Neuroendocrinology of Bone Metabolism

  • Gherardo Mazziotti
  • Mauro Doga
  • Annamaria Formenti
  • Stefano Frara
  • Filippo Maffezzoni
  • Andrea Giustina
Reference work entry
Part of the Endocrinology book series (ENDOCR)

Abstract

Neuroendocrinology of bone is a new area of research based on the evidence that pituitary hormones may directly modulate bone remodeling and metabolism. As a matter of fact, skeletal fragility associated with high risk of fractures is a common complication of pituitary diseases characterized by either hypo- or hyperfunction of the pituitary gland. This chapter deals with physiological, pathophysiological, clinical, and therapeutic aspects concerning the effects of pituitary hormones on skeletal health.

Keywords

Pituitary diseases Osteoporosis Bone mineral density Fractures Growth hormone Prolactin Cortisol Sex steroids 

References

  1. Abdallah BM, Ding M, Jensen CH, et al. Dlk1/FA1 is a novel endocrine regulator of bone and fat mass and its serum level is modulated by growth hormone. Endocrinology. 2007;148:3111–21.PubMedCrossRefGoogle Scholar
  2. Abdel-Kader N, Cardiel MH, Navarro Compan V, et al. Cushing’s disease as a cause of severe osteoporosis: a clinical challenge. Reumatol Clin. 2012;8:278–9.PubMedCrossRefGoogle Scholar
  3. Abe E, Marians RC, Yu W, et al. TSH is a negative regulator of skeletal remodeling. Cell. 2003;115:151–62.PubMedCrossRefGoogle Scholar
  4. Abrahamsen B, Hangaard J, Horn HC, et al. Evaluation of the optimum dose of growth hormone (GH) for restoring bone mass in adult-onset GH deficiency: results from two 12-month randomized studies. Clin Endocrinol. 2002;57:273–81.CrossRefGoogle Scholar
  5. Arwert LI, Roos JC, Lips P, et al. Effects of 10 years of growth hormone (GH) replacement therapy in adult GH-deficient men. Clin Endocrinol. 2005;63:310–6.CrossRefGoogle Scholar
  6. Barake M, Klibanski A, Tritos NA. Effects of recombinant human growth hormone therapy on bone mineral density in adults with growth hormone deficiency: a meta-analysis. J Clin Endocrinol Metab. 2014;99:852–60.PubMedCrossRefGoogle Scholar
  7. Biller BMK, Sesmilo G, Baum HBA, Hayden D, Schoenfeld D, Klibanski A. Withdrawal of long-term physiological growth hormone (GH) administration: differential effects on bone density and body composition in men with adult-onset GH deficiency. J Clin Endocrinol Metab. 2000;85:970–6.PubMedGoogle Scholar
  8. Bonadonna S, Mazziotti G, Nuzzo M, et al. Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women. J Bone Miner Res. 2005;20:1837–44.PubMedCrossRefGoogle Scholar
  9. Canalis E, Giustina A, Bilezikian JP. Mechanisms of anabolic therapies for osteoporosis. N Engl J Med. 2007a;35:905–16.CrossRefGoogle Scholar
  10. Canalis E, Mazziotti G, Giustina A, Bilezikian JP. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int. 2007b;18:1319–28.PubMedCrossRefGoogle Scholar
  11. Claessen KM, Kroon HM, Pereira AM, et al. Progression of vertebral fractures despite long-term biochemical control of acromegaly: a prospective follow-up study. J Clin Endocrinol Metab. 2013;98:4808–15.PubMedCrossRefGoogle Scholar
  12. Claessen KM, Mazziotti G, Biermasz NR, Giustina A. Bone and joint disorders in acromegaly. Neuroendocrinology. 2016;103:86–95.PubMedCrossRefGoogle Scholar
  13. Clark EM, Carter L, Gould VC, et al. Vertebral fracture assessment (VFA) by lateral DXA scanning may be cost-effective when used as part of fracture liaison services or primary care screening. Osteoporos Int. 2014;25:953–64.PubMedCrossRefGoogle Scholar
