Osteoarthritis in Small Animals

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18/05/20 Biology Reference this

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OSTEOARTHRITIS IN SMALL ANIMAL GENERAL PRACTICE

– AN OVERVIEW FOR RECENT GRADUATES –

1.0 Introduction to osteoarthritis

Osteoarthritis (OA) or degenerative joint disease is a common cause of arthritis in canine and feline patients. The major presenting signs are lameness, stiffness, exercise intolerance and an unwillingness or inability to climb or jump. These signs can be attributed to the primary inciting cause, the pain associated with arthritis or a combination of both.

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Patients in general practice typically present with the secondary form of OA. Secondary OA occurs as a reactive process caused by abnormalities that result in either joint instability (e.g. cranial cruciate ligament rupture) or abnormal loading of articular cartilage (developmental abnormalities, articular fractures) or in response to another recognisable joint disease (e.g. septic or immune-mediated arthritis). Primary OA is an idiopathic condition that tends to affect multiple joints in young animals and is a rare disease presentation.

OA is a persistent, low-grade inflammatory, non-infectious disease process. The pathological changes associated with osteoarthritis include degeneration and loss of articular cartilage, accompanied by subchondral bone sclerosis, marginal osteophytosis, synovitis, capsular fibrosis and changes to the composition and viscosity of synovial fluid. Once initiated, OA becomes a self-perpetuating degenerative condition that results in further deterioration, pain and loss of functionality in the affected joint (Fig 1).

 

Fig 1: Cadaver bones of a Labrador retriever with severe osteoarthritis secondary to elbow dysplasia. Note the pronounced periarticular osteophyte formation and abnormal morphology (‘steps’) affecting the medial compartment of the joint where there was complete loss of articular cartilage.

From McKee M. In Practice 2013. 35:227-242

2.0 Investigating osteoarthritis

The typical osteoarthritic patient presents with a chronic lameness or stiffness with an insidious onset.

2.1 Clinical history

An accurate and complete history is necessary for investigating suspected OA. In dogs, osteoarthritis has specific breed and age predilections. Therefore, the signalment may provide important clues to help identify OA. For example, hip dysplasia is present in very young medium- to large-breed dogs and the secondary radiographic changes are evident from a very early age.

Owners will often report that their animal is stiff after resting and this is particularly noticeable after a period of rest following exercise. This “inactivity stiffness” is often reported to resolve during exercise (“warm out of the stiffness”) but worsens after periods of rest following such activity. The amount of time taken to warm out of this stiffness will normally increase with progression of the disease. Owners will often report that cold and damp weather will exacerbate the clinical signs. Other common presentations include a change in the animal’s ability or apparent willingness to climb or jump.

Owners will normally only recognise a lameness when there is gait asymmetry. Owners may report a shortened stride or stiffened gait reflecting a decreased range of motion in the joint, often due to joint capsule fibrosis and osteophyte formation. However, dogs with bilateral OA (e.g. hip or elbow dysplasia) will often have a symmetrically abnormal gait and do not favour a single limb. These patients will shift weight from pelvic to thoracic limbs or vice versa, with muscle atrophy of the affected limbs and increased development in compensating limbs. It would be extremely are for a non-weight bearing lameness to be solely attributable to OA.

2.2 Clinical examination

A complete analysis of the patient’s gait should be performed before the physical examination. Observing the unrestrained patient in the consultation room during the history taking can often reveal very subtle lameness and any discomfort associated with lying down and standing up. The gait should also be assessed in an area that allows the animal to be walked and trotted in a straight line. The animal should be assessed while both moving away from and towards the clinician, to allow assessment of the pelvic and thoracic limb lameness, respectively.

During the examination, all joints should be critically examined, with particular attention paid to those that are causing pain and lameness. A consistent examination pattern (e.g. distal limb to proximal limb) is necessary to avoid missing a structure during the examination. A comparison to the contralateral limbs can be used when assessing the range of motion, joint effusions, soft tissue oedema and muscle atrophy. However, the most common forms of orthopaedic disease (e.g. cruciate disease, elbow dysplasia and hip dysplasia) can frequently present bilaterally, this may not always applicable. It is recommended that the “lame” limb be examined last as this avoids eliciting pain which may cause the animal to be noncompliant to further examination.

An orthopaedic examination should be part of every routine examination and should be conducted in conjunction with a neurological examination to identify neurological causes for pain or lameness. A systematic, reproducible orthopaedic examination of a patient is essential and often requires the aid of an assistant who is adequately trained to hold and restrain the animal. The assistant is also important for identifying the animal’s painful response to examination, such as body shifts and change of facial expression. The osteoarthritic joint may be palpably thickened due to capsular fibrosis and/or osteophyte production. The range of motion in an affected joint may be decreased or increased (e.g. cranial draw for cruciate ligament disease) depending on the underlying disease process. A moderate joint effusion may be palpable, and manipulation of the joint may reveal crepitation and elicit a pain response.

