The partnership for early knee OA definition through imaging and tissue biomarkers (PEARL-OA)

Concept

Osteoarthritis (OA) is the fastest growing cause of disability worldwide. The development of OA structural and symptom-modifying therapy is hampered by the complex phenotypes of this disease and difficulties in accurate quantification of OA pathologies.

We used 2 existing, longitudinal cohorts, selected for «early» OA risk factors, and applied novel MRI analysis using active appearance models (Imorphics UK Ltd). We studied bone features associated with progression to clinical knee OA.

Facts and Figures

Project Lead
P Conaghan
University of Leeds
p.conaghan@leeds.ac.uk
FOREUM pump prime grant: € 75.000
2015–2017

Meet the team

P Conaghan
University of Leeds
R Frobell
Lund University

Final results

Using the Swedish KANON cohort, an RCT which includes 121 individuals who experienced an acute anterior cruciate ligament (ACL) injury, we found that bone shape changes occur rapidly after ACL injury and are already evident at 3 months. These changes post-ACL tear are similar to those reported in established knee OA.
In the Osteoarthritis Initiative Cohort, it was found that bone shape predicted progression to total joint replacement, and that bone shape was associated with prevalent frequent knee symptoms  but not incident symptoms.
On the basis of the 3D imaging biomarkers evolved through this grant, the applicants were  part of a successful IMI application, APPROACH-OA, which will utilise these biomarkers to further explore the relationship of bone to OA development and progression.

Publications

  • Bowes MA, Lohmander LS, Wolstenholme C, Vincent GR, Conaghan PG, Frobell RB. Marked and rapid change of bone shape in acutely ACL injured knees – an exploratory analysis of the KANON trial. Osteoarthritis and Cartilage, April 2019 Volume 27, Issue 4, Pages 638–645
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  • Barr AJ, Dube B, Hensor EM, Kingsbury SR, Peat G, Bowes MA, Sharples LD, Conaghan PG. The relationship between three-dimensional knee MRI bone shape and total knee replacement-a case control study: data from the Osteoarthritis Initiative. Rheumatology (Oxford) 2016;55(9):1585-93.
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Lay summary

Osteoarthritis (OA) is the fastest growing cause of disability worldwide. The development of new OA treatments is hampered by the complexity of the disease which over time involves multiple joint tissues including bone and cartilage. We especially don’t understand the early stages of the disease, a time when treatments may be effective. In this collaborative project we used two existing, longitudinal clinical and imaging cohorts, selected for “early” OA risk factors, and applied novel imaging (MRI) measures associated with progression of pre-symptomatic states to clinical knee OA.
Using the large American NIH Osteoarthritis Initiative cohort, which includes people at risk of developing OA, we were able to show that the three-dimensional (3D) shape of the knee bones is positively associated with later progression to total knee replacement. In addition, we found that 3D bone shape is associated with current frequent OA knee symptoms but not with incident symptoms, which may represent early OA. Using the Swedish KANON cohort, which includes 121 people who have experienced an acute anterior cruciate ligament (ACL) injury, we found that bone shape changes occur rapidly after ACL injury and are already evident at 3 months. The changes to knee bone shape post-ACL tear are similar to those reported in established knee OA. We also found that the shapes of all the bones within the knee (the femur, tibia and patella) are different in people who have just suffered an ACL injury compared to young healthy individuals without an injury. This suggests that people at risk of subsequent injury could be identified and advised to pursue sports with less chance of high impact injury.
The results of this work will inform further studies to explore the relationship of bone to OA development and progression, funded through a large collaborative European grant. Ultimately, the aim of this work is to revolutionise our understanding of the mechanisms of OA progression, define pre-OA asymptomatic and symptomatic states, identify post-traumatic OA risk factors and enable targeted OA interventions.