Skip to main content
SpringerLink
Log in

Pathophysiology of osteoporosis

Pathophysiologie der Osteoporose

  • Themenschwerpunkt
  • Published:
Wiener Medizinische Wochenschrift Aims and scope Submit manuscript

Zusammenfassung

Die Osteoporose ist eine klassische altersassoziierte Erkrankung, welche Frauen häufiger als Männer betrifft. Die Hypothese, daß die Osteoporose infolge einer Östrogendefizienz auftritt, wurde bereits 1941 von Albright et al. [1] aufgestellt. Die molekularbiologischen Wirkungsmechnismen der Östrogendefizienz postmenopausaler Frauen sowie älterer Männer werden in einer Vielzahl laufender Studien untersucht. Die Östrogendefizienz hat sowohl direkte als auch indirekte Einflüsse auf den Knochenmetabolismus, welche allesamt zu einer intensivierten Osteoklastogenese führen. Diese Übersichtsarbeit beleuchtet sowohl die endokrinologischen als auch die osteoimmunologischen Mechanismen, die zur Involutionsosteoporose führen.

Summary

Osteoporosis is a classical age-related disease that affects women more often than men. The hypothesis that osteoporosis is a consequence of estrogen deficiency, has been proposed as early as 1941 by Albright and colleagues [1]. The exact mechanisms of this steroid hormone deficiency in postmenopausal women as well as in the elderly men are continuously being unraveled. Collectively, estrogen deficiency has direct as well as indirect impacts on bone metabolism all of which promote osteoclastogenesis. This review aims at shedding light on the endocrine and osteoimmunological mechanisms that lead to involutional osteoporosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Albright F, Smith PH, Richardson AM. Postmenopausal osteoporosis. J Am Med Assoc, 116: 2465–2474, 1941

    Google Scholar 

  • Anonymous. Osteoporosis prevention, diagnosis and therapy. J Am Med Assoc, 285: 785–795, 2001

  • Kanis JA, Melton LJ III, Christiansen C, Johnston CC, Khaltaev N. Perspective. The diagnosis of osteoporosis. J Bone Miner Res, 9: 1137–1141, 1994

    PubMed  CAS  Google Scholar 

  • Riggs BL, Melton LJ III. Evidence for two distinct syndromes of involutional osteoporosis. Am J Med, 75: 899–901, 1983

    Article  PubMed  CAS  Google Scholar 

  • Riggs BL, Khosla S, Melton LJ III. 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, 13: 763–773, 1998

    Article  PubMed  CAS  Google Scholar 

  • Duque G, Troen BR. Understanding the mechanisms of senile osteoporosis: new facts for a major Geriatric syndrome. J Am Geriatr Soc, 56: 935–941, 2008

    Article  PubMed  Google Scholar 

  • Rauner M, Sipos W, Pietschmann P. Osteoimmunology. Int Arch Allergy Immunol, 143: 31–48, 2007

    Article  PubMed  Google Scholar 

  • Sipos W, Pietschmann P, Rauner M. Strategies for novel therapeutic approaches targeting cytokines and signalling pathways of osteoclasto- and osteoblastogenesis in the fight against immune-mediated bone and joint diseases. Curr Med Chem, 15: 127–136, 2008

    Article  PubMed  CAS  Google Scholar 

  • Eriksen EF, Colvard DS, Berg NJ, Graham ML, Mann KG, Spelsberg TC, Riggs BL. Evidence of estrogen receptors in normal human osteoblast-like cells. Science, 241: 84–86, 1988

    Article  PubMed  CAS  Google Scholar 

  • Komm BS, Terpening CM, Benz DJ, Graeme KA, O'Malley BW, Haussler MR. Estrogen binding receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells. Science, 241: 81–84, 1988

    Article  PubMed  CAS  Google Scholar 

  • Oursler MJ, Osdoby P, Pyfferoen J, Riggs BL, Spelsberg TC. Avian osteoclasts as estrogen target cells. Proc Natl Acad Sci USA, 88: 6613–6617, 1998

    Article  Google Scholar 

  • Saika M, Inoue D, Kido S, Matsumoto T. 17beta-estradiol stimulates expression of osteoprotegerin by a mouse stromal cell line, ST-2, via estrogen receptor-alpha. Endocrinology, 142: 2205–2212, 2001

    Article  PubMed  CAS  Google Scholar 

  • Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest, 111: 1120–1122, 2003

    Google Scholar 

  • Bord S, Ireland DC, Beavan SR, Compston JE. The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts. Bone, 32: 136–141, 2003

