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Study on canine hip dysplasia and its diagnosis by imaging and molecular
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Study on canine hip dysplasia and its diagnosis by imaging and


molecular genetics techniques
Felix Daniel LUCACI1, Radu LĂCĂTUȘ1, Robert Cristian PURDOIU1 and
Dana Liana PUSTA1

1
Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, Mănăştur
St. 3-5, 400372 Cluj-Napoca, Romania.
*Corresponding author: Felix Daniel LUCACI e-mail: [email protected]

Abstract
The present paper is a bibliographical research on canine hip dysplasia using imaging and molecular genetics techniques.
Ever since the first description in 1935 made by Schnelle, canine hip dysplasia has remained one of the most diagnosed
orthopedic conditions present in the dog breeds. The gold standard method of diagnosis of hip dysplasia is the
radiological examination in hip-extended position. While the radiological examination focuses mainly on the individual
for the diagnosis of this condition, methods of diagnosis of an entire population are sought, and these methods are
represented by molecular genetics techniques. Naming the etiology of canine hip dysplasia and finding out the latest
methods of genetically and radiologically diagnosis of canine hip dysplasia and the best alternatives of treatment for
this disease. Canine hip dysplasia continues to be a major problem for owners, breeders and veterinarians. Currently,
there are five standardized systems worldwide that deal with the grading of canine hip dysplasia. In addition to digital
radiology, CT and ultrasonographic examination are feasible diagnosis methods. Even if the standard method of
diagnosis remains the radiological examination in the present, the near future provides to be of the molecular genetic
techniques.

Keywords: canine hip dysplasia; CT; digital radiology; molecular genetics techniques; ultrasonography.

INTRODUCTION
The present paper is a bibliographical research on canine hip dysplasia using imaging
and molecular genetics techniques. We will make references to the etiology of the
disease, the methods of diagnosis and treatment as well as certain aspects regarding the
genetics of the disease.
Since it was first described by Schnelle in 1935, canine hip dysplasia has remained
one of the most diagnosed orthopedic conditions present in the canine breed (King M.,
2017).
Canine hip dysplasia is characterized by joint instability, subluxation, or even
dislocation of the femoral head, which will result in a deformation of the joint with the
early development of coxarthrosis (Mortellaro et al, 2008). The gold standard
method of diagnosis is a radiological examination with the hip joint in forced extension
(Schachner, and Mandi, 2015). Radiological screening of canine hip dysplasia had
provided moderate success in decreasing the prevalence of this condition (Merca
Roxana et al., 2020).

THE ETIOLOGY OF CANINE HIP DYSPLASIA


Genetic factors
The literature presents two genes and a protein that could be directly related to
canine hip dysplasia.
The CHST3 gene is the one that encodes the synthesis of the sulfotransferase enzyme. In dysplastic dogs, a mutation
in exon 3 of this gene causes the substitution of glycine with arginine, thus causing deficiencies in the formation of articular
cartilage (Peterson C., 2017).
The FBN2 is a gene that encodes the synthesis of fibrillin II. Fibrillin II is located on chromosome 11 in dogs and has
an important role in the elastic tissue of the extracellular matrix present in the joints, especially in the tendons. In dysplastic
patients, it occurs a deletion of this gene from the chromosome causing changes in the connective tissue around the joint
(Todhunter J. R., 2018).
Fibronectin I is a glycoprotein with a role in the extracellular matrix of cartilage. An increased amount of this
glycoprotein has been found in dysplastic subjects (Peterson C., 2017).

ENVIRONMENTAL FACTORS
Nutrition factors
They are among the most important environmental factors in terms of the development of canine hip dysplasia. Studies
have shown that an adequate nutritional intake, correct during the growing period, can reduce the risk of developing canine
hip dysplasia (Kealy et al 1997).
Puppies do not have a protective mechanism against exogenous calcium intake, so calcium or vitamin D supplements
decrease osteoclastic activity and normal ossification will be delayed, which may cause hip dysplasia in individuals with a
genetic predisposition (King M, 2017).

