Adrenal Function and Skeletal Regulation

  • Iacopo ChiodiniEmail author
  • Claudia Battista
  • Elisa Cairoli
  • Cristina Eller-Vainicher
  • Valentina Morelli
  • Serena Palmieri
  • Antonio Stefano Salcuni
  • Alfredo Scillitani


The hormones produced by the adrenal gland have important effects on the bone both in physiological and pathological conditions. The role of cortisol secretion on the bone physiology during growth is not fully understood. During the adult life, the degree of the cortisol secretion, still in the normal range, seems to directly correlate with the bone mineral density in elderly individuals and in osteoporotic women. The overt and subclinical cortisol excess leads to an increased risk of fracture partially independent of the bone mineral density reduction and possibly related to a reduced bone quality. The individual sensitivity to cortisol due to the different polymorphisms of the glucocorticoid receptor (GR) or of the 11β-hydroxysteroid dehydrogenase may modulate the effect of glucocorticoids (GCs) on the bone, thus explaining, at least in part, the wide interindividual variability of the skeletal consequences of the hypercortisolism. The adrenal androgens excess in congenital adrenal hyperplasia (CAH) importantly affects the bone, leading not only to an early growth acceleration but to a reduction in the final adult height. On the other hand, the reduction of the adrenal androgens during aging has been considered among the pathophysiological mechanisms of the osteoporosis in the elderly, but the effects of the restoration of the androgen levels in the aging-related osteoporosis are conflicting. Finally, the presence of mineralocorticoid receptors has been demonstrated in osteoblast, osteoclast, and osteocyte, and an association exists between indexes of bone strength and some genes involved in aldosterone pathways. In keeping, the condition of hyperaldosteronism has been associated with an increased fracture risk.


  1. 1.
    Hardy R, Cooper MS. Adrenal gland and bone. Arch Biochem Biophys. 2010;503:137–45.CrossRefPubMedGoogle Scholar
  2. 2.
    Clarke BL, Khosla S. Androgens and bone. Steroids. 2009;74:296–305.CrossRefPubMedGoogle Scholar
  3. 3.
    Chiodini I, Eller Vainicher C, Morelli V, Palmieri S, Cairoli E, Salcuni AS, Copetti M, Scillitani A. Mechanisms in endocrinology: endogenous subclinical hypercortisolism and bone: a clinical review. Eur J Endocrinol. 2016;175(6):R265–82.CrossRefPubMedGoogle Scholar
  4. 4.
    Osella G, Ventura M, Ardito A, Allasino B, Termine A, Saba L, Vitetta R, Terzolo M, Angeli A. Cortisol secretion, bone health, and bone loss: a cross-sectional and prospective study in normal non-osteoporotic women in the early postmenopausal period. Eur J Endocrinol. 2012;166:855–60.CrossRefPubMedGoogle Scholar
  5. 5.
    Cetin A, Gökçe-Kutsal Y, Celiker R. Predictors of bone mineral density in healthy males. Rheumatol Int. 2001;21:85–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Zhukouskaya VV, Eller-Vainicher C, Gaudio A, Cairoli E, Ulivieri FM, Palmieri S, Morelli V, Orsi E, Masserini B, Barbieri AM, Polledri E, Fustinoni S, Spada A, Fiore CE, Chiodini I. In postmenopausal female subjects with type 2 diabetes mellitus, vertebral fractures are independently associated with cortisol secretion and sensitivity. J Clin Endocrinol Metab. 2015;100:1417–25.CrossRefPubMedGoogle Scholar
  7. 7.
    Cain DW, Cidlowski JA. Specificity and sensitivity of glucocorticoid signaling in health and disease. Best Pract Res Clin Endocrinol Metab. 2015;29:545–56.PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Siggelkow H, Etmanski M, Bozkurt S, Groβ P, Koepp R, Brockmöller J, Tzvetkov MV. Genetic polymorphisms in 11β-hydroxysteroid dehydrogenase type 1 correlate with the postdexamethasone cortisol levels and bone mineral density in patients evaluated for osteoporosis. J Clin Endocrinol Metab. 2014;99:293–302.CrossRefGoogle Scholar
  9. 9.
    Larsen PR, et al. The adrenal cortex (chap. 14, adrenal cortex and endocrine hypertension by Paul M. Stewart). In: William textbook of endocrinology. 10th ed. New York: Elsevier; 2002. p. 492–506.Google Scholar
  10. 10.
    Draper N, Stewart PM. 11beta-hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action. J Endocrinol. 2005;186(2):251–71.CrossRefPubMedGoogle Scholar
  11. 11.
    Durbridge TC, Morris HA, Parsons AM, Parkinson IH, Moore RJ, Porter S, Need AG, Nordin BE, Vernon-Roberts B. Progressive cancellous bone loss in rats after adrenalectomy and oophorectomy. Calcif Tissue Int. 1990;47(6):383–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Björnsdottir S, Sääf M, Bensing S, Kämpe O, Michaëlsson K, Ludvigsson JF. Risk of hip fracture in Addison's disease: a population-based cohort study. J Intern Med. 2011;270(2):187–95.CrossRefPubMedGoogle Scholar
  13. 13.
    Hartmann K, Koenen M, Schauer S, Wittig-Blaich S, Ahmad M, Baschant U, Tuckermann JP. Molecular actions of glucocorticoids in cartilage and bone during health, disease, and steroid therapy. Physiol Rev. 2016;96(2):409–47.CrossRefPubMedGoogle Scholar
  14. 14.
    Kalak R, Zhou H, Street J, Day RE, Modzelewski JR, Spies CM, Liu PY, Li G, Dunstan CR, Seibel MJ. Endogenous glucocorticoid signaling in osteoblasts is necessary to maintain normal bone structure in mice. Bone. 2009;45(1):61–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Sher LB, Woitge HW, Adams DJ, Gronowicz GA, Krozowski Z, Harrison JR, Kream BE. Transgenic expression of 11beta-hydroxysteroid dehydrogenase type 2 in osteoblasts reveals an anabolic role for endogenous glucocorticoids in bone. Endocrinology. 2004;145(2):922–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Sher LB, Harrison JR, Adams DJ, Kream BE. Impaired cortical bone acquisition and osteoblast differentiation in mice with osteoblast-targeted disruption of glucocorticoid signaling. Calcif Tissue Int. 2006;79(2):118–25.CrossRefPubMedGoogle Scholar
  17. 17.
