Whole-Body Bone Scintigraphy Provides a Measure of the Total-Body Burden of Osteoarthritis for the Purpose of Systemic Biomarker Validation

Objective. To evaluate the association of serum and synovial fluid cartilage oligomeric matrix protein (COMP) with systemic and local measures of osteoarthritis (OA) activity by bone scintigraphy. Methods. Samples of serum and knee joint synovial fluid (275 knees) were obtained from 159 patients with symptomatic OA of at least 1 knee. Bone scintigraphy using Tc-99m-labeled methylene diphosphonate was performed, and early-phase knee scans and late-phase whole-body bone scans of 15 additional joint sites were scored semiquantitatively. To control for within-subject correlations of knee data, generalized linear modeling was used in the correlation of the bone scan scores with the COMP levels. Principal components analysis was used to explore the contribution of each joint site to the variance in serum COMP levels. Results. The correlation between synovial fluid and serum COMP levels was significant (r = 0.206, P = 0.006). Synovial fluid COMP levels correlated most strongly with the early-phase knee bone scan scores (P = 0.0003), even after adjustment for OA severity according to the late-phase bone scan scores (P = 0.015), as well as synovial fluid volumes (P < 0.0001). Serum COMP levels correlated with the total-body bone scan scores (r = 0.188, P = 0.018) and with a factor composed of the bone scan scores in the shoulders, spine, lateral knees, and sacroiliac joints (P = 0.0004). Conclusion. Synovial fluid COMP levels correlated strongly with 2 indicators of knee joint inflammation: early-phase bone scintigraphic findings and synovial fluid volume. Serum COMP levels correlated with total-body joint disease severity as determined by late-phase bone scintigraphy, supporting the hypothesis that whole-body bone scintigraphy is a means of quantifying the total-body burden of OA for systemic biomarker validation.