Top

Published in:

01-05-2010 | Original Article

Immune changes in post-menopausal osteoporosis: the Immunos study

Authors: V. Breuil, M. Ticchioni, J. Testa, C. H. Roux, P. Ferrari, J. P. Breittmayer, C. Albert-Sabonnadière, J. Durant, F. De Perreti, A. Bernard, L. Euller-Ziegler, G. F. Carle

Published in: Osteoporosis International | Issue 5/2010

Abstract

Summary

The phenotypic and functional characteristics of immune cells of osteoporotic women compared to healthy controls similar for age and estrogen level showed for the first time significant changes in several B lymphocytes populations in postmenopausal osteoporosis, related to bone mineral density (BMD) and fractures, and a significant lower basal secretion of interferon-gamma (IFN-γ) by CD4⁺.

Introduction

To investigate the interactions between bone and immune system, we studied the phenotypic and functional characteristics of immune cells of 26 postmenopausal women with osteoporotic (OP) fractures compared to 24 healthy controls.

Methods

We analyzed surface markers of peripheral B, CD4⁺ and CD8⁺ lymphocytes and cytokine secretion in supernatants of these cells cultured with or without stimulation. Body composition was assessed by dual energy X-ray absorptiometry.

Results

The two groups were similar for age and estrogen level. OP women had a significantly lower body mass index, fat mass, and lean mass. The number of CD19⁺, CD19⁺/CD27⁺, CD19⁺/CD27⁺/CD5⁻/CD38⁺ and CD19⁺/CD27⁺/RANK⁺, CD4⁺/CD27⁺/CD45RA⁻/RANK⁺, and CD4⁺/CD27⁺/CD45RA⁻/CD28⁺ was lower in OP women and positively correlated to BMD. In OP women, under basal conditions, CD4⁺ secreted less IFN-γ and B lymphocytes more granulocyte macrophage colony-stimulating factor (GM-CSF). GM-CSF was positively correlated to fracture rate and negatively to BMD.

Conclusions

Our results suggest that, regardless of age and estrogen status, postmenopausal OP is associated with immune changes, highlighting a possible role of IFN-γ in the pathophysiology of OP and reporting, for the first time, changes in several B lymphocyte populations. These alterations may reflect the frailty observed after fracture, providing new insight into the mechanisms of morbidity and mortality associated with OP fractures.

Available only for authorised users

Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 17:1726–33CrossRefPubMed

Kado DM, Browner WS, Palermo L et al (1999) Vertebral fractures and mortality in older women: a prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med. 159:1215–20CrossRefPubMed

Lorenzo J, Horowitz M, Choi Y (2008) Osteoimmunology: interactions of the bone and immune system. Endocr. Rev. 29:403–40CrossRefPubMed

Takayanagi H, Sato K, Takaoka A et al (2005) Interplay between interferon and other cytokine systems in bone metabolism. Immunol Rev 208:181–193CrossRefPubMed

Mundy GR (2007) Osteoporosis and inflammation. Nutr. Rev. 65:S147–51CrossRefPubMed

Horwood N (2008) Lymphocyte-derived cytokines in inflammatory arthritis. Autoimmunity. 41:230–8CrossRefPubMed

Kong YY, Feige U, Sarosi I et al (1999) Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402:304–9CrossRefPubMed

Briot K, Garnero P, Le Henanff A et al (2005) Body weight, body composition, and bone turnover changes in patients with spondyloarthropathy receiving anti-tumour necrosis factor alpha treatment. Ann Rheum Dis. 64:1137–40CrossRefPubMed

Visvanathan S, van der Heijde D, Deodhar A et al (2008) Effects of infliximab on markers of inflammation and bone turnover and associations with bone mineral density in patients with ankylosing spondylitis. Ann Rheum Dis. 68:175–82CrossRefPubMed

10.

Lorenzo JA, Naprta A, Rao Y et al (1998) Mice lacking the type I interleukin-1 receptor do not lose bone mass after ovariectomy. Endocrinology. 139:3022–5CrossRefPubMed

11.

Poli V, Balena R, Fattori E et al (1994) Interleukin-6 deficient mice are protected from bone loss caused by estrogen depletion. EMBO J. 13:1189–96PubMed

12.

Cenci S, Weitzmann MN, Roggia C et al (2000) Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. J Clin Invest. 106:1229–37CrossRefPubMed

13.

Blin-Wakkach C, Wakkach A, Rochet N et al (2004) Characterization of a novel bipotent hematopoietic progenitor population in normal and osteopetrotic mice. J Bone Miner Res 19:1137–43CrossRefPubMed

14.

Li Y, Li A, Yang X et al (2007) Ovariectomy-induced bone loss occurs independently of B cells. J Cell Biochem. 100:1370–5CrossRefPubMed

15.

World Health Organization (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. WHO Technical Report Series. WHO, Geneva

16.

Delmonico MJ, Harris TB, Lee JS et al (2007) Health, Aging and Body Composition Study.Alternative definitions of sarcopenia, lower extremity performance, and functional impairment with aging in older men and women. J Am Geriatr Soc 55:769–74CrossRefPubMed

17.

Lane NE (2006) Epidemiology, etiology, and diagnosis of osteoporosis. Am J Obstet Gynecol. 194:S3–11CrossRefPubMed

18.

Ravn P, Cizza G, Bjarnason NH et al (1999) Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group. J Bone Miner Res 14:1622–7CrossRefPubMed

19.

Martini G, Valenti R, Giovani S et al (1997) Age-related changes in body composition of healthy and osteoporotic women. Maturitas. 27:25–33CrossRefPubMed

20.

Schott AM, Cormier C, Hans D et al (1998) How hip and whole-body bone mineral density predict hip fracture in elderly women: the EPIDOS Prospective Study. Osteoporos Int. 8:247–54CrossRefPubMed

21.

