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Leptin and Bone

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Leptin

Abstract

Bone grows then constantly renews itself during adulthood through the succession of cycles of formation by osteoblasts and resorption by osteoclasts. This is a costly process in terms of energy that needs to be coordinated with the amount of available resources, suggesting that bone and appetite and/or energy metabolisms could share common regulator(s). Searching for such molecule(s) identified leptin as a major inhibitor of bone mass accrual that uses central relays to fulfill this function. One of them involves a brain serotonin-dependent regulation of the sympathetic tone, which acts as an inhibitor of bone formation via CREB and the molecular clock and as a positive regulator of bone resorption through an ATF4-Rankl mechanism that takes place in osteoblasts. In contrast, the second mediator of leptin central effect on bone mass accrual, CART, inhibits bone resorption. This chapter details the molecular bases and biological relevance of this regulation of bone mass accrual by leptin.

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References

  1. Kronenberg HM. Developmental regulation of the growth plate. Nature. 2003;423(6937):332–6.

    CAS  PubMed  Google Scholar 

  2. Karsenty G, Wagner EF. Reaching a genetic and molecular understanding of skeletal development. Dev Cell. 2002;2(4):389–406.

    CAS  PubMed  Google Scholar 

  3. Ducy P, Schinke T, Karsenty G. The osteoblast: a sophisticated fibroblast under central surveillance. Science. 2000;289:1501–4.

    CAS  PubMed  Google Scholar 

  4. Teitelbaum SL. Bone resorption by osteoclasts. Science. 2000;289:1504–8.

    CAS  PubMed  Google Scholar 

  5. Karsenty G, Ferron M. The contribution of bone to whole-organism physiology. Nature. 2012;481(7381):314–20.

    CAS  PubMed  Google Scholar 

  6. Denver RJ, Bonett RM, Boorse GC. Evolution of leptin structure and function. Neuroendocrinology. 2011;94(1):21–38.

    CAS  PubMed  Google Scholar 

  7. Holbrook TL, Barrett-Connor E. The association of lifetime weight and weight control patterns with bone mineral density in an adult community. Bone Miner. 1993;20(2):141–9. Epub 1993/02/01.

    CAS  PubMed  Google Scholar 

  8. Legroux-Gerot I, Vignau J, Collier F, Cortet B. Bone loss associated with anorexia nervosa. Joint Bone Spine. 2005;72(6):489–95. Epub 2005/10/26.

    PubMed  Google Scholar 

  9. Legroux-Gerot I, Vignau J, D’Herbomez M, Collier F, Marchandise X, Duquesnoy B, et al. Evaluation of bone loss and its mechanisms in anorexia nervosa. Calcif Tissue Int. 2007;81(3):174–82. Epub 2007/08/02.

    CAS  PubMed  Google Scholar 

  10. Misra M, Klibanski A. Bone health in anorexia nervosa. Curr Opin Endocrinol Diabetes Obes. 2011;18(6):376–82. doi:10.1097/MED.0b013e32834b4bdc.

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Riggs BL, Khosla S, Melton 3rd LJ. A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res. 1998;13(5):763–73.

    CAS  PubMed  Google Scholar 

  12. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;100(2):197–207.

    CAS  PubMed  Google Scholar 

  13. Friedman JM. Obesity in the new millennium. Nature. 2000;404:632–4.

    CAS  PubMed  Google Scholar 

  14. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395(6704):763–70.

    CAS  PubMed  Google Scholar 

  15. Spiegelman BM, Flier JS. Adipogenesis and obesity: rounding out the big picture. Cell. 1996;87(3):377–89.

    CAS  PubMed  Google Scholar 

  16. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, et al. Identification and expression cloning of a leptin receptor OB-R. Cell. 1995;83(7):1263–71.

    CAS  PubMed  Google Scholar 

  17. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.