2.3 Further investigation

The basis for diagnosing OA is a thorough clinical and orthopaedic examination. However, OA commonly presents secondary to an underlying orthopaedic disease, and establishing the inciting cause is important as management strategies and prognosis can vary significantly. Diagnostic imaging is therefore often indicated but any abnormalities of joints detected on investigations should be consistent with the historical and clinical features. In cases where Owners choose to pursue symptomatic therapy initially, further diagnostics should be considered when the clinical response to management is believed to be disappointing or inadequate.

The indications for diagnostic imaging include to

- confirm or refute a clinically suspected lesion,

- suggest or document the site of a suspected lesion,

- characterise the nature and extent of a known or suspected lesion,

- follow the progression of disease or healing,

- aid in establishing prognosis,

- plan or evaluate surgical therapies,

- suggest or guide additional diagnostic procedures, and

- screen for diseases with obscure clinical signs.

2.3.1  Radiography

Radiography is the key method of imaging chronically painful joints. Orthogonal projections should be obtained routinely and compared to radiographs of the contralateral joint if necessary. Additional oblique or stressed projections may be necessary depending on the suspected lesion and anatomic structure being imaged. Radiographs should always be evaluated with respect to severity of disease and the clinical situation.

Radiographic changes seen on conventional radiographs consistent with an osteoarthritic joint include narrowing or ablation of the joint space (in standing position), eburnation (increased density) of the subchondral bone, osteophytosis of joint margins, joint deformity, proliferative and lytic changes at the attachment sites of the joint capsule and supporting ligaments, meniscal calcification, partial-to-complete ankylosis and soft tissue density swelling. The most common radiographic changes are osteophytosis, subchondral bone sclerosis, remodelling and narrowing of the joint space and soft tissue density swelling.

2.3.2  Advanced imaging

Advanced imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI) are gradually becoming more accessible to general practice clinicians, and have obvious application in the diagnosis and management of orthopaedic disease. CT (with or without contrast) produces cross-sectional imaging that may provide valuable osseous and soft tissue detail, compared with conventional radiography (Fig 2), particularly in complex joints such as the elbow, carpus and tarsus.

 

Fig 2: Volume-rendered CT scan in a rottweiler with chronic elbow joint pain. Fragmentation of the coronoid process is evident (arrow) that was not visible on conventional radiographs

From McKee M. In Practice 2013. 35:227-242

3.0 Conservative management of osteoarthritis

Pain is the clinical sign most frequently associated with osteoarthritis (OA) and the clinical manifestation of this pain is lameness. When an animal presents with clinical lameness, a determination must be made whether the animal is either unable or unwilling to use the affected limb. The inability to use the limb may be attributable to musculoskeletal changes (e.g. joint contracture, muscle atrophy) and are best addressed with physical rehabilitation. An unwillingness to use a limb is most often attributable to pain and represents an avoidance behaviour.

The treatment goals when managing OA are to alleviate discomfort, slow disease progression, restore near-normal function and minimise joint instabilities. The key aspects when managing chronic joint pain conservatively are physical rehabilitation, weight control, use of structure-modifying medications and integrated analgesic therapy.

3.1 Physical rehabilitation

Physical rehabilitation is an important component of a multimodal approach to managing OA. Physical rehabilitation describes a broad spectrum of methods with the goal of restoring, maintaining and promoting optimal function, wellness and quality of life in patients with orthopaedic disease. Patients suffering from chronic OA are often reluctant to exercise, which may be due to an unwillingness or inability to exercise. The inability to exercise is often a consequence of the decreased muscle mass and decreased joint range of motion, commonly seen in patients with OA. Physical rehabilitation focuses on addressing this effect by providing “freedom of movement” and palliation of the disease progression.

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Passive and active exercise programs are beneficial for the OA patient with the goal or reducing pain and disability. This is achieved by improving muscle strength, joint stability, range of motion and aerobic fitness. It is better to provide multiple short duration sessions rather than one extended session when initiating a therapeutic exercise program.

Passive range of motion is implemented with the patient in lateral recumbency in a quiet and comfortable area. The OA joints are slowly and gently flexed and extended until the patient shows initial signs of discomfort. Stretching is an extension of these exercises, designed to increase flexibility of tissues. The stretch should be applied at the end of available range of motion for at least 15 seconds to encourage elongation of the limiting soft tissue structures to increase available joint motion.

