Role of doxycycline as an osteoarthritis disease-modifying drug

Doxycycline is a drug that has been proposed to modify osteoarthritis (OA) progression, in addition to its role as an antibiotic. However, available evidence thus far comprises sporadic reports, with no consensus on its benefits. Hence, this review attempts to analyze the evidence available thus far on the role of doxycycline as a disease-modifying osteoarthritis drug (DMOAD) in knee osteoarthritis. The earliest evidence of doxycycline in OA appeared in 1991 when doxycycline was found to inhibit the type XI collagenolytic activity of extracts from the human osteoarthritic cartilage, and gelatinase and tetracycline were found to inhibit this metalloproteinase activity in articular cartilage in vivo, which could modify cartilage breakdown in osteoarthritis. Apart from the inhibition of cartilage damage by metalloproteinases (MMPs) and other cartilage-related mechanisms, doxycycline also affects the bone and interferes with many enzyme systems. The most significant finding after reviewing various studies was that doxycycline has a definitive role in structural changes in osteoarthritis progression and radiological joint space width, but its role in the improvement of clinical outcomes as a DMOAD has not been established. However, there is much of a gap and lack of evidence in this regard. Doxycycline, as an MMP inhibitor, has theoretical advantages for clinical outcomes, but the present studies reveal only beneficial structural changes in osteoarthritis and very minimal or nonexistent advantages in clinical outcomes. Current evidence does not favor the regular use of doxycycline for the treatment of osteoarthritis as an individual treatment option or in combination with others. However, multicenter large cohort studies are warranted to determine the long-term benefits of doxycycline.