  14. Cooper C, Atkinson EJ, O’Fallon WM, Melton LJ III. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985–1989. J Bone Miner Res. 1993;7:221–7.CrossRefGoogle Scholar
  15. Coss D, Yang L, Kuo CB, et al. Effects of prolactin on osteoblast alkaline phosphatase and bone formation in the developing rat. Am J Physiol Endocrinol Metab. 2000;279:E1216–25.PubMedCrossRefGoogle Scholar
  16. D’Sylva C, Khan T, Van Uum S, Fraser LA. Osteoporotic fractures in patients with untreated hyperprolactinemia vs. those taking dopamine agonists: a systematic review and meta-analysis. Neuro Endocrinol Lett. 2015;36:745–9.PubMedGoogle Scholar
  17. Davidson P, Milne R, Chase D, et al. Growth hormone replacement in adults and bone mineral density: a systematic review and meta-analysis. Clin Endocrinol. 2004;60:92–8.CrossRefGoogle Scholar
  18. Devleta B, Adem B, Senada S. Hypergonadotropic amenorrhea and bone density: new approach to an old problem. J Bone Miner Metab. 2004;22:360–4.PubMedCrossRefGoogle Scholar
  19. Di Somma C, Colao A, Di Sarno A, et al. Bone marker and bone density responses to dopamine agonist therapy in hyperprolactinemic males. J Clin Endocrinol Metab. 1998;83:807–13.PubMedCrossRefGoogle Scholar
  20. Diamond T, Nery L, Posen S. Spinal and peripheral bone mineral densities in acromegaly: the effects of excess growth hormone and hypogonadism. Ann Intern Med. 1989;111:567–73.PubMedCrossRefGoogle Scholar
  21. Digirolamo DJ, Mukherjee A, Fulzele K, et al. Mode of growth hormone action in osteoblasts. J Biol Chem. 2007;282:31666–74.PubMedCrossRefGoogle Scholar
  22. Drake MT, McCready LK, Hoey KA, Atkinson EJ, Khosla S. Effects of suppression of follicle-stimulating hormone (FSH) secretion on bone resorption markers in postmenopausal women. J Clin Endocrinol Metab. 2010;95:5063–8.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Elbornsson M, Gotherstrom G, Bosaeus I, et al. Fifteen years of GH replacement increases bone mineral density in hypopituitary patients with adult-onset GH deficiency. Eur J Endocrinol. 2012;166:787–95.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Faggiano A, Pivonello R, Filippella M, et al. Spine abnormalities and damage in patients cured from Cushing’s disease. Pituitary. 2001;4:153–61.PubMedCrossRefGoogle Scholar
  25. Genant HK, Jergas M, Palermo L, et al. Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res. 1996;11:984–96.PubMedCrossRefGoogle Scholar
  26. Giavoli C, Libé R, Corbetta S, et al. Effect of recombinant human growth hormone (GH) replacement on the hypothalamic-pituitary-adrenal axis in adult GH-deficient patients. J Clin Endocrinol Metab. 2004;89:5397–401.PubMedCrossRefGoogle Scholar
  27. Giustina A, Veldhuis JD. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev. 1998;19:717–97.PubMedGoogle Scholar
  28. Giustina A, Casanueva FF, Cavagnini F, et al. Diagnosis and treatment of acromegaly complications. J Endocrinol Invest. 2003;26:1242–7.PubMedCrossRefGoogle Scholar
  29. Giustina A, Mazziotti G, Canalis E. Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev. 2008;29:535–59.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Giustina A, Mazziotti G. Growth hormone replacement therapy and fracture risk. Lancet Diabetes Endocrinol. 2015;3:307–8.PubMedCrossRefGoogle Scholar
  31. Gogakos AI, Duncan Bassett JH, Williams GR. Thyroid and bone. Arch Biochem Biophys. 2010;503:129–36.PubMedCrossRefGoogle Scholar
  32. Griffith JF, Genant HK. New advances in imaging osteoporosis and its complications. Endocrine. 2012;42:39–51.PubMedCrossRefGoogle Scholar
