Skip to main content
SpringerLink
Log in

Osteoporosis, Inflammation, and Aging

  • Reference work entry
  • First Online:
Handbook of Immunosenescence

Abstract

Osteoporosis is substantially an age-related condition characterized by low bone mass and increased bone fragility, putting the patients at risk of fractures, which are major causes of morbidity and mortality in older people. Although aging and estrogen deficiency are probably the two most important risk factors, osteoporosis can occur in any age of life. There are a large number of risk factors for the development of senile osteoporosis. Osteoporosis is currently attributed to various endocrine, metabolic, and mechanical factors. However, recent discoveries suggest that these risk factors could exert their effects through immunologically mediated modulation of bone remodeling. Emerging clinical and molecular evidences suggest that inflammation exerts significant influence on bone turnover, inducing osteoporosis. Currently, growing understanding of bone physiology suggests that factors involved in inflammation are linked with those critical for bone remodeling process. Numerous proinflammatory cytokines have been implicated in the regulation of osteoblasts and osteoclasts, and a shift towards an activated immune profile has been hypothesized as important risk factor. Chronic inflammation and the immune system remodeling characteristic of aging may be determinant pathogenetic factors. Inflamm-aging itself plays a role in bone remodeling through proinflammatory cytokines, together with other more recently discovered immunological mediators and transcription factors. Senile osteoporosis is an example of the central role of immune-mediated inflammation in determining bone resorption.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 899.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Abrahamsen B, Andersen I, Christensen SS, Skov Madsen J, Brixen K (2005) Utility of testing for monoclonal bands in serum patients with suspected osteoporosis: retrospective, cross sectional study. BMJ 330:818

    Article  PubMed  PubMed Central  Google Scholar 

  • Adami S, Giannini S, Giorgino GCI, Maggi S, Sinigalia L et al (2003) The effect of age, weight and lifestyle factors on calcaneal quantitative ultrasound: the ESOPO study. Osteoporos Int 14: 198–207

    Article  PubMed  Google Scholar 

  • Akbari O, Stock P, Dekruyff RH, Umetsu DT (2003) Role of regulatory T cells in allergy and asthma. Curr Opin Immunol 15(6):627–633

    Article  CAS  PubMed  Google Scholar 

  • Alberti S, Cevenini E, capri m SS et al (2006) Age-dependent modifications of type 1 and Type 2 cytokines within virgin and memory CD4+ T cells in humans. Mech Ageing Dev 127:560–566

    Article  CAS  PubMed  Google Scholar 

  • Almeida M (2012) Aging mechanisms in bone. BoneKey Rep 1:102. https://doi.org/10.1038/bonekey.2012.102

    Article  PubMed  PubMed Central  Google Scholar 

  • Alswat KA (2017) Gender disparities in osteoporosis. J Clin Med Res 9(5):382–387

    Article  PubMed  PubMed Central  Google Scholar 

  • Ambrogini E, Toraldo G, Macocci C (2005) Post-menopausal osteoporosis: is it autoimmune disease? J Endocrinol Invest 28(Suppl to no 10):43–47

    CAS  PubMed  Google Scholar 

  • Annapoorna N, Rao GV, Reddy NS, Rambabu P, Rao KR (2004) An increased risk of osteoporosis during acquired immunodeficiency syndrome. Int J Med Sci 1:152–164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arai F, Hirao A, Ohmura M, Sato H, Matsouka S et al (2004) Tie 2/angiopectin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118:149–161

    Article  CAS  PubMed  Google Scholar 

  • Armour KJ, Armour KE, Von’t Hof RJ, Reid DM, Wei X-Q et al (2001) Activation of the inducible nitric syntase pathway contributes to inflammation-induced osteoporosis by suppressing bone formation and causing osteoblast apoptosis. Arthritis Rheum 44:2779–2795

    Google Scholar 

  • Arron JR, Choi Y (2000) Bone versus immune system. Nature 408:535–536

    Article  CAS  PubMed  Google Scholar 

  • Atchins GJ, Kostakis P, Pan B, Farrugia A, Gronthos S et al (2003) RANKL expression is related to the differentiation state of human osteoblasts. J Bone Miner Res 18:1088–1098

    Article  Google Scholar 

  • Bancherau J, Ste Bruunsgard H (2002) Effects of tumor necrosis factor-alpha and interleukin- 6 in elderly populations. Eur Cytokine Netw 13:389–391

    Google Scholar 

  • Barbour KE, Boudreau R, Danielson ME et al (2012) Inflammatory markers and the risk of hip fracture: the women’s health initiative. J Bone Miner Res 27:1167–1176

    Article  CAS  PubMed  Google Scholar 

  • Barrow AD, Raynal N, Andersen TL et al (2011) OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice. J Clin Invest 121:3505–3516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bekker PJ, Holloway D, Nakanishi A, Arrighi M, Luse PT, Dunstan CR (2001) The effect of a single dose of osteoprotegerin in postmenopausal women. J Bone Miner Res 16:348–360

    Article  CAS  PubMed  Google Scholar 

  • Bennermo M, Held C, Stemme S, Ericsson CG, Silveira A et al (2004) Genetic predispotition of the interleukin-6 response to inflammation: inplications for a variety of major diseases? Clin Chem 50(11):2136–2140

