Clin Osteol 2013; 18(3): 82-86
Adipose tissue and the skeleton - new insights into pathogenesis of osteoporosisOriginal contributions
Osteoporosis and obesity are chronic conditions with increasing prevalence rates. For a long time, they were considered separate en tities rarely found in a single individual. Recently, however, there has been growing evidence from clinical studies suggesting impor tant interactions between adipose tissue and the skeleton. Adipose tissue may influence bone remodeling by three mechanisms: (1) se cretion of endocrine cytokines and growth factors directly targeting the bone, (2) production of adipokines affecting the CNS and thus changing sympathetic impulses into the bone, and (3) paracrine effects on the adjacent bone cells (adipocytes in bone marrow). Excess subcutaneous fat contributes to maintaining cortical bone mass. On the other side, visceral fat gain is associated with a loss in trabe cular bone mass. Individuals with metabolic syndrome, and thus with excess visceral fat, are at a higher risk of fractures despite their normal BMD values. Whether obesity is a risk factor for osteoporosis remains an open question.
Keywords: bone, fat, obesity, osteoporosis, osteocalcin, insulin
Published: December 11, 2013 Show citation
References
- Fulzele K, Riddle RC, Digirolamo DJ et al. Insulin receptor signaling in os lasts regulates postnatal bone acquisition and body composition. Cell 2010; 142:309-319.
Go to original source... - Ahima RS, Osei SY. Leptin signaling. Physiol behav 2004;81:223-241.
Go to original source... - Myers MG, Cowley MA, Munzberg H. Mechanisms of leptin action and leptin resistence. Annu Rev Physiol 2008;70:537-556.
Go to original source... - Ducy P, Amling M, Takeda S et al. Leptin inhibits bone formation thr potalamic relay: a central control of bone mass. Cell 2000;100:197-207.
Go to original source... - Bjornholm M, Munzberg H, Leshan RL et al. Mice lacking inhibitory leptin re ceptor sig 1354-1360.
- Shi Y, Yadav VK, Suda N et al. Dissociation of the neuronal regulation of b mass and energy metabolism by leptin in vivo. Proc Natl Acad Sci USA 2008;105: 20529-33.
Go to original source... - Karsenty G, Ferron M. Nature 2012;481:314-320.
Go to original source... - Takeda S, Elefteriou F, Levasseur R et al. Leptin regulates bone formation via sympathetic nervous systém. Cell 2002;111:305-317.
Go to original source... - Yadav VK, Oury F, Suda N et al. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell 2009;138: 976-989.
Go to original source... - Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest 2011;121:2094-2101.
Go to original source... - Shea MK, Gundberg CM, Meigs JB et al. Gamma-carboxylation of osteocalcin and insulin resistence in older men and women. Am J Clin Nutr 2009;90: 1230-1235.
Go to original source... - Ferron M, Wei J, Yoshizawa T et al. Insulin signaling in osteoblasts integrates ne remodeling and energy metabolism. Cell 2010;142:296-308.
Go to original source... - Lee NK, Sowa H, Hinoi E et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007;130:456^69.
Go to original source... - Kayath MJ, Dib SA, Vieira JG. Prevalence and magnitude of osteopenia associa ted with insulin-dependent diabetes mellitus. J Diabetes Complications 1994;8: 97-104.
Go to original source... - Tuorninen JT, Impivaara O, Puukka P, Ronnemaa T. Bone mineral density in patiens with type 1 and type 2 diabetes. Diabetes care 1999;22:1196-1200.
Go to original source... - Motyl KJ, McCauley LK, McCabe LR. Amelioration of type 1 diabetes-induced osteoporosis by parathyroid hormone is associated with improved osteoblast sur vival. J Cell Physiol 2012;227:1326-1334.
Go to original source... - Darlington GJ, Ross SE, MacDougald OA The role of C/EBP genes in adipocyte differentiation. J Biol Chem 1998;273:30057-3060.
Go to original source... - Tanakan T, Yoshida N, Kishimoto T, Akira S. Defective adipocyte differen in mice lacking the C/EBPbeta nad/or C/EBPdelta gene. EMBO J 1997;16: 7432-7443.
Go to original source... - Flemmer M, Scott J. Mechanism of action of thiazolidinediones. Curr Opin Investig Drugs 2001;2:1564-1567.
- Kahn SE, Haffner SM, Heise MA et al. Glycemic durability of ro formin, or glyburide monotherapy. N Engl J Med 2006;355:2427-2443.
Go to original source... - Grey A, Bolland M, Gamble G et al. The peroxisome proliferator-activated rec tor-gamma agonist rosiglitasone decreases bone formation and bone mineral den sity in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab 2007;92:1305-1310.