    Rauch A, Seitz S, Baschant U, Schilling AF, Illing A, Stride B, Kirilov M, Mandic V, Takacz A, Schmidt-Ullrich R, Ostermay S, Schinke T, Spanbroek R, Zaiss MM, Angel PE, Lerner UH, David JP, Reichardt HM, Amling M, Schütz G, Tuckermann JP. Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor. Cell Metab. 2010;11(6):517–31.CrossRefPubMedGoogle Scholar
  18. 18.
    Zhou H, Mak W, Zheng Y, Dunstan CR, Seibel MJ. Osteoblasts directly control lineage commitment of mesenchymal progenitor cells through Wnt signaling. J Biol Chem. 2008;283(4):1936–45.CrossRefPubMedGoogle Scholar
  19. 19.
    Leclerc N, Luppen CA, Ho VV, Nagpal S, Hacia JG, Smith E, Frenkel B. Gene expression profiling of glucocorticoid-inhibited osteoblasts. J Mol Endocrinol. 2004;33(1):175–93.CrossRefPubMedGoogle Scholar
  20. 20.
    Zhou H, Mak W, Kalak R, Street J, Fong-Yee C, Zheng Y, Dunstan CR, Seibel MJ. Glucocorticoid-dependent Wnt signaling by mature osteoblasts is a key regulator of cranial skeletal development in mice. Development. 2009;136(3):427–36.CrossRefPubMedGoogle Scholar
  21. 21.
    Van Cauter E, Leproult R, Kupfer DJ. Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol. J Clin Endocrinol Metab. 1996;81:2468–73.PubMedGoogle Scholar
  22. 22.
    Dennison E, Hindmarsh P, Fall C, Kellingray S, Barker D, Phillips D, Cooper C. Profiles of endogenous circulating cortisol and bone mineral density in healthy elderly men. J Clin Endocrinol Metab. 1999;84:3058–63.PubMedGoogle Scholar
  23. 23.
    Purnell JQ, Brandon DD, Isabelle LM, Loriaux DL, Samuels MH. Association of 24-hour cortisol production rates, cortisol-binding globulin, and plasma-free cortisol levels with body composition, leptin levels, and aging in adult men and women. J Clin Endocrinol Metab. 2004;89:281–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Reynolds RM, Dennison EM, Walker BR, Syddall HE, Wood PJ, Andrew R, Phillips DI, Cooper C. Cortisol secretion and rate of bone loss in a population-based cohort of elderly men and women. Calcif Tissue Int. 2005;77:134–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Weinstein RS, Wan C, Liu Q, Wang Y, Almeida M, O'Brien CA, Thostenson J, Roberson PK, Boskey AL, Clemens TL, Manolagas SC. Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in aged mice. Aging Cell. 2010;9(2):147–61.CrossRefPubMedGoogle Scholar
  26. 26.
    Wilkinson CW, Petrie EC, Murray SR, Colasurdo EA, Raskind MA, Peskind ER. Human glucocorticoid feedback inhibitions reduced in older individuals: evening study. J Clin Endocrinol Metab. 2001;86:545–50.PubMedGoogle Scholar
  27. 27.
    Cooper MS, Rabbitt EH, Goddard PE, Bartlett WA, Hewison M, Stewart PM. Osteoblastic 11beta-hydroxysteroid dehydrogenase type 1 activity increases with age and glucocorticoid exposure. J Bone Miner Res. 2002;17:979–86.CrossRefPubMedGoogle Scholar
  28. 28.
    Huizenga NA, Koper JW, De Lange P, Pols HA, Stolk RP, Burger H, Grobbee DE, Brinkmann AO, De Jong FH, Lamberts SW. A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo. J Clin Endocrinol Metab. 1998;83(1):144–51.PubMedGoogle Scholar
  29. 29.
    van Schoor NM, Dennison E, Lips P, Uitterlinden AG, Cooper C. Serum fasting cortisol in relation to bone, and the role of genetic variations in the glucocorticoid receptor. Clin Endocrinol. 2007;67(6):871–8.CrossRefGoogle Scholar
  30. 30.
    Enjuanes A, Garcia-Giralt N, Supervía A, Nogués X, Ruiz-Gaspà S, Bustamante M, Mellibovsky L, Grinberg D, Balcells S, Díez-Pérez A. Functional analysis of the I.3, I.6, pII and I.4 promoters of CYP19 (aromatase) gene in human osteoblasts and their role in vitamin D and dexamethasone stimulation. Eur J Endocrinol. 2005;153(6):981–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Watanabe M, Noda M, Nakajin S. Aromatase expression in a human osteoblastic cell line increases in response to prostaglandin E(2) in a dexamethasone-dependent fashion. Steroids. 2007;72(9–10):686–92.CrossRefPubMedGoogle Scholar
  32. 32.
    Abu EO, Horner A, Kusec V, Triffitt JT, Compston JE. The localization of androgen receptors in human bone. J Clin Endocrinol Metab. 1997;82(10):3493–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Bord S, Horner A, Beavan S, Compston J. Estrogen receptors alpha and beta are differentially expressed in developing human bone. J Clin Endocrinol Metab. 2001;86(5):2309–14.PubMedGoogle Scholar
  34. 34.
    Kerrigan JR, Rogol AD. The impact of gonadal steroid hormone action on growth hormone secretion during childhood and adolescence. Endocr Rev. 1992;13(2):281–98.PubMedGoogle Scholar
  35. 35.
    Kasperk C, Helmboldt A, Börcsök I, Heuthe S, Cloos O, Niethard F, Ziegler R. Skeletal site-dependent expression of the androgen receptor in human osteoblastic cell populations. Calcif Tissue Int. 1997;61(6):464–73.CrossRefPubMedGoogle Scholar
  36. 36.
    Wiren K, Keenan E, Zhang X, Ramsey B, Orwoll E. Homologous androgen receptor up-regulation in osteoblastic cells may be associated with enhanced functional androgen responsiveness. Endocrinology. 1999;140(7):3114–24.CrossRefPubMedGoogle Scholar
  37. 37.
