Association Between Biochemical Markers of Bone Turnover and Bone Changes on Imaging: Data From the Osteoarthritis Initiative

Abstract

Objective To determine the relationship between biochemical markers involved in bone turnover and bone features on imaging in knees with osteoarthritis (OA). Methods We analysed data from the OA Biomarkers Consortium within the Osteoarthritis Initiative (n=600). Bone marrow lesions (BMLs), osteophytes, subchondral bone area (mm2) and shape (position on 3D vector) were assessed on MRIs and bone trabecular integrity (BTI) was assessed on radiographs. Serum (s) and urinary (u) markers (sCTX-I, sNTX-I, uNTX-I, uCTX-II, uCTX-I alpha and beta) were measured. The associations between biochemical and imaging markers at baseline and over 24 months were assessed using regression models adjusted for covariates. Results At baseline, most biochemical markers were associated with BMLs, with c-statistics for the presence/absence of any BML ranging from 0.675 to 0.688. At baseline, uCTX-II was the marker most consistently associated with BMLs (odds of having ≥ 5 subregions affected compared to no BML increasing by 1.92-fold [95% CI 1.25, 2.96] per 1 SD of uCTX-II), large osteophytes (OR 1.39 [1.10, 1.77]), bone area and shape (highest partial R2 0.032), and changes in bone shape over 24 months (partial R2 from 0.008 to 0.024). Overall, biochemical markers were not predictive of changes in BMLs or osteophytes. Serum NTX-I was inversely associated with BTI of the vertical trabeculae (quadratic slope) in all analyses (highest partial R2 0.028). Conclusions We found multiple significant associations, albeit most were weak. The role of systemic biochemical markers as predictors of individual bone anatomic features of single knees is limited based on our findings.

Osteoarthritis year in review 2018: biomarkers (biochemical markers)

“…Changes in bone remodeling are frequently present early in the OA process 7 . Using data of the Osteoarthritis Initiative, association between serum (S) and urine (U) biochemical markers of bone turnover and bone features on magnetic resonance images (MRI) was evaluated.…”

“…Using data of the Osteoarthritis Initiative, association between serum (S) and urine (U) biochemical markers of bone turnover and bone features on magnetic resonance images (MRI) was evaluated. Although at baseline, most biomarkers, in particular urinary C-telopeptide of type II collagen (uCTX-II), were associated with bone marrow lesions (BMLs), the markers were not predictive of changes in BMLs or osteophytes at follow-up 7 . Serum biomarkers of synovial inflammation, MMP-3 and hyaluronic acid (HA), were associated with moderate to large effusion MRI-detected synovitis; but there was no association between the markers and changes in MRI features of synovitis (Hoffa and effusion synovitis) 8 .…”

Osteoarthritis biomarkers: year in review

“…Specific bone biomarkers (sCTX-I, sNTX-I, uNTX-I, uCTX-II, uCTX-Ia/b) were tested by the consortium in 600 OAI participants' serum and urine for associations with bony features on imaging, at baseline and over 24 months 14 . Most markers were associated with baseline bone marrow lesions (BMLs); uCTX-II was also associated with large osteophytes (OR 1.39 [1.10, 1.77]) and bone shape.…”

The relationship between two different measures of osteoarthritis bone pathology, bone marrow lesions and 3D bone shape: data from the Osteoarthritis Initiative

“…Using the same FNIH cohort, Hunter et al. showed that bone shape was associated with radiographic and pain progression longitudinally 6 , while imaging biomarkers of bone (including bone shape and BML measures used in this study) were only weakly associated with OA biochemical biomarkers; however bone shape and BMLs were not directly compared 11 . In the same cohort, Collins et al.…”