Exercise
Krontveit, 2011, made an investigation on four large dog breeds (Labrador retriever, Irish wolfhounds, Newfoundlands,
and Leonbergers) in Norway and found out that dogs that descend and climb stairs from birth to 3 months of age are more
prone for developing hip dysplasia because during this period of life the musculoskeletal system is most vulnerable to the
action of mechanical stress and the development of orthopedic disorders.
Another study, contradictory to the first one, also realized by Krontveit et al, 2012, shows that off-leash activity performed
on soft ground, as early as possible in the life of the puppy increases muscle mass and strength in the coxo-femoral joint.
However, the authors point out that any activity on the stairs should be avoided and physical effort should be moderate in
duration and intensity.

Body type
In general, small breeds of dogs have a lower incidence of hip dysplasia compared to large and giant breeds. Heavy
breeds, those with round conformation, poorly developed muscle mass, and those with early physical maturity are most
susceptible to hip dysplasia, while breeds with well-defined muscles, with right limbs, are less prone because a strong
muscle mass with a correct posture is considered to inhibit the transformation of passive joint laxity into functional laxity
when the dog is in motion (Krontveit, 2012).

Hormones
Exogenous estrogen or relaxin administered to the puppies or to the pregnant bitches can accelerate the development
of hip dysplasia by increasing joint laxity. Pregnant bitches with hip dysplasia may have a modified metabolism, and
therefore puppies may be exposed to increased amounts of relaxin before birth. Colostrum contains estrogens and relaxin,
and these can induce joint laxity in puppies with a predisposition to hip dysplasia. However, there is no clear evidence to
confirm that relaxin, estrogen, or other hormones can play a decisive role in a biologically healthy field. (Krontveit, 2012,
King M., 2017).

Rate of growth
In German Shepherd breed dogs, it was concluded that specimens that at 60 days of age were overweight will show in
adulthood signs of hip dysplasia, compared to those with normal weight at 60 days of age. Excessive feeding can maximize
the expression of canine hip dysplasia, but only in individuals with a genetic predisposition (Krontveit, 2012). Weight
reduction for dogs was accepted as a preventive action or as a delay in clinical signs (Tobias, and Johnston, 2012).

Diagnosis of canine hip dysplasia


The diagnosis of the canine hip dysplasia is initially based on the anamnesis obtained by the veterinarian from the
patient owner, then he will perform a functional examination following the patient at rest and while he is walking, after
that the clinical examination is continued with the inspection, palpation and orthopedic examination. After the clinical
examination, the veterinarian will continue with the paraclinical examination (Papuc, and Lăcătuș, 2013).
Radiological examination Open Access
The radiological examination remains the gold standard method in the diagnosis of canine hip dysplasia. The first
visible radiological sign is a radiopaque line from the base of the femoral neck to the trochanteric fossa, which is the result
of new bone formations along the insertion of the joint capsule and is known as Morgan's line (Figure1.) (Thrall, 2018).

Figure 1. Morgan’s line (black arrow)


Source: Thrall D.E., 2018
Worldwide there are five screening approaches for canine hip dysplasia: Federation Cynologique Internationale, British
Veterinary Association/Kennel Club, the Orthopedic Foundation for Animals, Pennsylvania Hip Improvement Program,
and Dorsolateral Subluxation Approach (Schachner and Mandi, 2015).
In Romania, as well as in countries that use either the British system or that of the international canine federation, for
the diagnosis of canine hip dysplasia, among other measurements, the Norberg angle is also used as presented in Figure 2
m(Papuc et al, 2013).

Figure 2. Norberg’s angle


Source: www.superveterinary.com

Federation Cynologique Internationale (FCI)


Currently, the screening system for canine hip dysplasia at FCI is used in most countries in Europe, Russia, South
America, South Africa, and Asia (Figure 3). The scoring system combines the subjective standard hip-extended
radiographic evaluation with the Norberg’s angle measurement.