    Article  PubMed  CAS  Google Scholar 

  • Heaney RP, Recker RR, Saville PD. Menopause changes in calcium balance performance. J Lab Clin Med, 92: 953–963, 1978

    PubMed  CAS  Google Scholar 

  • McKane WR, Khosla S, Burritt MF, Kao PC, Wilson DM, Ory SJ, Riggs BL. Mechanism of renal calcium conservation with estrogen replacement therapy in women in early postmenopause – a clinical research center study. J Clin Endocrinol Metab, 80: 3458–3464, 1995

    Article  PubMed  CAS  Google Scholar 

  • Gennari C, Agnusdei D, Nardi P, Civitelli R. Estrogen preserves a normal intestinal responsiveness to 1,25-dihydroxyvitamin D3 in oophorectomized women. J Clin Endocrinol Metab, 71: 1288–1293, 1990

    PubMed  CAS  Google Scholar 

  • Cosman F, Nieves J, Horton J, Shen V, Lindsay R. Effects of estrogen on response to edetic acid infusion in postmenopausal osteoporotic women. J Clin Endocrinol Metab, 78: 939–943, 1994

    Article  PubMed  CAS  Google Scholar 

  • Cosman F, Shen V, Xie F, Seibel M, Ratcliffe A, Lindsay R. Estrogen protection against bone resorbing effects of parathyroid hormone infusion. Ann Intern Med, 118: 337–343, 1993

    PubMed  CAS  Google Scholar 

  • Gallagher JC, Riggs BL, Eisman J, Hamstra A, Arnaud SB, DeLuca HF. Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients: effect of age and dietary calcium. J Clin Invest, 64: 729–736, 1979

    Article  PubMed  CAS  Google Scholar 

  • Tsai K-S, Heath H III, Kumar R, Riggs BL. Impaired vitamin D metabolism with aging in women: possible role in pathogenesis of senile osteoporosis. J Clin Invest, 73: 1668–1672, 1984

    Article  PubMed  CAS  Google Scholar 

  • Ebeling PR, Snadgren ME, DiMagno EP, Lane AW, DeLuca HF, Riggs BL. Evidence of an age-related decrease in intestinal responsiveness to vitamin D: Relationship between serum 1,25-dihydroxyvitamin D3 and intestinal vitamin D receptor concentrations in normal women. J Clin Endocrinol Metab, 75: 176–182, 1992

    Article  PubMed  CAS  Google Scholar 

  • Pacifici R, Rifas L, McCracken R, Vered I, McMurtry C, Avioli LV, Peck WA. Ovarian steroid treatment blocks a postmenopausal increase in blood monocyte interleukin 1 release. Proc Natl Acad Sci USA, 86: 2398–2402, 1989

    Article  PubMed  CAS  Google Scholar 

  • Ernst M, Heath JK, Rodan GA. Estradiol effects on proliferation, messenger ribonucleic acid for collagen and insulin-like growth factor-I, and parathyroid hormone-stimulated adenylate cyclase activity in osteoblastic cells from calvariae and long bones. Endocrinology, 125: 825–833, 1989

    PubMed  CAS  Google Scholar 

  • Oursler MJ, Cortese C, Keeting PE, Anderson MA, Bonde SK, Riggs BL, Spelsberg TC. Modulation of transforming growth factor-β production in normal human osteoblast-like cells by 17β-estradiol and parathyroid hormone. Endocrinology, 129: 3313–3320, 1991

    Article  PubMed  CAS  Google Scholar 

  • Pacifici R. T cells and post menopausal osteoporosis in murine models. Arthritis Res Ther, 9: 102, 2007

    Article  PubMed  CAS  Google Scholar 

  • Robbie-Ryan M, Pacifici R, Weitzmann MN. IL-7 drives T cell-mediated bone loss following ovariectomy. Ann N Y Acad Sci, 1068: 348–351, 2006

    Article  PubMed  CAS  Google Scholar 

  • Gao Y, Grassi F, Ryan MR, Terauchi M, Page K, Yang X, Weitzmann MN, Pacifici R. IFN-γ stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation. J Clin Invest, 117: 122–132, 2007

    Article  PubMed  CAS  Google Scholar 

  • Pietschmann P, Grisar J, Thien R, Willheim M, Kerschan-Schindl K, Preisinger E, Peterlik M. Immune phenotype and intracellular cytokine production of peripheral blood mononuclear cells from postmenopausal patients with osteoporotic fractues. Exp Gerontol, 36: 1749–1759, 2001

