Objective: To determine whether oral administration of doxycycline, in a dose that inhibits cartilage breakdown in a canine cruciate deficiency model of osteoarthritis (OA), affected formation or resorption of subchondral bone.
Methods: Ten healthy adult mongrel dogs underwent transection of the left anterior cruciate ligament. Five were given doxycycline, 3.5 mg/kg/day, orally, from the day after surgery until they were sacrificed 6 weeks later; the other 5 dogs served as positive OA controls. Three weeks before sacrifice, each dog was given an intravenous injection of the fluorochrome label, calcein, on each of 2 consecutive days; 10 days later, the injection regimen was repeated. At sacrifice, samples of bone from the medial femoral condyle of both knees of each dog were obtained for staining with Villanueva tetrachrome to localize the fluorochrome label and McNeal's tetrachrome for measurement of osteoid and cell counts.
Results: Cruciate deficiency resulted in a marked decrease in bone mass, with increased osteoclastic activity and increased bone formation. Doxycycline treatment did not significantly affect either bone formation or bone resorption.
Conclusion: Doxycycline protects against joint breakdown in this OA model via inhibition of matrix metalloproteinases in articular cartilage, rather than through an effect on subchondral bone.