Cellular and molecular mechanisms underlying subchondral bone remodeling and associated pain in osteoarthritis

Osteoarthritis (OA) is the most common musculoskeletal-related disease affecting over 27 million US adults, and no disease-modifying agents are currently available. Signs of bone remodeling are a major hallmark of OA, and include subchondral sclerosis (seen on x-ray), subchondral bone marrow lesions (seen on MRI), and osteophytosis. Recent work suggests subchondral bone remodeling is likely a driver of pain in OA. In this review, we seek to provide an overview on what is known about the cellular and molecular mechanisms that play a role in osteoarthritic subchondral bone remodeling and associated pain. Searching for "subchondral bone remodeling" "pain" and "osteoarthritis," we reviewed publications from 2015 onward. We found new details of how osteoblasts, osteoclasts, and osteocytes communicate in both autocrine and paracrine manners in OA, allowing identification of potential candidates that play a role in the aberrant bone remodeling seen in OA. Furthermore, there is new knowledge regarding mechanisms of how bone cells communicate with nociceptive neurons, providing potential candidates to target for treatment of OA pain. Recent clinical trials targeting OA-associated bone remodeling have been published with some encouraging results. In the future, more work is necessary to understand the inciting events that lead to the pathogenic cell behaviors, and unravel the complex cellular communication detailed in this review. In addition, efforts to understand the discordant results from recent trials of existing agents targeting bone remodeling and to develop novel bone-targeted agents for OA are needed.