    Article  PubMed  CAS  Google Scholar 

  • Zheng SX, Vrindts Y, Lopez M, De Groote D, Zngerle PF, Collette J, Franchimont N, Geenen V, Albert A, Reginster JY. Increase in cytokine production (IL-1β, IL-6, TNF-α but not IFN-γ, GM-CSF or LIF) by stimulated whole blood cells in postmenopausal osteoporosis. Maturitas, 26: 63–71, 1997

    Article  PubMed  CAS  Google Scholar 

  • Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci, 908: 244–254, 2000

    Article  PubMed  CAS  Google Scholar 

  • Pietschmann P, Gollob E, Brosch S, Hahn P, Kudlacek S, Willheim M, Woloszczuk W, Peterlik M, Tragl KH. The effect of age and gender on cytokine production by human peripheral blood mononuclear cells and markers of bone metabolism. Exp Gerontol, 38: 1119–1127, 2003

    Article  PubMed  CAS  Google Scholar 

  • Weitzamnn MN, Pacifici R. T cells: unexpected plyaers in the bone loss induced by estrogen deficieny and in basal bone homeostasis. Ann N Y Acad Sci, 1116:360–375, 2007

    Article  CAS  Google Scholar 

  • Grassi F, Tell G, Robbie-Ryan M, Gao Y, Terauchi M, Yang X, Romanello M, Jones DP Weitzmann MN, Pacifici R. Oxidative stress causes bone loss in estrogen-deficient mice through enhanced bone marrow dendritic cell activation. Proc Natl Acad Sci USA, 104: 15087–15092, 2007

    Article  PubMed  CAS  Google Scholar 

  • Cenci S, Toraldo G, Weitzmann MN, Roggin C, Gao Y, Qian WP, Sierra O, Pacifici R. Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-γ-induced class II transactivator. Proc Natl Acad Sci USA, 100: 10405–10410, 2003

    Article  PubMed  CAS  Google Scholar 

  • Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell, 89: 747–754, 1997

    Article  PubMed  CAS  Google Scholar 

  • Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell, 89: 755–764, 1997

    Article  PubMed  CAS  Google Scholar 

  • Rosen ED, Spiegelman BM. PPARgamma: a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem, 276: 37731–37734, 2001

    Article  PubMed  CAS  Google Scholar 

  • Lecka-Czernik B, Moerman EJ, Grant DF, Lehmann JM, Manolagas SC, Jilka RL. Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation. Endocrinology, 143: 2376–2384, 2002

    Article  PubMed  CAS  Google Scholar 

  • Kim SW, Her SJ, Kim SY, Shin CS. Ectopic overexpression of adipogenic transcription factors induces transdifferentiation of MC3T3-E1 osteoblasts. Biochem Biophys Res Commun, 327: 811–819, 2005

    Article  PubMed  CAS  Google Scholar 

  • Taleb S, Lacasa D, Bastard JP, Poitou C, Cancello R, Pelloux V, Viguerie N, Benis A, Zucker JD, Bouillot JL, Coussieu C, Basdevant A, Langin D, Clement K, Cathepsin S. A novel biomarker of adiposity: relevance to atherogenesis. FASEB J, 19: 1540–1542, 2005

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Clinic II, University of Veterinary Medicine Vienna, Vienna, Austria

    Wolfgang Sipos

  2. Ludwig Boltzmann-Institute of Aging Research, Vienna, Austria

    Peter Pietschmann

  3. Center for Physiology, Pathophysiology and Immunology, Department of Pathophysiology, Medical University of Vienna, Vienna, Austria

    Peter Pietschmann & Janina Patsch

  4. Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine III, Technical University, Dresden, Germany

    Martina Rauner

  5. Department of Physical Medicine and Rehabilitation, Medical University of Vienna, Vienna, Austria

    Katharina Kerschan-Schindl

Authors
  1. Wolfgang Sipos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Pietschmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martina Rauner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katharina Kerschan-Schindl
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Janina Patsch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wolfgang Sipos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sipos, W., Pietschmann, P., Rauner, M. et al. Pathophysiology of osteoporosis. Wien Med Wochenschr 159, 230–234 (2009). https://doi.org/10.1007/s10354-009-0647-y

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10354-009-0647-y

Schlüsselwörter

Keywords

Search

Navigation