    Bertelloni S, Baroncelli GI, Federico G, Cappa M, Lala R, Saggese G. Altered bone mineral density in patients with complete androgen insensitivity syndrome. Horm Res. 1998;50(6):309–14.CrossRefPubMedGoogle Scholar
  38. 38.
    Jones ME, Boon WC, McInnes K, Maffei L, Carani C, Simpson ER. Recognizing rare disorders: aromatase deficiency. Nat Clin Pract Endocrinol Metab. 2007;3(5):414–21.CrossRefPubMedGoogle Scholar
  39. 39.
    Barrett-Connor E, Kritz-Silverstein D, Edelstein SL. A prospective study of dehydroepiandrosterone sulfate (DHEAS) and bone mineral density in older men and women. Am J Epidemiol. 1993;137(2):201–6.CrossRefPubMedGoogle Scholar
  40. 40.
    Greendale GA, Edelstein S, Barrett-Connor E. Endogenous sex steroids and bone mineral density in older women and men: the Rancho Bernardo Study. J Bone Miner Res. 1997;12(11):1833–43.CrossRefPubMedGoogle Scholar
  41. 41.
    Remer T, Manz F, Hartmann MF, Schoenau E, Wudy SA. Prepubertal healthy children's urinary androstenediol predicts diaphyseal bone strength in late puberty. J Clin Endocrinol Metab. 2009;94(2):575–8.CrossRefPubMedGoogle Scholar
  42. 42.
    Chiodini I. Clinical review: diagnosis and treatment of subclinical hypercortisolism. J Clin Endocrinol Metab. 2011;96:1223–36.CrossRefPubMedGoogle Scholar
  43. 43.
    Bovio S, Cataldi A, Reimondo G, Sperone P, Novello S, Berruti A, Borasio P, Fava C, Dogliotti L, Scagliotti GV, et al. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J Endocrinol Investig. 2006;29:298–302.CrossRefGoogle Scholar
  44. 44.
    Toini A, Dolci A, Ferrante E, Verrua E, Malchiodi E, Sala E, Lania AG, Chiodini I, Beck-Peccoz P, Arosio M, et al. Screening for ACTH-dependent hypercortisolism in patients affected with pituitary incidentaloma. Eur J Endocrinol. 2015;172:363–9.CrossRefPubMedGoogle Scholar
  45. 45.
    Chiodini I, Torlontano M, Carnevale V, Trischitta V, Scillitani A. Skeletal involvement in adult patients with endogenous hypercortisolism. J Endocrinol Investig. 2008;31:267–76.CrossRefGoogle Scholar
  46. 46.
    Chiodini I, Morelli V, Masserini B, Salcuni AS, Eller-Vainicher C, Viti R, Coletti F, Guglielmi G, Battista C, Carnevale V, et al. Bone mineral density, prevalence of vertebral fractures and bone quality in patients with adrenal incidentalomas with and without subclinical hypercortisolism: an Italian Multicenter Study. J Clin Endocrinol Metab. 2009;94:3207–14.CrossRefPubMedGoogle Scholar
  47. 47.
    Eller-Vainicher C, Morelli V, Ulivieri FM, Palmieri S, Zhukouskaya VV, Cairoli E, Pino R, Naccarato A, Scillitani A, Beck-Peccoz P, et al. Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism. J Bone Miner Res. 2012;27:2223–30.CrossRefPubMedGoogle Scholar
  48. 48.
    Morelli V, Eller-Vainicher C, Salcuni AS, Coletti F, Iorio L, Muscogiuri G, Della Casa S, Arosio M, Ambrosi B, Beck-Peccoz P, et al. Risk of new vertebral fractures in patients with adrenal incidentaloma with and without subclinical hypercortisolism: a multicenter longitudinal study. J Bone Miner Res. 2011;26:1816–21.CrossRefPubMedGoogle Scholar
  49. 49.
    Salcuni AS, Morelli V, Eller-Vainicher C, Palmieri S, Cairoli E, Spada A, Scillitani A, Chiodini I. Adrenalectomy reduces the risk of vertebral fractures in patients with monolateral adrenal incidentalomas and subclinical hypercortisolism. Eur J Endocrinol. 2016;174:261–9.CrossRefPubMedGoogle Scholar
  50. 50.
    Morelli V, Eller-Vainicher C, Palmieri S, Cairoli E, Salcuni AS, Scillitani A, Carnevale V, Corbetta S, Arosio M, Della Casa S, Muscogiuri G, Spada A, Chiodini I. Prediction of vertebral fractures in patients with monolateral adrenal incidentalomas. J Clin Endocrinol Metab. 2016;101(7):2768–75.CrossRefPubMedGoogle Scholar
  51. 51.
    Chiodini I, Viti R, Coletti F, Guglielmi G, Battista C, Ermetici F, Morelli V, Salcuni A, Carnevale V, Urbano F, et al. Eugonadal male patients with adrenal incidentalomas and subclinical hypercortisolism have increased rate of vertebral fractures. Clin Endocrinol (Oxf). 2009;70:208–13.CrossRefGoogle Scholar
  52. 52.
    Canalis E, Mazziotti G, Giustina A, Bilezikian JP. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int. 2007;18:1319–28.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Chiodini I, Mascia ML, Muscarella S, Battista C, Minisola S, Arosio M, Santini SA, Guglielmi G, Carnevale V, Scillitani A. Subclinical hypercortisolism among outpatients referred for osteoporosis. Ann Intern Med. 2007;147:541–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Hofbauer LC, Hamann C, Ebeling PR. Approach to the patient with secondary osteoporosis. Eur J Endocrinol. 2010;162(6):1009–20.CrossRefPubMedGoogle Scholar
  55. 55.
    Scillitani A, Mazziotti G, Di Somma C, Moretti S, Stigliano A, Pivonello R, Giustina A, Colao A, on behalf of ABC Group. Treatment of skeletal impairment in patients with endogenous hypercortisolism: when and how? Osteoporos Int. 2014;25:441–6.CrossRefPubMedGoogle Scholar
  56. 56.
    Nieman LK, Biller BMK, Finding JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing’s syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2008;93:1526–40.PubMedCentralCrossRefPubMedGoogle Scholar
  57. 57.