Figure 3. FCI scheme for grading CHD


Source : Kyriazis A. et al, 2016
Norberg's angle is used in the ventrodorsally incidence for the pelvis and is a measurement of the relationship between
the center of the femoral head and the margin of the acetabular cavity. Patients with a Norberg angle ≥105⁰ are considered
non-dysplastic, while those with a Norberg angle below 105⁰ are diagnosed with varying degrees of dysplasia, depending
on the congruence between the femoral head and the acetabular cavity, the presence or absence of osteoarthritis, and of
thickening the acetabular cavity (Schachner, and Mandi, 2015; Papuc, and Lăcătuș, 2013). There are five grades, from A-
E, where A-B is for non-dysplastic patients and E is a patient with severe hip-dysplasia. The minimum age for scoring is
from 12-18 months of age (Schachner, and Mandi, 2015).

British Veterinary Association/Kennel Club (BVA/KC)


Since 1965, for the screening of canine hip dysplasia in the British system, dogs have been marked with „pass” or
„failed” in Great Britain, Ireland, and Australia. Radiographs are performed with the hips in forced extension, in patients
at least one-year-old, and a score is obtained using nine criteria, and the score varies between 0-6. The left and right hips
are measured separately, after which the sum is made, the interval being between 0-106 (53 for each hip) (Verhoeven Et
al, 2011; Schachner, and Mandi, 2015).

The Orthopedic Foundation for Animals (OFA)


OFA is the organization that has been screening for canine hip dysplasia since 1966, in the United States and Canada.
Dogs over 2 years of age are examined radiologically in the standard position with their hips in forced extension. Patients
are classified according to the degree of dysplasia as follow: excellent, good, correct, borderline, mild dysplasia, moderate
dysplasia, and severe dysplasia. Signs of incongruence and degenerative joint disease and hip joint laxity are considered
scoring criteria (Figure 4). The scoring system does not use the Norberg angle measurement. Patients with the score
excellent, good and correct are considered nondysplastic while dogs with mild, moderate, and severe are considered
dysplastic patients (Schachner, and Mandi, 2015; Verhoeven Et al, 2011).

(a) (b)
Figure 4. Hip joint anatomical characteristics and distraction index: (a): 1- craniolateral acetabular rim,
2-cranial acetabular margin, 3-femoral head, 4-fovea capitis, 5-acetabular notch, 6-caudal acetabular
margin, 7-dorsal acetabular margin, 8-junction of femoral head and neck, and 9-trochanteric fossa
(Source: Schachner et al, 2015); (b): the distance between femoral head and acetabulum (Source:
Schachner et al, 2015).

Pennsylvania Hip Improvement Program (PenHIPP)


The PennHIP method is based on passive joint laxity, with the goal of detecting passive joint laxity as quickly as
possible, at a minimum of 16 weeks of age. The patient will be in a recumbency position, and the femurs are held in a 10–
15◦ extension, thus the proximal aspect of the femurs is compressed into the acetabulum obtaining the compression index.
With a specially made distractor placed between the patient's pelvic limbs, the femoral bones will undergo an abduction
thus allowing a lateral movement of the femoral head from the acetabulum. On the radiograph obtained in this position is
calculated the distraction index (DI), which represents the distance between the center of the femoral head and the center
of the acetabulum (Fig.5). Distraction index values are between 0-1, where 0 being total congruence between the center of
the femoral head and the center of the acetabulum, and 1 meaning complete dislocation. Dogs with a score between 0-3 DI
are unlikely to develop hip joint degeneration, while those with values above 0.7 DI, will certainly develop hip joint
pathologies (Soo M. Et al, 2015; Verhoeven G. Et al, 2011).

Dorsolateral Subluxation Approach (DLS)


In the DLS system, the position of the dog is described as a weight-bearing position, thus DLS method obtained a more
functional hip laxity than the PennHip method. The patient will be in a sternal position, on a special support that allows the
Open Access
knee joint to flex, so it will not be a bone overlap during the x-ray (Figure 6a). Both femoral bones are perpendicular to the
radiological table, thus supporting body weight and putting additional stress on the coxo-femoral joint. On the dorsoventral
radiograph, the DLS percent is obtained by calculating the percentage of femoral head that remains medial to the most
lateral aspect of the cranial acetabular rim (Figure b). Patients with a DLS score above 55% will be unlikely to develop
canine hip dysplasia during their lifetime, those with a DLS score below 45% have chances for developing the disease. The
DLS score is used more often in genetic studies (Saunders and Broeckx 2017; Verhoeven et al, 2011).

