Abstract
Background: Adiponectin, a fat derived cytokine, is a potential independent contributor to bone mineral density (BMD); however, its action on bone metabolism in humans is still unclear. Aim: The aim of this study was to investigate the relationship of adiponectin with bone mass indices and bone metabolic markers in middle-aged post-menopausal women without diabetes. Subjects and methods: A random sample consisted of 81 post-menopausal women (age range 45–61 yr, osteopenic/osteoporotic no.=43) was studied. Lumbar-spine BMD (BMDL2-L4) and total-body bone mineral content (TBBMC) were measured with dual X-ray absorptiometry. Plasma levels of total and high-molecular weight (HMW) adiponectin, osteoprotegerin (OPG), soluble receptor activator of nuclear factor-κB ligand (sRANKL) and IGF-I were determined. Results: No association was observed between total or HMW adiponectin and BMDL2-L4 or TBBMC. On the contrary, adiponectin levels were positively associated with OPG levels (partial r=0.276, p=0.015) and negatively with IGF-I (partial r=−0.438, p<0.001), in multiple regression models after adjustment for potential confounders. HMW adiponectin showed a negative association with IGF-I (partial r=−0.266, p=0.049) in the multiple regression models but not with OPG, TBBMC or BMDL2-L4. Conclusions: Although we failed to show statistically significant association between circulating adiponectin levels and indices of bone mass in women during the postmenopausal period, we showed significant associations with OPG and IGF-I levels, suggesting an anabolic role of adiponectin, which may contribute in the understanding of the interplay between adipose tissue-derived hormones and bone metabolism.
Similar content being viewed by others
References
Reid IR. Relationships among body mass, its components, and bone. Bone 2002, 31: 547–55.
De Laet C, Kanis JA, Oden A, et al. Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int 2005, 16: 1330–8.
Rubin CT, Lanyon LE. Regulation of bone mass by mechanical strain magnitude. Calcif Tissue Int 1985, 37: 411–7.
Reid IR. Relationships between fat and bone. Osteoporos Int 2008, 19: 595–606.
Zillikens MC, Uitterlinden AG, van Leeuwen JP, et al. The role of body mass index, insulin, and adiponectin in the relation between fat distribution and bone mineral density. Calcif Tissue Int 2010, 86: 116–25.
Reid IR. Fat and bone. Arch Biochem Biophys 2010, 503: 20–7.
Gavrila A, Chan JL, Yiannakouris N, et al. Serum adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: cross-sectional and interventional studies. J Clin Endocrinol Metab 2003, 88: 4823–31.
Berner HS, Lyngstadaas SP, Spahr A, et al. Adiponectin and its receptors are expressed in bone-forming cells. Bone 2004, 35: 842–9.
Lee WY, Rhee EJ, Oh KW, et al. Identification of adiponectin and its receptors in human osteoblast-like cells and association of T45G polymorphism in exon 2 of adiponectin gene with lumbar spine bone mineral density in Korean women. Clin Endocrinol (Oxf) 2006, 65: 631–7.
Luo XH, Guo LJ, Xie H, et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts through the MAPK signaling pathway. J Bone Miner Res 2006, 21: 1648–56.
Williams GA, Wang Y, Callon KE, et al. In vitro and in vivo effects of adiponectin on bone. Endocrinology 2009, 150: 3603–10.
Kontogianni MD, Dafni UG, Routsias JG, Skopouli FN. Blood leptin and adiponectin as possible mediators of the relation between fat mass and BMD in perimenopausal women. J Bone Miner Res 2004, 19: 546–51.
Gonnelli S, Caffarelli C, Del Santo K, et al. The relationship of ghrelin and adiponectin with bone mineral density and bone turnover markers in elderly men. Calcif Tissue Int 2008, 83: 55–60.
Sodi R, Hazell MJ, Durham BH, Rees C, Ranganath LR, Fraser WD. The circulating concentration and ratio of total and high molecular weight adiponectin in post-menopausal women with and without osteoporosis and its association with body mass index and biochemical markers of bone metabolism. Clin Biochem 2009, 42: 1375–80.
Araneta MR, von Mühlen D, Barrett-Connor E. Sex differences in the association between adiponectin and BMD, bone loss, and fractures: the Rancho Bernardo study. J Bone Miner Res 2009, 24: 2016–22.
Basurto L, Galván R, Cordova N, et al. Adiponectin is associated with low bone mineral density in elderly men. Eur J Endocrinol 2009, 160: 289–93.
Michaëlsson K, Lind L, Frystyk J, et al. Serum adiponectin in elderly men does not correlate with fracture risk. J Clin Endocrinol Metab 2008, 93: 4041–7.
Jürimäe J, Jürimäe T, Leppik A, Kums T. The influence of ghrelin, adiponectin, and leptin on bone mineral density in healthy post-menopausal women. J Bone Miner Metab 2008, 26: 618–23.
Zoico E, Zamboni M, Di Francesco V, et al. Relation between adiponectin and bone mineral density in elderly post-menopausal women: role of body composition, leptin, insulin resistance, and dehydroepiandrosterone sulfate. J Endocrinol Invest 2008, 31: 297–302.
Iacobellis G, Iorio M, Napoli N, et al. Relation of adiponectin, visfatin and bone mineral density in patients with metabolic syndrome. J Endocrinol Invest 2011, 34: e12–5.
Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T. Relationships between serum adiponectin levels versus bone mineral density, bone metabolic markers, and vertebral fractures in type 2 diabetes mellitus. Eur J Endocrinol 2009, 160: 265–73.
