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Osteoporosis International
Published in: Osteoporosis International 9/2007

01-09-2007 | Original Article

Telomere length in leukocytes correlates with bone mineral density and is shorter in women with osteoporosis

Authors: A. M. Valdes, J. B. Richards, J. P. Gardner, R. Swaminathan, M. Kimura, L. Xiaobin, A. Aviv, T. D. Spector

Published in: Osteoporosis International | Issue 9/2007

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Abstract

Summary

Telomere length decreases with age and is associated with osteoblast senescence. In 2,150 unselected women, leukocyte telomere length was significantly correlated with bone mineral density. Clinical osteoporosis was associated with shorter telomeres, suggesting that telomere length can be used as a marker of bone aging.

Introduction

The length of telomeres in proliferative cells diminishes with age. Telomere shortening and telomerase activity have been linked to in vitro osteoblast senescence and to increased secretion of pro-inflammatory cytokines. We explored whether bone mineral density correlates with telomere length in leukocytes.

Materials and methods

The relationship between leukocyte telomere length, bone mineral density (BMD) and osteoporosis (as defined by the World Health Organization) was examined in a cohort of 2,150 women from a population-based twin cohort aged 18–79.

Results

After adjusting for age, body mass index, menopausal status, smoking, hormone replacement therapy status, telomere length was positively correlated with BMD of the spine (p < 0.005), forearm (p < 0.013), but not the femoral neck (p < 0.06). Longer telomeres were associated with reduced the risk of clinical OP at two or more sites (odds ratio = 0.594 95% CI 0.42–0.84 p < 0.003) and in women over the age of 50, clinical osteoporosis was associated with 117 bp shorter telomere length (p < 0.02) equivalent to 5.2 years of telomeric aging.

