Leptin and Adiponectin Mediate the Association between Body Mass Index and Hand and Knee Osteoarthritis

F.P.B. Kroon¹, A. Veenbrink¹, R. de Mutsert², A.W. Visser¹, Saskia le Cessie³, F.R. Rosendaal² and M. Kloppenburg^1,2, ¹Rheumatology, Leiden University Medical Center, Leiden, Netherlands, ²Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands, ³Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, Netherlands

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Adipokines, Epidemiologic methods, Mediation, obesity and osteoarthritis

Session Information

Date: Tuesday, November 7, 2017

Title: Osteoarthritis – Clinical Aspects Poster II: Observational and Epidemiological Studies

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Associations between obesity and osteoarthritis (OA) in non-weight bearing joints suggest that systemic influences also contribute to OA. Systemically active substances secreted by adipose tissue, including adipokines, are hypothesized to play a role in OA. We examined whether two adipokines, leptin and adiponectin, mediate the association between body mass index (BMI) and hand and knee OA.

Methods: Participants of a cross-sectional population-based study completed questionnaires and underwent standardized physical examination of hands and knees to define OA according to clinical ACR criteria. Fasting serum leptin and adiponectin were measured with immunoassays. Potential mediation was investigated using the Baron and Kenny framework. Four assumptions were investigated: associations between (1) BMI and OA (pathway C), (2) BMI and adipokines (pathway A), (3) adipokines and OA (pathway B), and (4) attenuation of the association between BMI and OA after including adipokines (pathway C’). No exposure-mediator interaction and mediator-outcome confounding was assumed. Assumptions were investigated using logistic and linear regression analyses as appropriate. Odds Ratios (ORs) were calculated per standard deviation (SD) in BMI, and per 10 and 5 units in leptin and adiponectin. Percentage mediation with 95% confidence intervals (CIs) was estimated when all four assumptions were fulfilled, using causal mediation analyses in Stata (medeff). Models were adjusted for age, ethnicity and education, and stratified by sex.

Results: In 6462 participants (56% women, median age 56 years (range 45-65), mean BMI 26.3 kg/m²), prevalence of hand OA, knee OA and combined hand and knee OA were 8%, 10% and 4%, respectively. Median leptin and adiponectin concentrations were 7.1 ug/L (range 0.9-60.9) and 6.0 mg/L (0.5-23.7) in men, and 19.1 ug/L (0.5-262.0) and 10.5 mg/L (0.5-98.6) in women. BMI was positively associated with OA presence and serum leptin in both men and women (Table). A negative association was observed between BMI and serum adiponectin (-0.73 mg/L per SD BMI, 95% CI -0.55;-0.91). Leptin was positively associated with most OA types, except knee OA in men. Leptin partially mediated the association of BMI with hand OA in men (9% mediation, 95% CI 5;17) and women (30%, 13;198), and the association of BMI with knee OA in women (15%, 12;21). Similar analyses for adiponectin revealed a negative association of adiponectin with hand OA in men and partial mediation of the association of BMI with hand OA in men (19%, 12;37), whereas mediation was absent in other subgroups.

Conclusion: Leptin partially mediated the association of BMI and hand OA in both men and women, as did adiponectin in men. Moreover, mediation by leptin for the association of BMI and knee OA was demonstrated in women. These findings suggest that systemic mediators contribute to hand OA, and to a lesser extent to knee OA.

Table. Associations of BMI with leptin and different types of OA (OR, 95% CI)
*MEN*	Pathway A BMI – log leptin* b (95% CI)		Pathway B Leptin – OA OR (95% CI)	Pathway C BMI – OA OR (95% CI)	Pathway C’ BMI – OA OR (95% CI)	Mediation % (95% CI)
SD BMI: 3.72	1.70 (1.64 – 1.77)	Hand OA	1.30 (1.13 – 1.50)	1.39 (1.18 – 1.64)	1.34 (1.06 – 1.70)	8.6 (5.4 – 17.2)
		Knee OA	1.14 (0.98 – 1.43)	1.25 (1.06 – 1.48)	^{^}	^{^}
		Hand and knee OA	1.28 (1.07 – 1.52)	1.59 (1.31 – 1.93)	1.82 (1.39 – 2.39)	^‡
*WOMEN*	Pathway A BMI – log leptin* b (95% CI)		Pathway B Leptin – OA OR (95% CI)	Pathway C BMI – OA OR (95% CI)	Pathway C’ BMI – OA OR (95% CI)	Mediation % (95% CI)
SD BMI: 4.88	1.82 (1.77 – 1.88)	Hand OA	1.08 (1.01 – 1.15)	1.18 (1.01 – 1.37)	1.12 (0.89 – 1.40)	30.3 (13.3 – 198.2)
		Knee OA	1.21 (1.14 – 1.29)	1.62 (1.42 – 1.85)	1.50 (1.25 – 1.81)	15.4 (11.7 – 21.3)
		Hand and knee OA	1.13 (1.05 – 1.22)	1.48 (1.26 – 1.74)	1.55 (1.25 – 1.93)	^‡
BMI, body mass index; CI, confidence interval; OA, osteoarthritis; OR, Odds Ratio; SD, standard deviation. Adjusted for age, ethnicity and education. *logarithmic transformation performed to obtain normal distribution. ^{^}Mediation not calculated (no association within pathway B). ^‡Mediation not calculated (no attenuation of the total association of BMI and OA after including leptin in the model).

Disclosure: F. P. B. Kroon, Dutch Arthritis Fund, 2; A. Veenbrink, None; R. de Mutsert, None; A. W. Visser, None; S. le Cessie, None; F. R. Rosendaal, None; M. Kloppenburg, Pfizer, 2,AbbVie, GlaxoSmithKline, Merck, Levicept, 5,Dutch Arthritis Fund, 2.

To cite this abstract in AMA style:

Kroon FPB, Veenbrink A, de Mutsert R, Visser AW, le Cessie S, Rosendaal FR, Kloppenburg M. Leptin and Adiponectin Mediate the Association between Body Mass Index and Hand and Knee Osteoarthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/leptin-and-adiponectin-mediate-the-association-between-body-mass-index-and-hand-and-knee-osteoarthritis/. Accessed .

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