool (accurate, precise, continuous ratio scale, measurable early, heritable, 4) high correlation between distraction index and later osteoarthritis 5) hip metric with the highest heritability> when used as a means to apply selection pressure, will yield the most rapid genetic change toward improved hip status in the offspring

Answer 27

- **Accurate** (closely assoc with the unwanted phenotype) + high positive and negative predictive value - **Precise** (good interobserver agreement) - Desireable to have a metric that is reprentable as a **continuous scale**, DI is proportional (more desirable than interval scale -Norberg angle or % head coverage - or noncontinuous scale, such as OFA) - Should be **measureable early** as possible in life - Must have a **heritable** component (portion of variation in the phenotype is under genetic control. Heritability is a number between 0 and 1, where 1= all phenotype dt gene) - **Selection pressure** (sufficient range in phenotype to permit selection of dogs much better than average)

Answer 28

accuracy = square root of the heritability of the phenotype in the population of interest. for heritability of 0.25, the square root would be 0.5, equating to an accuracy of 50%. This is equivalent to “flipping a coin.” (i.e OFA hip score heritibility is <0.25) heritability 0.6, the square root becomes 0.77, an accuracy of 77% >much better chance that the selection will yield the desired outcome.

Answer 29

the ratio of additive genetic variation to overall phenotypic variation of a given trait

Answer 30

phenotype has high heritability (≥0.5) - rapid genetic change can be made in that phenotype by simply selecting breeding dogs by mass selection - i.e., breeding dogs based on individual hip joint phenotypes [hip scores]). - phenotype is a rather accurate predictor of the dog's genotype. low heritability (≤0.35) - mass selection is no longer optimal because the individual phenotype is no longer a very accurate predictor of the dog's true genotype - better to use estimated breeding values (EBV)

Answer 31

- quantitative genetic tool that more accurately predicts an individual's genotype - combine pedigree and phenotypic information to calculate the EBV for each trait or phenotype for each candidate - more accurately predict the relative value of an individual dog's phenotype - enables more rapid improvement in polygenic or multifactorial traits, particularly low heritabilities - incorporate the phenotypes of both close and more distant relatives of a dog considered for breeding - arrive at a genetic value, ranked from most to least genetically likely to improve a trait - require maintaining a costly and organized database

Answer 32

Genetic change = Heritability (h^2) x (Avg parent - Avg population)

Answer 33

0.46 - 0.83 Anything above 0.5 is expected to make rapid changes

Answer 34

- **Mass selection**: choosing breeding stock based on the individual dog's hip joint phenotype (not consider relatives) - highly heritable traits (≥0.5), mass selection is an acceptable approach for choosing replacement breeders, but, as heritability decreases (≤0.35), it becomes increasingly important to consider the phenotypes of relatives (like EBV) - environmental and nongenetic factors contribute to the variation observed, further obscuring the underlying genotype giving rise to that phenotype - lower heritability > observed phenotype should be recognized as a poor predictor of genetic value - mass selection, if linked to a highly heritable phenotype, such as the PennHIP distraction index, holds the greatest promise to reduce the frequency and severity of osteoarthritis - heritibility = ratio of additive genetic variation (VG) to overall phenotypic variation (VP genetic and nongenetic)) of a given trait (h2 = VG/VP) **selection pressure** - amount of selection pressure applied to genetically improve a trait is determined by the magnitude of the selection differential. - selection differential = amount by which the average parental hip score differs from the overall population average (Avgparents − Avgpopulation). - heritability + selection pressure determine the rate of expected genetic change (ΔG) in the ensuing generation. - ΔG is the difference in average of the offspring minus the mean of the parents: - genetic improvement = heritability (h2) of the hip score x selection differential (determined by the parents) - campred to subjective OFA hip score, Higher estimates of heritability have been found for (PennHIP) distraction index (>0.46 to 0.83) | DI the only hip scoring metric having high correlation with OA

Answer 35

Another study went further to show that approximately 50% of the Labrador Retrievers receiving normal OFA-type hip scores at 2 years of age went on to develop characteristic radiographic signs of canine hip dysplasia by the end of life. This means that the age of the dog at the time of evaluation is immensely important in understanding canine hip dysplasia