    CAS  PubMed  Google Scholar 

  18. Ahima RS. Body fat, leptin, and hypothalamic amenorrhea. N Engl J Med. 2004;351(10):959–62.

    CAS  PubMed  Google Scholar 

  19. Baldock PA, Sainsbury A, Allison S, Lin EJ, Couzens M, Boey D, et al. Hypothalamic control of bone formation: distinct actions of leptin and y2 receptor pathways. J Bone Miner Res. 2005;20(10):1851–7.

    CAS  PubMed  Google Scholar 

  20. Vaira S, Yang C, McCoy A, Keys K, Xue S, Weinstein EJ, et al. Creation and preliminary characterization of a leptin knockout rat. Endocrinology. 2012;153(11):5622–8. Epub 2012/09/06.

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Solomon G, Atkins A, Shahar R, Gertler A, Monsonego-Ornan E. Effect of peripherally administered leptin antagonist on whole body metabolism and bone microarchitecture and biomechanical properties in the mouse. Am J Physiol Endocrinol Metab. 2014;306(1):E14–27. Epub 2013/10/31.

    CAS  PubMed  Google Scholar 

  22. Ahima RS, Kelly J, Elmquist JK, Flier JS. Distinct physiologic and neuronal responses to decreased leptin and mild hyperleptinemia. Endocrinology. 1999;140(11):4923–31. Epub 1999/10/28.

    CAS  PubMed  Google Scholar 

  23. Reid IR. Glucocorticoid osteoporosis–mechanisms and management. Eur J Endocrinol. 1997;137(3):209–17. Epub 1997/10/23.

    CAS  PubMed  Google Scholar 

  24. Reid IR. Steroid-induced osteoporosis. Osteoporos Int. 1997;7 Suppl 3:S213–6. Epub 1997/01/01.

    PubMed  Google Scholar 

  25. Suva LJ, Gaddy D, Perrien DS, Thomas RL, Findlay DM. Regulation of bone mass by mechanical loading: microarchitecture and genetics. Curr Osteoporos Rep. 2005;3(2):46–51. Epub 2005/07/23.

    PubMed  Google Scholar 

  26. Ahn JD, Dubern B, Lubrano-Berthelier C, Clement K, Karsenty G. Cart overexpression is the only identifiable cause of high bone mass in melanocortin 4 receptor deficiency. Endocrinology. 2006;147(7):3196–202.

    CAS  PubMed  Google Scholar 

  27. Moitra J, Mason MM, Olive M, Krylov D, Gavrilova O, Marcus-Samuels B, et al. Life without white fat: a transgenic mouse. Genes Dev. 1998;12(20):3168–81. Epub 1998/10/24.

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Elefteriou F, Takeda S, Ebihara K, Magre J, Patano N, Kim CA, et al. Serum leptin level is a regulator of bone mass. Proc Natl Acad Sci U S A. 2004;101(9):3258–63.

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet. 1996;12(3):318–20.

    CAS  PubMed  Google Scholar 

  30. Shi Y, Yadav VK, Suda N, Liu XS, Guo XE, Myers Jr MG, et al. Dissociation of the neuronal regulation of bone mass and energy metabolism by leptin in vivo. Proc Natl Acad Sci U S A. 2008;105:20529.

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Iwaniec UT, Boghossian S, Lapke PD, Turner RT, Kalra SP. Central leptin gene therapy corrects skeletal abnormalities in leptin-deficient ob/ob mice. Peptides. 2007;28(5):1012–9. Epub 2007/03/10.

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Pogoda P, Egermann M, Schnell JC, Priemel M, Schilling AF, Alini M, et al. Leptin inhibits bone formation not only in rodents, but also in sheep. J Bone Miner Res. 2006;21(10):1591–9.

    CAS  PubMed  Google Scholar 

  33. Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, et al. Leptin regulates bone formation via the sympathetic nervous system. Cell. 2002;111(3):305–17.

    CAS  PubMed  Google Scholar 

  34. Sato S, Hanada R, Kimura A, Abe T, Matsumoto T, Iwasaki M, et al. Central control of bone remodeling by neuromedin U. Nat Med. 2007;13:1234.

    CAS  PubMed  Google Scholar 

  35. Bjorbak C, Lavery HJ, Bates SH, Olson RK, Davis SM, Flier JS, et al. SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J Biol Chem. 2000;275(51):40649–57.