(a) (b)

Figure 6. A. The Dorsolateral Subluxation position; B. The DLS score is calculated as a percentage
d/0x100, where d- distance between a line dropped from the cranial acetabular lateral margin and a
parallel line, tangential with the most medial surface of femoral head; and 0- diameter of the best
fitting circle of the femoral head (Source: Verhoeven et al., 2011).

Computed tomography
CT scan has become very popular in recent years in the diagnosis of canine hip dysplasia. CT images in two dimensions
can measure: percentage of coverage of the femoral head, acetabular index and certain angles: acetabular, ventral and dorsal
anteversion angle, horizontal acetabular sector, center edge angle (CEA) and on CT images in three dimensions can be
measured: the volume of the head and neck of the femur, the rays of the head and of the femoral neck, and the angle of the
femoral neck. The measurement of the center edge angle (CEA) and distraction index (DI) combined with the measure of
the dorsal acetabular sector angle and Norberg angle at 16 and 32 weeks of age can have a predictive value on osteoarthritis
in mature dogs (Butler, and Gambino, 2017; Schachner E.R. et al, 2015). Due to the high price for a single examination, a
CT scan is not used as a routine method for diagnosing canine hip dysplasia.

Ultrasound
Ultrasonography is not a part of the current methodology for diagnosing this condition. The results are often
contradictory, especially in puppies under 8 weeks. Ultrasonographic evaluation is based on a subjective evaluation of
acetabular bone morphology and measurement of two angles ά and β. At the ultrasound examination, there are three
markers to be followed for being sure for the accuracy of the position: the caudal edge of the ilium in the acetabular fossa,
the bone edge of the acetabular bone with the iliac silhouette, and the cartilage triangle 'labrum acetabulare’ (Schachner
and Mandi, 2015; Shipov et al., 2019).

MRI
Magnetic resonance, as an imaging modality, is not currently used for diagnosing canine hip dysplasia. Magnetic
resonance can be used for the evaluation of ligamentous structures, soft tissues, joint capsules, and the proximal femoral
physis. MRI technique is a non-invasive method that can be helpful for assessing the diseases of articular cartilage. With
dGEMRIC (delayed gadolinium-enhanced MRI of cartilage) in conjunction with T1-weighted spin-echo an early stage of
osteoarthritis can be revealed. In the T2 imaging modality, the sensitivity of tissue hydration and water content can be
assessed, so an increase of the T2-weighted relaxation times is equivalent to cartilage damage. There are some other factors,
such as the cost, time, the expertise required, and the need for general anesthesia for an increased length of time, which
determines both owners and veterinarians to choose another imaging method for diagnosing canine hip dysplasia (Butler,
and Gambino, 2017).

Genetic tests
Largely the current methods of diagnosis and treatment focus on the individual, while genetic testing seeks to solve the
problem of an entire population. Current genetic studies are aimed at identifying genes responsible for canine hip dysplasia,
genetic mutations, and quantitative trait loci (regions of chromosomes containing DNA for a specific trait) (Schachner, and
Mandi, 2015).
Pfahler and Distl, 2012, identified in their study three single nucleotide polymorphisms (SNPs) associated with canine
hip dysplasia on the CFA14 chromosome and 37 in the Mountain Bernese breed with candidate genes of interest being
Paraoxonase-2(PON-2) on CFA14 and Fibronectin-1(FNI-1) on CFA37. PON-2 and FNI-1 are considered to be part of the
pathogenesis of canine hip dysplasia due to their involvement in bone mineral density and extracellular matrix cartilage.
Dysgen Test – Researchers from Bioiberica, University of Barcelona, and Progenica Inc. have developed a genetic test
that can assess the individual probability of developing canine hip dysplasia in Labrador Retrievers. The test has an
accuracy of 85%, a sensitivity of 80%, and a specificity of 78%, but when is in conjunction with the results from the x-ray
exam those numbers increased and the test can be applied in breeding programs. The researchers tried to find the presence
or absence of 7 single nucleotide polymorphisms (SNPs) which have been linked to canine hip dysplasia. At the end of the
study, it was concluded that there is no significant statistical evidence to support the predictive value of the Dysgen test
(Bank and Ström, 2016). Bruun et al, 2020, has conducted a study on 39 dogs from the Danish Labrador Retrievers breed.
In this study, 14 dogs were with hip dysplasia (grade D or E) and 25 dogs were without hip dysplasia. The authors concluded
that for their study group the Dysgen Test has no prognostic value against canine hip dysplasia.
It is considered that a genomic selection scheme will be the alternative for reducing the prevalence of canine hip
dysplasia, so a genomic (DNA) test is needed as long as it can provide information about a large number of genotype
markers in a population of phenotypic marked dogs. Until such a test is available, selection against canine hip dysplasia
will be made according to the criteria described above (Soo et al, 2015).