    Chiodini I, Carnevale V, Torlontano M, Fusilli S, Guglielmi G, Pileri M, Modoni S, Di Giorgio A, Liuzzi A, Minisola S, Cammisa M, Trischitta V, Scillitani A. Alterations of bone turnover and bone mass at different skeletal sites due to pure glucocorticoid excess: study in eumenorrheic patients with Cushing's syndrome. J Clin Endocrinol Metab. 1998;83(6):1863–7.PubMedGoogle Scholar
  58. 58.
    Mancini T, Doga M, Mazziotti G, et al. Cushing’s syndrome and bone. Pituitary. 2004;7:249–52.CrossRefPubMedGoogle Scholar
  59. 59.
    Kawamata A, Iihara M, Okamoto T, et al. Bone mineral density before and after surgical cure of Cushing’s syndrome due to adrenocortical adenoma: prospective study. World J Surg. 2008;32:890–6.CrossRefPubMedGoogle Scholar
  60. 60.
    van der Eerden AW, den Heijer M, Oyen WJ, et al. Cushing’s syndrome and bone mineral density: lowest Z scores in young patients. Neth J Med. 2007;65:137–41.PubMedGoogle Scholar
  61. 61.
    Dekkers OM, Horvath-Puho E, Jorgensen JO, et al. Multisystem morbidity and mortality in Cushing’s syndrome: a cohort study. J Clin Endocrinol Metab. 2013;98:2277–84.CrossRefPubMedGoogle Scholar
  62. 62.
    Vestergaard P, Lindholm J, Jorgensen JO, et al. Increased risk of osteoporotic fractures in patients with Cushing’s syndrome. Eur J Endocrinol. 2002;146:51–6.CrossRefPubMedGoogle Scholar
  63. 63.
    Valassi E, Santos A, Yaneva M, the ERCUSYN Study Group, et al. The European registry on Cushing’s syndrome: 2-year experience. Baseline demographic and clinical characteristics. Eur J Endocrinol. 2011;165:383–92.CrossRefPubMedGoogle Scholar
  64. 64.
    Tauchmanova L, Pivonello R, De Martino MC, et al. Effects of sex steroids on bone in women with subclinical or overt endogenous hypercortisolism. Eur J Endocrinol. 2007;157:359–66.CrossRefPubMedGoogle Scholar
  65. 65.
    Tauchmanova L, Pivonello R, Di Somma C, et al. Bone demineralization and vertebral fractures in endogenous cortisol excess: role of disease etiology and gonadal status. J Clin Endocrinol Metab. 2006;91:1779–84.CrossRefPubMedGoogle Scholar
  66. 66.
    Karavitaki N, Ioannidis G, Giannakopoulos F, Mavrokefalos P, Thalassinos N. Evaluation of bone mineral density of the peripheral skeleton in pre- and postmenopausal women with newly diagnosed endogenous Cushing’s syndrome. Clin Endocrinol. 2004;60:264–70.CrossRefGoogle Scholar
  67. 67.
    Mazziotti G, Angeli A, Bilezikian JP, Canalis E, Giustina A. Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab. 2006;17:144–9.CrossRefPubMedGoogle Scholar
  68. 68.
    Pivonello R, De Leo M, Vitale P, et al. Pathophysiology of diabetes mellitus in Cushing’s syndrome. Neuroendocrinology. 2010;92:77–81.CrossRefPubMedGoogle Scholar
  69. 69.
    Thrailkill KM, Lumpkin CK Jr, Bunn RC, et al. Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Phys Endocrinol Metab. 2005;289:E735–45.CrossRefGoogle Scholar
  70. 70.
    Manolagas SC. Corticosteroids and fractures: a close encounter of the third cell kind. J Bone Miner Res. 2000;15:1001–5.CrossRefPubMedGoogle Scholar
  71. 71.
    Abu EO, Horner A, Kusec V, et al. The localization of the functional glucocorticoid receptor alpha in human bone. J Clin Endocrinol Metab. 2000;85:883–9.PubMedGoogle Scholar
  72. 72.
    Cooper MS, Walker EA, Bland R, et al. Expression and functional consequences of 11beta-hydroxysteroid dehydrogenase activity in human bone. Bone. 2000;27:375–81.CrossRefPubMedGoogle Scholar
  73. 73.
    Morrison NA, Shine J, Fragonas JC, et al. 1,25- dihydroxyvitamin D-responsive element and glucocorticoid repression in the osteocalcin gene. Science. 1989;246:1158–61.CrossRefPubMedGoogle Scholar
  74. 74.
    Seibel MJ, Cooper MS, Zhou H. Glucocorticoid-induced osteoporosis: mechanisms, management, and future perspectives. Lancet Diabetes Endocrinol. 2013;1:59–70.CrossRefPubMedGoogle Scholar
  75. 75.
    Yaneva M, Kalinov K, Zacharieva S. Mortality in Cushing’s syndrome: data from 386 patients from a single tertiary referral center. Eur J Endocrinol. 2013;169:621–7.CrossRefPubMedGoogle Scholar
  76. 76.
    Ntali G, Asimakopoulou A, Siamatras T, et al. Mortality in Cushing’s syndrome: systematic analysis of a large series with prolonged follow-up. Eur J Endocrinol. 2013;169:715–23.CrossRefPubMedGoogle Scholar
  77. 77.
    Hochberg Z, Pacak K, Chrousos GP. Endocrine withdrawal syndromes. Endocr Rev. 2003;24:523–38.CrossRefPubMedGoogle Scholar
  78. 78.
    Brandi ML. Microarchitecture, the key to bone quality. Rheumatology (Oxford). 2009;48(Suppl 4):iv3–8.CrossRefGoogle Scholar
  79. 79.
    Nicks KM, Amin S, Atkinson EJ, et al. Relationship of age to bone microstructure independent of areal bone mineral density. J Bone Miner Res. 2012;27:637–44.PubMedCentralCrossRefPubMedGoogle Scholar
  80. 80.
    Nishiyama KK, Macdonald HM, Buie HR, et al. Postmenopausal women with osteopenia have higher cortical porosity and thinner cortices at the distal radius and tibia than women with normal aBMD: an in vivo HR-pQCT study. J Bone Miner Res. 2010;25:882–90.PubMedGoogle Scholar
  81. 81.