Conclusions

Shortened leukocyte telomere length is independently associated with a decrease in BMD and the presence of osteoporosis in women. Our data provide evidence that leukocyte telomere length could be a marker of biological aging of bone.
Literature
1.
Lane NE (2006) Epidemiology, etiology, and diagnosis of osteoporosis. Am J Obstet Gynecol 194(2 Suppl):S3–S11PubMedCrossRef
2.
Rodan GA, Raisz LG, Bilezikian JP (1996) Pathophysiology of osteoporosis. In: Bilezikian JP, Raisz LG, Rodan LG (eds) Principles of bone biology, 1st edn. Academic Press, San Diego, pp 979–990
3.
Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312(7041):1254–1259PubMed
4.
Manolagas SC, Jilka RL (1995) Mechanisms of disease: bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 332:305–311PubMedCrossRef
5.
Inoue K, Ohgushi H, Yoshikawa T, Okumura M, Sempuku T, Tamani S, Dohi Y (1997) The effect of aging on bone formation in porous hydroxyapatite: Biochemical and histological analysis. J Bone Miner Res 12:989–994PubMedCrossRef
6.
Garcia-Moreno C, Catalan MP, Ortiz A, Alvarez L, De la Piedra C (2004) Modulation of survival in osteoblasts from postmenopausal women. Bone 35(1):170–177PubMedCrossRef
7.
8.
Browner WS, Kahn AJ, Ziv E, Reiner AP, Oshima J, Cawthon RM, Hsueh WC, Cummings SR (2004) The genetics of human longevity. Am J Med 117(11):851–860PubMedCrossRef
9.
Saretzki G, Von Zglinicki T (2002) Replicative ageing, telomeres, and oxidative stress. Ann NY Acad Sci 959:24–29PubMedCrossRef
10.
Valdes AM, Andrew T, Gardner JP, Kimura M, Oelsner E, Cherkas LF, Aviv A, Spector TD (2005) Obesity and cigarette smoking are associated with short telomeres in women. The Lancet 366:662–664CrossRef
11.
Benetos A, Okuda K, Lajemi M, Kimura M, Thomas F, Skurnick J, Labat C, Bean K, Aviv A (2001) Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity. Hypertension 37:381–385
12.
Slagboom PE, Droog S, Boomsma DI (1994) Genetic determination of telomere size in humans: a twin study of three age groups. Am J Hum Genet 55:876–882PubMed
13.
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 36(10):1749–1759PubMedCrossRef
14.
Takayanagi H, Sato K, Takaoka A, Taniguchi T (2005) Interplay between interferon and other cytokine systems in bone metabolism. Immunol Rev 208:181–193PubMedCrossRef
15.
Cenci S, Weitzmann MN, Roggia C, Namba N, Novack D, Woodring J, Pacifici R (2000) Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. J Clin Invest 106(10):1229–1237PubMedCrossRef
16.
Kimble RB, Bain S, Pacifici R (1997) The functional block of TNF but not of IL-6 prevents bone loss in ovariectomized mice. J Bone Miner Res 12(6):935–941PubMedCrossRef
17.
Beyne-Rauzy O, Recher C, Dastugue N, et al (2004) Tumor necrosis factor alpha induces senescence and chromosomal instability in human leukemic cells. Oncogene 23(45):7507–7516PubMedCrossRef
18.
Benetos A, Gardner JP, Zureik M, Labat C, Xiaobin L, Adamopoulos C, Temmar M, Bean KE, Aviv A (2004) Short telomeres are associated with increased carotid artery atherosclerosis in hypertensive subjects. Hypertension 43:182–185PubMedCrossRef
19.
Samani NJ, Boultby R, Butler R, Thompson JR, Goodall AH (2001) Telomere shortening in atherosclerosis. The Lancet 358:472–473CrossRef
20.
Brouilette S, Singh RK,Thompson JR, Goodall AH, Samani NJ (2003) White cell telomere length and risk of premature myocardial infarction. Arterioscler Throm Vasc Biol 23:842–846CrossRef
21.
Erdmann J, Kogler C, Diel I, Ziegler R, Pfeilschifter J (1999) Age-associated changes in the stimulatory effect of transforming growth factor beta on human osteogenic colony formation. Mech Ageing Dev 1 110(1–2):73–85CrossRef
22.
Yudoh K, Matsuno H, Nakazawa F, Katayama R, Kimura T (2001) Reconstituting telomerase activity using the telomerase catalytic subunit prevents the telomere shorting and replicative senescence in human osteoblasts. J Bone Miner Res 16(8):1453–1464PubMedCrossRef
23.
Ginaldi L, Di Benedetto MC, De Martinis M (2005) Osteoporosis, inflammation and ageing. Immun Ageing 4(2):14CrossRef
24.
Hunter DJ, de Lange M, Andrew T, Snieder H, MacGregor AJ, Spector TD (2001) Genetic variation in bone mineral density and calcaneal ultrasound: a study of the influence of menopause using female twins. Osteoporos Int 12(5):406–411PubMedCrossRef
25.
World Health Organization (1994)Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser 843:1–129
26.
Etherington J, Harris PA, Nandra D, Hart DJ, Wolman RL, Doyle DV, Spector TD (1996) The effect of weight-bearing exercise on bone mineral density: a study of female ex-elite athletes and the general population. J Bone Miner Res 11(9):1333–1338PubMedCrossRef
27.
Pratt DA, Daniloff Y, Duncan A, Robins SP (1992) Automated analysis of the pyridinium crosslinks of collagen in tissue and urine using solid-phase extraction and reversed-phase high-performance liquid chromatography. Anal Biochem 207(1):168–175PubMedCrossRef
28.
Gabay C, Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340(6):448–454PubMedCrossRef
29.
Bekaert S, Van Pottelbergh I, De Meyer T, Zmierczak H, Kaufman JM, Van Oostveldt P, Goemaere S (2005) Telomere length versus hormonal and bone mineral status in healthy elderly men. Mech Ageing Dev 126(10):1115–1122PubMedCrossRef
30.
Aviv A, Valdes AM, Spector TD (2006) Human telomere biology: pitfalls of moving from the laboratory to epidemiology. Int J Epidemiol Oct Epub ahead of print
31.
Kveiborg M, Kassem M, Langdahl B, Eriksen EF, Clark BF, Rattan SI (1999) Telomere shortening during aging of human osteoblasts in vitro and leukocytes in vivo: lack of excessive telomere loss in osteoporotic patients. Mech Ageing Dev 106(3):261–271PubMedCrossRef
32.
Schnabl B, Purbeck CA, Choi YH, Hagedorn CH, Brenner D (2003) Replicative senescence of activated human hepatic stellate cells is accompanied by a pronounced inflammatory but less fibrogenic phenotype. Hepatology 37(3):653–664PubMedCrossRef
33.
Sivas F, Barca N, Onder M, Ozoran K (2006) The relation between joint erosion and generalized osteoporosis and disease activity in patients with rheumatoid arthritis. Rheumatol Int 26(10):896–899PubMedCrossRef
34.
Maggio D, Barabani M, Pierandrei M, Polidori MC, Catani M, Mecocci P, Senin U, Pacifici R, Cherubini A (2003) Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study. J Clin Endocrinol Metab 88(4):1523–1527PubMedCrossRef
35.
Effros RB (2004) Replicative senescence of CD8 T cells: effect on human ageing. Exp Gerontol 39(4):517–524PubMedCrossRef
36.
Butler MG, Tilburt J, DeVries A, Muralidhar B, Aue G, Hedges L, Atkinson J, Schwartz H (1998) Comparison of chromosome telomere integrity in multiple tissues from subjects at different ages. Cancer Genet Cytogenet 105:138–144PubMedCrossRef
37.
Friedrich U, Griese E, Schwab M, Fritz P, Thon K, Klotz U (2000) Telomere length in different tissues of elderly patients. Mech Ageing Dev 119(3):89–99PubMedCrossRef
38.
Andrew T, Hart DJ, Snieder H, de LM, Spector TD, MacGregor AJ (2001) Are twins and singletons comparable? A study of disease-related and lifestyle characteristics in adult women. Twin Res 4:464–477PubMedCrossRef
Metadata
Title
Telomere length in leukocytes correlates with bone mineral density and is shorter in women with osteoporosis
Authors
A. M. Valdes
J. B. Richards
J. P. Gardner
R. Swaminathan
M. Kimura
L. Xiaobin
A. Aviv
T. D. Spector
Publication date
01-09-2007
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 9/2007
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-007-0357-5

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