Immunology of Osteoporosis

  • Katharina Kerschan-Schindl
  • Elena Nebot Valenzuela
  • Peter PietschmannEmail author
Living reference work entry


In healthy bone, resorption and formation are balanced. Bone metabolism involves different cells and is influenced by many regulatory factors: age, genetics, mechanical stimulus, hormones, endocrine diseases, and medication. Disturbances in bone metabolism may lead to osteoporosis, a frequent disease in postmenopausal women, elderly subjects, patients suffering from inflammatory diseases, as well as patients who need glucocorticoids or immunosuppressive medication. Osteoclasts and immune cells share the same progenitors, the same microenvironment, and a number of regulatory molecules as well. The tight connection between the bone and immune cells explains the cross talk between these systems. In this chapter, the negative effects of the decline of ovarian function, senescence-associated inflammaging, pro-inflammatory cytokines expressed by immune cells, and immunosuppressive therapy on bone metabolism are described, and especially immunological aspects are highlighted. Studies further evaluating the cross talk between the bone and immune cells may lead to new, even more effective therapeutic strategies for the prevention and treatment of primary and secondary osteoporosis.


Osteoporosis Osteoimmunology Osteoclast Osteoblast RANKL Osteoprotegerin Rheumatoid arthritis Organ transplantation 


  1. Alikhani M, Alikhani Z, Boyd C, MacLellan CM, Raptis M, Liu R, Pischon N, Trackman PC, Gerstenfeld L, Graves DT (2007) Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways. Bone 40:345–353PubMedCrossRefPubMedCentralGoogle Scholar
  2. Ammann P, Rizzoli R, Bonjour JP, Bourrin S, Meyer JM, Vassalli P, Garcia I (1997) Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiency. J Clin Invest 99(7):1699–1703PubMedPubMedCentralCrossRefGoogle Scholar
  3. Andersen TL, Sondergaard TE et al (2009) A physical mechanism for coupling bone resorption and formation in adult human bone. Am J Pathol 174(1):239–247PubMedPubMedCentralCrossRefGoogle Scholar
  4. Anderson HC (2003) Matrix vesicles and calcification. Curr Rheumatol Rep 5(3):222–226PubMedCrossRefPubMedCentralGoogle Scholar
  5. Arron JR, Choi Y (2000) Bone versus immune system. Nature 408:535–536PubMedCrossRefPubMedCentralGoogle Scholar
  6. Bakker AD, da Silva VC, Krishnan R, Bacabac RG, Blaauboer ME, Lin YC et al (2009) Tumor necrosis factor α and interleukin-1ß modulate calcium and nitric oxide signaling in mechanically stimulated osteocytes. Arthritis Rheum 60:3336–3345PubMedCrossRefPubMedCentralGoogle Scholar
  7. Baschant U, Culemann S, Tuckermann J (2013) Molecular determinants of glucocorticoid actions in inflammatory joint diseases. Mol Cell Endocrinol 380:108–118PubMedCrossRefPubMedCentralGoogle Scholar
  8. Bauer ME, De la Fuente M (2016) The role of oxidative and inflammatory stress and persistent viral infections in immunosenescence. Mech Ageing Dev 158:27–37PubMedCrossRefPubMedCentralGoogle Scholar
  9. Bellido T (2014) Osteocyte-driven bone remodeling. Calcif Tissue Int 94(1):25–34PubMedCrossRefPubMedCentralGoogle Scholar
  10. Bellido T, Stahl N, Farruggella TJ et al (1996) Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal/osteoblastic cells. J Clin Invest 97(2):431–437PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bin G, Cuifang W, Bp Z, Jing W, Jin J, Xianyi T et al (2015) Fluid shear stress inhibits TNF-α-induced osteoblast apoptosis via ERK5 signaling pathway. Biochem Biophys Res Commun 466:117–123PubMedCrossRefPubMedCentralGoogle Scholar
  12. Boskey AL (2013) Bone composition: relationship to bone fragility and antiosteoporotic drug effects. BoneKEy Rep 2:447PubMedPubMedCentralCrossRefGoogle Scholar