    Article  CAS  PubMed  Google Scholar 

  • Bennet CN, Longo KA, Wright WS, Suva LS, Lane TF et al (2005) Regulation of osteoblastogenesis and bone mass by Wnt 10b. Proc Natl Acad Sci USA 102:3324–3329

    Article  CAS  Google Scholar 

  • Brown JP, Reid IR, Wagman RB et al (2014) Effects of up to 5 years of denosumab treatment on bone histology and histomorphometry: the FREEDOM study extension. J Bone Miner Res 29:2051–2056

    Article  CAS  PubMed  Google Scholar 

  • Brunsgard H, Nanes M (2002) Effects of tumor necrosis factor-alpha and interleukin-6 in elderly populations. Eur Cytokine Netw 13:389–391

    Google Scholar 

  • Brunsgard H, Pedersen BK (2003) Age-related inflammatory cytokines and disease. Immunol Allergy Clin North Am 23:15–39

    Article  Google Scholar 

  • Buckner GH, Ziegler SF (2004) Regulating the immune system: the induction of regulatory T cells in the periphery. Arthritis Res Ther 6(5):215–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bultink IE, Lems WF, Costense PJ, Dijkmans BA, Voskuyl AE (2005) Prevalence of and risk factors for low bone mineral density and vertebral fractures in patients with systemic lupus erythematosus. Arthritis Rheum 52(7):2044–2050

    Article  PubMed  Google Scholar 

  • Cagnetta V, Patella V (2012) The role of the immune system in the physiopathology of osteoporosis. Clin Cases Mineral Bone Metab 9:85–88

    Google Scholar 

  • Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP et al (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–846

    Article  CAS  PubMed  Google Scholar 

  • Cao JJ, Wronski TS, Iwaniec U, Phleger L, Kurimoto P et al (2005) Aging increases stromal/osteoblastic cell-induced osteoclastogenesis and alters the osteoclast precursor pool in the mouse. J Bone Miner Res 20(9):1659–1668

    Article  CAS  PubMed  Google Scholar 

  • Cenci S, Toraldo G, Weitzmann MN, Roggia G, Gao Y et al (2003) Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-gamma-induced class II transactivator. Proc Natl Acad Sci USA 100:10405–10410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen HY, Chen WC, Wu MC, Tsai FJ, Lin CC (2002) Interleukin-1β and interleukin-1 receptor antagonist gene polymorphism in postmenopausal women: correlation to bone mineral density and suscepttibility to osteoporosis. Maturitas 44:49–54

    Article  Google Scholar 

  • Cheng X, Kinosaki M, Takami M, Choi Y, Zhang H, Murali R (2004) Disabling of RANK receptor complex by novel osteoprotegerin like peptidomimetics restores bone loss in vivo. J Biol Chem 279:8269–8277

    Article  CAS  PubMed  Google Scholar 

  • Cohen-Solal ME, Graulet SM, Denne MA, Gueris J, Baylink D, de Vernejoul MC (1993) Peripheral monocyte culture supernatants of menopausal women can induce bone resorption: involvement of cytokines. J Clin Endocrinol Metab 77:1648–1653

    CAS  PubMed  Google Scholar 

  • Coutinho A, Caramalho I, Seixas E, Demengeot J (2005) Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection that isolates repertoires undergoing positive or negative selection. Curr Top Microbiol Immunol 293:43–71

    CAS  PubMed  Google Scholar 

  • Cremer I, Diau Nosjean MC, Marechal S, Dezutter-Dambuyant C, Goddard S et al (2002) Long-lived immature dendritc cells mediated by TRANCE-RANK interaction. Blood 100:3646–3655

    Article  CAS  PubMed  Google Scholar 

  • De Martinis M, Di Benedetto MC, Mengoli LP, Ginaldi L (2006) Senile osteoporosis: is it an immune-mediated disease? Inflamm Res 55(10):399–404

    Article  PubMed  CAS  Google Scholar 

  • Delmas PD (2002) Treatment of post-menopausal osteoporosis. Lancet 359:2018–2026

    Article  CAS  PubMed  Google Scholar 

  • Effros RB (2004) Replicative senescence of CD8 T cells: effect on human ageing. Exp Gerontol 39:517–524

    Article  CAS  PubMed  Google Scholar 

  • Elenkov IJ, Iezzoni DJ, Daly A, Harris AG, Chroussos GP (2005) Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation 12(5):255–269

    Article  CAS  PubMed  Google Scholar 

  • Engelmann F, Messaoudi I (2012) The impact of menopause on immune senescence. Open Longevity Sci 6:101–111

    Article  CAS  Google Scholar 

  • Faienza MF, Ventura A, Marzano F, Cavallo L (2013) Postmenopausal osteoporosis: the role of immune system cells. Clin Dev Immunol 2013:575936

    Article  PubMed  PubMed Central  Google Scholar 

  • Fazzalari NL, Kuliwaba JS, Atkins GJ, Forwood MR, Findlay DM (2001) The ratio of messenger RNA levels of receptor activator of nuclear factor Kappa B ligand to osteoprotegerin correlates With bone remodeling indices in normal human cancelloy bone but not in osteoarthritis. J Bone Miner Res 16:1015–1027

