Top

Published in:

01-09-2008 | Review

The Bone-Adipose Axis in Obesity and Weight Loss

Authors: J. Gómez-Ambrosi, A. Rodríguez, V. Catalán, G. Frühbeck

Published in: Obesity Surgery | Issue 9/2008

Abstract

Body fat and lean mass are correlated with bone mineral density, with obesity apparently exerting protection against osteoporosis. The pathophysiological relevance of adipose tissue in bone integrity resides in the participation of adipokines in bone remodeling through effects on deposition and resorption. On the other hand, the skeleton has recently emerged as an endocrine organ with effects on body weight control and glucose homeostasis through the actions of bone-derived factors such as osteocalcin and osteopontin. The cross-talk between adipose tissue and the skeleton constitutes a homeostatic feedback system with adipokines and molecules secreted by osteoblasts and osteoclasts representing the links of an active bone–adipose axis. Given the impact of bariatric surgery on absorption and the adipokine secretory pattern, to focus on the changes taking place following surgical-induced weight loss on this dynamic system merits detailed consideration.

Zaidi M. Skeletal remodeling in health and disease. Nat Med. 2007;13:791–801.PubMed

Rosen CJ, Bouxsein ML. Mehanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol. 2006;2:35–43.PubMed

Frühbeck G. Hunting for new pieces to the complex puzzle of obesity. Proc Nutr Soc. 2006;65:329–47.PubMed

Reid IR. Relationships between fat and bone. Osteoporos Int. 2008;19:595–606.PubMed

Zhao LJ, Liu YJ, Liu PY, et al. Relationship of obesity with osteoporosis. J Clin Endocrinol Metab. 2007;92:1640–6.PubMed

Galusca B, Zouch M, Germain N, et al. Constitutional thinness: unusual human phenotype of low bone quality. J Clin Endocrinol Metab. 2008;93:110–7.PubMed

Hla MM, Davis JW, Ross PD, et al. A multicenter study of the influence of fat and lean mass on bone mineral content: evidence for differences in their relative influence at major fracture sites. Early Postmenopausal Intervention Cohort (EPIC) Study Group. Am J Clin Nutr. 1996;64:354–60.PubMed

Bélanger C, Luu-The V, Dupont P, et al. Adipose tissue intracrinology: potential importance of local androgen/estrogen metabolism in the regulation of adiposity. Horm Metab Res. 2002;34:737–45.PubMed

Anandacoomarasamy A, Caterson I, Sambrook P, et al. The impact of obesity on the musculoskeletal system. Int J Obes. 2008;32:211–22.

10.

Frühbeck G, Gómez-Ambrosi J, Muruzábal FJ, et al. The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endocrinol Metab. 2001;280:E827–47.PubMed

11.

Gómez-Ambrosi J, Frühbeck G. Unlocking the molecular basis of obesity. Future Lipidol. 2007;2:577–81.

12.

Oh KW, Lee WY, Rhee EJ, et al. The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men. Clin Endocrinol. 2005;63:131–8.

13.

Misra M, Miller KK, Cord J, et al. Relationships between serum adipokines, insulin levels, and bone density in girls with anorexia nervosa. J Clin Endocrinol Metab. 2007;92:2046–52.PubMed

14.

Peng XD, Xie H, Zhao Q, et al. 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.PubMed

15.

Lee NK, Sowa H, Hinoi E, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130:456–69.PubMed

16.

Frühbeck G. Intracellular signalling pathways activated by leptin. Biochem J. 2006;393:7–20.PubMed

17.

Steppan CM, Crawford DT, Chidsey-Frink KL, et al. Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept. 2000;92:73–8.PubMed

18.

Burguera B, Hofbauer LC, Thomas T, et al. Leptin reduces ovariectomy-induced bone loss in rats. Endocrinology. 2001;142:3546–53.PubMed

19.

Hamrick MW, Della-Fera MA, Choi YH, et al. Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice. J Bone Miner Res. 2005;20:994–1001.PubMed

20.

Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;100:197–207.PubMed

21.

Karsenty G. Convergence between bone and energy homeostases: leptin regulation of bone mass. Cell Metab. 2006;4:341–8.PubMed

22.

Takeda S, Elefteriou F, Levasseur R, et al. Leptin regulates bone formation via the sympathetic nervous system. Cell. 2002;111:305–17.PubMed

23.

