Whole-body bone scintigraphy provides a measure of the total-body burden of osteoarthritis for the purpose of systemic biomarker validation

Abstract

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 (99m)Tc-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.

Figure 1. Representative bone scan images of a participant enrolled on the basis of symptomatic radiographic knee osteoarthritis

A) Spot images of the knees (first and third rows) and ankles (second and fourth rows) obtained starting 4 minutes after injection of the radiopharmaceutical (upper 2 rows) and 2 hours after injection (bottom 2 rows). Abnormal activity is noted in the right knee (medial, lateral and patellofemoral compartments) and in the right ankle and midfoot. B) Whole body bone scan obtained starting 2 hours after injection of the radiopharmaceutical. Abnormal activity is noted in both acromioclavicular, shoulder, and wrist joints, the cervical and thoracic spine, and the right knee, ankle and foot joints as described in A.