  33. Högler W, Shaw N. Childhood growth hormone deficiency, bone density, structures and fractures: scrutinizing the evidence. Clin Endocrinol. 2010;72:281–9.CrossRefGoogle Scholar
  34. Hubina E, Lakatos P, Kovacs L, et al. Effects of 24 months of growth hormone (GH) treatment on serum carboxylated and undercarboxylated osteocalcin levels in GH-deficient adults. Calcif Tissue Int. 2004;74:55–9.PubMedCrossRefGoogle Scholar
  35. Iqbal J, Blair HC, Zallone A, et al. Further evidence that FSH causes bone loss independently of low estrogen. Endocrine. 2012;412:171–5.CrossRefGoogle Scholar
  36. Isales CM, Zaidi M, Blair HC. ACTH is a novel regulator of bone mass. Ann N Y Acad Sci. 2010;1192:110–6.PubMedCrossRefGoogle Scholar
  37. Kaji H, Sugimoto T, Nakaoka D, et al. Bone metabolism and body composition in Japanese patients with active acromegaly. Clin Endocrinol. 2001;55:175–81.CrossRefGoogle Scholar
  38. Kamenický P, Mazziotti G, Lombès M, Giustina A, Chanson P. Growth hormone, insulin-like growth factor-1, and the kidney: pathophysiological and clinical implications. Endocr Rev. 2014;35:234–81.PubMedCrossRefGoogle Scholar
  39. Kassem M, Blum W, Ristelli J, et al. Growth hormone stimulates proliferation and differentiation of normal human osteoblast-like cells in vitro. Calcif Tissue Int. 1993;52:222–6.PubMedCrossRefGoogle Scholar
  40. Kaufman JM, Taelman P, Vermeulen A, Vandeweghe M. Bone mineral status in growth hormone-deficient males with isolated and multiple pituitary deficiencies of childhood onset. J Clin Endocrinol Metab. 1992;74:118–23.PubMedGoogle Scholar
  41. Kayath MJ, Vieira JG. Osteopenia occurs in a minority of patients with acromegaly and is predominant in the spine. Osteoporos Int. 1997;7:226–30.PubMedCrossRefGoogle Scholar
  42. Klibanski A, Greenspan SL. Increase in bone mass after treatment of hyperprolactinemic amenorrhea. N Engl J Med. 1986;315:542–6.PubMedCrossRefGoogle Scholar
  43. Klibanski A, Biller BM, Rosenthal DI, et al. Effects of prolactin and estrogen deficiency in amenorrheic bone loss. J Clin Endocrinol Metab. 1988;67:124–30.PubMedCrossRefGoogle Scholar
  44. Kotzmann H, Bernecker P, Hubsch P, et al. Bone mineral density and parameters of bone metabolism in patients with acromegaly. J Bone Miner Res. 1993;8:459–65.PubMedCrossRefGoogle Scholar
  45. Longobardi S, Di Somma C, Di Rella F, et al. Bone mineral density and circulating cytokines in patients with acromegaly. J Endocrinol Invest. 1998;21:688–93.PubMedCrossRefGoogle Scholar
  46. Madeira M, Neto LV, de Paula Paranhos Neto F, et al. Acromegaly has a negative influence on trabecular bone, but not on cortical bone, as assessed by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab. 2013;98:1734–41.PubMedCrossRefGoogle Scholar
  47. Maffezzoni F, Maddalo M, Frara S, et al. Cone beam tomography analysis of bone microarchitecture in patients with acromegaly and vertebral fractures. Endocrine. 2016;54:532–42.PubMedCrossRefGoogle Scholar
  48. Mancini T, Porcelli T, Giustina A. Treatment of Cushing disease: overview and recent findings. Ther Clin Risk Manag. 2010;6:505–16.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Martins MR, Doin FC, Komatsu WR, et al. Growth hormone replacement improves thyroxine biological effects: implications for management of central hypothyroidism. J Clin Endocrinol Metab. 2007;92:4144–53.PubMedCrossRefGoogle Scholar
  50. Mazziotti G, Sorvillo F, Piscopo M, et al. Recombinant human TSH modulates in vivo C-telopeptides of type-1 collagen and bone alkaline phosphatase, but not osteoprotegerin production in postmenopausal women monitored for differentiated thyroid carcinoma. J Bone Miner Res. 2005;20:480–6.PubMedCrossRefGoogle Scholar