    Article  CAS  PubMed  Google Scholar 

  • Ferrari SL, Ahn-Luong L, Garnero P, Humphries SE, Greenspon SL (2003) Two promoter polymorphisms regulating interleukin-6 gene expression are associated with circulating levels of C-reactive protein and markers of bone resorption in postmenopausal women. J Clin Endocrinol Metab 88(1):255–259

    Article  CAS  PubMed  Google Scholar 

  • Franceschi C, Bonafe M, Valesin S, Olivieri F, De Luca M et al (2000) Inflamm-aging. An evolutionary perpective on immunoscence. Ann NY Acad Sci 908:244–254. Review

    Article  CAS  PubMed  Google Scholar 

  • Franceschi C, Capri M, Monti D, Giunta S, Olivieri F et al (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevità emerged from studies in humans. Mech Aging Dev 128(1):102–105

    Article  CAS  Google Scholar 

  • Gao Y, Qian WP, Dark K, oraldo G, Lian AS et al (2004) Estrogen prevents bone loss through transforming growth factor β signalling in T cells. Proc Natl Acad Sci USA 100:10405–10410

    Google Scholar 

  • Gianesan K, Teklehaimanot S, Trant H, Asuncion M, Noms K (2005) Relationship of C-reactive protein and bone mineral density in community-dwelling elderly females. J Natl Med Assoc 97:329–333

    Google Scholar 

  • Ginaldi L, De Martinis M, Monti D, Franceschi C (2005a) Chronic antigenico load and apoptosis in immunosenescence. Trends Immunol 26:79–84

    Article  CAS  PubMed  Google Scholar 

  • Ginaldi L, Di Benedetto MC, De Martinis M (2005b) Osteoporosis, inflammation and ageing. Immun Ageing 2:14

    Article  PubMed  PubMed Central  Google Scholar 

  • Goettsch C, Helas S, Jessberger R et al (2011) The role of osteoclast-associated receptor in osteoimmunology. J Immunol 186:13–18

    Article  PubMed  Google Scholar 

  • Goldring SR (2003) Inflammatory mediators as essential elements in bone remodelling. Calcif Tissue 73:97–100

    Article  CAS  Google Scholar 

  • Goronzy JJ, Weyand CM (2003) Aging, autoimmunity and arthrits: T cell senescence and contraction of T cell repertoire diversity-catalysts of autoimmunity and chronic inflammation. Arthritis Res Ther 5:225–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goronzy JJ, Weyand CM (2005) T cell denvelopment and receptor diversity during again. Curr Opin Immunol 17(5):468–475

    Article  CAS  PubMed  Google Scholar 

  • Greenblatt MB, Shim J-H (2013) Osteoimmunology: a brief introduction. Immune Netw 13:111–115

    Article  PubMed  PubMed Central  Google Scholar 

  • Gregg R, Smith CM, Clark FJ, Dunnion D, Khan N et al (2005) The number of human peripheral blood CD4+ CD25+ high regulatory T cells increases with age. Clin Exp Nuclear Immunol 240(3):540–546

    Article  CAS  Google Scholar 

  • Grimaud E, Soubigou L, Covillaud S, Moreau a CP et al (2003) Receptor activator of factor kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio is increased in severe osteolysis. Am J Pathol 163:2021–2031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gupta S, Bi R, Suk Yel L, Chiplintar S, Gallapudi S (2004) Characterization of naive, memory, and effector CD8+T cells: effect of age. Exp Gerontol 39:545–550

    Article  CAS  PubMed  Google Scholar 

  • Gupta S, Bi R, Gallapudi S (2005) Central memory and effector memory subsets of human CD4+T cell display differential sensitivity to TNF α-induced apoptosis. Ann N Y Acad Sci 1050: 108–114

    Article  CAS  PubMed  Google Scholar 

  • Gupta S, Agraual A, Agraual S, Su H, Gllapudi S (2006) A paradox of immunodeficiency and inflammation in human aging: lessons learned from apoptosis. Immunity. Aging 3:5–13

    Google Scholar 

  • Harsløf T, Langdahl B (2016) New horizons in osteoporosis therapies. Curr Opin Pharmacol 28:38–42

    Article  PubMed  CAS  Google Scholar 

  • Haugeberg G, Lodder MC, Lems WF, Uhlig T, Orstavik RE, Dijkmans BA, Kvien TK, Woolf AD (2004) Hand cortical bone mass and its associations with radiographic joint damage and fractures in 50–70 year old female patients with rheumatoid arthritis: cross sectional Oslo-Truro-Amsterdam (OSTRA) collaborative study. Ann Rheum Dis 63(10):1331–1341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ho KW et al (2005) Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system are associated with bone metabolism in middle-aged males. Clin Endocrinol (Oxf) 62:92–98

    Article  CAS  Google Scholar 

  • Hochweller K, Anderton SM (2005) Kinetics of costimulatory molecule expression by T cells and dendritic cells during the induction of tollerance versus immunity in vivo. Eur J Immunol 35:1086–1096

    Article  CAS  PubMed  Google Scholar 

  • Hofbauer LC, Dunstan CR, Spelberg TC, Riggs BL, Khosla S (1998) Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin D, bone morphogenetic protein-2, and cytokines. Biochem Biophys Res Commun 250:776–781

    Article  CAS  PubMed  Google Scholar 

  • Ima Y, Tsunenari T, Fukase M, Fujita T (1990) Quantitative bone histomorphometry and cir culating T lymphocyte. Res 5(4):393–399

