Can biochemical markers serve as surrogates for imaging in knee osteoarthritis?

Abstract

Objective. Osteoarthritis (OA) is a complex heterogeneous joint disease affecting more than 35 million people worldwide. The current gold standard diagnostic investigation is the plain radiograph, which lacks sensitivity. Biochemical markers have the potential to act as adjunct markers for imaging in the assessment of knee OA. We undertook this study to determine the association between individual biochemical markers and radiographic features, and to establish whether the association is strengthened when selected biochemical markers are combined into a single factor (a theoretical marker).Methods. Twenty serum and urinary biochemical markers were analyzed in 119 patients with predominantly tibiofemoral knee OA. Pearson's correlation was performed, and corresponding coefficients of determination (R 2 ) were calculated to determine the association between biochemical markers and a range of imaging features from radiographs and dual x-ray absorptiometry of the knee. Biochemical markers demonstrating a significant association (P < 0.05) with a specific imaging feature were combined by principal components analysis (PCA). Pearson's correlation was repeated to establish whether the combined panel of biochemical markers showed a stronger association with imaging than the best single marker.Results. Fourteen biochemical markers showed significant associations with one or more imaging features. By combining specific panels of biochemical markers to form factors, the association of markers with imaging features (R 2 ) increased from 11.9% to 22.7% for the Kellgren/Lawrence (K/L) score, from 5.9% to 9.2% for joint space width (JSW), from 6.6% to 10.8% for sclerosis, from 13.5% to 22.6% for osteophytes, and from 12.0% to 14.2% for bone mineral density (BMD). Biochemical markers identifying patients with osteophytes overlapped with those correlated with a high K/L score, while markers of subchondral BMD formed a completely separate group. Biochemical markers of JSW included markers associated with both osteophytes and BMD.Conclusion. The PCA results suggest that biochemical marker combinations may be more sensitive than individual biochemical markers for reflecting structural damage in patients with knee OA. The differences in biochemical marker profiles associated with osteophytes compared with those associated with subchondral BMD raise the possibility that these 2 processes, commonly seen in bone in knee OA, have underlying biologic differences.Osteoarthritis (OA) is a complex heterogeneous joint disease with a prevalence of 18% in persons age Ͼ55 years in the UK (1). With ϳ35 million people affected worldwide, OA is a major cause of pain and disability, and its incidence is increasing as life expectancy continues to rise (2). The current gold standard for diagnosing OA is the plain radiograph, which has many methodologic shortcomings, and, in spite of efforts to improve techniques (3,4), inaccuracies may occur from subtly different views of the image, degree of flexion, intra-and interobserver discrepancies, and "anticip...

Correlation between WOMAC score and hyalrunoic acid levels in knee osteoarthritis

“…It has also been reported other studies. 8,14,15 This might be because the comparable BMI of Case group and Control group in our study as the controls were siblings or first degree relatives of the patients in the same age group. On the contrary positive correlation between HA levels and BMI has also been reported.…”

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

“…In recent years, however, the trend has shifted from assessments of individual markers to uncovering clusters of markers that may correlate with disease progression and activity. Indeed, it was recently demonstrated, using an approach based on the association of selected biochemical markers combined into a single factor, that a combined panel of biochemical markers showed a stronger association with OA than any individual markers [118]. Moreover, their analysis also suggested that markers identifying patients with osteophytes overlapped those with a high Kellgren-Lawrence score while markers for BMD of the subchondral bone were uncovering a totally different group, hence raising the possibility that although osteophytes and subchondral BMD are associated with OA, they may have underlying biological differences.…”

Analysis of Serum Proteins and Enzymes Level in Human Subjects with Osteoarthritis

“…It appears that variation in peptides is more frequent in the low molecular weight (LMW) component of the sera of OA subjects. Earlier reports have also deduced that most of the variation in human proteome lies in the LMW region which is rich in cytokines, chemokines, peptide hormones and a few proteolytic fragments (35,47,50). We suggest further investigations in this direction to identify and characterize these novel LMW fractions present in the sera of OA subjects.…”

“…We have, therefore, selected sera as the potential source of chan ging proteomic profiles in subjects with osteoarthritis (OA). Various studies have identified potential biochemical markers as a means of diagnosing and monitoring OA, and investigators in some of these studies have reported radiographic assessment (35), hyaluronan (36), C-reactive proteins (37)(38), enzymes (20, 22-23, 25, 39-41) and many more (42)(43)(44)(45)(46). Even the estimation of absolute protein values provides relatively better options and puts forward the marker value of many useful protein fractions (16,33,35,47).…”