The aetiology and diagnosis of osteoarthritis

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1 The aetiology and diagnosis of osteoarthritis Dr. Eithne J. Comerford Senior Lecturer in Small Animal Orthopaedics University of Liverpool, UK Introduction Osteoarthritis (OA) (osteoarthrosis or degenerative joint disease (DJD)) is a disease of synovial joints. Whilst the apophyseal joints of the spine can also be affected, the association between OA of these joints, disc disease and clinical signs is unclear. Consequently the following discussion is limited to the joints of the appendicular skeleton. OA is the most common arthropathy of the domestic species (and man) and the cause of much chronic suffering in dogs (up to 20% of canine population reported in one study) and cats. OA is a heterogeneous disease and assessment of the disorder is difficult. The poor correlation between radiographic and clinical data highlights this difficulty. The typical example of this, in dogs, is the dysplastic hip with secondary OA - severe radiographic changes may be present in a clinically silent joint and conversely, severe signs may be present in another dog with only mild radiographic signs. Expression of different facets of the disease seems to vary between individuals and even between different joints in the same individual. The current model of OA (Figure 1) attempts to incorporate the heterogenic nature of OA and how various contributing factors may interact. It is thus helpful to think of OA as a disease process as opposed to a disease. Genetics: variable, polygenic Joint biomechanics shape, trauma, selected usage) Age Breed Gender Susceptibility to OA Other systemic factors hormonal, disease, etc.. Site and severity of OA Figure 1: Current model of OA Disease mechanisms of OA The progression of OA can be largely attributed to enzymatic degradation of the extracellular matrix (ECM) of the articular cartilage. The initiation of this process is poorly understood, but current theories can be grouped into two:

2 1. The joint develops normally but it is loaded with abnormal forces (Primary OA) 2. The joint develops abnormally and normal forces acting on the abnormal joint lead to OA (Secondary OA) Secondary OA is the OA almost exclusively seen in dogs. The main tissue affected is the articular cartilage but the subchondral bone, synovium and intra-articular ligaments are also affected and indeed may be important in terms of disease progression. Articular cartilage is comprised of ECM and chondrocytes (which produce the ECM). The ECM is composed of proteoglycans (aggrecan), collagens (mainly type II) and water (up to 75%) (Figure 2). In normal cartilage there is a very slow turnover of collagens but the proteoglycan is constantly being renewed. In OA, the proteoglycans and collagens are degraded by cytokines (inflammatory mediators) released by inflammatory cells within the joint. These inflammatory mediators are enzymes known as metalloproteinases (ADAMTs and MMPs) [1] [2]. Reducing the degradation of the ECM by these enzymes is the main aim of the medical treatment of OA. Figure 2: Schematic diagram of the molecular components of articular cartilage Classification of OA OA is classified as idiopathic (primary), secondary or erosive (atrophic). Idiopathic (primary) OA Primary OA is extremely rare in the dog as one can usually identify an underlying cause (e.g. OCD, cruciate disease). However, a generalised disease is occasionally seen in certain breeds such as the Chow Chow, Dalmatian, Labrador retriever and spaniels. This is usually a symmetrical disease affecting both carpi, both stifles or elbows for example. In man,

3 primary OA is caused by a fundamental defect in the extracellular matrix. To date, no such defects have been characterised in dogs with disease that resembles primary OA. Once established, the path of primary OA is exactly the same as that of secondary OA. Secondary OA This is the most common form of OA in dogs. Some common causes are listed below although the list is far from exhaustive; Hip dysplasia, Osteochondrosis, Cranial cruciate ligament disease, Legg-Calvé- Perthes disease, Joint trauma (e.g. collateral ligament damage, joint luxation, articular fractures), other forms of arthritis (septic, immune mediated) For many of these diseases, the OA may not be the major problem at initial presentation and the primary condition may be more pressing (e.g. articular fractures) but there will be other cases where the contribution of the OA may be more important (e.g. hip dysplasia with secondary changes in a mature dog). The contribution of OA and the primary condition may differ in their contribution to the overall presentation as the disease progresses (see lecture). Diagnosis The diagnosis of joint disease/oa can involve many different steps from clinical examination to the utilisation of more advanced procedures such as magnetic resonance imaging. This lecture will review the most common tools used in the diagnosis of joint disease/osteoarthritis and highlight some of the newer techniques used in the diagnosis of joint disease and occult lameness in small animals. The following diagnostic tools will be reviewed: Gait evaluation, clinical and orthopaedic examination Radiography including conventional and digital and arthrography Arthocenthesis Ultrasonography Scintigraphy Computed tomography (CT) Magnetic resonance imaging (MRI) Arthroscopy Gait evaluation, clinical and orthopaedic examinations Observation of dog/cats at stance, walk and at trot is an important and essential part in the diagnosis of osteoarthritis and joint disease. Kinetic and kinematic gait analysis