    Google Scholar 

  • Ishihara K, Hirano T (2002) IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev 13:357–368

    Article  CAS  PubMed  Google Scholar 

  • Janeway C Jr, Medzhitov R (2002) Viral interference with IL-1 and toll signaling. Annu Rev Immunol 20:197–216

    Article  CAS  PubMed  Google Scholar 

  • Jensen T, Klarlund M, Hansen M, Jensen KE, Skjødt H, Hyldstrup L, the Danisit TIRA Group (2004) Connective tissue metabolism in patients with unclassified polyarthritis to disease activity, bone mineral density and radigraphic outcome. J Rheumatol 31:1698–1708

    CAS  PubMed  Google Scholar 

  • Jilka RL (1998) Cytokines, bone remodelling, and estrogen deficiency: a 1998 update. Bone 23:75–81

    Article  CAS  PubMed  Google Scholar 

  • Jilka RL, O’Brien CA (2016) The role of osteocytes in age-related bone loss. Curr Osteoporos Rep 14:16–25

    Article  PubMed  Google Scholar 

  • Jilka RL, Noble B, Weinstein RS (2013) Osteocyte apoptosis. Bone 54:264–271

    Article  PubMed  Google Scholar 

  • Jones D, Glimcher LH, Aliprantis AO (2011) Osteoimmunology at the nexus of arthritis, osteoporosis, cancer, and infection. J Clin Invest 121:2534–2542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joscen R, Li HL, Ingulli E, Sarmq S, Wong BR et al (2000) TRANCE, a tumor necrosis factor family member, enhances the longevity. J Exp Med 191:495–502

    Article  Google Scholar 

  • Kabelitz D, Wesch D, Oberg HH (2006) Regulation of regulatory T cells: role of dendritic cells and toll-like receptors. Crit Rev Immunol 26(4):291–306

    Article  CAS  PubMed  Google Scholar 

  • Kaech SM, Ahmed R (2001) Memory CD8+ T cell differentation: initial antigen encounter triggers a denvelopmental program in naive cells. Nat Immunol 2001:415–422

    Article  CAS  Google Scholar 

  • Kameda Y, Takahata M, Komatsu M et al (2013) Siglec-15 regulates osteoclast differentiation by modulating RANKL-induced phosphatidylinositol 3-kinase/Akt and Erk pathways in association with signaling Adaptor DAP12. J Bone Miner Res 28:2463–2475

    Article  CAS  PubMed  Google Scholar 

  • Kassem A, Henning P, Kindlund B, Lindholm C, Lerner UH (2015) TLR5, a novel mediator of innate immunity-induced osteoclastogenesis and bone loss. FASEB J 29:4449–4460

    Article  CAS  PubMed  Google Scholar 

  • Kato M, Patel MS, Levasseur R, Lobow I, Chang BH et al (2002) Cbfa 1-indipendent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp 5, a wnt coreceptor. J Cell Biol 157:303–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khosola S (2001) The OPG/RANKL/RANK system. Endocrinology 142:5050–5055

    Article  Google Scholar 

  • Kim JC, Ku SY, Lim KS, Jee BC, Such CS et al (2005) Cytokine production by whole blood cells: relationship to interleukin gene polymorphism and bone mass. J Korean Med Sci 20(6): 1017–1022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klontzas E, Kenanidis I, MacFarlane J et al (2016) Investigational drugs for fracture healing: preclinical & clinical data. Expert Opin Investig Drugs 25:585–596

    Article  CAS  PubMed  Google Scholar 

  • Knothe Tate ML, Adamson JR, Tami AE, Bauer TW (2004) The osteocyte. Int J Biochem Cell Biol 36:1–8

    Article  CAS  PubMed  Google Scholar 

  • Koh JM, Khang YH, Jung CH, Bae S, Kim DJ et al (2005) Higher circulating hsCRP levels are associated with hower bone mineral density in healthy preand post-menopausal women: evidence for a link between systemic inflammation and osteoporosis. Osteoporos Int 16:1263–1271

    Article  CAS  PubMed  Google Scholar 

  • Kong YY, Feige U, Sarosi I (1999) Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402:304–309

    Article  CAS  PubMed  Google Scholar 

  • Kotake S, Udagawa N, Ha Koda M, Mogi M, Yano K et al (2001) Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients. Arthritis Rheum 44:1003–1012

    Article  CAS  PubMed  Google Scholar 

  • Langdahl BL, Løkke E, Carstens M, Stenkjaer LL, Eriksen EF (2000) Osteoporotic fractures are associated with an 86-base pair repeat polymorphism in the interleukin-1 – receptor antagonist gene but not with polymorphisms in the interleukin-1beta gene. J Bone Miner Res 15:402–414

    Article  CAS  PubMed  Google Scholar 

  • Lange U, Teichmann J, Stracke H (2000) Correlation between plasma TNF-α, IGF-1, biochemical markers of bone metabolism, markers of inflammation/disease activity, and clinical manifestations in ankylosing spondylitis. 2000. Eur J Med Res 5(12):507–511

    CAS  PubMed  Google Scholar 

  • Leung DY, Geha RS (1988) Clinical and immunologic aspects of the hyperimmunoglobulin E syndrome. Hematol Oncol Clin North Am 2(1):81–100