Treatment for canine hip dysplasia


Treatment for canine hip dysplasia pursues two directions, conservative, drug treatments, and surgical treatments. Bell
J, 2015, states in its study that about 75% of dogs diagnosed with varying degrees of dysplasia may exhibit a good quality
of life and good functionality of the coxo-femoral joint only using drug treatment, without the need for surgical intervention.
Nonsteroidal anti-inflammatory drugs are found in the primary medical management of CHD.
The main objectives of conservative treatment in dogs involve reducing pain, maintaining the function and range of
movement of the hip, returning as quickly as possible to normal physical activity, slowing the progression of the condition,
all without major adverse effects. It is also very important to maintain an optimal weight, control the pain, strengthen the
periarticular muscles, maintaining healthy cartilage, and limiting inflammation. Treatment is done depending on the phase
of the disease. In the acute condition, rest is necessary alongside anti-inflammatory medication, analgesic medication, and
physiotherapy, while in the chronic phase it is intended to maintain a balanced diet but also physical activity is very
important for a normal quality of life (Harper, 2017; Hamish, 2004).
Nonsteroidal anti-inflammatory drugs such as carprofen, ketoprofen, meloxicam, robenacoxib, tolfenamic acid, etc. are
used in canine hip dysplasia, and analgesic medication such as tramadol, acetaminophen, gabapentin. To reduce weight in
obese animals, protein inhibitors such as mitratapid or drilotapid may be used as a medication. Glucosamines can also be
used in combination with chondroitin sulfate, omega 3 fatty acids, and hyaluronan (Harper, 2017).
Among the most common surgical interventions, is juvenile pubic simphysiodesis, triple pelvic osteotomy, total hip
replacement, and femoral osteotomy (Tobias and Johnston, 2012).
- Juvenile pubic simphysiodesis: involves electrocautery of the pubic growth plate which will cause thermal necrosis of
chondrocytes and premature closure of the growth plate. Is recommended to be performed around 15 weeks of age. This
method is simple, fast, and does not require orthopedic implants and results in a bilateral acetabular rotation, and the return
to normal activity is rapid, while complications are extremely rare (Anderson, 2011).
- Triple pelvic osteotomy: the main objective of this procedure is to prevent the subluxation of the femoral head by
increasing the dorsal acetabular coverage achieved by osteotomy of the ilium, ischium, and pubis. It is recommended that
the intervention be performed on patients up to 1 year of age (Anderson, 2011).
- Total hip replacement: It is a salvage procedure, which involves replacing the femoral head as well as the affected
acetabular bone with implants. This intervention is carried out with caution in young dogs because there has been a higher
rate of postoperative complications than in adult dogs (Vezzoni et al., 2008).
- Femoral osteotomy: It is also a salvage procedure that aims to excise the femoral head so that the pain decreases in
intensity or even disappears (Tobias et al., 2012).

Author Contributions:
F.L. wrote the manuscript with support from D.L.P; R.L. and C.R.P. helped supervise the project; D.L.P. supervised the
project. All authors provided critical feedback and helped shape the research, analysis, and manuscript.

Acknowledgments
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit
sectors but the study was part of the regular monitoring of the health of SB laboratory animals.

Conflicts of Interest
The authors declare that they do not have any conflict of interest.
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