Answer 36

- Dog breeders cannot influence magnitude of heritability , but can control applied selection pressure - purpose of selective breeding > maximize the proportion of dogs within a population that have the target phenotype - breeders who use mass selection, rapid genetic change is achieved by mating dogs with the extreme best hip joints (OFA excellent scores; PennHIP better than the 95th percentile) > HOWEVER, using small pool of ideal dogs may increase the coefficient of inbreeding and may contribute to the loss of other desirable traits - By applying at least moderate selection pressure, eventually the average of the population will shift toward tighter (better) hip joints with each generation, systematically changing the minimum standard for the breed *By selecting from the tightest 40% of a breed (60th percentile or better) as the minimum criterion, meaningful genetic change can be expected to occur without extreme loss of genetic diversity*

Answer 37

Pennhip DI

Answer 38

a few reports: - the OFA system of hip screening (bias dt voluntary submission thus any change is not accurate reflection, > overall rate of improvement over 37yr slow (0.08 OFA unit), low heritbaility of OFA score like plays a part - two related to the BVA/KC system of hip scoring (excluded breeding of only the worst 15%) - one from the New Zealand VMA system (genetic trends from three common breeds were not significantly different from 0, apart from GSD) - Another study reported the relationship of official OFA score to PennHIP distraction index in a pool of 439 dogs Studies from OFA, BVA/KC, and New Zealand Veterinary Association (NZVA) data show extremely slow genetic progress toward a desirable phenotype - suggest that using EBV would speed up genetic improvement for all scoring systems - finding consistent accross studies 0f the importance of joint laxity in the ultimate development of hip osteoarthritis -

Answer 39

defined by (1) the heritability of the selection phenotype, (2) the selection pressure that can be applied, (3) the “value” of the target outcome (phenotype) and how it relates to the disease or trait of interest (OA) A life span study of Labrador Retrievers showed a high number of false-negative diagnoses associated with both OFA scoring and official Australia Veterinary Association both AVA and PFA have very low negative predictive vaules @ 2 yrs of age and end of life OA histopath versus pennHIP at 2yr that predected all would have OA and 98% proven to by histopath or rads This demonstrated the profound importance of hip joint laxity in predicting the susceptibility of dogs to manifest, at some point in their lives, the osteoarthritis of hip dysplasia *For all hip screening methods, the phenotypic goal is to breed for dogs that are both free of hip dysplasia at the time of examination and, more importantly, free of the susceptibility to acquire hip dysplasia throughout life*

Answer 40

High heritability Selection pressure can be applied Highly correlated with the phenotype of interest

Answer 41

investigation of 439 dogs - OFA excellent hip scores, 52% had a PennHIP osteoarthritis-susceptible range (DI > 0.3) - OFA good scores, 82% had DI > 0.3, - 94% of OFA fair scores had DI > 0.3. The relationship appeared to be breed specific, Similar results would be expected from all hip scoring systems that rely on the hip-extended radiograph to determine hip joint phenotype

Answer 42

The PennHIP method provides marked advantages over scoring systems based on the hip-extended radiograph and, if PennHIP were widely adopted, it could result in rapid improvement of hip joint quality among puppies born into future generations. Genomic testing shows promise for identification of dogs carrying the susceptibility to canine hip dysplasia, but, based on current reports, no reliable tests are currently available.

Answer 43

Retrospective (36 joints). Correlation of DI with arthroscopic findings arthroscopic assessment of dogs selected for DPO - DI not correlated to arthroscopic change - low positive correlation between synovitis and DI - DI not accurate for predicting magnitude of joint pathology on arthroscopy - DI not a measure of articular cartilage injury, likely related to the relatively static nature of the DI lesions at the insertion of the ligament of the femoral head - Pathological changes not seen on rads seen in up to 69% of hips > these dogs may not be the best candidates for a DPO This study did not include clinical or radiographic follow-up; therefore, we were unable to correlate long-term outcome after DPO with either preoperative DI or arthroscopically identified intra-articular wear grades increased synovitis correlated to cartilage signs

