The effects of doxycycline on the mechanical and morphometric properties of early and established osteoarthritic bone in a canine model following anterior cruciate ligament injury

Osteoarthritis (OA), also know as “degenerative joint disease”, is the most prevalent type of arthritis and chronic joint disease in the elderly (Fife, 1992; Moore et al., 1993). OA is characterized by focal loss of articular cartilage with reactive changes in subchondral and marginal bone, synovium and para-articular structures, frequently leading to chronic pain and disability (Rottensten, 1996).

The mechanics and morphomerry are compromised in the cancellous bone located at the epiphyses of long bone in OA (Boyd et al., 2000; Boyd et al., 2002; Wohl et al., 2001). Although the aetiology of OA is unknown, physiological, mechanical, and morphometric bone changes are important contributors. Hence, an agent that inhibits bone loss in osteoarthritic bone while concurrently restoring an optimised environment is essential for the overall maintenance of the joint. Doxycycline is an antibiotic that reportedly can influence cartilage and bone by significantly reduce degenerative changes in the OA joints in both animal and human models (Brandt, 1995a; Brandt, 1995b; Shlopov et al., 1999; Smith et al., 1998; Yu et al., 1996;Yu et al., 1992).

In the present study, doxycycline was administered orally twice daily (4 mg/kg/d) in skeletally mature canines following anterior cruciate ligament transection (ACLX) to see if it prevented initiation and progression of OA. Macro- and micro-structural osteoarthritic bone alterations were assessed by bone mineral density (BMD), bone mechanics, subchondral sclerosis, bone mineral content, and micro-computed tomography to test if doxycycline had a significant effect on bone structure and function.