    CAS  PubMed  Google Scholar 

  36. Bjornholm M, Munzberg H, Leshan RL, Villanueva EC, Bates SH, Louis GW, et al. Mice lacking inhibitory leptin receptor signals are lean with normal endocrine function. J Clin Invest. 2007;117(5):1354–60.

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Könner AC, Brüning Jens C. Selective insulin and leptin resistance in metabolic disorders. Cell Metab. 2012;16(2):144–52.

    PubMed  Google Scholar 

  38. Mark AL. Selective leptin resistance revisited. Am J Physiol Regul Integr Comp Physiol. 2013;305(6):R566–81.

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Motyl KJ, Rosen CJ. Understanding leptin-dependent regulation of skeletal homeostasis. Biochimie. 2012;94(10):2089–96.

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Steppan CM, Crawford DT, Chidsey-Frink KL, Ke H, Swick AG. Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept. 2000;92(1–3):73–8.

    CAS  PubMed  Google Scholar 

  41. Cornish J, Callon KE, Bava U, Lin C, Naot D, Hill BL, et al. Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo. J Endocrinol. 2002;175(2):405–15.

    CAS  PubMed  Google Scholar 

  42. Ding L, Saunders TL, Enikolopov G, Morrison SJ. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. 2012;481(7382):457–62.

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Yadav VK, Oury F, Suda N, Liu ZW, Gao XB, Confavreux C, et al. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell. 2009;138(5):976–89.

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Balthasar N, Coppari R, McMinn J, Liu SM, Lee CE, Tang V, et al. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron. 2004;42(6):983–91.

    CAS  PubMed  Google Scholar 

  45. Oury F, Karsenty G. Towards a serotonin-dependent leptin roadmap in the brain. Trends Endocrinol Metab. 2011;22(9):382–7. Epub 2011/05/24.

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Ducy P, Karsenty G. The two faces of serotonin in bone biology. J Cell Biol. 2010;191(1):7–13. Epub 2010/10/06.

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Hay-Schmidt A, Helboe L, Larsen PJ. Leptin receptor immunoreactivity is present in ascending serotonergic and catecholaminergic neurons of the rat. Neuroendocrinology. 2001;73(4):215–26. Epub 2001/05/08.

    CAS  PubMed  Google Scholar 

  48. Scott MM, Lachey JL, Sternson SM, Lee CE, Elias CF, Friedman JM, et al. Leptin targets in the mouse brain. J Comp Neurol. 2009;514(5):518–32. Epub 2009/04/08.

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Collin M, Håkansson-Ovesjö M-L, Misane I, Ögren SO, Meister B. Decreased 5-HT transporter mRNA in neurons of the dorsal raphe nucleus and behavioral depression in the obese leptin-deficient ob/ob mouse. Mol Brain Res. 2000;81(1–2):51–61.

    CAS  PubMed  Google Scholar 

  50. Heath MJ, Hen R. Serotonin receptors. Genetic insights into serotonin function. Curr Biol. 1995;5(9):997–9. Epub 1995/09/01.

    CAS  PubMed  Google Scholar 

  51. Berger M, Gray JA, Roth BL. The expanded biology of serotonin. Annu Rev Med. 2009;60:355–66. Epub 2009/07/28.

    CAS  PubMed  Google Scholar 

  52. Flomen R, Knight J, Sham P, Kerwin R, Makoff A. Evidence that RNA editing modulates splice site selection in the 5‐HT2C receptor gene. Nucleic Acids Res. 2004;32(7):2113–22.

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Drago A, Serretti A. Focus on HTR2C: a possible suggestion for genetic studies of complex disorders. Am J Med Genet B Neuropsychiatr Genet. 2009;150B(5):601–37.

    CAS  PubMed  Google Scholar 

  54. Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, et al. Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature. 1997;387(6630):303–8.