  13. Boskey AL, Coleman R (2010) Aging and bone. J Dent Res 89(12):1333–1348PubMedPubMedCentralCrossRefGoogle Scholar
  14. Boskey A, Mendelsohn R (2005) Infrared analysis of bone in health and disease. J Biomed Opt 10(3):031102PubMedCrossRefPubMedCentralGoogle Scholar
  15. Bouxsein ML (2005) Determinants of skeletal fragility. Best Pract Res Clin Rheumatol 19(6):897–911PubMedCrossRefPubMedCentralGoogle Scholar
  16. Boyce BF, Hughes DE et al (1999) Recent advances in bone biology provide insight into the pathogenesis of bone diseases. Lab Investig; J Tech Methods Pathol 79(2):83–94Google Scholar
  17. Brabnikova Maresova K, Pavelka K, Stepan JJ (2013) Acute effects of glucocorticoids on serum markers of osteoclasts, osteoblasts, and osteocytes. Clacif Tissue Int 92:354–361CrossRefGoogle Scholar
  18. Breuil V, Ticchioni M, Testa J et al (2010) Immune changes in post-menopausal osteoporosis: the immunos study. Osteoporos Int 21(5):805–814PubMedCrossRefPubMedCentralGoogle Scholar
  19. Bultnik IEM, Vis M, van der Horst-Bruinsma IE, Lems WF (2012) Inflammatory rheumatic disorders and bone. Curr Rheumatol Rep 14:224–230CrossRefGoogle Scholar
  20. Capulli M, Paone R et al (2014) Osteoblast and osteocyte: games without frontiers. Arch Biochem Biophys 561:3–12PubMedCrossRefPubMedCentralGoogle Scholar
  21. Casals-Seoane F et al (2016) Clinical course of bone metabolism disorders in patients with inflammatory bowel disease: a 5-year prospective study. Inflamm Bowel Dis 22:1929–1936, epubPubMedCrossRefPubMedCentralGoogle Scholar
  22. Chrischilles EA, Butler CD et al (1991) A model of lifetime osteoporosis impact. Arch Intern Med 151(10):2026–2032PubMedCrossRefPubMedCentralGoogle Scholar
  23. Crockett JC, Mellis DJ et al (2011) New knowledge on critical osteoclast formation and activation pathways from study of rare genetic diseases of osteoclasts: focus on the RANK/RANKL axis. Osteoporos Int: J Established Result Cooperation Between Eur Found Osteopor Natl Osteopor Found USA 22(1):1–20CrossRefGoogle Scholar
  24. Croess M, Oner FC, Kruyt MC, Blokhuis TJ, Bastian O, Dhert WJA et al (2015) Proinflammatory mediators enhance the osteogenesis of human mesenchymal stem cells after lineage commitment. PLoS One 10:e0132781CrossRefGoogle Scholar
  25. D’Amelio P, Grimaldi A, Di Bella S, Brianza SZ, Cristofaro MA, Tamone C, Giribaldi G, Ulliers D, Pescarmona GP, Isia G (2008) Estrogen deficiency increases osteoclastogenesis upregulating T cells activity: a key mechanism in osteoporosis. Bone 43:92–100PubMedCrossRefPubMedCentralGoogle Scholar
  26. Dahl T, Veis A (2003) Electrostatic interactions lead to the formation of asymmetric collagen-phosphophoryn aggregates. Connect Tissue Res 44(Suppl 1):206–213PubMedCrossRefPubMedCentralGoogle Scholar
  27. Dallas SL, Prideaux M et al (2013) The osteocyte: an endocrine cell ... and more. Endocr Rev 34(5):658–690PubMedPubMedCentralCrossRefGoogle Scholar
  28. Devlin RD, Reddy SV, Savino R et al (1998) IL-6 mediates the effects of IL-1 or TNF, but not PTHrP or 1,25(OH)2D3, on osteoclast-like cell formation in normal human bone marrow cultures. J Bone Miner Res 13(3):393–399PubMedCrossRefPubMedCentralGoogle Scholar
  29. Donahue HJ, McLeod KJ et al (1995) Cell-to-cell communication in osteoblastic networks: cell line-dependent hormonal regulation of gap junction function. J Bone Miner Res: Off J Am Soc Bone Miner Res 10(6):881–889CrossRefGoogle Scholar
  30. Donnelly E, Meredith DS et al (2012) Bone tissue composition varies across anatomic sites in the proximal femur and the iliac crest. J Orthop Res: Off Publ Orthop Res Soc 30(5):700–706CrossRefGoogle Scholar
