There are a very wide variety of different options available for managing osteoarthritis.  This reflects the complexity and the dynamic nature of the disease.  However, the sheer number of options can lead to confusion about what should be used.  A good way to simplify management is to identify exactly what each option will modify and determine if this is an appropriate target for the case being treated. This more focused approach addresses the different ways in which OA can present over time as the disease evolves and directs the clinician away from the notion of a single or panacea treatment for OA.

3.1 Medical Treatment Options – Systemic Options

Popular management options and their actions are listed in Table 2

These medical treatments mainly target pain although several have anti-inflammatory functions which impact on the inflammatory pathology within the joint

Table 2 – Common Systemic Medical Treatment Options

Class	Mode of Action	Targets in OA	Comments
Non-Steroidal Anti-Inflammatory Drugs2 (NSAIDs)	Block PG action via inhibiting cyclo-oxygenase (COX) in the Arachidonic  acid pathway PG is a pro-inflammatory mediator which enhances both inflammation and stimulation of nociceptors resulting in pain	Main action is within joint impacting synovial inflammation and nociceptive pain. Mainly alter transduction Some evidence of central action	Toxicity due to blocking PG responsible for homeostatic functions mainly in the GIT and Renal systems COX-1 inhibition responsible for most of these leading to development of Coxibs which are COX-2 selective Most NSAIDs have short action (24hrs) but new longer acting drugs are available which are useful for extended treatment
Piprant NSAIDs3 (Grapiprant)	Selectively block the PGE2 EP4 receptor, the key COX-mediated prostaglandin responsible for synovial pain and inflammation	Main action within joint Modifies PGE2 action but does not block COX activity	Less toxicity expected due to selective action
Corticosteroids	Inhibition of phospholipase effectively blocking PG production in addition to other mediators such as leukotrienes	Powerful Anti-inflammatory Action on many systems	Not used widely due to side-effects
Anti-NGF Monoclonal Antibodies4 (Bedinvetmab Frunevetmab)	Bind free NGF reducing binding to receptors	Nociceptive nerve endings in synovial membrane. Work best in chronic pain scenarios rather than against acute Pain	Very effective analgesic administered monthly More favourable SE profile for gastrointestinal, hepatic or renal issues, but PUPD and immune-mediated hypersensitivity reactions, with other adverse events emerging with ongoing field use
Adjunctive Analgesics (Pregablin; gabapentin; amantadine; tramadol etc)	Act in CNS to modify neural transmission	Used in multimodal analgesia targeting spinal transmission or central perception of pain. Most unlicenced	Used to supplement analgesia in cases experiencing pain that is difficult to control. Best used short term  Response is patient dependant
Codeine	Mostly act in CNS as a full MOP (mu opioid peptide receptors)	Available as a combination with paracetamol for analgesia	Codeine has a very low bioavailability in the dog, but a metabolite may provide analgesia Controversial
Paracetamol	Action largely unknown but central analgesic. No anti-inflammatory action Proposed Cox-3 inhibitor modulating the concentration of PG intermediates.	Adjunctive central analgesic	Controversial efficacy but often used in combination therapy Highly hepatotoxic in cats as they lack enzymes to metabolise the drug
Pentosan Polysulphate (Cartrofen)	Controversial  Putative binding to cartilage matrix in a disease modifying role	Action within joint	Injectable and long-term action (4w) made this a convenient choice for treatment Poor proof of effectiveness other than anecdotal reports

 

3.2 Common Intra-Articular Medical Options

These are introduced directly into the joint.  Most target the inflammatory process within the joint attempting to modify the pathological process. The aspiration for many is that they are able to modify the disease by reducing pathological progression or restoring homeostasis within the joint.

Many are used as a single treatment method while the disease process demands a more multimodal approach. Because many have different actions to many of the systemic medications they could be used in co-therapy.

Table 3 Common Intra-articular Options

Class	Mode of Action	Targets in OA	Comments
Mesenchymal Stem Cells (MSCs)5	Paracrine action on existing synovial and other cells in joint Deliver anabolic factors	Cellular elements within joint	Until recently mainly autogenous adipose cells cultured from patient. This involved an additional surgical procedure. Now ‘off the shelf’ preparations available
Platelet Rich Plasma (PRP)5	Deliver anabolic factors	Intra-articular cellular elements	Easily prepared from patient
Autologous Conditioned Serum IL-Ra (iRAP)	Interleukin-1 antagonist Growth Factors	Intra-articular inflammation main target via IL-1 inhibition	Prepared as an autologous preparation from the patient
Polyacrylamide Hydrogel (PAAG)6	Provides an intrasynovial scaffold which alters the activity within the synovium Increases the elasticity of the fibrous joint capsule	Synovial Membrane	Essentially an intra-articular implant rather than a medication
TIN-117m Radionucleotide7	Radioisotope to partially ablate the synovium	Synovitis	Used in early OA to try and modify synovium and prevent progression
Hyaluronic Acid	Increases lubrication within joint	Synovial Fluid	Short acting Benefits controversial

 

3.3 Non-Medical Treatment Modalities

3.3.1 Physical Modalities

Various physical modalities are also useful in therapy. Techniques such as photobiomodulation; Extracorporeal Shock-wave therapy; Therapeutic Ultrasound; Electrotherapy Thermal therapy and Pulsed Electromagnetic Field Therapy are all used by specialists as part of multimodal management plans. 

3.3.2 Other Non-Medical Therapies

Other non-medical therapies include Acupuncture, Manual Therapies and Massage, Therapeutic Exercise, Aquatic Therapy and Orthotics and Assistive devices

The rational for selecting these should be the same as with medical therapies and be guided by their specific modes of action and by what targets they satisfy in a therapeutic plan. There should be a clearly defined objective for use and a strategy to cease use once that objective has been achieved8. Similarly if the objective set is not achieved within a set time, then the intervention should be stopped and replaced. 

The specific details of these are covered in other Modules.