    CAS  PubMed  Google Scholar 

  55. Oury F, Yadav VK, Wang Y, Zhou B, Liu XS, Guo XE, et al. CREB mediates brain serotonin regulation of bone mass through its expression in ventromedial hypothalamic neurons. Genes Dev. 2010;24(20):2330–42. Epub 2010/10/19.

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Coleman DL. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia. 1973;9(4):294–8.

    CAS  PubMed  Google Scholar 

  57. Bray GA, York DA. The MONA LISA hypothesis in the time of leptin. Recent Prog Horm Res. 1998;53:95–117.

    CAS  PubMed  Google Scholar 

  58. Kajimura D, Hinoi E, Ferron M, Kode A, Riley KJ, Zhou B, et al. Genetic determination of the cellular basis of the sympathetic regulation of bone mass accrual. J Exp Med. 2011;208(4):841–51. Epub 2011/03/30.

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Bonnet N, Benhamou CL, Beaupied H, Laroche N, Vico L, Dolleans E, et al. Doping dose of salbutamol and exercise: deleterious effect on cancellous and cortical bones in adult rats. J Appl Physiol. 2007;102(4):1502–9.

    CAS  PubMed  Google Scholar 

  60. Bonnet N, Benhamou CL, Brunet-Imbault B, Arlettaz A, Horcajada MN, Richard O, et al. Severe bone alterations under β2 agonist treatments: bone mass, microarchitecture and strength analyses in female rats. Bone. 2005;37(5):622–33.

    CAS  PubMed  Google Scholar 

  61. Kondo H, Togari A. Continuous treatment with a low-dose β-agonist reduces bone mass by increasing bone resorption without suppressing bone formation. Calcif Tissue Int. 2011;88(1):23–32.

    CAS  PubMed  Google Scholar 

  62. Bonnet N, Laroche N, Vico L, Dolleans E, Benhamou CL, Courteix D. Dose effects of propranolol on cancellous and cortical bone in ovariectomized adult rats. J Pharmacol Exp Ther. 2006;318(3):1118–27.

    CAS  PubMed  Google Scholar 

  63. Bonnet N, Benhamou CL, Malaval L, Goncalves C, Vico L, Eder V, et al. Low dose beta-blocker prevents ovariectomy-induced bone loss in rats without affecting heart functions. J Cell Physiol. 2008;217(3):819–27.

    CAS  PubMed  Google Scholar 

  64. Thim L, Kristensen P, Larsen PJ, Wulff BS. CART, a new anorectic peptide. Int J Biochem Cell Biol. 1998;30(12):1281–4.

    CAS  PubMed  Google Scholar 

  65. Thim L, Kristensen P, Nielsen PF, Wulff BS, Clausen JT. Tissue-specific processing of cocaine- and amphetamine-regulated transcript peptides in the rat. Proc Natl Acad Sci. 1999;96(6):2722–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Wierup N, Kuhar M, Nilsson BO, Mulder H, Ekblad E, Sundler F. Cocaine- and amphetamine-regulated transcript (CART) is expressed in several islet cell types during rat development. J Histochem Cytochem. 2004;52(2):169–77.

    CAS  PubMed  Google Scholar 

  67. Vrang N, Kristensen P, Tang-Christensen M, Larsen PJ. Effects of leptin on arcuate pro-opiomelanocortin and cocaine-amphetamine-regulated transcript expression are independent of circulating levels of corticosterone. J Neuroendocrinol. 2002;14(11):880–6.

    CAS  PubMed  Google Scholar 

  68. Kristensen P, Judge ME, Thim L, Ribel U, Christjansen KN, Wulff BS, et al. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature. 1998;393(6680):72–6.

    CAS  PubMed  Google Scholar 

  69. Elias CF, Lee C, Kelly J, Aschkenasi C, Ahima RS, Couceyro PR, et al. Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron. 1998;21(6):1375–85.

    CAS  PubMed  Google Scholar 

  70. Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature. 2005;434(7032):514–20.

    CAS  PubMed  Google Scholar 

  71. Mounzih K, Lu R, Chehab FF. Leptin treatment rescues the sterility of genetically obese ob/ob males. Endocrinology. 1997;138(3):1190–3.