  51. Mazziotti G, Angeli A, Bilezikian JP, et al. Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab. 2006a;17:144–9.PubMedCrossRefGoogle Scholar
  52. Mazziotti G, Bianchi A, Bonadonna S, et al. Increased prevalence of radiological spinal deformities in adult patients with GH deficiency: influence of GH replacement therapy. J Bone Miner Res. 2006b;21:520–8.PubMedCrossRefGoogle Scholar
  53. Mazziotti G, Bianchi A, Cimino V, et al. Effect of gonadal status on bone mineral density and radiological spinal deformities in adult patients with growth hormone deficiency. Pituitary. 2008a;11:55–61.PubMedCrossRefGoogle Scholar
  54. Mazziotti G, Bianchi A, Bonadonna S, et al. Prevalence of vertebral fractures in men with acromegaly. J Clin Endocrinol Metab. 2008b;93:4649–55.PubMedCrossRefGoogle Scholar
  55. Mazziotti G, Porcelli T, Patelli I, et al. Serum TSH values and risk of vertebral fractures in euthyroid post-menopausal women with low bone mineral density. Bone. 2010a;46:747–51.PubMedCrossRefGoogle Scholar
  56. Mazziotti G, Canalis E, Giustina A. Drug-induced osteoporosis: mechanisms and clinical implications. Am J Med. 2010b;123:877–84.PubMedCrossRefGoogle Scholar
  57. Mazziotti G, Porcelli T, Bianchi A, et al. Glucocorticoid replacement therapy and vertebral fractures in hypopituitary adult males with GH deficiency. Eur J Endocrinol. 2010c;163:15–20.PubMedCrossRefGoogle Scholar
  58. Mazziotti G, Mancini T, Mormando M, et al. High prevalence of radiological vertebral fractures in women with prolactin-secreting pituitary adenomas. Pituitary. 2011a;14:299–306.PubMedCrossRefGoogle Scholar
  59. Mazziotti G, Porcelli T, Mormando M, et al. Vertebral fractures in males with prolactinoma. Endocrine. 2011b;39:288–93.PubMedCrossRefGoogle Scholar
  60. Mazziotti G, Bilezikian J, Canalis E, et al. New understanding and treatments for osteoporosis. Endocrine. 2012;41:58–69.PubMedCrossRefGoogle Scholar
  61. Mazziotti G, Giustina A. Glucocorticoids and the regulation of growth hormone secretion. Nat Rev Endocrinol. 2013a;95:265–76.CrossRefGoogle Scholar
  62. Mazziotti G, Bianchi A, Porcelli T, et al. Vertebral fractures in patients with acromegaly: a 3-year prospective study. J Clin Endocrinol Metab. 2013b;98:3402–10.PubMedCrossRefGoogle Scholar
  63. Mazziotti G, Mormando M, Cristiano A, et al. Association between l-thyroxine treatment, GH deficiency, and radiological vertebral fractures in patients with adult-onset hypopituitarism. Eur J Endocrinol. 2014;170:893–9.PubMedCrossRefGoogle Scholar
  64. Mazziotti G, Chiavistelli S, Giustina A. Pituitary diseases and bone. Endocrinol Metab Clin North Am. 2015a;44:171–80.PubMedCrossRefGoogle Scholar
  65. Mazziotti G, Biagioli E, Maffezzoni F, et al. Bone turnover, bone mineral density, and fracture risk in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2015b;100:384–94.PubMedCrossRefGoogle Scholar
  66. Mazziotti G, Delgado A, Maffezzoni F, Formenti AM, Giustina A. Skeletal fragility in endogenous hypercortisolism. Front Horm Res. 2016a;46:66–73.PubMedCrossRefGoogle Scholar
  67. Mazziotti G, Formenti AM, Adler RA, et al. Glucocorticoid-induced osteoporosis: pathophysiological role of GH/IGF-I and PTH/vitamin D axes, treatment options and guidelines. Endocrine. 2016b;54:603–11.PubMedCrossRefGoogle Scholar
  68. Mazziotti G, Doga M, Frara S, et al. Incidence of morphometric vertebral fractures in adult patients with growth hormone deficiency. Endocrine. 2016c;52:103–10.PubMedCrossRefGoogle Scholar
  69. Mazziotti G, Maffezzoni F, Frara S, Giustina A. Acromegalic osteopathy. Pituitary. 2017;20:63–9.PubMedCrossRefGoogle Scholar
