Investigational approaches to the management of osteoarthritis
- Shirley Yu, BSc (Med), MBBS, MPH, FRACP
Shirley Yu, BSc (Med), MBBS, MPH, FRACP
- Royal North Shore Hospital
The management of osteoarthritis (OA) consists of nonpharmacologic, pharmacologic, and surgical approaches. Conventional pharmacologic therapy for OA has mainly targeted symptomatic relief, with agents such as nonsteroidal antiinflammatory drugs (NSAIDs), acetaminophen, opioid analgesia, and intraarticular injections.
As we gain a better understanding of the pathogenetic mechanisms in OA, there has been a growing interest in the development of drugs whose mechanism of action are directed towards different pain pathways, as well as the inhibition of catabolic processes or stimulation of anabolic processes in the OA joint. These drugs are referred to as disease-modifying OA drugs (DMOADs) or structure-modifying OA drugs (SMOADs).
To date, no pharmacologic agents have been approved of by regulatory authorities for disease modification in OA. Existing trial strategies have failed to detect clinical efficacy of potential disease-modifying OA drugs (DMOADs) based on the lack of responsive outcome measures to record treatment-related improvements in pain, function, or joint structure, or just due to lack of efficacy of these agents. While there has been progress with potential new analgesics, including targeting nerve growth factor, the availability of a potential structural modification agent appears distant.
A review of investigational approaches to the pharmacotherapy of OA will be discussed here. Established therapies for OA and surgical interventions are discussed elsewhere. (See "Overview of surgical therapy of knee and hip osteoarthritis" and "Overview of the management of osteoarthritis".)
TARGETS FOR TREATMENT
The major goals of osteoarthritis (OA) management are pain control, functional improvement, education about the disease, self-management, and prevention or slowing of structural changes to the joints. However, developing agents to address these goals are challenging given the complexity of pain pathways and the etiology of structural changes.
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- TARGETS FOR TREATMENT
- Pain modification
- - Inhibition of nerve growth factor
- Structural modification
- - Inflammatory pathways
- Tumor necrosis factor-alpha inhibitors
- Interleukin-1beta inhibitors
- Matrix metalloproteinase inhibitors
- Mitogen-activated protein kinase inhibitor
- Inducible nitric oxide synthase inhibition
- Bradykinin receptor B2 antagonist
- - Cartilage catabolism and anabolism
- Bone morphogenetic protein-7
- Fibroblast growth factor
- Platelet-rich plasma
- - Bone remodelling