    CAS  PubMed  Google Scholar 

  72. Pierroz D, Baldock PA, Bouxsein ML, Ferrari S. Low cortical bone mass in mice lacking beta 1 and beta 2 adrenergic recptors is associated with low bone formation and circulating IGF-1. J Bone Miner Res. 2006;21 Suppl 1:S26 (Abstract no 1091).

    Google Scholar 

  73. Dhillon H, Zigman JM, Ye C, Lee CE, McGovern RA, Tang V, et al. Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron. 2006;49(2):191–203.

    CAS  PubMed  Google Scholar 

  74. Benovic JL, Bouvier M, Caron MG, Lefkowitz RJ. Regulation of adenylyl cyclase-coupled beta-adrenergic receptors. Annu Rev Cell Biol. 1988;4:405–28.

    CAS  PubMed  Google Scholar 

  75. Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schutz G, et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell. 2008;135(5):825–37.

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Kode A, Mosialou I, Silva BC, Rached MT, Zhou B, Wang J, et al. FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin. J Clin Invest. 2012;122(10):3490–503. Epub 2012/09/05.

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Russell JE, Simmons DJ, Huber B, Roos BA. Meal timing as a zeitgeber for skeletal deoxyribonucleic acid and collagen synthesis rhythms. Endocrinology. 1983;113(6):2035–42.

    CAS  PubMed  Google Scholar 

  78. Nielsen HK. Circadian and circatrigintan changes in osteoblastic activity assessed by serum osteocalcin. Physiological and methodological aspects. Dan Med Bull. 1994;41(2):216–27. Epub 1994/04/01.

    CAS  PubMed  Google Scholar 

  79. Szulc P, Seeman E, Delmas PD. Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int. 2000;11(4):281–94. Epub 2000/08/06.

    CAS  PubMed  Google Scholar 

  80. Fu L, Patel MS, Bradley A, Wagner EF, Karsenty G. The molecular clock mediates leptin-regulated bone formation. Cell. 2005;122(5):803–15.

    CAS  PubMed  Google Scholar 

  81. Thomas T, Gori F, Khosla S, Jensen MD, Burguera B, Riggs BL. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology. 1999;140(4):1630–8.

    CAS  PubMed  Google Scholar 

  82. Gordeladze JO, Drevon CA, Syversen U, Reseland JE. Leptin stimulates human osteoblastic cell proliferation, de novo collagen synthesis, and mineralization: impact on differentiation markers, apoptosis, and osteoclastic signaling. J Cell Biochem. 2002;85(4):825–36.

    CAS  PubMed  Google Scholar 

  83. Kim GS, Hong JS, Kim SW, Koh JM, An CS, Choi JY, et al. Leptin induces apoptosis via ERK/cPLA2/cytochrome c pathway in human bone marrow stromal cells. J Biol Chem. 2003;278(24):21920–9.

    CAS  PubMed  Google Scholar 

  84. Scheller EL, Leinninger GM, Hankenson KD, Myers JMG, Krebsbach PH. Ectopic expression of Col2.3 and Col3.6 promoters in the brain and association with leptin signaling. Cells Tissues Organs. 2011;194(2–4):268–73.

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Dacquin R, Starbuck M, Schinke T, Karsenty G. Mouse alpha1(I)-collagen promoter is the best known promoter to drive efficient Cre recombinase expression in osteoblast. Dev Dyn. 2002;224(2):245–51.

    CAS  PubMed  Google Scholar 

  86. Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet. 2003;4(8):638–49.

    CAS  PubMed  Google Scholar 

  87. Yang X, Matsuda K, Bialek P, Jacquot S, Masuoka HC, Schinke T, et al. ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome. Cell. 2004;117(3):387–98.

    CAS  PubMed  Google Scholar 

  88. Elefteriou F, Benson MD, Sowa H, Starbuck M, Liu X, Ron D, et al. ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae. Cell Metab. 2006;4(6):441–51.

