Markers involved in bone turnover only modestly linked with bone features

In patents with knee osteoarthritis, systemic biochemical markers involved in bone turnover appear to be weak predictors of individual bone features, according to recently published findings.

Researchers evaluated data for 600 patients in the osteoarthritis (OA) sample of the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative. The researchers scored bone marrow lesions (BMLs) using the MRI Osteoarthritis Knee Score (MOAKS) method. They determined the maximum BML size score for the joint as the highest BML grade across the whole knee and established the total number of subregions impacted by any BML. They also classified the number of affected subregions.

They used the MOAKS to score osteophytes at 12 sites in the patella, femur and tibia. As with BMLs, the researchers scored osteophytes according to size in each subregion. They assessed the area of subchondral bone (tAB) in the medial and lateral compartments of the femur and tibia. They evaluated bone shape by the position on 3-D bone shape vectors in the femur, tibia and patella. The researchers also measured the following serum and urinary markers: serum C-terminal crosslinked telopeptide of type I collagen (CTX-I); serum crosslinked N-telopeptide of type I collagen (NTX-I); urinary NTX-I; urinary C-terminal crosslinked telopeptide of type II collagen (CTX-II); and urinary CTX-I alpha and CTX I beta. Regression models adjusted for covariates were utilized to assess the correlations between biochemical and imaging markers at baseline and during the course of 24 months.

Researchers found that at baseline, there was an association was between most biochemical markers and BMLs, with C statistics for the presence or absence of any BML ranging from 0.675 to 0.688.

Serum CTX-I and urinary CTX-I alpha were significantly associated with large BMLs (grade 3), with the likelihood of the presence of a large BML increasing by 1.47-fold with CTX-I and by 1.48-fold for urinary CTX-I alpha per 1 SD increase in each marker. Urinary CTX-II was linked to moderate and large (grades 2 and 3) BMLs in an adjusted analysis, but became statistically significant for grade 2 BMLs (OR = 1.81) in an analysis with covariates added. The likelihood of having at least five subregions with BML vs. no BML increased by 1.92-fold per 1 SD of urinary CTX-II. Urinary CTX-II was also the only biochemical marker linked to osteophytes, with the odds of having a grade 3 osteophyte vs. no osteophyte increased by 1.39-fold per 1 SD increase in urinary CTX. Urinary CTX-II was also most consistently associated with bone shape, with significant links to the femur, tibia and patella 3-D shape vectors. Urinary CTX-II, as well as serum CTX-1, were correlated with tAB in all joint sites evaluated in the adjusted analysis, but not in adjusted analysis. During the 24-month follow-up, an association was identified between changes in the position of 3-D shape vectors toward an OA shape and higher baseline levels of urinary CTX-II for the patellar and tibial bones.

Overall, biochemical markers did not predict changes in BMLs or osteophytes. In all analyses, an inverse correlation was seen between serum NTX-I and BTI of the vertical trabeculae.
– by Jennifer Byrne

Disclosures: One author is an employee of Imorphics and another author is an employee of Merck KGaA. Please see the full study for a list of the other authors’ relevant financial disclosures.