Go to original source... - Bianco P, Riminucci M, Gronthos S, Robey PG. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem cells 2001;19:180-192.
Go to original source... - Jiang V, Jahagirdar BN, Reinhardt RL et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002;418:41-49.
Go to original source... - Minguell JJ, Erices A, Conget P. Mesenchymal stem cells. Exp Biol Med (Maywood) 2001;226:507-520.
Go to original source... - Shockley KR, Lazarenko OP, Czernik PJ, Rosen CJ, Churchill GA, Lecka-Czernik B. PPARgamma2 nuclear receptor controls multiple regulatory pathways of oste oblast differentiation from marrow mesenchymal stem cells. J Cell Biochem 2009;106:232-246.
Go to original source... - Lecka-Czernik B, Gubrij I, Moerman EJ et al. Inhibition of Osf2/Cbfa1 expre on and terminal osteoblast differentiation by PPRAgamma2. J Cell Biochem 1999;74:357-371.
Go to original source... - Cheng SI, Shao JS, Charlton-Kachigian N, Loewy AP, TowlerDA MSX2 promo tes osteogenesis and supresses adipogenic differentiation of multipotent mesen chymal progenitors. J Biol Chem 2003;278:45969^5977.
Go to original source... - Ichida F, Nishimura R, Hata K et al. Reciprocal roles of MSX2 in regulation osteoblast and adipocyte differentiation. J Biol Chem 2004;279:34015-34022.
Go to original source... - Kang S, Bennet CN, Gerin I, Rapp La, Henkenson KD, Macdougald OA Wnt sig naling stimulates osteoblastogenesis of mesenchymal precursors by suppressing CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated re ceptor gamma. J Biol Chem 2007;282:14515-14524.
Go to original source... - Moerman EJ, Teng K, Lipschitz DA, Lecka-Czernik B. Aging activates adipoge nic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell 2004;3:379-389.
Go to original source... - Akune T, Ohba S, Kamekura S et al. PPARgamma insufficiency enhances osteo genesis through o 2004;113:846-855.
- Cock TA, Back J, Elefteriou F et al. Enhanced bone formation in lipod PPRAgamma (hyp/hyp) mice relocates haematopoiesis to the spleen. EMBO Rep 2004;5:1007-1012.
Go to original source... - Li M, Pan LC, Simmons HA et al. Surface-specific effec nist, darglitazone, on bone in mice. Bone 2006;39:796-806.
Go to original source... - Sottile V, Seuwen K, Kneissel M. Enhanced marrow adipogenesis and sorption in estrogen-dependent rats treated with the PPARgamma agonist BRL49653 (rosiglitazone). Calcif Tissue Int 2004;75:329-337.
Go to original source... - Wan Y, Chong LW, Evans RM. PPAR-gamma regulates osteoclastogenesis in ce. Nat Med 2007;13:1496-1503.
Go to original source... - Wei W, Wang X, Yang M, Smith LC, Dechow PC, Wan Y. PGC1beta mediates PPARgamma activation of osteoclastogenesis and rosiglitazone-induced bone loss. Cell Metab 2010;11:503-516.
Go to original source... - Lazarenko OP, Rzonca SO, Hogue WR, Swain FL, Suva LJ, Lecka-Czernik B. Rosiglitazone induced decreases in bone mass aged bone. Endocrinology 2007;148:2669-2680.
Go to original source... - Kawai M, Rosen CJ. Insulin-like gro men. Pediatr Nephrol 2009;24:1277-1285.
Go to original source... - Di lorgi N, Mittelman SD, Gilsanz V. Differential effect of marrow adiposity visceral and subcutaneous fat on cardiovascular risk in young healthy adults. Int J Obes (Lond) 2008;32:1854-1860.
Go to original source... - Bredella MA, Torriani M, Ghomi Rh et al. Vertebral bone marrow fat is positi ly associated with visceral fat and inversely associated with IGF-1 in obese wo men. Obesity (Silver Spring) 2011;19:49-53.
Go to original source... - Krings A, Rahman S, Huang S, Lu Y, Czernik PJ, Lecka-Czernik B. Bone marrow fat has brown adipose tissue ch diabetes. Bone 2012;50:546-552.
Go to original source... - Dazzi F, Ramasary R, Glennie S, Jones SP, Roberts stem cells in haemopoiesis. Blood Rev 2006;20:161-171.
Go to original source... - Gimble JM, Zvonic S, Floyd ZE, K fat. J Cell Biochem 2006;98:251-266.
Go to original source... - Rozman C, Feliu E, Berga L, Reverter JC, Climent C, Ferran MJ. Age-related riations of fat tissue fraction in normal human bone marrow depend both on size and number of adipocytes: a stereological study. Exp Hematol 1989;17:34-37.