    Article  CAS  PubMed  Google Scholar 

  • Li H, Lu Y, Qian J et al (2014) Human osteoclasts are inducible immunosuppressive cells in response to T cell-derived IFN-γ and CD40 ligand in vitro. J Bone Miner Res 29:2666–2675

    Article  CAS  PubMed  Google Scholar 

  • Lopez I, Buchman AL (2000) Metabolic bone disease in IBD. Curr Gastroenterol Rep 2:317–322

    Article  CAS  PubMed  Google Scholar 

  • Loucks J, Pope JE (2005) Osteoporosis in scleroderma. Semin Arthritis Rheum 34:678–682

    Article  PubMed  Google Scholar 

  • Maggi E, Cosmi L, Liotta F, Romagnani P, Romagnani S, Annunziato F (2005) Thymic regulatory T cells. Autoimmun Rev 4(8):579–586

    Article  CAS  PubMed  Google Scholar 

  • Mansoori MN, Tyagi AM, Shukla P et al (2016) Methoxyisoflavones formononetin and isoformononetin inhibit the differentiation of Th17 cells and B-cell lymphopoesis to promote osteogenesis in estrogen-deficient bone loss conditions. Menopause 23:565–576

    Article  PubMed  Google Scholar 

  • Matsuo K (2010) Eph and ephrin interactions in bone. Adv Exp Med Biol 658:95–103

    Article  CAS  PubMed  Google Scholar 

  • Mikuls TR, Saag KG, Curtis J, Bridges SL Jr, Alarcon GS et al (2005) Prevalence of osteoporosis and osteopenia among African Americans with early rheumatoid arthritis: the impact of ethnic-specific normative data. J Natl Med Assoc 98:1155–1160

    Google Scholar 

  • Mondy K, Tebas P (2003) Emerging bone problems in patients infected with human immunodeficiency virus. Clin Infect Dis 36(Suppl2):S101–S105

    Article  PubMed  Google Scholar 

  • Morgolis RN, Wimalawansa J (2006) Novel targets and therapeutics for bone loss. Ann N Y Acad Sci 1068:402–409

    Article  CAS  Google Scholar 

  • Mori G, D’Amelio P, Faccio R, Brunetti G (2015) Bone-immune cell crosstalk: bone diseases. J Immunol Res 2015:108451

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Moser Boloetscher P (2001) Lymphocyte traffic control by chemokines. Nat Immunol 2:123–128

    Article  CAS  Google Scholar 

  • Mosken AR, Kaser A, Enrich B, Ludwiczek O, Gabriel M et al (2005) The RANKL/OPG system is activated in inflammatory bowel disease and relates to the state of bone loss. Gut 54:479–487

    Article  CAS  Google Scholar 

  • Musso G, Paschetta E, Gambino R, Cassader M, Molinaro F (2013) Interactions among bone, liver, and adipose tissue predisposing to diabesity and fatty liver. Trends Mol Med 19:522–535

    Article  CAS  PubMed  Google Scholar 

  • Nanes MSL (2003) Tumor necrosis factor-alpha: molecular and cellular mechanisms in skeletal patology. Gene 4:1–15

    Article  CAS  Google Scholar 

  • Nevalainen T, Kananen L, Marttila S, Jylhä M, Hervonen A, Hurme M, Jylhävä J (2015) Transcriptomic and epigenetic analyses reveal a gender difference in aging-associated inflammation: the Vitality 90+ study T. Age 37:76. https://doi.org/10.1007/s11357-015-9814-9

    Article  CAS  PubMed Central  Google Scholar 

  • Obermayer-Pietsch BM, Lange U, Tauber G, Fruhauf G, Fahrleitner A et al (2003) Vitamin D receptor initiation codon poliymorphism, bone density and inflammatory activity of patients with ankylosing spondylitis. Osteoporos Int 14:995–1000

    Article  CAS  PubMed  Google Scholar 

  • Ostan R, Monti D, Gueres P, Bussolotto M, Franceschi C, Baggio G (2016) Gender, aging and longevity in humans: an update of an intriguing/neglected scenario paving the way to a gender-specific medicine. Clin Sci 130:1711–1725

    Article  Google Scholar 

  • Pacifici R (1999) Aging and cytokine production. Calcif Tissue Int 65:345–351

    Article  CAS  PubMed  Google Scholar 

  • Pfeilschifter J, Diel I, Scheppach B, Bretz A, Krempien R et al (1998) Concentration of transforming growth factor β in human bone tissue: relationship to age, menopause, bone turnover and bone volume. J Bone Miner Res 13:716–730

    Article  CAS  PubMed  Google Scholar 

  • Pietschmann P, Rauner M, Sipos W, Kerschan-Schindl K (2009) Osteoporosis: an age-related and gender-specific disease. Gerontology 55:3–12

    Article  PubMed  Google Scholar 

  • Pociot F, Molvig J, Wogensen L et al (1992) A tagl polymorphism with IL-1β secrection in vitro. Eur J Clin Invest 22:396–402

    Article  CAS  PubMed  Google Scholar 

  • Ridker PM, Rifai N, Pfeffer M, Sacks F, Lepage S, Braunwald E (2000) Elevation of tumor necrosis factor-α and increased risk of recurrent coronary events after myocardial infarction. Circulation 1001:2149–2153

