Cross-Talk between Fat-Derived Proteins and Bone Remodeling Factors in Lean and Obese Girls

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 199-233-Bone Biology
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-224
Christina Kanaka-Gantenbein*1, Ioannis Papassotiriou2, Evangelos Terpos1 and George P. Chrousos3
1University of Athens School of Medicine, Athens, Greece, 2Agia Sophia Children's Hospital, Athens, Greece, 3First Department of Pediatrics, Athens, Greece
Background and Aims: Fat and bone are linked by a multitude of pathways supporting a skeleton appropriate for the mass of adipose tissue of the organism. Insulin, leptin, adiponectin and adipocytic estrogens are all likely to be involved in this connection. Among them the fat-cell derived hormone leptin significantly contributes to bone health. Leptin binds to the leptin receptor inhibiting bone formation and promoting bone absorption. Furthermore, it inhibits the secretion of the receptor activator of the NF-κB ligand (RANKL) by osteoblasts by stimulating the production of osteoprotegerin (OPG) and up-regulating the OPG/RANKL balance1. The main biological function of OPG is to neutralize RANKL and control the formation, activity, and survival of osteoclasts, so that bone absorption is inhibited. In this context we aimed to investigate the relations of adipose tissue hormones, such as leptin, adiponectin, RBP-4 and lipocalin-2, along with the low grade inflammation marker hs-CRP, with makers of bone metabolism such as OPG, RANKL, osteocalcin, C-terminal cross-linking telopeptide of collagen type-I (CTX), bone alkaline phosphatase (bALP) and tartrate-resistant acid phosphatase isoform-5b (bone TRACP-5b) in girls with various degrees of BMI.

Methods: Eighty girls (age 9–15 years) were enrolled in the study divided by their BMI standard deviation scores (BMI-SDSs) into 4 groups of 20 girls each: overweight 1.8±0.4; obese 2.2±0.4; morbidly obese 3.6±0.4 and lean controls -0.11±0.4, in whom adipocytokines, hs-CRP and bone markers were measured by means of immunoenzymatic techniques.

Results: The main results of the study showed that: a) OPG, RANKL and bALP levels decreased significantly as BMI-SDSs increased (p=0.03, p=0.03 and p<0.01, respectively), while osteocalcin, CTX and bone TRACP5 show no relations (p>0.60); b) leptin correlated negatively with bALP, bone TRACP-5b, osteocalcin, OPG and RANKL (p<0.05, p=0.02 and p=0.006, respectively); adiponectin correlated positively with CTX and OPG (p=0.004 and p=0.04, respectively); RBP-4 correlated positively with OPG and bALP (p<0.01 and p=0.002, respectively), while lipocalin-2 correlated positively with bALP (p<0.001); c) obesity-related systemic inflammation expressed as hs-CRP correlated positively only with OPG.

Conclusion: Our findings suggest that there are important links between adipose tissue-derived proteins and bone remodeling factors. Bone turnover was altered in obese girls mainly due to decreased OPG levels. There were significant correlations of OPG with leptin, adiponectin and hs-CRP, indicating that, probably, the bone mass is regulated by adipokines, as well as by low grade inflammation in obese children.

1Dimitri et al. Bone 50: 457–466, 2012.

Nothing to Disclose: CK, IP, ET, GPC

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