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The Pituitary-Bone Axis

  • Mone ZaidiEmail author
  • Li Sun
  • Jameel Iqbal
Conference paper
  • 1.2k Downloads
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 707)

Abstract

Osteoporosis is a crippling disease, marked by skeletal fragility and resulting in a fracture in one out of every two individuals over the age of 50. What causes this increased bone fragility and resulting susceptibility fractures has, however, remained unclear. In the early 1700s the British surgeon John Hunter hypothesized that bone undergoes remodeling, that is, bone is forever changing itself by reorganizing into a newer, stronger configuration to resist ongoing stresses, such as physical activity [1]. Bone is lost when the cells degrading old bone, the osteoclasts, outpace the cells re-laying new collagen and mineral, the osteoblasts.

Keywords

Bone Loss Osteoclast Formation Final Menstrual Period Perimenopausal Period Estrogen Hormone Replacement Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

M.Z. and L.S. are supported by grants from the National Institutes of Health. J.I. acknowledges the support of the American Federation for Aging Research.

References

  1. 1.
    Evans CH. John Hunter and the origins of modern orthopaedic research. J Orthop Res 2007 25 556–560.PubMedCrossRefGoogle Scholar
  2. 2.
    Reifenstein EC, Jr. & Albright F. The metabolic effects of steroid hormones in osteoporosis. J Clin Invest 1947 26 24–56.CrossRefGoogle Scholar
  3. 3.
    Randolph JF, Jr., Sowers M, Bondarenko IV, Harlow SD, Luborsky JL & Little RJ. Change in estradiol and follicle-stimulating hormone across the early menopausal transition: effects of ethnicity and age. J Clin Endocrinol Metab 2004 89 1555–1561.PubMedCrossRefGoogle Scholar
  4. 4.
    Sowers MR, Jannausch M, McConnell D, Little R, Greendale GA, Finkelstein JS, Neer RM, Johnston J & Ettinger B. Hormone predictors of bone mineral density changes during the menopausal transition. J Clin Endocrinol Metab 2006 91 1261–1267.PubMedCrossRefGoogle Scholar
  5. 5.
    Akhter MP, Lappe JM, Davies KM & Recker RR. Transmenopausal changes in the trabecular bone structure. Bone 2007 41 111–116.PubMedCrossRefGoogle Scholar
  6. 6.
    Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, Harada Y, Azuma Y, Krust A, Yamamoto Y, Nishina H, Takeda S, Takayanagi H, Metzger D, Kanno J, Takaoka K, Martin TJ, Chambon P & Kato S. Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell 2007 130 811–823.PubMedCrossRefGoogle Scholar
  7. 7.
    Shevde NK, Bendixen AC, Dienger KM & Pike JW. Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression. Proc Natl Acad Sci USA 2000 97 7829–7834.PubMedCrossRefGoogle Scholar
  8. 8.
    Srivastava S, Toraldo G, Weitzmann MN, Cenci S, Ross FP & Pacifici R. Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-kappa B ligand (RANKL)-induced JNK activation. J Biol Chem 2001 276 8836–8840.PubMedCrossRefGoogle Scholar
  9. 9.
    Srivastava S, Weitzmann MN, Kimble RB, Rizzo M, Zahner M, Milbrandt J, Ross FP & Pacifici R. Estrogen blocks M-CSF gene expression and osteoclast formation by regulating phosphorylation of Egr-1 and its interaction with Sp-1. J Clin Invest 1998 102 1850–1859.PubMedCrossRefGoogle Scholar
  10. 10.
    Armour KE, Armour KJ, Gallagher ME, Godecke A, Helfrich MH, Reid DM & Ralston SH. Defective bone formation and anabolic response to exogenous estrogen in mice with targeted disruption of endothelial nitric oxide synthase. Endocrinology 2001 142 760–766.PubMedCrossRefGoogle Scholar
  11. 11.
    Garcia Palacios V, Robinson LJ, Borysenko CW, Lehmann T, Kalla SE & Blair HC. Negative regulation of RANKL-induced osteoclastic differentiation in RAW264.7 Cells by estrogen and phytoestrogens. J Biol Chem 2005 280 13720–13727.PubMedCrossRefGoogle Scholar
  12. 12.
    Roggia C, Gao Y, Cenci S, Weitzmann MN, Toraldo G, Isaia G & Pacifici R. Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo. Proc Natl Acad Sci USA 2001 98 13960–13965.PubMedCrossRefGoogle Scholar
  13. 13.
    Jagger CJ, Chow JW & Chambers TJ. Estrogen suppresses activation but enhances formation phase of osteogenic response to mechanical stimulation in rat bone. J Clin Invest 1996 98 2351–2357.PubMedCrossRefGoogle Scholar
  14. 14.
    Abe E, Marians RC, Yu W, Wu XB, Ando T, Li Y, Iqbal J, Eldeiry L, Rajendren G, Blair HC, Davies TF & Zaidi M. TSH is a negative regulator of skeletal remodeling. Cell 2003 115 151–162.PubMedCrossRefGoogle Scholar
  15. 15.
