Joint structure modification in osteoarthritis: development of SMOAD drugs.

Primary osteoarthritis (OA) is a polygenic disease associated with age and obesity. In the OA disease setting, abnormal bone anatomy and biomechanics can set off a tissue repair response (intertwined with a mild inflammatory state) that can be seen with the imaging tools of bone scintigraphy and magnetic resonance imaging. This report focuses on weight-bearing OA (knee and hip) and looks at initiating and disease expression events in the subchondral trabecular bone. Multiple drug development targets in soft tissue (cartilage) and hard tissue (bone) can be justified. A successful structure-modifying OA drug (SMOAD) approach that preserves joint structure will likely impact both tissues. The bone and cartilage tissues may signal each other via activation of cytokine pathways and via activation of a generalized tissue repair/mild inflammation response that impacts bone and cartilage.