    Article  Google Scholar 

  • Riggs BL, Khosla S, Melton LJ III (1998) A unitary model for involutional osteoporosis: estrogen deficiency cause 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

    Article  CAS  PubMed  Google Scholar 

  • Rodan GA, Martin TJ (2000) Therapeutic approaches to bone diseases. Science 289:1508–1514

    Article  CAS  PubMed  Google Scholar 

  • Roggia C, Gao Y, Cenci S et al (2001) 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 98:13960–13965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Romas E, Gillespie MI, Martin TS (2002) Involvement of receptor activator of NF Kappa B ligand and tumor necrosis factor-alpha in bone destruction in rheumatoid arthritis. Bone 30:340–346

    Article  CAS  PubMed  Google Scholar 

  • Rosen CJ, Usikin K, Owens M, Barlascini CO, Belsky M, Adler RA (1990) T lymphocyte surface antigen markers in osteoporosis. J Bone Miner Res 5(8):851–855

    Article  CAS  PubMed  Google Scholar 

  • Saidenberg-Kermanac N, Bessis N, Cohen Solal M, De Varnejoul MC, Boissier MC (2002) Osteoprotegerin and inflammation. Eur Cytokine Netw 13:144–153

    Google Scholar 

  • Saidenberg-Kermanac’h N, Cohen-solal M, Bessis N, Devemejoul MC, Boissier MC (2004a) Role for osteoprotegerin in rheumatoid inflammation. Joint Bone Spine 71:9–31

    Article  PubMed  Google Scholar 

  • Saidenberg-Kermanac’h N, Corrado A, Lemeiter D, de Vernejoul MC, Boissier MC, Cohen-Solal ME (2004b) TNF-α antibodies and osteoprotegerin decrease systemic bone loss associated with inflammation through distinct mechanisms in collagen induced arthritis. Bone 35:1200–1207

    Article  PubMed  CAS  Google Scholar 

  • Salamone LM, Whitaside T, Friberg D, Epstein RS, Kuller LH, Cauley JA (1998) Cytokine production and bone mineral density at the lumbar spine and femoral nech in premenopausal women. Calcif Tissue Int 63:466–470

    Article  CAS  PubMed  Google Scholar 

  • Sallusto F, Geginat J, Lanzavecchia A (2004) Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 22:745–763

    Article  CAS  PubMed  Google Scholar 

  • Santini D, Fratto ME, Vincenzi B, Cesa A, Dianzani C, Tonini G (2004) Bisphosponate effects in cancer and inflammatory diseases: in vitro and in vivo modulation of cytokine activities. BioDrugs 18:269–278

    Article  CAS  PubMed  Google Scholar 

  • Saurwein-Teissi M, Lung TL, Max F, Gschosser C, Asch E et al (2002) Lach of antibody production following immunization in old age: association with CD8+ CD28- T cell clonal expansion and an imbalance in the production of Th1 and Th2 cytokines. J Immunol 168:5893–5858

    Article  Google Scholar 

  • Savil J, Dransfield I, Gregory C, Haslett C (2002) A blast from the past: clearance of apoptotic cells regulates immune response. Nat Rev Immunol 2:965

    Article  CAS  Google Scholar 

  • Schaffler MB, Cheung WY, Majeska R, Kennedy O (2014) Osteocytes: master orchestrators of bone. Calcif Tissue Int 94:5–24

    Article  CAS  PubMed  Google Scholar 

  • Scheidt-Nave C, Bismar H, Leidig-Brucker G, Waitge H, Seibel MJ, Ziegler R, Pfeilschifter J (2001) Serum interleukin 6 is a major predictor of bone loss in women specific to the first decade post menopause. J Clin Endocrinol Metab 86:2032–2042

    CAS  PubMed  Google Scholar 

  • Schett G (2009) Osteoimmunology in rheumatic diseases. Arthritis Res Ther 11:210. https://doi.org/10.1186/ar2571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schluns KS, Lefrancois L (2003) Cytokine control of memory T-cell development and survival. Nat Rev Immunol 3:269–279

    Article  CAS  PubMed  Google Scholar 

  • Schwarz EM, Looney RJ, Drissi MK, Jo’K refe RG, Boyce BF et al (2006) Autoimmunity and bone. Ann N Y Acad Sci 1068:275–283

    Article  CAS  PubMed  Google Scholar 

  • Siggelkow H, Eidner T, Lehmann G, Viereck V, Munzel U et al (2003) Cytokines, osteoprotegerin and RANKL in vitro and histomorphometric indices of bone turnover in patients with different bone diseases. J Bone Miner Res 18:529–538

    Article  CAS  PubMed  Google Scholar 

  • Stassen M, Fondel S, Bopp T, Richter C, Muller C et al (2004) Human CD25+ regulatory T cells: two subsets defined by the integrins α 4 β 7 or α 4 β 1 confer distinct suppressive properties upon CD4+ T helper cells. Eur J Immunol 34:1303–1311

    Article  CAS  PubMed  Google Scholar 

  • Takayanagi H (2012) New developments in osteoimmunology. Nat Rev Rheumatol 8:684–689

    Article  CAS  PubMed  Google Scholar 

  • Tanaka Y, Nakayamada S, Akada Y (2005) Osteoblsts and osteoclasts in bone remodeling and inflammation. Curr Drug Targets Inflamm Allergy 4:325–328