4 can be used to objectively detect subtle lameness in dogs (and hopefully soon in cats!). These require specialised equipment and training. Pain on manipulation of the joint is at the centre of the clinical diagnosis. Flexion, extension, pronation and supination should be performed and compared to the contralateral side. One must appreciate the nature of the patient and some dogs will react to the slightest manipulation whereas others may be very stoic. The range of movement may be decreased in chronic joint disease or there may be abnormal movement in the case of injury to supporting structures such as ligaments and tendons. The joint may be palpably enlarged due to joint effusion or chronic extracapsular fibrosis. Obviously this will not be detectable in the hip and shoulder. The stifle joint should be palpated with the forefinger and thumb either side of the patellar ligament. This should enable the edges of the ligament to be defined - effusion or fibrosis will make this less easy to feel. In the same way, one can palpate and displace synovial swellings in the carpus and hock. There may be heat detectable in some acute inflammatory conditions. Similarly effusions can be palpated on the caudolateral aspect of the elbow, between the lateral supracondylar crest and the triceps muscle, and on the dorsal aspect of the carpus. Palpation of hock effusions is difficult. Extension of the joint may allow a palpation dorsally. Alternatively the dorsal aspect of the hock can be pressed to assess if the effusion can be felt bulging caudally. Radiography Conventional radiography is an excellent imaging technique for imaging bony structures but is a poor method for visualising soft tissue structures. It also provides better spatial resolution than MRI or CT. As well as standard orthogonal views specialist views such as may be employed in certain situations. A top tip is to always radiograph the contralateral limb/bone/joint as this provides a comparator. Stressed views can be used to assess collateral stifle, tarsal or carpal ligament injury. Specialist views such as skyline, oblique, dorsal acetabular trim (DAR) and dorsolateral subluxations views (DLS) can be used in a variety of circumstances and conditions to aid in their diagnosis. Digital radiography has become increasingly used in practice (for comprehensive review see [3]) with new high resolution monitors and advanced patient collection (picture archiving and communication systems (PACS)) systems, it is set to become the future of musculoskeletal imaging. Arthrography The use of positive contrast within joints may be employed when suspecting or investigating certain diseases. Arthrography can give information on the articular

5 surface, integrity of the synovial capsule, position of cartilaginous joint mice, adhesions in bursae The shoulder joint is the most common site for the use of this procedure. OCD of this joint may be delineated in this way and information regarding the state of the bicipital bursa can be gained. To look at the articular surface, a low volume arthrogram is used (1-2ml in a shoulder) but to look at the bicipital bursa a high volume (5-6ml) is used to fill the bursa (see later in notes on the shoulder). Ionic water soluble agents are indicated e.g. meglumine and sodium diatrizoate ( Urograffin:, Schering-Plough,) and non-ionic agents are also used e.g. iohexol ( Omnipaque, Nyegaard) A needle is placed as for arthrocentesis (q.v.) and synovial fluid aspirated. The contrast is injected, the needle removed and the joint manipulated. Radiographs should be taken immediately. Arthrocentesis The analysis of synovial fluid is under-used. It is in most cases a very straightforward procedure and may be carried out under heavy sedation for most joints although the shoulder and hip may require heavy sedation/general anaesthesia. The area for insertion of the needle should be clipped and washed with an antiseptic (e.g. chlorhexidine) and sprayed with alcohol. If the area is to be handled, gloves should be worn needles are used in most cases although some larger, well muscled animals may require longer needles. If longer needles are required it is often useful to increase the size (i.e. use a lower number of gauge!!) in order to prevent bending of the needle as it is advanced. The most common problem with fluid aspiration is iatrogenic blood contamination. This is recognised as a string of blood within the fluid whereas a joint with haemarthrosis will have sanguinous fluid which is consistent in its colour. This can potentially be minimized by NOT applying negative pressure on the syringe until you are satisfied the needle is within the joint and releasing the negative pressure before removal of the needle from the joint. The handling of the sample will depend somewhat on the differential diagnosis and the volume available. A subjective assessment of colour, turbidity and viscosity can be made. Direct smears may be made for cytological assessment and a differential count and this should be done promptly. A total cell count can be performed and the sample should be placed in an EDTA tube (since there may be fibrinogen present). The viscosity of fluid may be assessed by the mucin clot test (This test is almost never used clinically). This involves dropping some fluid into 5% acetic acid. Good viscosity produces a tight mucin clot whereas poor viscosity does not. The viscosity is a function of the length of the hyaluronan chains in the fluid. These are shorter than normal in inflammatory conditions such as infective arthritis or polyarthritis but near