  31. Downey PA, Siegel MI (2006) Bone biology and the clinical implications for osteoporosis. Phys Ther 86(1):77–91PubMedCrossRefPubMedCentralGoogle Scholar
  32. Effros RB (2004) Replicative senescence of CD8 T cells: effect on human aeing. Exp Gerontol 39(4):517–524PubMedCrossRefPubMedCentralGoogle Scholar
  33. Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL (2003) Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Investig 111(8):1221–1230PubMedPubMedCentralCrossRefGoogle Scholar
  34. Everts V, Delaisse JM et al (2002) The bone lining cell: its role in cleaning Howship’s lacunae and initiating bone formation. J Bone Miner Res: Off J Am Soc Bone Miner Res 17(1):77–90CrossRefGoogle Scholar
  35. Faienza MF, Ventura A, Marzano F, Cavallo L (2013) Postmenopausal osteoporosis: the role of immune cells. Clin Dev Immunol 2013:575936PubMedPubMedCentralCrossRefGoogle Scholar
  36. Felsenberg D, Boonen S (2005) The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther 27(1):1–11PubMedCrossRefPubMedCentralGoogle Scholar
  37. Feng X, McDonald JM (2011) Disorders of bone remodeling. Annu Rev Pathol 6:121–145PubMedPubMedCentralCrossRefGoogle Scholar
  38. Florencio-Silva R, Sasso GR et al (2015) Biology of bone tissue: structure, function, and factors that influence bone cells. Biomed Res Int 2015:421746PubMedPubMedCentralCrossRefGoogle Scholar
  39. Föger-Samwald U, Vekszler G, Hörz-Schuch E, Salem S, Wipperich M, Ritschl P, Mousavi M, Pietschmann P (2016) Molecular mechanisms of osteoporotic hip fractures in ledery women. Exp Gerontol 73:49–58PubMedCrossRefGoogle Scholar
  40. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging: an evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254PubMedCrossRefPubMedCentralGoogle Scholar
  41. Franke S, Siggelkow H, Wolf G, Hein G (2007) Advanced glycation endproducts influence the mRNA expression of RAGE, RANKL and various osteoblastic genes in human osteoblast. Arch Physiol Biochem 113(3):154–161PubMedCrossRefPubMedCentralGoogle Scholar
  42. Franz-Odendaal TA, Hall BK et al (2006) Buried alive: how osteoblasts become osteocytes. Dev Dyn: Off Publ Am Assoc Anatomists 235(1):176–190CrossRefGoogle Scholar
  43. Garnero P, Tabassi NC, Voorzanger-Rousselot N (2008) Circulating dickkopf-1 and radiological progression in patients with early rheumatoid arthritis treated with etanercept. J Rheumatol 35(12):2313–2315PubMedCrossRefPubMedCentralGoogle Scholar
  44. Ginaldi L, De Martins M, Ciccarelli F, Saitta S, Imbesi S, Mannucci C, Gangemi S (2015) Increased levels of interleukin 31 (IL-31) in osteoporosis. BMC Immunol 16:60PubMedPubMedCentralCrossRefGoogle Scholar
  45. Girasole G, Jilka RL, Passeri G et al (1992) 17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. J Clin Invest 89(3):883–891PubMedPubMedCentralCrossRefGoogle Scholar
  46. Glimcher MJ (1998) In: Glimcher MJ (ed) The nature of the mineral phase in bone. Metabolic bone disease. Academic, San Diego, pp 23–50Google Scholar
  47. Gregson CL, Paggiosi MA et al (2013) Analysis of body composition in individuals with high bone mass reveals a marked increase in fat mass in women but not men. J Clin Endocrinol Metab 98(2):818–828PubMedPubMedCentralCrossRefGoogle Scholar
  48. Harvey N, Dennison E et al (2014) Osteoporosis: a life course approach. J Bone Miner Res: Off J Am Soc Bone Miner Res 29(9):1917–1925CrossRefGoogle Scholar
  49. Haugberg G, Morton S, Emery P, Conaghan PG (2005) Effect of intra-articular corticosteroid injections and inflammation on periarticular and generalised bone loss in early rheumatoid arthritis. Arch Int Med 70(1):184–187Google Scholar
