Temporal relationship between serum adipokines, biomarkers of bone and cartilage turnover, and cartilage volume loss in a population with clinical knee osteoarthritis

Abstract

Objective: The association of obesity with both hand and knee osteoarthritis (OA) is suggestive of a link between dysfunctional metabolism and joint integrity. Given the role of adipokines in mediating bone and cartilage homeostasis, we undertook this study to examine the relationship between adipokines and bone and cartilage biomarkers in a population of subjects with OA, and to determine whether adipokine levels predicted 2-year cartilage integrity.

Methods: One hundred seventeen subjects underwent magnetic resonance imaging at baseline and at 2-year followup. Cartilage volume was assessed from these images. Serum adipokine levels were measured at baseline. Bone and cartilage biomarker levels were measured at baseline and at 2-year followup. Linear regression was used to examine the relationship between baseline levels of adipokines and adipokine receptors (leptin, soluble leptin receptor [sOB-Rb], resistin, and adiponectin) and changes in levels of bone biomarkers (osteocalcin, N-terminal type I procollagen propeptide [PINP], C-terminal crosslinking telopeptide of type I collagen, N-terminal crosslinking telopeptide of type I collagen, or C-terminal crosslinking telopeptide of type I collagen generated by matrix metalloproteinases), levels of cartilage biomarkers (cartilage oligomeric matrix protein, N-terminal type IIA procollagen propeptide [PIIANP], or C2C), cartilage defects score, and cartilage volume over 2 years.

Results: Baseline leptin was associated with increased levels of bone formation biomarkers (osteocalcin and PINP) over 2 years, while sOB-Rb was associated with reduced levels of osteocalcin. Baseline sOB-Rb was associated with reduced levels of the cartilage formation biomarker PIIANP, an increased cartilage defects score, and increased cartilage volume loss over 2 years. All results were independent of age, sex, and body mass index.

Conclusion: The findings of this study support the concept that serum adipokines may provide a nonmechanical link between obesity and joint integrity (which may be mediated by bone and cartilage turnover) that subsequently results in changes to the cartilage defects score and cartilage volume loss. This may facilitate our understanding of the mechanisms by which obesity is involved in the pathogenesis of OA.