6 normal in osteoarthritis (OA). Effusion in OA may dilute the fluid and make it appear less viscous but the mucin clot test will be normal. Ultrasonography Ultrasonography is useful for assessing joint disease. High frequency transducers (7.5-15MHz) are recommended and considerable experience is needed to identify joint abnormalities. Sedation is sometimes required for joint examination because of the need to manipulate a painful area, hair must clipped around the area of interest and ultrasound gel applied to ensure good contact between the skin and the transducer [4]. The contralateral joint may need to be examined for comparison. Joint effusion, thickening of the joint capsule and cartilage defects can be identified sonographically [5]. Ultrasonography was not found to be an accurate test for cruciate rupture evaluation [6], identifying 20% of CCL ruptures when compared with cadaver findings [7]. Some experienced operators have a high success rate of identifying medial meniscal tears using a 15MHz linear transducer [8]. Ultrasound examination has been used to identify Legg-Calve-Perthes disease, hip dysplasia and OA as well as soft tissues injuries around the shoulder joint [4]. Scintigraphy Scintigraphy has been used in assessing dogs with joint disease, namely stifle osteoarthrosis [9], but its main application is in lameness investigation if pain is not easily localisable to any one joint [10]. Dogs are injected intravenously with 99m Technetium methylene diphosphonate, which binds to the osteoblasts of active bone, and then scanned immediately to obtain soft tissue phase images. Bone phase images are obtained hours later. Joints with erosive, osteophytic or sclerotic processes will be highlighted on the image obtained using a gamma camera. Technique is sensitive but non-specific. Computed Tomography CT is becoming more readily available and is a cross sectional imaging technique using X- rays and computers. CT is better for bone imaging than for soft tissues but better soft tissue differentiation and absence of superimposition are the major advantages of CT over conventional X-Ray techniques. CT greatly facilitates examining complex joint structures such as the elbow and tarsus and has been used in diagnosing talocrural OCD and elbow incongruity. Magnetic Resonance Imaging MRI is becoming more available for imaging the joints of small animals. It is expensive but an excellent imaging tool. MRI has clear advantages over CT in delineating peri-articular and intra-articular soft tissue structures. It allows simultaneous visualisation of all of the joint components and can detect a wide range of abnormalities. With the current MRI technology it is often difficult to identify cartilage and its lesions in dogs, this may improve

7 with higher frequency magnets and contrast imaging (dgemric). The most common indications are for investigation of the internal structures of the stifle joint (menisci and cruciate ligaments) when the diagnosis is not clear, and for investigation of soft tissues in and around the shoulder and elbow joints [11]. On T1-weighted images synovial fluid has low signal intensity (dark) compared to the infrapatellar fat pad, which has a high signal intensity (bright). Articular cartilage has an intermediate bright signal and is separated from trabecular bone by a dark line representing subchondral bone. Arthroscopy Arthroscopy is an excellent technique to visualise articular structures not visible on radiographs. Arthroscopy allows biopsy and assessment of degenerative joint lesions and can replace the necessity of an exploratory arthrotomy. It has been used extensively in the diagnosis of meniscal lesions in the stifle, soft tissue injuries of the shoulder, ununited aconeal process and incomplete ossification of the humeral condyle of the elbow joint. It can also be used to assess articular cartilage damage prior to joint modification surgery such as triple pelvic osteotomy. References 1. Innes, J.F., et al., Products resulting from cleavage of the interglobular domain of aggrecan in samples of synovial fluid collected from dogs with early- and late-stage osteoarthritis. Am J Vet Res, (10): p Murphy, G. and H. Nagase, Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair? Nat Clin Pract Rheumatol, (3): p Mattoon, J., Digital radiography. Veterinary Comparative Orthopaedics and Traumatology, 2006: p Kramer, M., Gerwing, M., Michele, U., Flock, A., Risselada, M., van Bree, P., Thiel, C. What does ultrsound tell us about orthopaedic problems. in 12th ESVOT Congress Munich. 5. Kramer, M., Gerwing, M., Hach, V., Schmike, E., Sonography of the Musculoskeletal System in Dogs and Cats. Vet Radiol Ultrasound, (2): p Engelke, A., A. MeyerLindenberg, and I. Nolte, Ultrasonography of the stifle joint in dogs with rupture of the cruciate ligaments. Deutsche Tierarztliche Wochenschrift, (3): p Gnudi, G. and G. Bertoni, Echographic examination of the stifle joint affected by cranial cruciate ligament rupture in the dog. Veterinary Radiology and Ultrasound, (3): p Mahn, M.M., et al., Arthroscopic verification of ultrasonographic diagnosis of meniscal pathology in dogs. Vet Surg, (4): p

8 9. Innes, J.F., et al., Scintigraphy in the evaluation of osteoarthritis of the canine stifle joint - Relationship with clinical, radiographic and surgical observations. Veterinary and Comparative Orthopaedics and Traumatology, (2): p Schwarz, T., Johnson, V.S., Voute, L., Sullivan, M., Bone scintigraphy in the investigation of occult lameness in the dog. Journal of Small Animal Practice, : p Snaps, F., Balligand, MH., Sauders, JH., Park, RD., Dondelinger, RF., Comparison of radiography, magnetic resonance imaging and surgical findings in dogs with elbow dysplasia. American Journal of Veterinary Research, (12): p

Small animal osteoarthritis

Vet Times The website for the veterinary profession https://www.vettimes.co.uk Small animal osteoarthritis Author : Kelly Bowlt Categories : Vets Date : April 13, 2009 Normal joints A healthy synovial