Elefteriou F, Ahn JD, Takeda S, et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature. 2005;434:514–20.PubMed

24.

Fu L, Patel MS, Bradley A, et al. The molecular clock mediates leptin-regulated bone formation. Cell. 2005;122:803–15.PubMed

25.

Reid IR. Leptin deficiency-lessons in regional differences in the regulation of bone mass. Bone. 2004;34:369–71.PubMed

26.

Hamrick MW, Ferrari SL. Leptin and the sympathetic connection of fat to bone. Osteoporos Int. 2008;19:905–12.PubMed

27.

Gordeladze JO, Reseland JE. A unified model for the action of leptin on bone turnover. J Cell Biochem. 2003;88:706–12.PubMed

28.

Pasco JA, Henry MJ, Kotowicz MA, et al. Serum leptin levels are associated with bone mass in nonobese women. J Clin Endocrinol Metab. 2001;86:1884–7.PubMed

29.

Blain H, Vuillemin A, Guillemin F, et al. Serum leptin level is a predictor of bone mineral density in postmenopausal women. J Clin Endocrinol Metab. 2002;87:1030–5.PubMed

30.

Thomas T, Burguera B, Melton LJ, 3rd et al. Role of serum leptin, insulin, and estrogen levels as potential mediators of the relationship between fat mass and bone mineral density in men versus women. Bone. 2001;29:114–20.PubMed

31.

Kadowaki T, Yamauchi T, Kubota N. The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS. FEBS Lett. 2008;582:74–80.PubMed

32.

Berner HS, Lyngstadaas SP, Spahr A, et al. Adiponectin and its receptors are expressed in bone-forming cells. Bone. 2004;35:842–9.PubMed

33.

Shinoda Y, Yamaguchi M, Ogata N, et al. Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J Cell Biochem. 2006;99:196–208.PubMed

34.

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.PubMed

35.

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.PubMed

36.

Yamaguchi N, Kukita T, Li YJ, et al. Adiponectin inhibits induction of TNF-α/RANKL-stimulated NFATc1 via the AMPK signaling. FEBS Lett. 2008;582:451–6.PubMed

37.

Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res. 2005;309:99–109.PubMed

38.

Lenchik L, Register TC, Hsu FC, et al. Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone. 2003;33:646–51.PubMed

39.

Jürimäe J, Jürimäe T. Adiponectin is a predictor of bone mineral density in middle-aged premenopausal women. Osteoporos Int. 2007;18:1253–9.PubMed

40.

Richards JB, Valdes AM, Burling K, et al. Serum adiponectin and bone mineral density in women. J Clin Endocrinol Metab. 2007;92:1517–23.PubMed

41.

Tamura T, Yoneda M, Yamane K, et al. Serum leptin and adiponectin are positively associated with bone mineral density at the distal radius in patients with type 2 diabetes mellitus. Metabolism. 2007;56:623–8.PubMed

42.

Gómez-Ambrosi J, Frühbeck G. Evidence for the involvement of resistin in inflammation and cardiovascular disease. Curr Diabetes Rev. 2005;1:227–34.PubMed

43.

Thommesen L, Stunes AK, Monjo M, et al. Expression and regulation of resistin in osteoblasts and osteoclasts indicate a role in bone metabolism. J Cell Biochem. 2006;99:824–34.PubMed

44.

Sethi JK, Vidal-Puig A. Visfatin: the missing link between intra-abdominal obesity and diabetes? Trends Mol Med. 2005;11:344–7.PubMed

45.

Xie H, Tang SY, Luo XH, et al. Insulin-like effects of visfatin on human osteoblasts. Calcif Tissue Int. 2007;80:201–10.PubMed

46.

Rodríguez A, Catalán V, Gómez-Ambrosi J, et al. Visceral and subcutaneous adiposity: are both potential therapeutic targets for tackling the metabolic syndrome? Curr Pharm Des. 2007;13:2169–75.PubMed

47.

Wallenius V, Wallenius K, Ahren B, et al. Interleukin-6-deficient mice develop mature-onset obesity. Nat Med. 2002;8:75–9.PubMed

48.

Jilka RL, Hangoc G, Girasole G, et al. Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science. 1992;257:88–91.PubMed

49.

Franchimont N, Wertz S, Malaise M. Interleukin-6: an osteotropic factor influencing bone formation? Bone. 2005;37:601–6.PubMed

50.

