Osteoarthritis (OA) is a highly prevalent, painful, disabling, and costly condition. Our understanding of OA has dramatically improved over the course of the 20th century, and it is now recognised as a whole-joint disease. Although its signature pathologic feature is articular cartilage loss, it commonly involves many other joint structures including subchondral bone, ligaments, menisci, muscles, peripheral nerves, and synovium.
Despite OA’s large disease burden there are currently no approved disease-modifying OA drugs (DMOADs) that can prevent or delay the progression of the disease. Current Food and Drug Administration (FDA)-approved treatments help to reduce symptoms but do not prevent ongoing joint structural damage. The overall lack of treatment efficacy may be partly due to a ‘one-size-fits-all’ treatment approach. OA has proven to be a more complex, heterogeneous disease than was originally thought and may require different approaches for each patient to optimise treatment. It is not only a disease of cartilage but can be divided into multiple phenotypes (e.g., bone-, inflammatory-, and cartilage- phenotypes). To some extent, these phenotypes overlap with one another. By targeting the most actively affected joint tissue in a patient, during a particular phase of disease, it may be possible to identify more effective treatments.
Bisphosphonates are a class of drugs that have been considered a promising candidate to treat bony phenotypes of OA. In a proof-of-principle study we demonstrated that zoledronic acid (a intravenous bisphosphonate) reduced knee pain and size of subchondral bone marrow lesions (BMLs) over 6 months in knee OA patients with a bony phenotype. This talk will present the findings from a larger, multicentre, double-blind, placebo-controlled trial which examined the effect of zoledronic acid on knee cartilage loss over 24-months. It will discuss the challenges faced for identifying new drug targets for osteoarthritis and possible steps to overcome these barriers