Gnudi S, Sitta E, Fiumi N (2007) Relationship between body composition and bone mineral density in women with and without osteoporosis: relative contribution of lean and fat mass. J Bone Miner Metab. 25:326–32CrossRefPubMed

22.

Joseph C, Kenny AM, Taxel P et al (2005) Role of endocrine-immune dysregulation in osteoporosis, sarcopenia, frailty and fracture risk. Mol Aspects Med. 26:181–201CrossRefPubMed

23.

Walsh MC, Hunter GR, Livingstone MB (2006) Sarcopenia in premenopausal and postmenopausal women with osteopenia, osteoporosis and normal bone mineral density. Osteoporos Int. 17:61–7CrossRefPubMed

24.

Rodríguez L, Graniel J, Ortiz R (2007) Effect of leptin on activation and cytokine synthesis in peripheral blood lymphocytes of malnourished infected children. Clin Exp Immunol 148:478–85PubMed

25.

Sansoni P, Vescovini R, Fagnoni F et al (2008) The immune system in extreme longevity. Exp Gerontol. 43:61–5CrossRefPubMed

26.

Hakim FT, Flomerfelt FA, Boyiadzis M et al (2004) Aging, immunity and cancer. Curr Opin Immunol 16:151–6CrossRefPubMed

27.

Lazuardi L, Jenewein B, Wolf AM et al (2005) Age-related loss of naïve T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes. Immunology 114:37–43CrossRefPubMed

28.

Weitzmann MN, Pacifici R (2006) Estrogen regulation of immune cell bone interactions. Ann N Y Acad Sci. 1068:256–74CrossRefPubMed

29.

D’Amelio P, Grimaldi A, Di Bella S et al (2008) Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis. Bone. 43:92–100CrossRefPubMed

30.

Cantorna MT, Yu S, Bruce D (2008) The paradoxical effects of vitamin D on type 1 mediated immunity. Mol Aspects Med. 29:369–75CrossRefPubMed

31.

Gao Y, Grassi F, Ryan MR et al (2007) IFN-gamma stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation. J Clin Invest. 117:122–32CrossRefPubMed

32.

Zheng SX, Vrindts Y, Lopez M et al (1997) Increase in cytokine production (IL-1 beta, IL-6, TNF-alpha but not IFN-gamma, GM-CSF or LIF) by stimulated whole blood cells in postmenopausal osteoporosis. Maturitas 26:63–71CrossRefPubMed

33.

Pietschmann P, Grisar J, Thien R et al (2001) Immune phenotype and intracellular cytokine production of peripheral blood mononuclear cells from postmenopausal patients with osteoporotic fractures. Exp Gerontol. 36:1749–59CrossRefPubMed

34.

Walsh MC, Kim N, Kadono Y et al (2006) Osteoimmunology: interplay between the immune system and bone metabolism. Annu Rev Immunol. 24:33–63CrossRefPubMed

35.

Mezquita-Raya P, De La Higuera M, Garcia DF et al (2005) The contribution of serum osteoprotegerin to bone mass and vertebral fractures in postmenopausal women. Osteoporos Int. 16:1368–1374CrossRefPubMed

36.

Stern A, Laughlin GA, Bergstrom J et al (2007) The sex-specific association of serum osteoprotegerin and receptor activator of nuclear factor kappaB legend with bone mineral density in older adults: the Rancho Bernardo study. Eur J Endocrinol. 156:555–62CrossRefPubMed

37.

Uemura H, Yasui T, Miyatani Y et al (2008) Circulating profiles of osteoprotegerin and soluble receptor activator of nuclear factor kappaB ligand in post-menopausal women. J Endocrinol Invest. 31:163–8PubMed

38.

Imai Y, Tsunenari T, Fukase M et al (1990) Quantitative bone histomorphometry and circulating T lymphocyte subsets in postmenopausal osteoporosis. J Bone Miner Res. 5:393–9CrossRefPubMed

39.

Montecino-Rodriguez E, Dorshkind K (2006) Evolving patterns of lymphopoiesis from embryogenesis through senescence. Immunity 24:659–662CrossRefPubMed

40.

Eghbali-Fatourechi G, Khosla S, Sanyal A et al (2003) Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J. Clin. Invest. 111:1221–1230PubMed

41.

Boyce BF, Xing L (2008) Bruton and Tec: new links in osteoimmunology. Cell Metab 7:283–5CrossRefPubMed

42.

Wu JY, Scadden DT, Kronenberg HM (2009) Role of the osteoblast lineage in the bone marrow hematopoietic niches. J Bone Miner Res 24:759–64CrossRefPubMed

Title: Immune changes in post-menopausal osteoporosis: the Immunos study
Authors: V. Breuil
M. Ticchioni
J. Testa
C. H. Roux
P. Ferrari
J. P. Breittmayer
C. Albert-Sabonnadière
J. Durant
F. De Perreti
A. Bernard
L. Euller-Ziegler
G. F. Carle
Publication date: 01-05-2010
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 5/2010
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-009-1018-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Immune changes in post-menopausal osteoporosis: the Immunos study

Abstract

Summary

Introduction

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 5/2010

Shorter unipedal standing time and lower bone mineral density in women with distal radius fractures

Women with hip fracture experience greater loss of geometric strength in the contralateral hip during the year following fracture than age-matched controls

No association between polymorphisms of proliferator-activated receptor-gamma gene and peak bone mineral density variation in Chinese nuclear families

A survey of bone mineral density of healthy Han adults in China

Bisphosphonates and BMU birth rate: response to comments by Ott

Estimation of serum osteocalcin and telopeptide-C in postmenopausal osteoporotic females