  50. Hernandez CJ, Gupta A et al (2006) A biomechanical analysis of the effects of resorption cavities on cancellous bone strength. J Bone Miner Res: Off J Am Soc Bone Miner Res 21(8):1248–1255CrossRefGoogle Scholar
  51. Hernlund E, Svedbom A et al (2013) Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 8:136PubMedPubMedCentralCrossRefGoogle Scholar
  52. Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL (1999) Estrogen stimulated gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 140(9):4367–4370PubMedCrossRefPubMedCentralGoogle Scholar
  53. Jilka RL, Weinstein RS et al (1998) Osteoblast programmed cell death (apoptosis): modulation by growth factors and cytokines. J Bone Miner Res: Off J Am Soc Bone Miner Res 13(5):793–802CrossRefGoogle Scholar
  54. Kanematsu M, Sato T, Takai K, Watanabe K, Ikeda K, Yamada Y (2000) Prostaglandin E-2 induces expression of receptor activator of nuclear factor -B ligand/osteoprotegerin ligand on pre-B cells: implications for accelerated osteoclastogenesis in estrogen deficiency. J Bone Miner Res 15(7):1321–1329PubMedCrossRefPubMedCentralGoogle Scholar
  55. Kanis JA, Burlet N et al (2008) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 19(4):399–428PubMedPubMedCentralCrossRefGoogle Scholar
  56. Kerschan-Schindl K, Strametz-Juranek J, Heinze G, Grampp S, Bieglmayer C, Pacher R et al (2003) Pathogenesis of bone loss in heart transplant candidates and recipients. J Heart Lung Transplant 22:843–850PubMedCrossRefPubMedCentralGoogle Scholar
  57. Kerschan-Schindl K, Mitterbauer M, Füreder W, Kudlacek S, Grampp S, Bieglmayer C et al (2004) Bone metabolism in patients more than five years after bone marrow transplantation. Bone Marrow Transplant 34:491–496PubMedCrossRefPubMedCentralGoogle Scholar
  58. Kim BJ, Bae J, Lee SY et al (2012) TNF-α mediates the stimulation of sclerostin expression in an estrogen-deficient condition. Biochem Biophys Res Commun 424:170–175PubMedCrossRefPubMedCentralGoogle Scholar
  59. Kjaer M (2004) Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev 84(2):649–698PubMedCrossRefPubMedCentralGoogle Scholar
  60. Krabbe KS, Pedersen M, Bruunsgard H (2004) Inflammatory mediators in the elderly. Exp Gerontol 39:687–699PubMedCrossRefPubMedCentralGoogle Scholar
  61. Kurihara N, Bertolini D, Suda T et al (1990) IL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release. J Immunol 144(11):4226–4230PubMedPubMedCentralGoogle Scholar
  62. Lee Y, Toraldo G, Li A, Yang X, Zhang H, Quian WP, Weitzmann MN (2007) B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo. Blood 109:3839–3848CrossRefGoogle Scholar
  63. Lohmann R, Haid K et al (2007) Epidemiology and perspectives in traumatology of the elderly. Unfallchirurg 110(6):553–560; quiz 561–552PubMedCrossRefPubMedCentralGoogle Scholar
  64. Lorenzo JA, Naprta A, Rao Y, Alander C, Glaccum M, Widmer M, Gronowicz G, Kalinowski J, Pilbeam CC (1998) Mice lacking the type I interleukin-1 receptor do not lose bone mass after ovariectomy. Endocrinology 139(6):3022–3035PubMedCrossRefPubMedCentralGoogle Scholar
  65. Manolagas SC (2000) Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21(2):115–137PubMedPubMedCentralGoogle Scholar
  66. Martin RM, Correa PH (2010) Bone quality and osteoporosis therapy. Arq Bras Endocrinol Metabol 54(2):186–199PubMedCrossRefPubMedCentralGoogle Scholar
  67. Mays S (1998) The archaeology of human bones. Routledge, LondonCrossRefGoogle Scholar
  68. Melek J, Sakuraba A (2014) Efficacy and safety of medical therapy for low bone mineral density in patients with inflammatory bowel disease: a meta-analysis and systematic review. Clin Gastroenterol Hepatol 12:32.44CrossRefGoogle Scholar
  69. Miller SC, de Saint-Georges L et al (1989) Bone lining cells: structure and function. Scanning Microsc 3(3):953–960; discussion 960–951PubMedPubMedCentralGoogle Scholar