Papadopoulos NG, Georganas K, Skoutellas V, et al. Correlation of interleukin-6 serum levels with bone density in postmenopausal women. Clin Rheumatol. 1997;16:162–5.PubMed

51.

Scheidt-Nave C, Bismar H, Leidig-Bruckner G, et al. Serum interleukin 6 is a major predictor of bone loss in women specific to the first decade past menopause. J Clin Endocrinol Metab. 2001;86:2032–42.PubMed

52.

Khosla S, Peterson JM, Egan K, et al. Circulating cytokine levels in osteoporotic and normal women. J Clin Endocrinol Metab. 1994;79:707–11.PubMed

53.

Bertolini DR, Nedwin GE, Bringman TS, et al. Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature. 1986;319:516–8.PubMed

54.

Wennberg P, Nordstrom P, Lorentzon R, et al. TNF-α gene polymorphism and plasma TNF-α levels are related to lumbar spine bone area in healthy female Caucasian adolescents. Eur J Endocrinol. 2002;146:629–34.PubMed

55.

Pfeilschifter J, Chenu C, Bird A, et al. Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro. J Bone Miner Res. 1989;4:113–8.PubMedCrossRef

56.

Kobayashi K, Takahashi N, Jimi E, et al. Tumor necrosis factor a stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med. 2000;191:275–86.PubMed

57.

Catalán V, Gómez-Ambrosi J, Ramírez B, et al. Proinflammatory cytokines in obesity: impact of type 2 diabetes mellitus and gastric bypass. Obes Surg. 2007;17:1464–74.PubMed

58.

Martin TJ. A skeleton key to metabolism. Nat Med. 2007;13:1021–3.PubMed

59.

Scatena M, Liaw L, Giachelli CM. Osteopontin. A multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler Thromb Vasc Biol. 2007;27:2302–9.PubMed

60.

Reinholt FP, Hultenby K, Oldberg A, et al. Osteopontin—a possible anchor of osteoclasts to bone. Proc Natl Acad Sci USA. 1990;87:4473–5.PubMed

61.

Gómez-Ambrosi J, Catalán V, Ramírez B, et al. Plasma osteopontin levels and expression in adipose tissue are increased in obesity. J Clin Endocrinol Metab. 2007;92:3719–27.PubMed

62.

Nomiyama T, Perez-Tilve D, Ogawa D, et al. Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. J Clin Invest. 2007;117:2877–88.PubMed

63.

Kiefer FW, Zeyda M, Todoric J, et al. Osteopontin expression in human and murine obesity: extensive local upregulation in adipose tissue but minimal systemic alterations. Endocrinology. 2008;149:1350–7.PubMed

64.

Calvo MS, Eyre DR, Gundberg CM. Molecular basis and clinical application of biological markers of bone turnover. Endocr Rev. 1996;17:333–68.PubMed

65.

Ferron M, Hinoi E, Karsenty G, et al. Osteocalcin differentially regulates β cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA. 2008;105:5266–70.PubMed

66.

Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89:309–19.PubMed

67.

Hofbauer LC, Schoppet M. Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA. 2004;292:490–5.PubMed

68.

Bucay N, Sarosi I, Dunstan CR, et al. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 1998;12:1260–8.PubMed

69.

Holecki M, Zahorska-Markiewicz B, Janowska J, et al. The influence of weight loss on serum osteoprotegerin concentration in obese perimenopausal women. Obesity. 2007;15:1925–9.PubMedCrossRef

70.

Gannagé-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.PubMed

71.

Jono S, Ikari Y, Shioi A, et al. Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation. 2002;106:1192–4.PubMed

72.

Browner WS, Lui LY, Cummings SR. Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J Clin Endocrinol Metab. 2001;86:631–7.PubMed

73.

Kiechl S, Schett G, Wenning G, et al. Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation. 2004;109:2175–80.PubMed

74.

An JJ, Han DH, Kim DM, et al. Expression and regulation of osteoprotegerin in adipose tissue. Yonsei Med J. 2007;48:765–72.PubMed

75.

Skopkova M, Penesova A, Sell H, et al. Protein array reveals differentially expressed proteins in subcutaneous adipose tissue in obesity. Obesity. 2007;15:2396–406.PubMedCrossRef

76.

Bradshaw AD, Sage EH. SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury. J Clin Invest. 2001;107:1049–54.PubMed

77.