- Meunier P, Aaron J, Edouard C, Vignon G. Osteoporosis and the replacement of cell population of the marrow by adipose tissue. A qu bone biopsies. Clin Orthop Relat Res 1971;80:147-154.
Go to original source... - Wagner W, Bork S, Leppendinger G et al. How to trac chymal stromal cells? Aging (Albany NY) 2010;2:224-230.
Go to original source... - Nuttall ME, Gimble JM. Controlling the balance between osteoblastogen adipogenesis and consequent therapeutic implications. Curr Opin Pharmacol 2004;4:290-294.
Go to original source... - Rodriguez JP, Garat S, Gajardo H, Pino AM, Seitz G. Abnormal osteogenesis in osteoporotic patients is refle J Cell Biochem 1999;75:414^23.
Go to original source... - Takahashi Y, Okimura Y, Mizuno I et al. Leptin induces mitogen-activated prot kinase-dependent proliferation of C3H10T1/2 cells. J Biol Chem 1997;272: 12897-12900.
Go to original source... - Thomas T, Gori F, Khosla S, Jensen MD, Burguera B, Ribbs BL. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhi bit differentiation to adipocytes. Endocrinology 1999;140:1630-1638.
Go to original source... - Reseland JE, Syversen U, Bakke I et al. Leptin is expressed in and secreted primary cultures of human osteoblasts and promotes bone mineralization. J Bone Miner Res 2001; 16:1426-1433.
Go to original source... - Hess R, Pino AM, Rios S, Fernandez M, Rodriguez JP. High affinity leptin re ceptors are present in human mesenchymal stem cells (MSCs) derived from con trol and osteoporotic donors. J Cell Biochem 2005;94:50-57.
Go to original source... - Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M. Adipocyte tissue volume in bone marrow is increased with aging in patients with osteoporosis. Biogerontology 2001;2:165-171.
Go to original source... - Gambacciani M, Ciaponi M, Cappagli B et al. Body weight, body fat distributi and hormonal replacement therapy in early postmenopausal women. J Clin Endocrinol Metab 1997;82:414^17.
Go to original source... - Pino AM, Rodriguez JM, Rios S et al. Aromatase activity of human mesenchymal stem cells is stimulated by early differentiation, vitamin D and leptin. J Endocri 2006;191:715-725.
Go to original source... - Heim M, Frank O, Kampmann G et al. The phytoestrogen genistein enhances os teogenesis and represses adipogenic differentiation of human primary bone mar row stromal cells. Endocrinology 2004;145:848-859.
Go to original source... - Janssen JM, Bland R, Hewison M et al. Estradiol formation by human osteoblasts via multiple pathways: relation with osteoblast function. J Cell Biochem 1999; 75:528-537.
Go to original source... - Sasano H, Uzuki M, Sawai T et al. Aromatase in human bone tissue. J Bone Miner Res 1997;12:1416-1423.
Go to original source... - Compston J. Local biosynthesis of sex steroids in bone. J Clin Endocrinol M 2002;87:5398-5400.
Go to original source... - Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS. Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proc Natl Acad Sci USA 2000;97:12729-12734.
Go to original source... - Okazaki R, Inoue D, Shibata M et al. Estrogen promotes early osteoblast di rentiation and inhibits adipocyty differentiation in mouse bone marrow stromal cell lines tha 143:2349-2356.
- Riggs BL, Khosla S, Melton LJ 3rd. Sex steroids and the construction and con vation of the adult skeleton. Endocr Rev 2002;23:279-302.
Go to original source... - Gennari L, Nuti R, Bilezikian JP. Aromatase activity and bone homeostasis in men. J Clin Endocrinol Metab 2004;89:5898-5907.
Go to original source... - von Muhlen D, Sahi S, Jassal SK, Svartberg J, Barrett-Connor E. Ass ween the metabolic syndrome and bone health in older men and women: the Rancho Bernardo Study. Osteoporosis Int 2007;18:1337-1344.
Go to original source... - Javaid MK, Prieto-Alhambra D, Lui LY et al. Self-reported weight at birth pred measures of femoral size but not volumetric BMD in elderly men: MrOS. J Bone Miner Res 2011;26:1802-1807.
Go to original source... - Řehořková P, Ihlička V, Živný P. Je obezita u mužů jedním z rizikových faktorů pro vznik osteoporotické fraktury? Osteol bull 2008;13:9-11.
- Bužga M, Šmajstrla V, Bortlík L, Švagera Z, Závacká I, Holéczy P. Překvapivě nízká denzita u obézních pacientů podstupujících bariatrický chirurgický výkon. Osteol Bull 2012;17(2):43-49.

