Background/Purpose: Osteoarthritis (OA) has not traditionally been considered a systemic joint disease. However, a growing body of evidence suggests that OA cannot solely be accounted for by a single phenotype, and that systemic factors may play a contributing role in its pathogenesis. Obesity is an important risk factor for OA, but the underlying mechanisms are not fully understood (e.g. strong association between obesity and hand OA cannot be explained by mechanical stresses). Finally, the presence of multiple symptomatic joints among many with OA further suggests potentially underlying systemic mechanisms. In this pilot study, we investigated the association between serum levels of adipokines and the extent of symptomatic joint involvement among patients scheduled for hip and knee replacement surgery for OA.

Methods: Serum levels of adipokines (leptin, adiponectin, adipsin, resistin) were determined by ELISA in 78 patients (45 females, 33 males) scheduled for total hip or knee replacement surgery for OA. Individuals reporting inflammatory arthritis, cardiovascular disease or diabetes were excluded.  Patients indicated on a homunculus all joints that were symptomatic on most days for at least a month in the past 12 months. A count score of symptomatic regions (neck; spine; shoulders; elbows; wrists; hands; hips; knees; ankles; feet) (not including surgical joint) was developed (range: 0 to 9). Analysis was stratified by sex, and Poisson analyses used to investigate associations.

Results: Bivariate associations suggested opposite effects of leptin, adiponectin, and adipsin between women and men.  Adjusted for age, BMI, and hip/knee group membership, higher levels of leptin and adiponectin, and lower levels of adipsin (all p<0.01) were associated with a greater regional joint count among women (Table 1). However, among men only resistin was significantly (p=0.03) associated in adjusted analyses, with higher levels of resistin associated with lower regional joint counts. 

Conclusion: This work suggests to some degree that there may be a dose-response association between OA (using extent of regional symptomatic joint involvement as an indicator) and serum levels of adipokines. However, these associations differ between women and men.  This suggests the possibility of distinct OA phenotypes, and supports potential systemic effects in OA. OA as a systemic disorder entails a need to reevaluate OA treatment and management strategies, with consideration for multimodal approaches. Systemic factors in OA may also help explain high levels of comorbidity in these populations and may be a target for comorbidity prevention.

 Table 1. Multivariate adjusted associations between regional joint count (outcome) and adipokines. 

		IRR*	Lower 95%CL	Upper 95%CL	Pr > ChiSq
Predictors		Females
Age		1.03	1.005	1.058	0.0204
BMI		1.01	0.973	1.054	0.5407
Knee vs. hip		1.25	0.765	2.048	0.3725
Leptin (ng/ml)		1.03	1.010	1.047	0.0021
Adiponectin (ug/ml)		1.03	1.011	1.056	0.0031
Adipsin (mg/ml)		0.85	0.751	0.961	0.0094
Resistin (ng/ml)		1.01	0.987	1.038	0.3613
		Males
Age		1.02	0.979	1.054	0.4017
BMI		1.03	0.933	1.143	0.5330
Knee vs. hip		0.92	0.430	1.949	0.8181
Leptin (ng/ml)		0.97	0.923	1.020	0.2485
Adiponectin (ug/ml)		0.97	0.937	1.010	0.1563
Adipsin (mg/ml)		0.96	0.790	1.176	0.7190
Resistin (ng/ml)		0.97	0.942	0.997	0.0307

*IRR: Incident rate ratio, per unit of measurement – Poisson analysis; 95% CL: 95% confidence limits.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-between-serum-adipokine-levels-and-extent-of-symptomatic-joint-involvement-in-hip-and-knee-osteoarthritis/