  70. Mirza FS, Padhi ID, Raisz LG, Lorenzo JA (2010) Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab 95(4):1991–1997PubMedPubMedCentralCrossRefGoogle Scholar
  71. Nakashima K, Zhou X et al (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108(1):17–29PubMedCrossRefPubMedCentralGoogle Scholar
  72. Ott C, Jacobs K, Hauke E, Navarrete Santos A, Grune T, Stimm A (2014) Role of advanced glycation end products in cellular signaling. Redox Biol 2:411–429PubMedPubMedCentralCrossRefGoogle Scholar
  73. Pacifici R (2010) T cells: critical bone regulators in health and disease. Bone 47(3):461–471PubMedPubMedCentralCrossRefGoogle Scholar
  74. Pacifici R, Brown C, Puscheck E, Friedrih E, Slatopolsky E, Maggio D, McCracken R, Avioli LV (1991) Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells. Proc Natl Acad Sci U S A 88(12):134–138CrossRefGoogle Scholar
  75. Pietschmann P (ed) (2012) Principles of osteoimmunology, molecular mechanism and clinical applications. Vienna, SpringerGoogle Scholar
  76. Pietschmann P, Grisar J, Thien R, Willheim M, Kerschan-Schindl K, Preisinger E, Peterlik M (2001) Immune phenotype and intracellular cytokine production of peripheral blood mononuclear cells from postmenopausal patients with osteoporotic fractures. Exp Gerontol 908:244–254Google Scholar
  77. Pietschmann P, Rauner M et al (2009) Osteoporosis: an age-related and gender-specific disease – a mini-review. Gerontology 55(1):3–12PubMedCrossRefPubMedCentralGoogle Scholar
  78. Pietschmann P, Mechtcheriakova D et al (2015) Immunology of osteoporosis: a mini-review. Gerontology 62:128–137PubMedPubMedCentralCrossRefGoogle Scholar
  79. Proyanka HP, Sharma U, Gopinath S, Sharma V, Hima L, ThyagaRajan S (2013) Menstrual cycle and reproductive aging alters immune reactivity, NGF expression, antioxidant enzyme activities, and intracellular signaling pathways in the peripheral blood mononuclear cells of healthy women. Brain Behav Immunol 32:131–143CrossRefGoogle Scholar
  80. Rachner TD, Khosla S et al (2011) Osteoporosis: now and the future. Lancet 377(9773):1276–1287PubMedPubMedCentralCrossRefGoogle Scholar
  81. Ralston SH (1994) Analysis of gene expression in human bone biopsies by polymerase chain reaction: evidence for enhanced cytokine expression in postmenopausal osteoporosis. J Bone Miner Res 9(6):883–890PubMedCrossRefPubMedCentralGoogle Scholar
  82. Rizzoli R, Biver E (2015) Glucocorticoid-induced osteoporosis: who to treat with what agent? Nat Rev Rheumatol 11(2):98–109PubMedCrossRefPubMedCentralGoogle Scholar
  83. Saeed H, Abdallah BM, Ditzel N, Catala-Lehnen P, Qiu W, Amling M, Kassem M (2011) Telomerase-deficient mice exhibit bone loss owing to defects in osteoblasts and increased osteoclastogenesis by inflammatory microenvironment. J Bone Miner Res 26(7):1494–1505PubMedCrossRefPubMedCentralGoogle Scholar
  84. Seeman E (2008) Structural basis of growth-related gain and age-related loss of bone strength. Rheumatology 47(Suppl 4):iv2–iv8PubMedPubMedCentralGoogle Scholar
  85. Sidney LE, Kirkham GR, Buttery LE (2014) Comparison of osteogenic differentiation of embryonic stem cells and primary osteoblasts revealed by responses to IL-1ß, TNF-α, and IFN-γ. Stem Cells Dev 23:605–617PubMedCrossRefPubMedCentralGoogle Scholar
  86. Sipos W, Föger-Samwald U, Pietschmann P (2014) Supporting apparatus of vertebrates skeleton and bones. In: Jensen-Jarolim E (ed) Comparative medicine – anatomy and physiology. Springer Verlag, Wien, pp 35–44Google Scholar
  87. Stein B, Yang MX (1995) Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta. Mol Cell Biol 15(9):4971–4979PubMedPubMedCentralCrossRefGoogle Scholar