Bradshaw AD, Graves DC, Motamed K, et al. SPARC-null mice exhibit increased adiposity without significant differences in overall body weight. Proc Natl Acad Sci USA. 2003;100:6045–50.PubMed

78.

Delany AM, Amling M, Priemel M, et al. Osteopenia and decreased bone formation in osteonectin-deficient mice. J Clin Invest. 2000;105:915–23.PubMed

79.

Tartare-Deckert S, Chavey C, Monthouel MN, et al. The matricellular protein SPARC/osteonectin as a newly identified factor up-regulated in obesity. J Biol Chem. 2001;276:22231–7.PubMed

80.

Chavey C, Boucher J, Monthouel-Kartmann MN, et al. Regulation of secreted protein acidic and rich in cysteine during adipose conversion and adipose tissue hyperplasia. Obesity. 2006;14:1890–7.PubMed

81.

Villareal DT, Fontana L, Weiss EP, et al. Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial. Arch Intern Med. 2006;166:2502–10.PubMed

82.

Bray GA, Greenway FL. Pharmacological treatment of the overweight patient. Pharmacol Rev. 2007;59:151–84.PubMed

83.

Pace DG, Blotner S, Guerciolini R. Short-term orlistat treatment does not affect mineral balance and bone turnover in obese men. J Nutr. 2001;131:1694–9.PubMed

84.

Gotfredsen A, Westergren Hendel H, Andersen T. Influence of orlistat on bone turnover and body composition. Int J Obes Relat Metab Disord. 2001;25:1154–60.PubMed

85.

Haney EM, Chan BK, Diem SJ, et al. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med. 2007;167:1246–51.PubMed

86.

Richards JB, Papaioannou A, Adachi JD, et al. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med. 2007;167:188–94.PubMed

87.

Pagotto U, Pasquali R. Fighting obesity and associated risk factors by antagonising cannabinoid type 1 receptors. Lancet. 2005;365:1363–4.PubMed

88.

Tam J, Trembovler V, Di Marzo V, et al. The cannabinoid CB1 receptor regulates bone formation by modulating adrenergic signaling. FASEB J. 2008;22:285–94.PubMed

89.

Bab I, Zimmer A. Cannabinoid receptors and the regulation of bone mass. Br J Pharmacol. 2008;153:182–8.PubMed

90.

Yki-Järvinen H. Thiazolidinediones. N Engl J Med. 2004;351:1106–18.PubMed

91.

Murphy CE, Rodgers PT. Effects of thiazolidinediones on bone loss and fracture. Ann Pharmacother. 2007;41:2014–8.PubMed

92.

Yaturu S, Bryant B, Jain SK. Thiazolidinedione treatment decreases bone mineral density in type 2 diabetic men. Diabetes Care. 2007;30:1574–6.PubMed

93.

Lin TH, Yang RS, Tang CH, et al. PPARγ inhibits osteogenesis via the down-regulation of the expression of COX-2 and iNOS in rats. Bone. 2007;41:562–74.PubMed

94.

Wan Y, Chong LW, Evans RM. PPAR-γ regulates osteoclastogenesis in mice. Nat Med. 2007;13:1496–503.PubMed

95.

Rosen CJ. Postmenopausal osteoporosis. N Engl J Med. 2005;353:595–603.PubMed

96.

Coates PS, Fernstrom JD, Fernstrom MH, et al. Gastric bypass surgery for morbid obesity leads to an increase in bone turnover and a decrease in bone mass. J Clin Endocrinol Metab. 2004;89:1061–5.PubMed

97.

Wucher H, Ciangura C, Poitou C, et al. Effects of weight loss on bone status after bariatric surgery: association between adipokines and bone markers. Obes Surg. 2008;18:58–65.PubMed

98.

Kral JG, Näslund E. Surgical treatment of obesity. Nat Clin Pract Endocrinol Metab. 2007;3:574–83.PubMed

99.

Saber AA, Elgamal MH, McLeod MK. Bariatric surgery: the past, present, and future. Obes Surg. 2008;18:121–8.PubMed

100.

Guney E, Kisakol G, Ozgen G, et al. Effect of weight loss on bone metabolism: comparison of vertical banded gastroplasty and medical intervention. Obes Surg. 2003;13:383–8.PubMed

101.

Olmos JM, Vazquez LA, Amado JA, et al. Mineral metabolism in obese patients following vertical banded gastroplasty. Obes Surg. 2008;18:197–203.PubMed

102.