    Stein EM, Liu XS, Nickolas TL, et al. Abnormal microarchitecture and reduced stiffness at the radius and tibia in postmenopausal women with fractures. J Bone Miner Res. 2010;25:2572–81.PubMedCentralCrossRefPubMedGoogle Scholar
  82. 82.
    Genant HK, Delmas PD, Chen P, et al. Severity of vertebral fracture reflects deterioration of bone microarchitecture. Osteoporos Int. 2007;18:69–76.CrossRefPubMedGoogle Scholar
  83. 83.
    Scommegna S, Greening JP, Storr HL, et al. Bone mineral density at diagnosis and following successful treatment of pediatric Cushing’s disease. J Endocrinol Investig. 2005;28:231–5.CrossRefGoogle Scholar
  84. 84.
    Acharya SV, Gopal RA, Lila A, et al. Bone age and factors affecting skeletal maturation at diagnosis of paediatric Cushing’s disease. Pituitary. 2010;13:355–60.CrossRefPubMedGoogle Scholar
  85. 85.
    Lodish MB, Hsiao HP, Serbis A, et al. Effects of Cushing disease on bone mineral density in a pediatric population. J Pediatr. 2010;156:1001–5.PubMedCentralCrossRefPubMedGoogle Scholar
  86. 86.
    Leong GM, Abad V, Charmandari E, et al. Effects of child- and adolescent-onset endogenous Cushing syndrome on bone mass, body composition, and growth: a 7-year prospective study into young adulthood. J Bone Miner Res. 2007;22:110–8.CrossRefPubMedGoogle Scholar
  87. 87.
    Bolland MJ, Holdaway IM, Berkeley JE, et al. Mortality and morbidity in Cushing’s syndrome in New Zealand. Clin Endocrinol. 2011;75:436–42.CrossRefGoogle Scholar
  88. 88.
    Di Somma C, Pivonello R, Loche S, et al. Effect of 2 years of cortisol normalization on the impaired bone mass and turnover in adolescent and adult patients with Cushing’s disease: a prospective study. Clin Endocrinol. 2003;58:302–8.CrossRefGoogle Scholar
  89. 89.
    Hermus AR, Smals AG, Swinkels LM, et al. Bone mineral density and bone turnover before and after surgical cure of Cushing’s syndrome. J Clin Endocrinol Metab. 1995;80:2859–65.PubMedGoogle Scholar
  90. 90.
    Randazzo ME, Grossrubatscher E, Dalino Ciaramella P, Vanzulli A, Loli P. Spontaneous recovery of bone mass after cure of endogenous hypercortisolism. Pituitary. 2012;15:193–201.CrossRefPubMedGoogle Scholar
  91. 91.
    Kristo C, Jemtland R, Ueland T, Godang K, Bollerslev J. Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing’s syndrome: a prospective, long-term study. Eur J Endocrinol. 2006;154:109–18.CrossRefPubMedGoogle Scholar
  92. 92.
    Futo L, Toke J, Patocs A, et al. Skeletal differences in bone mineral area and content before and after cure of endogenous Cushing’s syndrome. Osteoporos Int. 2008;19:941–9.CrossRefPubMedGoogle Scholar
  93. 93.
    Barahona MJ, Sucunza N, Resmini E, et al. Deleterious effects of glucocorticoid replacement on bone in women after long-term remission of Cushing’s syndrome. J Bone Miner Res. 2009;24:1841–6.CrossRefPubMedGoogle Scholar
  94. 94.
    Castinetti F, Morange I, Jaquet P, Conte-Devolx B, Brue T. Ketoconazole revisited: a preoperative or postoperative treatment in Cushing’s disease. Eur J Endocrinol. 2008;158:91–9.CrossRefPubMedGoogle Scholar
  95. 95.
    Di Somma C, Colao A, Pivonello R, et al. Effectiveness of chronic treatment with alendronate in the osteoporosis of Cushing’s disease. Clin Endocrinol. 1998;48:655–62.CrossRefGoogle Scholar
  96. 96.
    Luisetto G, Zangari M, Camozzi V, Boscaro M, Sonino N, Fallo F. Recovery of bone mineral density after surgical cure, but not by ketoconazole treatment, in Cushing’s syndrome. Osteoporos Int. 2001;12:956–60.CrossRefPubMedGoogle Scholar
  97. 97.
    van Rossum EF, Voorhoeve PG, de Velde SJ, Koper JW, Delemarre-van de Waal HA, Kemper HC, Lamberts SW. The ER22/23EK polymorphism in the glucocorticoid receptor gene is associated with a beneficial body composition and muscle strength in young adults. J Clin Endocrinol Metab. 2004;89:4004–9.CrossRefPubMedGoogle Scholar
  98. 98.
    Szappanos A, Patocs A, Toke J, Boyle B, Sereg M, Majnik J, Borgulya G, Varga I, Liko´ I, Racz K, et al. BclI polymorphism of the glucocorticoid receptor gene is associated with decreased bone mineral density in patients with endogenous hypercortisolism. Clin Endocrinol (Oxf). 2009;71:636–43.CrossRefGoogle Scholar
  99. 99.
    Peng YM, Lei SF, Guo Y, Xiong DH, Yan H, Wang L, Guo YF, Deng HW. Sex-specific association of the glucocorticoid receptor gene with extreme BMD. J Bone Miner Res. 2008;23:247–52.CrossRefPubMedGoogle Scholar
  100. 100.
    Trementino L, Appolloni G, Ceccoli L, Marcelli G, Concettoni C, Boscaro M, Arnaldi G. Bone complications in patients with Cushing's syndrome: looking for clinical, biochemical, and genetic determinants. Osteoporos Int. 2014;25:913–21.CrossRefPubMedGoogle Scholar
  101. 101.
    Morelli V, Donadio F, Eller-Vainicher C, Cirello V, Olgiati L, Savoca C, Cairoli E, Salcuni AS, Beck-Peccoz P, Chiodini I. Role of glucocorticoid receptor polymorphism in adrenal incidentalomas. Eur J Clin Investig. 2010;40:803–11.CrossRefGoogle Scholar
  102. 102.
    Tzanela M, Mantzou E, Saltiki K, Tampourlou M, Kalogeris N, Hadjidakis D, Tsagarakis S, Alevizaki M. Clinical and biochemical impact of BCL1 polymorphic genotype of the glucocorticoid receptor gene in patients with adrenal incidentalomas. J Endocrinol Investig. 2012;35:395–400.Google Scholar
  103. 103.
    Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM. 11β-Hydroxysteroid dehydrogenase type 1: a tissue specific regulator of glucocorticoid response. Endocr Rev. 2004;25:831–66.CrossRefPubMedGoogle Scholar
  104. 104.
    Cooper MS. 11beta-Hydroxysteroid dehydrogenase: a regulator of glucocorticoid response in osteoporosis. J Endocrinol Investig. 2008;31:16–21.CrossRefGoogle Scholar
  105. 105.
    Diederich S, Eigendorff E, Burkhardt P, et al. 11-Hydroxysteroid dehydrogenase types 1and 2:an important pharmacokinetic determinant for the activity of synthetic mineralo- and glucocorticoids. J Clin Endocrinol Metab. 2002;87:5695–701.CrossRefPubMedGoogle Scholar
  106. 106.
    Park JS, Bae SJ, Choi SW, Son YH, Park SB, Rhee SD, Kim HY, Jung WH, Kang SK, Ahn JH, et al. A novel 11β-HSD1 inhibitor improves diabesity and osteoblast differentiation. J Mol Endocrinol. 2014;52:191–202.CrossRefPubMedGoogle Scholar
  107. 107.
    Wu L, Qi H, Zhong Y, Lv S, Yu J, Liu J, Wang L, Bi J, Kong X, Di W, Zha J, et al. 11β-Hydroxysteroid dehydrogenase type 1 selective inhibitor BVT.2733 protects osteoblasts against endogenous glucocorticoid induced dysfunction. Endocr J. 2013;60:1047–58.CrossRefPubMedGoogle Scholar
  108. 108.
    Hwang JY, Lee SH, Kim GS, Koh JM, Go MJ, Kim YJ, Kim HC, Kim TH, Hong JM, Park EK, et al. HSD11β1 polymorphisms predicted bone mineral density and fracture risk in postmenopausal women without clinically apparent hypercortisolemia. Bone. 2009;45:1098–103.CrossRefPubMedGoogle Scholar
  109. 109.
    Feldman K, Szappanos A, Butz H, Grolmusz V, Majnik J, Likó I, Kriszt B, Lakatos P, Tóth M, Rácz K, et al. The rs4844880 polymorphism in the promoter region of the HSD11B1 gene associates with bone mineral density in healthy and postmenopausal osteoporotic women. Steroids. 2012;77:1345–51.CrossRefPubMedGoogle Scholar
  110. 110.
    Szappanos A, Patócs A, Gergics P, Bertalan R, Kerti A, Acs B, Feldmann K, Rácz K, Tóth M. The 83,557insA variant of the gene coding 11β-hydroxysteroid dehydrogenase type 1 enzyme associates with serum osteocalcin in patients with endogenous Cushing's syndrome. J Steroid Biochem Mol Biol. 2011;123:79–84.CrossRefPubMedGoogle Scholar
  111. 111.
    Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, Meyer-Bahlburg HF, Miller WL, Montori VM, Oberfield SE, Ritzen M, White PC, Endocrine Society. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(9):4133–60.PubMedCentralCrossRefPubMedGoogle Scholar
  112. 112.
    Mora S, Saggion F, Russo G, Weber G, Bellini A, Prinster C, Chiumello G. Bone density in young patients with congenital adrenal hyperplasia. Bone. 1996;18(4):337–40.CrossRefPubMedGoogle Scholar
  113. 113.
    Ceccato F, Barbot M, Albiger N, Zilio M, De Toni P, Luisetto G, Zaninotto M, Greggio NA, Boscaro M, Scaroni C, Camozzi V. Long-term glucocorticoid effect on bone mineral density in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Eur J Endocrinol. 2016;175(2):101–6.CrossRefPubMedGoogle Scholar
  114. 114.
    Falhammar H, Filipsson H, Holmdahl G, Janson PO, Nordenskjöld A, Hagenfeldt K, Thorén M. Fractures and bone mineral density in adult women with 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2007;92(12):4643–9.CrossRefPubMedGoogle Scholar
  115. 115.
    Raizada N, Jyotsna VP, Upadhyay AD, Gupta N. Bone mineral density in young adult women with congenital adrenal hyperplasia. Indian J Endocrinol Metab. 2016;20(1):62–6.PubMedCentralCrossRefPubMedGoogle Scholar
  116. 116.
    Falhammar H, Filipsson Nyström H, Wedell A, Brismar K, Thorén M. Bone mineral density, bone markers, and fractures in adult males with congenital adrenal hyperplasia. Eur J Endocrinol. 2013;168(3):331–41.CrossRefPubMedGoogle Scholar
  117. 117.
    Garcia Alves Junior PA, Schueftan DL, de Mendonça LM, Farias ML, Beserra IC. Bone mineral density in children and adolescents with congenital adrenal hyperplasia. Int J Endocrinol. 2014;2014:806895.PubMedCentralCrossRefPubMedGoogle Scholar
  118. 118.
    Zimmermann A, Sido PG, Schulze E, Al Khzouz C, Lazea C, Coldea C, Weber MM. Bone mineral density and bone turnover in Romanian children and young adults with classical 21-hydroxylase deficiency are influenced by glucocorticoid replacement therapy. Clin Endocrinol. 2009;71(4):477–84.CrossRefGoogle Scholar
  119. 119.
    Hatton R, Stimpel M, Chambers TJ. Angiotensin II is generated from angiotensin I by bone cells and stimulates osteoclastic bone resorption in vitro. J Endocrinol. 1997;152:5–10.CrossRefPubMedGoogle Scholar
  120. 120.
    Asaba Y, Ito M, Fumoto T, Watanabe K, Fukuhara R, Takeshita S, Nimura Y, Ishida J, Fukamizu A, Ikeda K. Activation of renin-angiotensin system induces osteoporosis independently of hypertension. J Bone Miner Res. 2009;24:241–50.CrossRefPubMedGoogle Scholar
  121. 121.
    Hagiwara H, Hiruma Y, Inoue A, Yamaguchi A, Hirose S. Deceleration by angiotensin II of the differentiation and bone formation of rat calvarial osteoblastic cells. J Endocrinol. 2006;156:543–50.CrossRefGoogle Scholar
  122. 122.