    Article  CAS  PubMed  Google Scholar 

  • Tanaka Y, Mori H, Aoki T et al (2015) Analysis of bone metabolism during early stage and clinical benefits of early intervention with alendronate in patients with systemic rheumatic diseases treated with high-dose glucocorticoid: Early DIagnosis and Treatment of OsteopoRosis in Japan (EDITOR-J) study. J Bone Miner Metab 34:646. https://doi.org/10.1007/s00774-015-0709-8

    Article  CAS  PubMed  Google Scholar 

  • Tarlow JK, Blakemore AF, Lennard A, Solari R, Hughes MN et al (1993) Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86 base pair tandem repeat. Hum Genet 91:403–404

    Article  CAS  PubMed  Google Scholar 

  • Taubman MA, Kawai T (2001) Involvement of T lymphocites in periodontal disease and in direct and indirect induption of bone resorption. Crit Rev Oral Biol Med 12:125–135

    Article  CAS  PubMed  Google Scholar 

  • Teitellaum SL (2000) Bone resorption by osteoclasts. Science 289:1504–1508

    Article  Google Scholar 

  • Teng YT, Nguyen H, Gao X, Kong YY, Gorezynski RM et al (2000) Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone distruction in periodontalinfection. J Clin Invest 106:59–67

    Article  Google Scholar 

  • Theill LE, Boyle WI, Penninger JM (2002) T cells, bone loss and mammalian evolution. Annu Rev Immunol 20:795–823

    Article  CAS  PubMed  Google Scholar 

  • Tilstra JS, Cheryl L, Clauson CL, Laura J, Niedernhofer LJ, Robbins PD (2011) NF-κB in aging and disease. Aging Dis 2:449–465

    PubMed  PubMed Central  Google Scholar 

  • Toraldo G, Roggia C, Quian W-P, Pacifici R, Weitzmann MN et al (2003) IL-7 induces bone loss in vivo by induction of receptor activator of nuclear factor kB ligand and tumor necrosis factor α from T cells. Proc Natl Acad Sci U S A 100:125–130

    Article  CAS  PubMed  Google Scholar 

  • Trzontwski P, Szmit E, Mysliwaska J, Mysliwski A (2006) CD4+ CD25+ T regulatory cells cytotoxic activity of CTL and NK cells in humans impact of immunosenescence. Clin Immunol 119:307–316

    Article  CAS  Google Scholar 

  • Tsaknaridis L, Spencer L, Culbertson N, Hicks K, La Toche T et al (2003) Functional assay for human CD4+ CD25+ Treg cells reveals an age-dependent loss of suppressive activity. J Neutron Res 74:296–308

    CAS  Google Scholar 

  • Tsuboi M, Kawakami A, Nakashima T, Matsuoka N, Urayama S et al (1999) J Lab Clin Med 134:190–191

    Article  Google Scholar 

  • Tyagi AM, Srivastava K, Mansoori MN et al (2012) Estrogen deficiency induces the differentiation of IL-17. Secreting Th17 cells: a new candidate in the pathogenesis of osteoporosis. PLoS One 7:e44552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Udagawa N (1990) Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenviroment prepared by bone marrowderived stromal cells. Proc Natl Acad Sci USA 87:7260–7264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Offel JF, Schuerwegh AJ, Bridts CH, Stevens WJ, De Clerck LS (2002) Effect of biphosphonates on viability, proliferation, and dexamethasone-induced apoptosis of articular chondrocytes. Ann Rheum Dis 61:925–928

    Article  PubMed  PubMed Central  Google Scholar 

  • Vikulina T, Fan X, Yamaguchi M et al (2010) Alterations in the immuno-skeletal interface drive bone destruction in HIV-1 transgenic rats. Proc Natl Acad Sci 107:13848–13853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walsh NC, Gavallese EM (2004) Bone loss in inflammatory arthritis: mechanisms and treatment strategies. Curr Opin Rheumatol 16:419–427

    Article  PubMed  Google Scholar 

  • Walsh NC, Crotti TN, Goldning SR, Gravallese EM (2005) Rheumatic diseases: the effects of inflammation on bone. Immunol Rev 208:228–251

    Article  CAS  PubMed  Google Scholar 

  • Walsh NC, Kim N, Kadono Y, Rho J, Lu SY et al (2006) Osteoimmunology interplay between the immune system and bone metabolism. Annu Rev Immunol 24:33–63

    Article  CAS  PubMed  Google Scholar 

  • Wang R, Zhang L, Zhang X, Moreno J, Celluzzi C et al (2002) Regulation of activation – induced receptor activator of NF-KB ligand (RANKL) expression in T cells. Eur J Immunol 32: 1090–1098

    Article  CAS  PubMed  Google Scholar 

  • Weinhold B, Ruther U (1997) Interleukin-6-dependent and-independent regulation of the human C-reactive protein gene. Biochem J 327:425–429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weitzmann MN (2013) The role of inflammatory cytokines, the RANKL/OPG axis, and the immunoskeletal interface in physiological bone turnover and osteoporosis. Scientifica 2013:125705. https://doi.org/10.1155/e125705