    Abe E, Sun L, Mechanick J, Iqbal J, Yamoah K, Baliram R, Arabi A, Moonga BS, Davies TF & Zaidi M. Bone loss in thyroid disease: role of low TSH and high thyroid hormone. Ann N Y Acad Sci 2007 1116 383–391.PubMedCrossRefGoogle Scholar
  16. 16.
    Sowers MR, Greendale GA, Bondarenko I, Finkelstein JS, Cauley JA, Neer RM & Ettinger B. Endogenous hormones and bone turnover markers in pre- and perimenopausal women: SWAN. Osteoporos Int 2003 14 191–197.PubMedCrossRefGoogle Scholar
  17. 17.
    Xu ZR, Wang AH, Wu XP, Zhang H, Sheng ZF, Wu XY, Xie H, Luo XH & Liao EY. Relationship of age-related concentrations of serum FSH and LH with bone mineral density, prevalence of osteoporosis in native Chinese women. Clin Chim Acta 2009 400 8–13.PubMedCrossRefGoogle Scholar
  18. 18.
    Sowers MR, Zheng H, Jannausch ML, McConnell D, Nan B, Harlow S & Randolph JF, Jr. Amount of Bone Loss in Relation to Time around the Final Menstrual Period and Follicle-Stimulating Hormone Staging of the Transmenopause. J Clin Endocrinol Metab 2010 95(5) 2155–2162.Google Scholar
  19. 19.
    Zaidi M, Turner CH, Canalis E, Pacifici R, Sun L, Iqbal J, Guo XE, Silverman S, Epstein S & Rosen CJ. Bone loss or lost bone: rationale and recommendations for the diagnosis and treatment of early postmenopausal bone loss. Curr Osteoporos Rep 2009 7 118–126.PubMedCrossRefGoogle Scholar
  20. 20.
    Sun L, Peng Y, Sharrow AC, Iqbal J, Zhang Z, Papachristou DJ, Zaidi S, Zhu LL, Yaroslavskiy BB, Zhou H, Zallone A, Sairam MR, Kumar TR, Bo W, Braun J, Cardoso-Landa L, Schaffler MB, Moonga BS, Blair HC & Zaidi M. FSH directly regulates bone mass. Cell 2006 125 247–260.PubMedCrossRefGoogle Scholar
  21. 21.
    Wu Y, Torchia J, Yao W, Lane NE, Lanier LL, Nakamura MC & Humphrey MB. Bone microenvironment specific roles of ITAM adapter signaling during bone remodeling induced by acute estrogen-deficiency. PLoS One 2007 2 e586.PubMedCrossRefGoogle Scholar
  22. 22.
    Iqbal J, Sun L, Kumar TR, Blair HC & Zaidi M. Follicle-stimulating hormone stimulates TNF production from immune cells to enhance osteoblast and osteoclast formation. Proc Natl Acad Sci USA 2006 103 14925–14930.PubMedCrossRefGoogle Scholar
  23. 23.
    Cannon JG, Cortez-Cooper M, Meaders E, Stallings J, Haddow S, Kraj B, Sloan G & Mulloy A. Follicle-stimulating hormone, interleukin-1, and bone density in adult women. Am J Physiol Regul Integr Comp Physiol 2010 298(3) R790–798.Google Scholar
  24. 24.
    Iqbal J & Zaidi M. Understanding estrogen action during menopause. Endocrinology 2009 150 3443–3445.PubMedCrossRefGoogle Scholar
  25. 25.
    Devleta B, Adem B & Senada S. Hypergonadotropic amenorrhea and bone density: new approach to an old problem. J Bone Miner Metab 2004 22 360–364.PubMedCrossRefGoogle Scholar
  26. 26.
    Liu S, Cheng Y, Fan M, Chen D & Bian Z. FSH aggravates periodontitis-related bone loss in ovariectomized rats. J Dent Res 2010 89(4) 366–371.Google Scholar
  27. 27.
    Liu S, Cheng Y, Xu W & Bian Z. Protective effects of follicle-stimulating hormone inhibitor on alveolar bone loss resulting from experimental periapical lesions in ovariectomized rats. J Endod 2010 36(4) 658–663.Google Scholar
  28. 28.
    Ralston SH. Genetics of osteoporosis. Ann N Y Acad Sci 2010 1192 181–189.Google Scholar
  29. 29.
    Rendina D, Gianfrancesco F, De Filippo G, Merlotti D, Esposito T, Mingione A, Nuti R, Strazzullo P, Mossetti G & Gennari L. FSHR gene polymorphisms influence bone mineral density and bone turnover in postmenopausal women. Eur J Endocrinol 2010 163(1) 165–172.Google Scholar
  30. 30.
    Iqbal J, Davies TF, Sun L, Abe E, Carpi A, Mechanick JI & Zaidi M. Skeletal morphofunctional considerations and the pituitary-thyroid axis. Front Biosci (Schol Ed) 2009 1 92–107.Google Scholar
  31. 31.
    van der Deure WM, Uitterlinden AG, Hofman A, Rivadeneira F, Pols HA, Peeters RP & Visser TJ. Effects of serum TSH and FT4 levels and the TSHR-Asp727Glu polymorphism on bone: the Rotterdam Study. Clin Endocrinol (Oxf) 2008 68 175–181.Google Scholar
  32. 32.
    Heemstra KA, van der Deure WM, Peeters RP, Hamdy NA, Stokkel MP, Corssmit EP, Romijn JA, Visser TJ & Smit JW. Thyroid hormone independent associations between serum TSH levels and indicators of bone turnover in cured patients with differentiated thyroid carcinoma. Eur J Endocrinol 2008 159 69–76.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.The Mount Sinai Bone Program, Mount Sinai School of MedicineNew YorkUSA
  2. 2.Departments of MedicineBaylor College of MedicineHoustonUSA

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