Waki H, Yamauchi T, Kamon J, et al. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003, 278: 40352–63.
Hara K, Horikoshi M, Yamauchi T, et al. Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care 2006, 29: 1357–62.
Richards JB, Valdes AM, Burling K, Perks UC, Spector TD. Serum adiponectin and bone mineral density in women. J Clin Endocrinol Metab 2007, 92: 1517–23.
Peng XD, Xie H, Zhao Q, Wu XP, Sun ZQ, Liao EY. Relationships between serum adiponectin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in Chinese men. Clin Chim Acta 2008, 387: 31–5.
Zhang H, Xie H, Zhao Q, et al. Relationships between serum adiponectin, apelin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in postmenopausal Chinese women. J Endocrinol Invest 2010, 33: 707–11.
Tenta R, Panagiotakos DB, Fragopoulou E, et al. Osteoprotegerin and nuclear factor-kappaB ligand are associated with leptin and adiponectin levels, in apparently healthy women. J Musculoskelet Neuronal Interact 2010, 10: 174–9.
Wittrant Y, Théoleyre S, Chipoy C, et al. RANKL/RANK/OPG: new therapeutic targets in bone tumours and associated osteolysis. Biochim Biophys Acta 2004, 1704: 49–57.
Yakar S, Rosen CJ, Beamer WG, et al. Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest 2002, 110: 771–81.
Hadjidakis DJ, Androulakis, II. Bone remodeling. Ann N Y Acad Sci 2006, 1092: 385–96.
Kollia M, Kavouras SA, Gioxari A, Maraki M, Sidossis LS. Development, validity and reliability of the Harokopio Physical Activity Questionnaire in Greek adults. Proceedings of the 8th Panhellenic Congress on Nutrition and Dietetics, Athens, Greece. 2006, Abstract Book, pp. 130–1.
WHO. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis; report of a World Health Organization Study Group. ed 843 (Study group on assessment of fracture risk and its application to screening for postmenopausal osteoporosis) 1994 Geneva, WHO.
Agbaht K, Gurlek A, Karakaya J, Bayraktar M. Circulating adiponectin represents a biomarker of the association between adiposity and bone mineral density. Endocrine 2009, 35: 371–9.
Kanazawa I, Yamaguchi T, Sugimoto T. Baseline serum total adiponectin level is positively associated with changes in bone mineral density after 1-year treatment of type 2 diabetes mellitus. Metabolism 2010, 59: 1252–6.
Yaturu S. Diabetes and skeletal health. J Diabetes 2010, 1: 246–54.
Ozkurt B, Ozkurt ZN, Altay M, Aktekin CN, Caglayan O, Tabak Y. The relationship between serum adiponectin level and anthropometry, bone mass, osteoporotic fracture risk in postmenopausal women. Eklem Hastalik Cerrahisi 2009, 20: 78–84.
Gannage-Yared MH, Yaghi C, Habre B, et al. Osteoprotegerin in relation to body weight, lipid parameters insulin sensitivity, adipocytokines, and C-reactive protein in obese and non-obese young individuals: results from both cross-sectional and interventional study. Eur J Endocrinol 2008, 158: 353–9.
Oshima K, Nampei A, Matsuda M, et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun 2005, 331: 520–6.
Takayanagi H. Inflammatory bone destruction and osteoimmunology. J Periodontal Res 2005, 40: 287–93.
Yamaguchi N, Kukita T, Li YJ, et al. Adiponectin inhibits induction of TNF-alpha/RANKL-stimulated NFATc1 via the AMPK signaling. FEBS Lett 2008, 582: 451–6.
Mochizuki H, Hakeda Y, Wakatsuki N, et al. Insulin-like growth factor-I supports formation and activation of osteoclasts. Endocrinology 1992, 131: 1075–80.
Rubin J, Ackert-Bicknell CL, Zhu L, et al. IGF-I regulates osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand in vitro and OPG in vivo. J Clin Endocrinol Metab 2002, 87: 4273–9.
Canalis E. Growth factor control of bone mass. J Cell Biochem 2009, 108: 769–77.
Niu T, Rosen CJ. The insulin-like growth factor-I gene and osteoporosis: a critical appraisal. Gene 2005, 361: 38–56.
Motobayashi Y, Izawa-Ishizawa Y, Ishizawa K, et al. Adiponectin inhibits insulin-like growth factor-1-induced cell migration by the suppression of extracellular signal-regulated kinase 1/2 activation, but not Akt in vascular smooth muscle cells. Hypertens Res 2009, 32: 188–93.
Ziemke F, Mantzoros CS. Adiponectin in insulin resistance: lessons from translational research. Am J Clin Nutr 2010, 91: 258S–61S.
Williams CJ, Fargnoli JL, Hwang JJ, et al. Coffee consumption is associated with higher plasma adiponectin concentrations in women with or without type 2 diabetes: a prospective cohort study. Diabetes Care 2008, 31: 504–7.
Yannakoulia M, Yiannakouris N, Melistas L, Kontogianni MD, Malagaris I, Mantzoros CS. A dietary pattern characterized by high consumption of whole-grain cereals and low-fat dairy products and low consumption of refined cereals is positively associated with plasma adiponectin levels in healthy women. Metabolism 2008, 57: 824–30.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tenta, R., Kontogianni, M.D. & Yiannakouris, N. Association between circulating levels of adiponectin and indices of bone mass and bone metabolism in middle-aged post-menopausal women. J Endocrinol Invest 35, 306–311 (2012). https://doi.org/10.3275/7744
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.3275/7744