Active range of motion exercises include walking, walking in water and swimming, which acts to build endurance, cardiovascular fitness and treat obesity. As strength and endurance are developed, activities are modified by incrementally increasing the frequency, then the length, and finally the speed of the activity.

Aquatic therapy allows the patient to exercise in an upright position, and may decrease pain by minimising the amount of weight bearing on joints due to buoyancy. The viscosity of water is greater than air, such that moving through water is harder than moving through air. Water can provide resistance that may strengthen patient muscles and improve cardiovascular fitness. Additionally, exercising in heated water increases circulation to muscles, increases joint flexibility and decreases joint pain.

3.2 Weight management

Weight is one of the most important health conditions affecting companion animals and is a major contributor to the progression of OA. Overweight dogs often have a number of health concerns and an increased risk of developing other diseases, most notably orthopaedic disease.

Weight reduction alone has been shown to produce a substantial improvement in clinical lameness in overweight dogs with pelvic limb OA and restricted feeding can reduce the prevalence and severity of disease and increase life-spans in dogs with multifocal OA. Weight control can be a useful adjunct therapy for overweight dogs with concurrent osteoarthritis and can significantly improve the gait of obese osteoarthritic dogs. The benefits of increased mobility can be demonstrated with only a modest amount of weight loss and is normally achievable with a simple weight loss program.

Owner may elect to transition their animals onto specially formulated commercial diets engineered for OA patients, such as Hill’s Prescription Diet j/d and Hill’s Prescription Diet Metabolic + Mobility, the latter of which has reduced caloric density to facilitate ongoing weight management.

3.3 Nutraceuticals

A nutraceutical is defined as a non-drug substance administered to provide the substrates necessary for normal function, with the goal of favouring regeneration to promote health and wellbeing. There has been considerable research on their possible chondroprotective and anti-inflammatory properties but their clinical efficacy is still controversial. There are many commercially available preparations available, including 4-cyte and Joint Guard.

Nutraceuticals (including glucosamine and chondroitin preparations) are widely used for the management of osteoarthritis in both animals and humans. Glucosamine is an amino monosaccharide thought to be a precursor to hyaluronan and keratan sulphate. Chondroitin sulphate is a disaccharide and a normal constituent of cartilage. Their exact mechanism of action is not understood but it has been suggested that dietary supplementation with substrate precursors for cartilage matrix in excess quantities favours the synthesis and repair of articular cartilage, via the increased production of aggrecan and collagen.

Dietary supplementation with omega-3 fatty acids can improve owner perception of comfort and function, improve weight bearing in the affected limb and decrease the need for NSAIDs therapy. The omega-3 fatty acids compete with and replace omega-6 fatty acids in cell membranes, resulting in a downregulation of the eicosanoid inflammatory cascade. Omega-3 fatty acids have also been shown to have anti-inflammatory properties and therapeutic effects on cartilage.

3.4 Structure-modifying medications

Pentosan polysulphate is a structure-modifying medication is commonly integrated into an OA management plan. The exact mechanism of action is not fully understood, but it is thought that pentosan may increase proteoglycan synthesis, reduce matrix metalloproteinase activity, promote biosynthesis of high molecular weight hyaluronan and increased subchondral blood flow via thrombolytic activity. Clinical trials of this drug have shown mixed results but two systematic reviews have concluded that only a moderate level of comfort is achieved when using this product for canine OA.

Pentosan is initially injected subcutaneously once weekly for four weeks, and then used either monthly or as necessary depending on the individual case and perceived response to treatment. A repeat initial course is usually recommended if more than six months has elapsed between successive injections.

3.5 Integrated analgesia

The underlying source of pain in the joint “organ” is multifocal and includes direct stimulation of the joint capsule and bone receptors by inflammatory and degradative mediators, physical stimulation of the joint capsule from distension (effusion) and stretch (abnormal articulation), subchondral bone from abnormal loading, and surrounding muscle and soft tissues. The bony changes at the joint margins and beneath areas of damaged cartilage can be major sources of OA pain. Subchondral bone contains unmyelinated nerve fibres, which increase in density with OA. Increased pressure on subchondral bone results in the stimulation of these nociceptors and is reported in humans to contribute to chronic pain, particularly nocturnal pain.

Many pet owners do not believe their pet is in pain if it does not vocalise and most canine patients do not vocalise from their pain of OA. Signs suggesting discomfort includes lameness, muscle atrophy, reluctance to exercise, general malaise, lethargy, hyporexia or anorexia, changes in temperament, licking or biting an affected joint, restlessness, insomnia, seeking warmth, seeking comfortable bedding and difficulty posturing to toilet.