Strauss BJ, Marks SJ, Growcott JP, et al. Body composition changes following laparoscopic gastric banding for morbid obesity. Acta Diabetol. 2003;40 Suppl 1:S266–9.PubMed

103.

von Mach MA, Stoeckli R, Bilz S, et al. Changes in bone mineral content after surgical treatment of morbid obesity. Metabolism. 2004;53:918–21.

104.

Giusti V, Gasteyger C, Suter M, et al. Gastric banding induces negative bone remodelling in the absence of secondary hyperparathyroidism: potential role of serum C telopeptides for follow-up. Int J Obes. 2005;29:1429–35.

105.

Goode LR, Brolin RE, Chowdhury HA, et al. Bone and gastric bypass surgery: effects of dietary calcium and vitamin D. Obes Res. 2004;12:40–7.PubMed

106.

Ott MT, Fanti P, Malluche HH, et al. Biochemical evidence of metabolic bone disease in women following Roux-Y gastric bypass for morbid obesity. Obes Surg. 1992;2:341–8.PubMed

107.

El-Kadre LJ, Rocha PRS, de Almeida Tinoco AC, et al. Calcium metabolism in pre- and postmenopausal morbidly obese women at baseline and after laparoscopic Roux-en-Y gastric bypass. Obes Surg. 2004;14:1062–6.PubMed

108.

Riedt CS, Brolin RE, Sherrell RM, et al. True fractional calcium absorption is decreased after Roux-en-Y gastric bypass surgery. Obes Res. 2006;14:1940–8.

109.

Schweitzer DH. Mineral metabolism and bone disease after bariatric surgery and ways to optimize bone health. Obes Surg. 2007;17:1510–6.PubMed

110.

Compher CW, Badellino KO, Boullata JI. Vitamin D and the bariatric surgical patient: a review. Obes Surg. 2008;18:220–4.PubMed

111.

Duran de Campos C, Dalcanale L, Pajecki D, et al. Calcium intake and metabolic bone disease after eight years of Roux-en-Y gastric bypass. Obes Surg. 2008;18:386–90.PubMed

112.

Johnson JM, Maher JW, Samuel I, et al. Effects of gastric bypass procedures on bone mineral density, calcium, parathyroid hormone, and vitamin D. J Gastrointest Surg. 2005;9:1106–10.PubMed

113.

Goldner WS, Stoner JA, Thompson J, et al. Prevalence of vitamin D insufficiency and deficiency in morbidly obese patients: a comparison with non-obese controls. Obes Surg. 2008;18:145–50.PubMed

114.

Newbury L, Dolan K, Hatzifotis M, et al. Calcium and vitamin D depletion and elevated parathyroid hormone following biliopancreatic diversion. Obes Surg. 2003;13:893–5.PubMed

115.

Slater GH, Ren CJ, Siegel N, et al. Serum fat-soluble vitamin deficiency and abnormal calcium metabolism after malabsorptive bariatric surgery. J Gastrointest Surg. 2004;8:48–55.PubMed

116.

Moreiro J, Ruiz O, Perez G, et al. Parathyroid hormone and bone marker levels in patients with morbid obesity before and after biliopancreatic diversion. Obes Surg. 2007;17:348–54.PubMed

Title: The Bone-Adipose Axis in Obesity and Weight Loss
Authors: J. Gómez-Ambrosi
A. Rodríguez
V. Catalán
G. Frühbeck
Publication date: 01-09-2008
Publisher: Springer-Verlag
Published in: Obesity Surgery / Issue 9/2008
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI: https://doi.org/10.1007/s11695-008-9548-1

At a glance: The STEP trials

Springer Medicine

The Bone-Adipose Axis in Obesity and Weight Loss

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 9/2008

Primary Results of Laparoscopic Mini-Gastric Bypass in a French Obesity-Surgery Specialized University Hospital

Laparoscopic Sleeve Gastrectomy—Volume and Pressure Assessment

The Effect of Laparoscopic Gastric Banding Surgery on Plasma Levels of Appetite-Control, Insulinotropic, and Digestive Hormones

Pregnancy in Formerly Type 2 Diabetes Obese Women Following Biliopancreatic Diversion for Obesity

Gastric Cancer After Laparoscopic Adjustable Gastric Banding

Laparoscopic Gastric Rebanding for Slippage with Pouch Dilation: Results on 29 Consecutive Patients