  70. Melmed S, Casanueva FF, Klibanski A, et al. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary. 2013;16:294–302.PubMedCrossRefGoogle Scholar
  71. Mo D, Fleseriu M, Qi R, et al. Fracture risk in adult patients treated with growth hormone replacement therapy for growth homone deficiency: a prospective cohort study. Lancet Diabetes Endocrinol. 2015;3:331–8.PubMedCrossRefGoogle Scholar
  72. Molitch ME, Clemmons DR, Malozowski S, et al. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2006;91:1621–34.PubMedCrossRefGoogle Scholar
  73. Mrak E, Villa I, Lanzi R, Losa M, Guidobono F, Rubinacci A. Growth hormone stimulates osteoprotegerin expression and secretion in human osteoblast-like cells. J Endocrinol. 2007;192:639–45.PubMedCrossRefGoogle Scholar
  74. Murray RD, Adams JE, Shalet SM. A densitometric and morphometric analysis of the skeleton in adults with varying degrees of growth hormone deficiency. J Clin Endocrinol Metab. 2006;91:432–8.PubMedCrossRefGoogle Scholar
  75. Naliato EC, Violante AH, Caldas D, et al. Bone density in women with prolactinoma treated with dopamine agonists. Pituitary. 2008;11:21–8.PubMedCrossRefGoogle Scholar
  76. Ohlsson C, Bengtsson BA, Isaksson OG, et al. Growth hormone and bone. Endocr Rev. 1998;19:55–79.PubMedGoogle Scholar
  77. Omodei U, Mazziotti G, Donarini G, et al. Effects of recombinant follicle-stimulating hormone on bone turnover markers in infertile women undergoing in vitro fertilization procedure. J Clin Endocrinol Metab. 2013;981:330–6.CrossRefGoogle Scholar
  78. Randazzo ME, Grossrubatscher E, Dalino Ciaramella P, et al. Spontaneous recovery of bone mass after cure of endogenous hypercortisolism. Pituitary. 2012;15:193–201.PubMedCrossRefGoogle Scholar
  79. Riggs BL, Khosla S, Melton LJ 3rd. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. 2002;23:279–302.PubMedCrossRefGoogle Scholar
  80. Rosen T, Wilhelmsen L, Landin-Wilhelmsen K, et al. Increased fracture frequency in adult patients with hypopituitarism and GH deficiency. Eur J Endocrinol. 1997;137:240–5.PubMedCrossRefGoogle Scholar
  81. Rubin J, Ackert-Bicknell CL, Zhu L, et al. IGF-I regulates osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand in vitro and OPG in vivo. J Clin Endocrinol Metab. 2002;87(9):4273.PubMedCrossRefGoogle Scholar
  82. Schousboe JT, Shepherd JA, Bilezikian JP, et al. Executive summary of the 2013 International Society for Clinical Densitometry Position Development Conference on bone densitometry. J Clin Densitom. 2013;16:455–66.PubMedCrossRefGoogle Scholar
  83. Scillitani A, Mazziotti G, Di Somma C, et al. Treatment of skeletal impairment in patients with endogenous hypercortisolism: when and how? Osteoporos Int. 2014;25:441–6.PubMedCrossRefGoogle Scholar
  84. Seriwatanachai D, Charoenphandhu N, Suthiphongchai T, et al. Prolactin decreases the expression ratio of receptor activator of nuclear factor kappaB ligand/osteoprotegerin in human fetal osteoblast cells. Cell Biol Int. 2008a;32:1126–35.PubMedCrossRefGoogle Scholar
  85. Seriwatanachai D, Thongchote K, Charoenphandhu N, et al. Prolactin directly enhances bone turnover by raising osteoblast-expressed receptor activator of nuclear factor kappaB ligand/osteoprotegerin ratio. Bone. 2008b;42:535–46.PubMedCrossRefGoogle Scholar
  86. Seriwatanachai D, Krishnamra N, van Leeuwen JP. Evidence for direct effects of prolactin on human osteoblasts: inhibition of cell growth and mineralization. J Cell Biochem. 2009;107:677–85.PubMedCrossRefGoogle Scholar