3.5.1  Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAIDs will likely remain the foundation for treating OA based on their anti-inflammatory, analgesic and antipyretic properties. NSAIDs relieve the clinical signs of pain via suppression of prostaglandin synthesis (principally PGE2). PGE2 contributes to the pathogenesis of OA by lowering the threshold of nociceptor activation, promoting synovitis, enhancing the formation of degradative metalloproteinases and by depressing cartilage matrix synthesis However, prostaglandins also have multiple physiological roles including promoting platelet aggregation, maintaining integrity of the gastrointestinal tract and modulating renal perfusion.

NSAIDs should be administered with a dosing protocol that provides the necessary beneficial effects, with the aim of achieving the lowest effective dose. A multimodal OA treatment protocol is anchored on this tenet of minimal effective dose. In some cases, NSAIDs (e.g. ketoprofen) may only be required to treat an acute flare-up of OA. Other patients may require ongoing therapy, and other NSAIDs (e.g. meloxicam, carprofen) are better suited for this application.

Possible gastrointestinal, renal and hepatic side effects should be monitored, especially as the patient ages. The most common complications documented with NSAID use are associated with overdosing and the concurrent use with other NSAIDs and/or corticosteroids. In refractory cases, additional analgesics such as tramadol, amantadine or gabapentin may be indicated.

3.5.2  Tramadol

Tramadol is an orally available, synthetic codeine analogue that is anecdotally reported to be a popular analgesic despite the lack of evidence pertaining to its efficacy. Approximately forty percent of tramadol’s activity is as a mu-receptor agonist, forty percent as a as noradrenaline reuptake inhibitor, and twenty percent is as a serotonin reuptake inhibitor (SRI). Therefore, it is a poor substitute for the “pure” opioids but has found use as an adjunct to opioid and NSAID analgesia.

3.5.3  Gabapentin and amantadine

Gabapentin and amantadine are medications that have found use in the management of chronic pain, and may be applicable in cases of OA that are refractory to more traditional multimodal analgesia. OA has elements of both an acute and chronic pain. Chronic pain is not just a prolonged version of acute pain but leads to physiochemical changes in neural pathways that render them hypersensitive to nociceptive input, and resistant to anti-nociceptive input. 

Gabapentin acts via the g-aminobutyric acid (GABA) receptor and is thought to reduce neuropathic pain. Amantadine acts on the N-methyl-D-aspartate (NMDA) receptor and reduces the prolonged inflammatory pain associated with chronic disease. These agents are occasionally administered together as adjuncts in a multimodal OA protocol (with applications in other chronic pain conditions).

3.5.4  Corticosteroids

In the context of OA, the use of corticosteroids is generally restricted to isolated joints, where a long-acting intra-articular injection is used to inhibit the formation of inflammatory mediators. The two most common corticosteroids used to manage OA are methylprednisolone acetate and triamcinolone acetonide. Their use may provide rapid alleviation of clinical signs without systemic effects. The response is typically rapid and significant, but patients often requires repeated injections to achieve an acceptable clinical effect. However, multiple repeated injections are contraindicated due to the detrimental effects of corticosteroids on articular cartilage. Systemic corticosteroid therapy should be avoided due to the host of potential systemic adverse effects associated with protracted of the medication.

4.0  Acupuncture

Acupuncture is a technique developed from traditional Chinese medicine utilising needles to initiate changes in the soft tissue. Acupuncture can be defined as a physiologic therapy coordinated by the brain, which responds to the stimulation of manual or electrical needling of peripheral sensory nerves. The technique does not inherently treat any particular pathology and the exact mechanism through which it achieves its clinical effects are uncertain. However, the needles and needle-induced changes are believed to activate the intrinsic mechanisms that promote regeneration and homeostasis.

Clinical observation suggests that acupuncture needling achieves at least four therapeutic goals

- release of physical and emotional stress,

- activation and control of immune and anti-inflammatory mechanisms,

- acceleration of tissue healing, and

- analgesia secondary to endorphin and serotonin release.

5.0  Surgical management of osteoarthritis

Most patients diagnosed with OA can be managed with conservative treatment. However, there may be rare cases where the response to treatment is insufficient and surgical management should be considered. The key surgical options when managing chronic joint pain are salvage procedures, including arthrodesis, joint replacement and excision arthroplasty. Dogs in their early adult years with painful OA may benefit from surgical intervention. However, many of these procedures are technically challenging and require specialist training to minimise the potential for significant postoperative complications.

In extreme cases amputation may be considered but many patients will present with multifocal OA, such that careful preoperative assessment is necessary to ensure the animal can ambulate following surgery. Euthanasia should be offered as an option in extreme cases where the welfare of the animal is sufficiently compromised and treatment options have been exhausted or are not affordable.

6.0 References

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