Early diagnosis to enable early treatment of pre-osteoarthritis

Arthritis Research & Therapy, Jun 2012

Osteoarthritis is a prevalent and disabling disease affecting an increasingly large swathe of the world population. While clinical osteoarthritis is a late-stage condition for which disease-modifying opportunities are limited, osteoarthritis typically develops over decades, offering a long window of time to potentially alter its course. The etiology of osteoarthritis is multifactorial, showing strong associations with highly modifiable risk factors of mechanical overload, obesity and joint injury. As such, characterization of pre-osteoarthritic disease states will be critical to support a paradigm shift from palliation of late disease towards prevention, through early diagnosis and early treatment of joint injury and degeneration to reduce osteoarthritis risk. Joint trauma accelerates development of osteoarthritis from a known point in time. Human joint injury cohorts therefore provide a unique opportunity for evaluation of pre-osteoarthritic conditions and potential interventions from the earliest stages of degeneration. This review focuses on recent advances in imaging and biochemical biomarkers suitable for characterization of the pre-osteoarthritic joint as well as implications for development of effective early treatment strategies.

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Early diagnosis to enable early treatment of pre-osteoarthritis

Arthritis Research & Therapy Early diagnosis to enable early treatment of pre-osteoarthritis Constance R Chu 0 Ashley A Williams Christian H Coyle Megan E Bowers 0 Department of Orthopaedic Surgery, University of Pittsburgh , 3471 Fifth Avenue, Suite 911, Pittsburgh, PA 15213 , USA Osteoarthritis is a prevalent and disabling disease affecting an increasingly large swathe of the world population. While clinical osteoarthritis is a late-stage condition for which disease-modifying opportunities are limited, osteoarthritis typically develops over decades, offering a long window of time to potentially alter its course. The etiology of osteoarthritis is multifactorial, showing strong associations with highly modifiable risk factors of mechanical overload, obesity and joint injury. As such, characterization of pre-osteoarthritic disease states will be critical to support a paradigm shift from palliation of late disease towards prevention, through early diagnosis and early treatment of joint injury and degeneration to reduce osteoarthritis risk. Joint trauma accelerates development of osteoarthritis from a known point in time. Human joint injury cohorts therefore provide a unique opportunity for evaluation of pre-osteoarthritic conditions and potential interventions from the earliest stages of degeneration. This review focuses on recent advances in imaging and biochemical biomarkers suitable for characterization of the pre-osteoarthritic joint as well as implications for development of effective early treatment strategies. - Introduction Osteoarthritis (OA), a leading cause of morbidity and disability, carries high socioeconomic costs. In 2004 arthritis was estimated to cost the United States $336billion, or 3% of gross domestic product [1]. OA is by far the most common form of arthritis. With increasing obesity and age in the population, a massive rise in morbidity and costs attributed to OA is expected. Pre-osteoarthritis is a modifiable disease process Epidemiological and genetic studies of OA indicate that many pre-OA disease states can be modified. While OA can affect any joint, substantial disability is attributed to OA of the weight-bearing joints, primarily the hip and knee. OA is a multifactorial decades-long process reflecting a complex interplay between intrinsic and extrinsic factors. While there is evidence for heritability of OA [2,3], the polygenic nature of the disease with multiple genes contributing small effects has made it difficult to identify the genetic etiologies of OA [4]. Genome-wide association studies have yielded few common genetic targets [5]. Whereas OA is the culmination of multivariate interactions between genetic, epigenetic, and environmental factors, extrinsic factors such as obesity, trauma, and joint loading patterns are known to heighten OA risk and to offer more definable targets for disease modification. The systematic study of large cohorts at increased risk for accelerated OA development therefore has potential not only to yield new disease-modifying treatments but to facilitate improved understanding of the complex interactions between genes and the environment in OA development [6]. Extrinsic events such as joint trauma accelerate osteoarthritis development Post-traumatic OA illustrates the concept that modifiable extrinsic factors play a substantial role in OA development. Joint trauma such as intra-articular fracture, dislocations, anterior cruciate ligament tear (ACLT), and other injuries lead to rapid joint degeneration in a high proportion of patients [7,8]. Articular surface incongruity, joint instability, altered kinematics, articular cartilage injury, and other joint-tissue changes attributable to the traumatic event accelerate OA development. In a longterm prospective cohort study, young adults with knee injuries showed substantially increased risk for later development of osteoarthritis of the index knee [8]. Another study showed that roughly one-half of individuals with ACLTs or meniscus tears developed radiographic signs of OA 10 to 20 years after injury [9]. Since ACLT is most frequently sustained by teenagers and young adults, it can be considered the cause of premature knee OA in these patients a devastating outcome with costly social and economic consequences. Joint injury cohorts enable characterization of preosteoarthritic processes from the earliest stages For the study of pre-OA conditions, joint injury cohorts offer the potential to study, characterize, and modify the disease process from its earliest stages. A recent American Orthopaedic Society for Sports Medicine/ National Institutes of Health U-13 multidisciplinary conference focused on post-joint injury OA described advantages for studying meniscus-injured and anterior cruciate ligament (ACL)-injured cohorts [6]. These cohorts represent populations that do not meet the classic radiographic or clinical criteria for OA [10]. Rather, subjects have joint pathologies placing them at risk for a (...truncated)


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Constance R Chu, Ashley A Williams, Christian H Coyle, Megan E Bowers. Early diagnosis to enable early treatment of pre-osteoarthritis, Arthritis Research & Therapy, 2012, pp. 212, 14, DOI: 10.1186/ar3845