    Lamparter S, Kling L, Schrader M, Ziegler R, Pfeilschifter J. Effects of angiotensin II on bone cells in vitro. J Cell Physiol. 1998;175:89–98.CrossRefPubMedGoogle Scholar
  123. 123.
    Yamamoto S, Kido R, Onishi Y, Fukuma S, Akizawa T, Fukugawa M, Kazama JJ, Narita I, Fukuhara S. Use of renin-angiotensin system inhibitors is associated with reduction of fracture risk in hemodialysis patients. PLoS One. 2015;10:e01222691.Google Scholar
  124. 124.
    Aoki M, Kawahata H, Sotobayashi D, Yu H, Moriguchi A, Nakagami H, Ogihara T, Morishita R. Effect of angiotensin II receptor blocker, olmesartan, on turnover of bone metabolism in bedridden elderly hypertensive women with disuse syndrome. Geriatr Gerontol Int. 2015;15:1064–72.CrossRefPubMedGoogle Scholar
  125. 125.
    Ghosh M, Majumda SR. Antihypertensive medications, bone mineral density, and fractures: a review of old cardiac drugs that provides new insights into osteoporosis. Endocrine. 2014;46:397–405.CrossRefPubMedGoogle Scholar
  126. 126.
    Nakagami H, Osako MK, Morishita R. Potential effect of angiotensin II receptor blockade in adipose tissue and bone. Curr Pharm Des. 2013;19:3049–53.CrossRefPubMedGoogle Scholar
  127. 127.
    Shimizu H, Nakagami H, Osako MK, Nakagami F, Kunugiza Y, Tomita T, Yoshikawa H, Rakugi H, Ogihara T, Morishita R. Prevention of osteoporosis by angiotensin-converting enzyme inhibitor in spontaneous hypertensive rats. Hypertens Res. 2009;32:786–90.CrossRefPubMedGoogle Scholar
  128. 128.
    Donmez BO, Ozdemir S, Sarikanat M, Yaras N, Koc P, Demir N, Karayalcin B, Oguz N. Effect of angiotensin II type 1 receptor blocker on osteoporotic rat femurs. Pharmacol Rep. 2012;64:878–88.CrossRefPubMedGoogle Scholar
  129. 129.
    Garcia P, Schwenzer S, Slotta JE, Scheuer C, Tami AE, Holstein JH, Histing T, Burkhardt M, Pohlemann T, Menge MD. Inhibition of angiotensin-converting enzyme stimulates fracture healing and periosteal callus formation – role of a local renin-angiotensin system. Br J Pharmacol. 2010;159:1672–80.PubMedCentralCrossRefPubMedGoogle Scholar
  130. 130.
    Tylavsky FA, Johnson KC, Wan JY, Harshfield G. Plasma renin activity is associated with bone mineral density in premenopausal women. Osteoporos Int. 1998;8:136–40.CrossRefPubMedGoogle Scholar
  131. 131.
    Altun B, Kiykim AA, Seyrantepe V, Usalana C, Arici M, Çağlar M, Erdem Y, Yasavul U, Turgan C, Çağlar S. Association between activated renin angiotensin system and bone formation in hemodialysis patients: is the bone mass genetically determined by ACE gene polymorphism? Ren Fail. 2004;26:425–31.CrossRefPubMedGoogle Scholar
  132. 132.
    Kuipers AL, Kammerer CM, Pratt JH, Bunker CH, Wheeler VW, Patrick AL, Zmuda JM. Association of circulating renin and aldosterone with osteocalcin and bone mineral density in African ancestry families. Hypertension. 2016;67:977–82.PubMedCentralCrossRefPubMedGoogle Scholar
  133. 133.
    Gu SS, Zhang Y, Li HL, Wu SY, Diao TY, Hai R, Deng HW. Involvement of the skeletal renin-angiotensin system in age-related osteoporosis of ageing mice. Biosci Biotechnol Biochem. 2012;76:1367–71.CrossRefPubMedGoogle Scholar
  134. 134.
    Yongtao Z, Kunzheng W, Jingjing Z, Hu S, Jianqiang K, Ruiyu L, Chunsheng W. Glucocorticoids activate the local renin–angiotensin system in bone: possible mechanism for glucocorticoid-induced osteoporosis. Endocrine. 2014;47:598–608.CrossRefPubMedGoogle Scholar
  135. 135.
    Chhokar VS, Sun Y, Bhattacharya SK, Ahokas RA, Myers LK, Xing Z, Smith RA, Gerling IC, Weber KT. Loss of bone minerals and strength in rats with aldosteronism. Am J Physiol Heart Circ Physiol. 2004;287:H2023–6.CrossRefPubMedGoogle Scholar
  136. 136.
    Pilz S, Kienreich K, Drechsler C, Ritz E, Fahrleitner-Pammer A, Gaksch M, Meinitzer A, März W, Pieber TR, Tomaschitz A. Hyperparathyroidism in patients with primary aldosteronism: cross-sectional and interventional data from the GECOH study. J Clin Endocrinol Metab. 2012;97:E75–9.CrossRefPubMedGoogle Scholar
  137. 137.
    Law PH, Sun Y, Bhattacharya SK, Chhokar VS, Weber KT. Diuretics and bone loss in rats with aldosteronism. J Am Coll Cardiol. 2005;46:142–6.CrossRefPubMedGoogle Scholar
  138. 138.
    Salcuni AS, Palmieri S, Carnevale V, Morelli V, Battista C, Guarnieri V, Guglielmi G, Desina G, Eller-Vainicher C, Beck-Peccoz P, Scillitani A, Chiodini I. Bone involvement in aldosteronism. J Bone Miner Res. 2012;27:2217–22.CrossRefPubMedGoogle Scholar
  139. 139.
    Ceccoli L, Ronconi V, Giovannini L, Marcheggiani M, Turchi F, Boscaro M, Giacchetti G. Bone health and aldosterone excess. Osteoporos Int. 2013;24:2801–7.CrossRefPubMedGoogle Scholar
  140. 140.
    Petramala L, Zinnamosca L, Settevendemmie A, Marinelli C, Nardi M, Concistrè A, Corpaci F, Tonnarini G, De Toma G, Letizia C. Bone and mineral metabolism in patients with primary aldosteronism. Int J Endocrinol. 2014;2014:836529.PubMedCentralCrossRefPubMedGoogle Scholar
  141. 141.