    Article  PubMed  PubMed Central  Google Scholar 

  • Weitzmann MN (2014) T-cells and B-cells in osteoporosis. Curr Opin Endocrinol Diabetes Obes 21:461–467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weitzmann MN, Ofotokun I (2016) Physiological and pathophysiological bone turnover – role of the immune system. Nat Rev Endocrinol 12:518–532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weitzmann MN, Pacifici R (2005) The role of T lymphocytes in bone metabolism. Immunol Rev 208:154–168

    Article  CAS  PubMed  Google Scholar 

  • Weitzmann MN, Pacifici R (2006) Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest 116:1186–1194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weyand CM, Goronzy J (2004) Stem cell aging and autoimmunity in rheumatoid arthritis. Trends Mol Med 10:426–433

    Article  CAS  PubMed  Google Scholar 

  • Weyand CM, Fulbright JW, Goronzy JJ (2003) Immunosenescence, autoimmunity, and rheumatoid arthritis. Exp Gerontol 38:833–841

    Article  CAS  PubMed  Google Scholar 

  • Wiethe C, Dittmar K, Daan T, Lindenmaier W, Tindle R (2003) Enhanced effector and memory CTL responses generated by incorporation of receptor activator of NF-KB (RANK)/RANK ligand costimulatory molecules into dendritic cell immunogens expressing a human tumorspecific antigen. J Immunol 171:4121–4130

    Article  CAS  PubMed  Google Scholar 

  • Willamson F, Bilsborough JM, Viney JL (2002) Regulation of mucosal dendritic cell function by receptor activator of NF-KB (RANK)/RANK ligand interactions: impact on tollerance induction. J Immunol 169:3606–3612

    Article  Google Scholar 

  • Wu H, Arron JR (2003) TRAF 6, a molecular bridge spanning adaptive immunity innate immunity and osteoimmunology. Bioessays 25:1096–1105

    Article  CAS  PubMed  Google Scholar 

  • Xing J, Titus AR, Humphrey MB (2015) The TREM2-DAP12 signaling pathway in Nasu-Hakola disease: a molecular genetics perspective. Res Rep Biochem 5:89–100

    PubMed  PubMed Central  Google Scholar 

  • Yang YH, Buhamrah A, Schneider A et al (2016) Semaphorin 4D promotes skeletal metastasis in breast cancer. PLoS One 11:e0150151. https://doi.org/10.1371/journal.pone.0150151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ylmaz N, Pence S, Kepekci Y, Geyikli I, Ozaslan J (2003) Association of immune function with bone mineral density and biochemical markers of bone turnover in patients with ankilosing spondylitis. Int J Clin Pract 57:681–685

    Google Scholar 

  • Yosida N, Ikemoto S, Narita K, Sugimura K, Walda S et al (2002) Interleukin-6, tumor necrosis factor α and interleukin-1β in patients with renal cell carcinoma. J Cancer 86:1396–1400

    Article  Google Scholar 

  • Yu B, Wang CY (2016) Osteoporosis: the result of an ‘Aged’ bone microenvironment. Trends Mol Med 22:641–644

    Article  PubMed  PubMed Central  Google Scholar 

  • Yudkin JS, Stehouwer CD, Emeis JJ, Coppack JW (1999) C-reactive protein in healthy subjects: associations with obesity, insulin resistence, and endothelial dysfunction a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 19:972–978

    Article  CAS  PubMed  Google Scholar 

  • Yun AJ, Lee PY (2004) Maladaptation of the link between inflammation and bone turnover may be a key determinant of osteoporosis. Med Hypotheses 63:532–537

    Article  PubMed  Google Scholar 

  • Zhao R (2012) Immune regulation of osteoclast function in postmenopausal osteoporosis: a critical interdisciplinary perspective. Int J Med Sci 9:825–832

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou Z, Xiong WC (2011) RAGE and its ligands in bone metabolism. Front Biosci 3:768–776

    Google Scholar 

  • Zon RY, Ansari AA, Lian ZX, Gershwin ME (2005) Regulatory T cells: development, function and role in autoimmunity. Autoimmun Rev 4(6):351–363

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Life, Health, and Environmental Sciences, University of L’Aquila, L’Aquila, Italy

    Lia Ginaldi, Lucia Paola Mengoli, Maria Maddalena Sirufo & Massimo De Martinis

  2. Department of Internal Medicine and Public Health, University of L’Aquila, L’Aquila, Italy

    Lia Ginaldi, Lucia Paola Mengoli, Maria Maddalena Sirufo & Massimo De Martinis

Authors
  1. Lia Ginaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lucia Paola Mengoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Maddalena Sirufo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Massimo De Martinis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lia Ginaldi .

Editor information

Editors and Affiliations

  1. Division of Geriatrics Research Center on Aging, University of Sherbrooke Department of Medicine, Sherbrooke, QC, Canada

    Tamas Fulop

  2. Department of Experimental Pathology, University of Bologna, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, Tokyo, Japan

    Katsuiku Hirokawa

  4. Center for Medical Research, University of Tübingen, Tübingen, Germany

    Graham Pawelec

Section Editor information

  1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Tamas Fulop

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Ginaldi, L., Mengoli, L.P., Sirufo, M.M., De Martinis, M. (2019). Osteoporosis, Inflammation, and Aging. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-99375-1_64

Download citation

Publish with us

Policies and ethics

Search

Navigation