  88. Steinbruch M, Youket TE, Cohen S (2004) Oral glucocorticoid use is associated with an increased risk of fracture. Osteoporos Int 15(4):323–328CrossRefGoogle Scholar
  89. Steves CJ, Bird S, Williams FMK, Spector TD (2016) The microbiome and musculoskeletal conditions of aging: a review of evidence for impact and potential therapeutics. JBMR 31(2):261–269CrossRefGoogle Scholar
  90. Straub RH, Cutolo M, Pacifici R (2015) Evolutionary medicine and bone loss in chronic inflammatory diseases – a theory of inflammation-related osteopenia. Semin Arthritis Rheum 45:220–228PubMedPubMedCentralCrossRefGoogle Scholar
  91. Taichman RS (2005) Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood 105(7):2631–2639PubMedCrossRefPubMedCentralGoogle Scholar
  92. Takayanagi H (2007) Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol 7(4):292–304PubMedCrossRefPubMedCentralGoogle Scholar
  93. Tyagi AM, Srivastava K, Mansoori MN, Trivedi R, Chattopadhyay N, Singh D (2012) Estrogen deficiency induces the differentiation of IL-17 secreting Th17 cells: a new candidate in the pathogenesis of osteoporosis. PLoS One 7:e44552PubMedPubMedCentralCrossRefGoogle Scholar
  94. Tzaphlidou M (2005) The role of collagen in bone structure: an image processing approach. Micron 36(7–8):593–601PubMedCrossRefPubMedCentralGoogle Scholar
  95. Unnanuntana A, Rebolledo BJ et al (2011) Diseases affecting bone quality: beyond osteoporosis. Clin Orthop Relat Res 469(8):2194–2206PubMedCrossRefPubMedCentralGoogle Scholar
  96. van Helden S, van Geel AC et al (2008) Bone and fall-related fracture risks in women and men with a recent clinical fracture. J Bone Joint Surg Am 90(2):241–248PubMedCrossRefPubMedCentralGoogle Scholar
  97. van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW (2005) Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther 7(5):R949–R958PubMedPubMedCentralCrossRefGoogle Scholar
  98. van Staa TP, Geusens P, Bijlsma JW, Leufkens HG, Cooper C (2006) Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 54(10):3104–3112PubMedCrossRefPubMedCentralGoogle Scholar
  99. Viguet-Carrin S, Garnero P et al (2006) The role of collagen in bone strength. Osteoporos Int: J Established Result Cooperation Between Eur Found Osteoporos Natl Osteoporos Found USA 17(3):319–336CrossRefGoogle Scholar
  100. Wang TK, O’Sullivan S, Gamble GD, Ruygrok PN (2013) Bone density in heart or lung transplant recipients – a longitudinal study. Transplant Proc 45:2357–2365PubMedCrossRefPubMedCentralGoogle Scholar
  101. Weitzmann MN (2013) The role of inflammatory cytokines, the RANKL/OPG axis, and the immunoskeletal interface in physiological bone turnover and osteoporosis. Scientifica 2013:125705PubMedPubMedCentralCrossRefGoogle Scholar
  102. Weitzmann MN, Cenci S, Rifas L et al (2000) Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines. Blood 96(5):1873–1878PubMedPubMedCentralGoogle Scholar
  103. Yavropoulou MP, Yovos JG (2008) Osteoclastogenesis – current knowledge and future perspectives. J Musculoskelet Neuronal Interact 8(3):204–216PubMedPubMedCentralGoogle Scholar
  104. Yoshiko Y, Candeliere GA et al (2007) Osteoblast autonomous Pi regulation via Pit1 plays a role in bone mineralization. Mol Cell Biol 27(12):4465–4474PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Katharina Kerschan-Schindl
    • 1
  • Elena Nebot Valenzuela
    • 2
    • 3
  • Peter Pietschmann
    • 2
    Email author
  1. 1.Department of Physical Medicine and RehabilitationMedical University of ViennaViennaAustria
  2. 2.Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
  3. 3.Department of Physiology and Department of Preventive Medicine and Public Health, School of PharmacyUniversity of GranadaGranadaSpain

Personalised recommendations