Answer 44

Kinetic and Kinematic Analysis of Dogs with HD. 20. Controls. Dysplastic - lower peak vertical force (4% ) - increased symmetry index (12.6%) - reduced maximum hip joint extension angle and (ROM) Peak vertical force (PVF) and vertical impulse (VI) are the most accurate kinetic gait parameters used in lameness diagnosis. sitting down tests are important tools in canine hip dysplasia assessment

Answer 45

DI varied over the first 12 months of life - DI increased from 4-6 months, decreased at 12 months - DI >0.7 at 4 months → significant decrease at 6 and 12 months - still high → high likelihood of OA - most appropriate time for measurement of DI uncertain

Answer 46

longitudinal study n=615 dogs selected with DI+OFA evaluations - OFA evaluations only from 2001-2014, DI+OFA 2015-2017 - DI selection threshold <0.3 - hip joint quality scores were unchanged using OFA measurements only - DI and OFA → improved hip joint quality scores over short space of time

Answer 47

evaluation of hip joint laxity in 59 dogs Intraoperator-reliability was slightly better for the NA compared with the DI. excellent results in intraobserver-reliability and interobserver-reliability for both the NA (ICC 0.975; 0.969) and the DI (ICC 0.986; 0.972). Thus, the NA as well as the DI can be considered as reliable measurements. For the PennHIP method, a study was published and showed high within- and between-examiner repeatability

Answer 48

– ventrodorsal hip flexed, not extended projection for assessment of hip laxity - VD hip flexed, not extended → demonstration of laxity with agreement to measurements performed with VD hip flexed, distracted (VMBDD) - using LI and NA - VD hip flexed, not extended does not require operator to maintain distraction

Answer 49

The overall prevalence of FHD was 24.9% (635/2548) in the OFA database, and was slightly higher in males Dysplasia was more severe in bilateral than unilateral cases and with increasing age It should be remembered that cats have shallower acetabulae and more hip laxity than dogs. HD confirmed by noting the shallow acetabulum, subluxation of the femoral head and often early degenerative changes at the cranial border of the acetabulum.

Answer 50

10 dogs As the LI measurements were acceptable after a short presentation, they support the use of VMBDD for a complete and correct in-house evaluation of the hip joint by trained clinicians. However, we propose that, in the context of screening, measurements should be performed by a limited number of experienced examiners, to limit the impact of the inter-observer variability. LI obtainedwith the VMBDD returns similar results compared with the DI obtained on the PennHIP distraction radiograph > previous study.

Answer 51

Three sets of radiographs with different positioning and projections were acquired using 10 canine cadavers Dorsoventral projections can be recognized based on the proximal position of the patella and should be excluded from evaluation, as the Norberg angle value can be falsely increased. Tilted images that are subjectively perceived evaluable have very little effect on the Norberg angle and are therefore probably acceptable.

Answer 52

compare the assessment of the distraction index (DI ≤ 0.3) and the Norberg angle (NA ≥ 105◦) to predict a nondysplastic and dysplastic hip joint 29 patients with OFA ≤ 3, 20 had DI > 0.3. These findings demonstrated that phenotypic healthy dogs according to OFA grading can present passive hip joint laxity, as demonstrated by radiographic evaluation with distraction. the use of OFA as the gold standard may underestimate the diagnosis of CHD when used in isolation to assess the hip joint in dogs. Thus, evaluating the hip joint based on a single radiographic method may be inadequate in correctly diagnosing a patient, and the combination of different radiographic methods can provide greater confidence in the diagnosis and decision-making in the management of hip dysplasia in dogs over 2 years of age.

Answer 53

The aim of this study was to evaluate the force–laxity relation to assess the repeatability of repeated cycles of stress on the hip joint and determine the force necessary tomeasure a sufficient proportion of laxity present in hip joints. Materials and Methods Thirty-four canine cadavers, using the Vezzoni modified Badertscher distension measuring device (VMBDmD). As expected, there is a marked relation between force and LI%, and a force of 95.32N seems to be the threshold to reach sufficient laxity for 90% of the population The LImax and the curve to reach the LImax are not influenced by degenerative changes, bodyweight, gender, or age. While the position of the VMBDmD does not influence the LImax, it can influence how fast the LImax is reached.