  87. Sun L, Peng Y, Sharrow AC, et al. FSH directly regulates bone mass. Cell. 2006;125:247–60.PubMedCrossRefGoogle Scholar
  88. Szappanos A, Toke J, Lippai D, et al. Bone turnover in patients with endogenous Cushing’s syndrome before and after successful treatment. Osteoporos Int. 2010;21:637–45.PubMedCrossRefGoogle Scholar
  89. Tamma R, Colaianni G, Zhu LL, et al. Oxytocin is an anabolic bone hormone. Proc Natl Acad Sci U S A. 2009;106:7149–54.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Tamma R, Sun L, Cuscito C, et al. Regulation of bone remodeling by vasopressin explains the bone loss in hyponatremia. Proc Natl Acad Sci U S A. 2013;110:18644–9.PubMedPubMedCentralCrossRefGoogle Scholar
  91. Trementino L, Appolloni G, Ceccoli L, et al. Bone complications in patients with Cushing’s syndrome: looking for clinical, biochemical, and genetic determinants. Osteoporos Int. 2014;25:913–21.PubMedCrossRefGoogle Scholar
  92. Ueland T, Bollerslev J, Flyvbjerg A, et al. Effects of 12 months of growth hormone (GH) treatment on cortical and trabecular bone content of insulin like growth factors (IGF) and osteoprotegerin in adults with acquired GH deficiency: a double-blind, randomized, placebo-controlled study. J Clin Endocrinol Metab. 2002;87:2760–3.PubMedCrossRefGoogle Scholar
  93. Ueland T, Fougner SL, Godang K, Schreiner T, Bollerslev J. Serum GH and IGF-I are significant determinants of bone turnover but not bone mineral density in active acromegaly: a prospective study of more than 70 consecutive patients. Eur J Endocrinol. 2006;155:709–15.PubMedCrossRefGoogle Scholar
  94. Ulivieri FM, Silva BC, Sardanelli F, et al. Utility of the trabecular bone score (TBS) in secondary osteoporosis. Endocrine. 2014;47:435–48.PubMedCrossRefGoogle Scholar
  95. Valassi E, Santos A, Yaneva M, et al. The European Registry on Cushing’s syndrome: 2-year experience. Baseline demographic and clinical characteristics. Eur J Endocrinol. 2011;165:383–92.PubMedCrossRefGoogle Scholar
  96. Vasikaran S, Eastell R, Bruyère O, et al. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int. 2011;22:391–420.PubMedCrossRefGoogle Scholar
  97. Vestergaard P, Mosekilde L. Hyperthyroidism, bone mineral, and fracture risk – a meta-analysis. Thyroid. 2003;13:585–93.PubMedCrossRefGoogle Scholar
  98. Vestergaard P, Jørgensen JO, Hagen C, et al. Fracture risk is increased in patients with GH deficiency or untreated prolactinomas – a case-control study. Clin Endocrinol. 2002a;56:159–67.CrossRefGoogle Scholar
  99. Vestergaard P, Lindholm J, Jørgensen JO, et al. Increased risk of osteoporotic fractures in patients with Cushing’s syndrome. Eur J Endocrinol. 2002b;146:51–6.PubMedCrossRefGoogle Scholar
  100. Wasnich RD. Vertebral fracture epidemiology. Bone. 1996;18:179S–83S.PubMedCrossRefGoogle Scholar
  101. Wuster C, Abs R, Bengtsson BA, et al. The influence of growth hormone deficiency, growth hormone replacement therapy, and other aspects of hypopituitarism on fracture rate and bone mineral density. J Bone Miner Res. 2001;16:398–405.PubMedCrossRefGoogle Scholar
  102. Zaidi M. Skeletal remodeling in health and disease. Nat Med. 2007;13:791–801.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Gherardo Mazziotti
    • 2
  • Mauro Doga
    • 1
  • Annamaria Formenti
    • 3
  • Stefano Frara
    • 1
  • Filippo Maffezzoni
    • 3
  • Andrea Giustina
    • 1
  1. 1.San Raffaele Vita-Salute UniversityMilanItaly
  2. 2.Endocrine Unit, Department of MedicineA.S.S.T. Carlo PomaMantovaItaly
  3. 3.Department of Molecular and Translational MedicineUniversity of BresciaBresciaItaly

Personalised recommendations