Osteoarthritis (OA) is a leading cause of disability and inflicts a growing socioeconomic cost worldwide. The risk of OA increases with age and largely affects the elderly, but joint injuries increase the risk of developing OA and can occur even in young adults. Injuries from sports, vehicle accidents, and other sources of trauma to joints can lead to OA in patients of all ages. This post-traumatic osteoarthritis (PTOA) represents 12% of the total OA patient population, affecting nearly 6 million people in the U.S. alone. A large portion of those afflicted are military personnel, 30% of whom develop PTOA from combat injuries.
There is currently no approved therapy to prevent onset of chronic PTOA, which can involve lifelong pain and dysfunction that inhibits daily activities, employment, and recreation.
Amidst the supplies for crew members and International Space Station (ISS) maintenance launching on SpaceX’s 17th commercial resupply services mission this week is a complex and promising ISS National Lab research study that aims to understand why some injuries result in PTOA while others heal and recover.
Perhaps more importantly, the research team from the Massachusetts Institute of Technology (MIT), led by Dr. Alan Grodzinsky, seeks to demonstrate that there is a time immediately following injury when currently available therapeutics can be effective in preventing PTOA.
Understanding Complex Joint Mechanisms
OA is the most common form of arthritis, or inflammation of a joint. In people with OA, the cartilage present on the ends of bones slowly deteriorates. Cartilage is a slippery tissue that allows near-frictionless motion within joints—but as it deteriorates, it becomes rough, leading to joint pain and dysfunction. The cartilage can eventually wear down completely, which can make joint replacement surgery necessary.
Knee injury, such as injury affecting the anterior cruciate ligament (ACL) or meniscus (the shock-absorbing cartilage in the knee), is the most prevalent contributor to PTOA worldwide, with 700,000 cases annually in the U.S. Approximately 50% of individuals with any type of knee injury develop PTOA within 10 years, and the frequency of the disease appears to be increasing.
Sadly, restoring joint stability, for example via ACL reconstruction in the knee, does not reduce the risk of developing PTOA. This indicates that mechanical factors are not the primary culprit in determining who develops chronic disease. Other factors are at play in the early initiation of cartilage breakdown, and their identification will play a critical role in early detection, diagnosis, and prevention of PTOA.
So how do researchers study this complex and important disease? Most studies investigate the impact of trauma on tissue models of human cartilage, as cartilage degradation is the primary cause of joint pain and dysfunction. However, joint injuries may damage cartilage, bone, ligaments, and/or the meniscus (in the knee), which alters the fundamental biomechanics of the joint—how it moves and interacts with the surrounding tissues, including the synovial membrane (the tissue that lines joints and produces a lubricating, plasma-like fluid).
Because many factors may contribute to how quickly the joint “wears out,” isolating the cartilage tissue type in research studies does not always reflect the complex mechanisms at play within a human joint. Molecular, mechanobiological, and cellular events in multiple tissues are likely involved in the onset and progression of PTOA. Animal models have helped in understanding some of the underlying disease mechanisms of PTOA, but ethical issues and difficulty extrapolating findings from the animal models limit these approaches.
Enabling Early Intervention
Better understanding individual molecular, mechanobiological, and cellular events involved in the onset and progression of chronic PTOA is paramount to identifying novel treatment approaches. Ideal therapy should include early clinical intervention during the first phases after joint injury—but we must first understand the complex tissue interactions within joints following these injuries.
Detection and diagnosis of those at high risk of developing PTOA could enable early treatment, before any major structural damage has occurred in the joint or before pain becomes chronic. Such early intervention is common in the management of diabetes, heart disease, and osteoporosis, but for those individuals suffering from chronic pain, preventive medicine is still beyond reach. Creative and advanced biomedical approaches to studying disease—on Earth and in space—can hopefully provide relief to the military personnel, student athletes, and millions of others afflicted by PTOA.
