Longitudinal validation of periarticular bone area and 3D shape as biomarkers for knee OA progression? Data from the FNIH OA Biomarkers Consortium.
OBJECTIVE
To perform a longitudinal validation study of imaging bone biomarkers of knee osteoarthritis (OA) progression.


METHODS
We undertook a nested case-control study within the Osteoarthritis Initiative in knees (one knee per subject) with a Kellgren and Lawrence grade of 1-3. Cases were defined as knees having the combination of medial tibiofemoral radiographic progression and pain progression at the 24-month, 36-month or 48-month follow-up compared with baseline. Controls (n=406) were eligible knees that did not meet both endpoint criteria and included 200 with neither radiographic nor pain progression, 103 with radiographic progression only and 103 with pain progression only. Bone surfaces in medial and lateral femur, tibia and patella compartments were segmented from MR images using active appearance models. Independent variables of primary interest included change from baseline to 24 months in (1) total area of bone and (2) position on three-dimensional (3D) bone shape vectors that discriminate OA versus non-OA shapes. We assessed the association of bone markers changes over 24 months with progression using logistic regression.


RESULTS
24-month changes in bone area and shape in all compartments were greater in cases than controls, with ORs of being a case per 1 SD increase in bone area ranging from 1.28 to 1.71 across compartments, and per 1 SD greater change in 3D shape vectors ranging from 1.22 to 1.64. Bone markers were associated most strongly with radiographic progression and only weakly with pain progression.


CONCLUSIONS
In knees with mild-to-moderate radiographic OA, changes in bone area and shape over 24 months are associated with the combination of radiographic and pain progression over 48 months. This finding of association with longer term clinical outcome underscores their potential for being an efficacy of intervention biomarker in clinical trials.
Rheumatology Department, Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia.
David
http://orcid.org/0000-0003-3197-752X
D
Hunter
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
Michael
M
Nevitt
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
John
J
Lynch
Duke Molecular Physiology Institute and Division of Rheumatology, Duke University School of Medicine, Durham, North Carolina, USA.
Virginia Byers
VB
Kraus
Brigham and Women's Hospital, Boston, Massachusetts, USA.
Jeffrey N
JN
Katz
Brigham and Women's Hospital, Boston, Massachusetts, USA.
Jamie E
JE
Collins
Imorphics, Manchester, UK.
Mike
M
Bowes
Department of Radiology, Boston University School of Medicine, Quantitative Imaging Center, Boston, Massachusetts, USA.
Ali
A
Guermazi
Department of Radiology, Boston University School of Medicine, Quantitative Imaging Center, Boston, Massachusetts, USA Department of Radiology, University of Erlangen-Nuremberg, Erlangen, Germany.
Frank W
FW
Roemer
Brigham and Women's Hospital, Boston, Massachusetts, USA.
Elena
E
Losina
D000368:Aged; D018771:Arthralgia / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology; D015415:Biomarkers; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology*; D010329:Patella / Q000000981:diagnostic imaging / Q000473:pathology; D013977:Tibia / Q000000981:diagnostic imaging / Q000473:pathology; D013997:Time Factors
D015415:Biomarkers
Knee Osteoarthritis; Magnetic Resonance Imaging; Osteoarthritis