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.
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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)