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Iwamoto I, Douchi T, Kosha S, Murakami M, Fujino T, Nagata Y. Relationships between serum leptin level and regional bone mineral density, bone metabolic markers in healthy women. Acta Obstet Gynecol Scand. 2000;79(12):1060–4.

    CAS  PubMed  Google Scholar 

  90. Sato M, Takeda N, Sarui H, Takami R, Takami K, Hayashi M, et al. Association between serum leptin concentrations and bone mineral density, and biochemical markers of bone turnover in adult men. J Clin Endocrinol Metab. 2001;86(11):5273–6.

    CAS  PubMed  Google Scholar 

  91. Blum M, Harris SS, Must A, Naumova EN, Phillips SM, Rand WM, et al. Leptin, body composition and bone mineral density in premenopausal women. Calcif Tissue Int. 2003;73(1):27–32. Epub 2003/09/26.

    CAS  PubMed  Google Scholar 

  92. Rauch F, Blum WF, Klein K, Allolio B, Schonau E. Does leptin have an effect on bone in adult women? Calcif Tissue Int. 1998;63(6):453–5. Epub 1998/11/18.

    CAS  PubMed  Google Scholar 

  93. Martini G, Valenti R, Giovani S, Franci B, Campagna S, Nuti R. Influence of insulin-like growth factor-1 and leptin on bone mass in healthy postmenopausal women. Bone. 2001;28(1):113–7.

    CAS  PubMed  Google Scholar 

  94. Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH, et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet. 1996;348(9021):159–61.

    CAS  PubMed  Google Scholar 

  95. Schwartz MW, Peskind E, Raskind M, Boyko EJ, Porte Jr D. Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nat Med. 1996;2(5):589–93. Epub 1996/05/01.

    CAS  PubMed  Google Scholar 

  96. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999;341(12):879–84. Epub 1999/09/16.

    CAS  PubMed  Google Scholar 

  97. Simha V, Zerwekh JE, Sakhaee K, Garg A. Effect of subcutaneous leptin replacement therapy on bone metabolism in patients with generalized lipodystrophy. J Clin Endocrinol Metabol. 2002;87(11):4942–5.

    CAS  Google Scholar 

  98. Yeo GS, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O’Rahilly S. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet. 1998;20(2):111–2.

    CAS  PubMed  Google Scholar 

  99. Schlienger RG, Kraenzlin ME, Jick SS, Meier CR. Use of beta-blockers and risk of fractures. JAMA. 2004;292(11):1326–32.

    CAS  PubMed  Google Scholar 

  100. Bonnet N, Gadois C, McCloskey E, Lemineur G, Lespessailles E, Courteix D, et al. Protective effect of beta blockers in postmenopausal women: influence on fractures, bone density, micro and macroarchitecture. Bone. 2007;40(5):1209–16.

    CAS  PubMed  Google Scholar 

  101. Pasco JA, Henry MJ, Nicholson GC, Schneider HG, Kotowicz MA. Beta-blockers reduce bone resorption marker in early postmenopausal women. Ann Hum Biol. 2005;32(6):738–45.

    PubMed  Google Scholar 

  102. Turker S, Karatosun V, Gunal I. Beta-blockers increase bone mineral density. Clin Orthop Relat Res. 2006;443:73–4.

    PubMed  Google Scholar 

  103. Wiens M, Etminan M, Gill SS, Takkouche B. Effects of antihypertensive drug treatments on fracture outcomes: a meta-analysis of observational studies. J Intern Med. 2006;260(4):350–62.

    CAS  PubMed  Google Scholar 

  104. Kurvers HA. Reflex sympathetic dystrophy: facts and hypotheses. Vasc Med. 1998;3(3):207–14.

    CAS  PubMed  Google Scholar 

  105. Patel MS, Elefteriou F. The new field of neuroskeletal biology. Calcif Tissue Int. 2007;80(5):337–47.

    CAS  PubMed  Google Scholar 

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Ducy, P., Kousteni, S. (2015). Leptin and Bone. In: Dagogo-Jack, MD, S. (eds) Leptin. Springer, Cham. https://doi.org/10.1007/978-3-319-09915-6_12

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