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.
Macro-structurally BMD was significantly different in the medial condyle at 36 wk post ACLX in both treated and non-treated cohorts, however, the same trends were not discovered for both 72 wk cohorts. Medial femoral subchondral bone was significantly thinner in ACLX limbs for all cohorts with and without doxycycline treatment. Significant mechanical changes discovered at 36 weeks post ACLX were less obvious at 72 wk in both treated and untreated cohorts. Doxycycline treatment conserved strain energy density (SED) at 72 wk. Drug treatment had little effect on the degradation of superficial osseous tissue early in the disease, however, 72 weeks post ACLX doxycycline diminished bone resorption within the first 3.0 mm of periarticular bone. Significant bone loss occurred in the deeper trabecular tissue for all cohorts.
Substantial architectural adaptation within deeper trabecular tissue shadowed changes in mechanics in early and established OA. To maintain normal cancellous bone after a traumatic injury, intervention may be most effectively focused on preventing trabecular alterations. The results from this study will contribute to a greater understanding of the role architectural changes in subchondral bone and the influence of doxycycline in the development and progression of early and established OA. Consequently, administration of doxycycline in an ACLX model exerted an OA-averting effect in established OA (72 wk treated cohort) by influencing superficial subchondral bone organization and reducing mechanical and morphometric deterioration.
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