Effect of an exercise and dietary intervention on serum biomarkers in overweight and obese adults with osteoarthritis of the knee.
OBJECTIVE
To determine the effects of exercise and weight loss interventions on serum levels of four biomarkers and to examine if changes in biomarker levels correlate with clinical outcome measures in obese and overweight adults with knee osteoarthritis (OA).


METHODS
Serum was obtained at baseline, 6 and 18 months from 193 participants in Arthritis, Diet and Activity Promotion Trial. This was a single-blind 18-month trial with subjects randomized to four groups: healthy-lifestyle (HL), diet (D), exercise (E) and diet plus exercise (D+E). Serum levels of cartilage oligomeric matrix protein (COMP), hyaluronan (HA), antigenic keratan sulfate (AgKS), and transforming growth factor-beta1 (TGF-beta1) were measured by enzyme linked immunosorbent assay.


RESULTS
At baseline there were no significant differences in biomarker levels between intervention groups. When results for all the intervention groups were combined, the levels of HA were found to be negatively correlated with medial joint space width and positively correlated with Kellgren-Lawrence scores (K-L scores) while TGF-beta1 levels negatively correlated with K-L scores. When biomarker levels measured at 6 and 18 months were adjusted for baseline values, age, gender, and body mass index, weak but significant differences between intervention groups were present for mean levels of COMP and TGF-beta1. Furthermore, AgKS levels averaged over all groups tended to decrease over time. There were no significant associations of baseline biomarkers and the follow-up outcomes. Weak associations were noted between change in the biomarkers at 18 months and change in outcome measures that included change in weight with AgKS and COMP and change in Western Ontario and McMaster Universities Osteoarthritis Index pain with AgKS.


CONCLUSIONS
Overall, the E and D interventions did not show a consistent effect on levels of potential OA biomarkers. The four biomarkers showed differences in correlations with outcome measures suggesting that they may measure different aspects of disease activity in OA. The strongest correlations were between serum HA and radiographic measures of OA at baseline.
Chua
S D
SD
Department of Internal Medicine, Rush Medical College, Chicago, IL, USA.
Messier
S P
SP
Legault
C
C
Lenz
M E
ME
Thonar
E J-M A
EJ
Loeser
R F
RF
D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D064236:Cartilage Oligomeric Matrix Protein; D004038:Diet, Reducing; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005081:Exercise Therapy; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D007632:Keratan Sulfate / Q000097:blood*; D008019:Life Style; D008297:Male; D064235:Matrilin Proteins; D009765:Obesity; D020370:Osteoarthritis, Knee / Q000097:blood* / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000097:blood*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000097:blood*; D013997:Time Factors; D016474:Weight-Bearing / Q000502:physiology
D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; D018125:Receptors, Transforming Growth Factor beta; C577553:TSP5 protein, human; D006820:Hyaluronic Acid; D007632:Keratan Sulfate; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I