Osteoarthritis: From Palliation to Prevention

Abstract

Osteoarthritis is a leading cause of disability. The traditional focus on late-stage osteoarthritis has not yielded effective disease-modifying treatments. Consequently, current clinical care focuses on palliation until joint replacement is indicated. A symposium format was used to examine emerging strategies that support the transformation of the clinical approach to osteoarthritis from palliation to prevention. Central to this discussion are concepts for diagnosis and treatment of pre-osteoarthritis, meaning joint conditions that increase the risk of accelerated development of osteoarthritis. The presentation of translational and clinical research on three common orthopaedic conditions-anterior cruciate ligament tear, intra-articular fracture, and hip dysplasia-were used to illustrate these ideas. New information regarding the use of novel quantitative magnetic resonance imaging (MRI) in the form of ultrashort echo time enhanced T2* (UTE-T2*) mapping to evaluate the potential for articular cartilage to heal subsurface damage in a mechanically sound environment was presented. These data indicate that improved diagnostics can both identify cartilage at risk and evaluate the effectiveness of early treatment strategies. With use of a new mouse model for intra-articular fracture, it was shown that inflammation correlated to fracture severity and that super-healer mice avoided early posttraumatic osteoarthritis in part through an enhanced ability to dampen inflammation. These findings suggest that there is a role for acute and sustained anti-inflammatory treatment in the prevention of osteoarthritis. For long-term treatment, contemporary gene-therapy approaches may offer an effective means for sustained intra-articular delivery of anti-inflammatory and other bioactive agents to restore joint homeostasis. To illustrate the potential of early treatment to prevent or delay the onset of disabling osteoarthritis, the positive clinical effects on articular cartilage and in long-term clinical follow-up after operative correction of structural abnormalities about the hip highlight the role for targeting mechanical factors in delaying the onset of osteoarthritis. Given that orthopaedic surgeons treat the full spectrum of joint problems, ranging from joint trauma to preosteoarthritic conditions and end-stage osteoarthritis, an awareness of the paradigm shift toward the prevention of osteoarthritis is critical to the promotion of improved clinical care and participation in clinical research involving new treatment strategies.

YouTube provides irrelevant information for the diagnosis and treatment of hip arthritis

“…Similar to MacLeod et al [11], current evidence [12][13][14][15][16][17] and expert opinion were used to design two new grading systems, one for the analysis of diagnostic information quality (Table 1) and a second for the assessment of treatment information quality (Table 2). Both grading systems had a scale of 0 to 12.…”

Histopathological assessment of primary osteoarthritic knees in large patient cohort reveal the possibility of several potential patterns of osteoarthritis initiation

“…However, current practice demands a greater emphasis on OA prevention, early diagnosis and treatment to block or delay disease progression. [16] A better understanding of the patterns and variation in initiation and progression of OA could influence the design and patient specific selection of therapies to OA. Animal models have been developed to examine stages of OA that involve either cartilage injury, meniscal injury, ligamentous instability or chemically or pharmacological induction of inflammation.…”

Chondroprotection by urocortin involves blockade of the mechanosensitive ion channel Piezo1

“…Chondrocyte cell death is essentially apoptotic in nature 4 , with a close correlation between p53 expression and death 5 . Currently, the only treatments for OA are steroidal and non-steroidal anti-inflammatory drugs, or in severe cases total joint replacement surgery 6 . However, these strategies only ameliorate symptoms and do not address the underlying pathology, namely chondrocyte death.…”