    Gupta M, Cheung CL, Hsu YH, Demissie S, Cupples LA, Kiel DP, Karasi D. Identification of homogeneous genetic architecture of multiple genetically correlated traits by block clustering of genome-wide associations. J Bone Miner Res. 2011;26:1261–71.PubMedCentralCrossRefPubMedGoogle Scholar
  142. 142.
    Beavan S, Horner A, Bord S, Ireland D, Compston J. Colocalization of glucocorticoid and mineralocorticoid receptors in human bone. J Bone Miner Res. 2001;16:1496–504.CrossRefPubMedGoogle Scholar
  143. 143.
    Fumoto T, Ishii KA, Ito M, Berger S, Schütz G, Ikeda K. Mineralocorticoid receptor function in bone metabolism and its role in glucocorticoid-induced osteopenia. Biochem Biophys Res Commun. 2014;447:407–12.CrossRefPubMedGoogle Scholar
  144. 144.
    Zhang B, Umbach AT, Chen H, Yana J, Fakhri H, Fajol A, Salker MS, Spichtig D, Daryadel A, Wagner CA, Föller M, Lang F. Up-regulation of FGF23 release by aldosterone. Biochem Biophys Res Commun. 2016;470:384–90.CrossRefPubMedGoogle Scholar
  145. 145.
    Lang F, Ritz E, Voelkl J, Alesutan I. Vascular calcification—is aldosterone a culprit? Nephrol Dial Transplant. 2013;28:1080–4.CrossRefPubMedGoogle Scholar
  146. 146.
    Ma TK, Szeto CC. Mineralocorticoid receptor antagonist for renal protection. Ren Fail. 2012;34:810–7.CrossRefPubMedGoogle Scholar
  147. 147.
    Ritz E, Koleganova N, Piecha G. Is there an obesity-metabolic syndrome related glomerulopathy? Curr Opin Nephrol Hypertens. 2011;20:44–9.CrossRefPubMedGoogle Scholar
  148. 148.
    Mihailidou AS. Aldosterone in heart disease. Curr Hypertens Rep. 2012;14:125–9.CrossRefPubMedGoogle Scholar
  149. 149.
    Sarraf M, Masoumi A, Schrier RW. Cardiorenal syndrome in acute decompensated heart failure. Clin J Am Soc Nephrol. 2009;4:2013–26.CrossRefPubMedGoogle Scholar
  150. 150.
    Schrier RW. Water and sodium retention in edematous disorders: role of vasopressin and aldosterone. Am J Med. 2006;119:S47–53.CrossRefPubMedGoogle Scholar
  151. 151.
    Schrier RW, Masoumi A, Elhassan E. Aldosterone: role in edematous disorders, hypertension, chronic renal failure, and metabolic syndrome. Clin J Am Soc Nephrol. 2010;5:1132–40.CrossRefPubMedGoogle Scholar
  152. 152.
    Imazu M, Takahama H, Asanuma H, Funada A, Sugano Y, Ohara T, Hasegawa T, Asakura M, Kanzaki H, Anzai T, Kitakaze M. Pathophysiological impact of serum fibroblast growth factor 23 in patients with non-ischemic cardiac disease and early chronic kidney disease. Am J Physiol Heart Circ Physiol. 2014;307:H1504–11.CrossRefPubMedGoogle Scholar
  153. 153.
    Hu MC, Shiizaki K, Kuro-o M, Moe OW. Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol. 2013;75:503–33.PubMedCentralCrossRefPubMedGoogle Scholar
  154. 154.
    Evenepoel P, Meijers B, Viaene L, Bammens B, Claes K, Kuypers D, Vanderschueren D, Vanrenterghem Y. Fibroblast growth factor-23 in early chronic kidney disease: additional support in favor of a phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism. Clin J Am Soc Nephrol. 2010;5:1268–76.PubMedCentralCrossRefPubMedGoogle Scholar
  155. 155.
    Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, Gutierrez OM, Aguillon-Prada R, Lincoln J, Hare JM, Mundel P, Morales A, Scialla J, Fischer M, Soliman EZ, Chen J, Go AS, Rosas SE, Nessel L, Townsend RR, Feldman HI, St John Sutton M, Ojo A, Gadegbeku C, Di Marco GS, Reuter S, Kentrup D, Tiemann K, Brand M, Hill JA, Moe OW, Kuro OM, Kusek JW, Keane MG, Wolf M. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011;121:4393–408.PubMedCentralCrossRefPubMedGoogle Scholar
  156. 156.
    Zanchi C, Locatelli M, Benigni A, Corna D, Tomasoni S, Rottoli D, Gaspari F, Remuzzi G, Zoja C. Renal expression of FGF23 in progressive renal disease of diabetes and the effect of ace inhibitor. PLoS One. 2013;8:e70775.PubMedCentralCrossRefPubMedGoogle Scholar
  157. 157.
    Prie D, Forand A, Francoz C, Elie C, Cohen I, Courbebaisse M, Eladari D, Lebrec D, Durand F, Friedlander G. Plasma fibroblast growth factor 23 concentration is increased and predicts mortality in patients on the liver-transplant waiting list. PLoS One. 2013;8:e66182.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Iacopo Chiodini
    • 1
    • 2
    Email author
  • Claudia Battista
    • 3
  • Elisa Cairoli
    • 1
    • 2
  • Cristina Eller-Vainicher
    • 4
  • Valentina Morelli
    • 2
    • 4
  • Serena Palmieri
    • 2
    • 4
  • Antonio Stefano Salcuni
    • 5
  • Alfredo Scillitani
    • 3
  1. 1.Unit for Bone Metabolism Diseases and DiabetesIRCCS Istituto Auxologico ItalianoMilanItaly
  2. 2.Department of Medical Sciences and Community HealthUniversity of MilanMilanItaly
  3. 3.Unit of Endocrinology“Casa Sollievo della Sofferenza”, Hospital, IRCCSSan Giovanni RotondoItaly
  4. 4.Unit of EndocrinologyFondazione Cà Granda IRCCSMilanItaly
  5. 5.Endocrine Unit, Department of Medical SciencesUniversity of CagliariCagliariItaly

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