Top

Osteoporosis International

Published in:

01-06-2010 | Original Article

Bone loss in relation to serum levels of osteoprotegerin and nuclear factor-κB ligand: the Tromsø Study

Authors: L. Jørgensen, A. Vik, N. Emaus, J. Brox, J.-B. Hansen, E. Mathiesen, P. Vestergaard

Published in: Osteoporosis International | Issue 6/2010

Abstract

Summary

In this longitudinal study of 4,137 persons, bone mineral density was negatively associated with osteoprotegerin at baseline in both genders. In postmenopausal women not using hormone replacement therapy (HRT), bone-loss increased with increasing osteoprotegerin levels, whereas no relationship was found in men, premenopausal women, or postmenopausal women taking HRT.

Introduction

In a population-based study of 2,003 men and 2,134 women, the relationship between the osteoprotegerin (OPG)/factor-κB ligand (RANKL) system and bone mineral density (BMD) and changes in BMD was examined.

Methods

Baseline measurements included height, weight, BMD of the forearm, OPG, RANKL, vitamin D, and serum parathyroid hormone (PTH) and information about lifestyle, prevalent diseases, and use of medication. BMD was remeasured at follow-up 6 years later.

Results

BMD was negatively associated with OPG at baseline in both men and women (p trend over OPG levels = 0.01 and 0.007, respectively, after adjustments for age, and other confounders). In postmenopausal women not on hormone replacement therapy, bone loss increased with increasing OPG (p = 0.005), whereas no relationship was found in men, premenopausal women, or postmenopausal women on HRT (p ≥ 0.28). BMD at baseline and BMD changes were not related to RANKL levels in any of the groups (p ≥ 0.14).

Conclusions

In postmenopausal women not using HRT, bone loss associated positively with OPG. The results indicate that in women deficient in sex steroids, the OPG/RANKL system may play an important counter regulatory role in order to avoid bone loss and maintain BMD. In men and women replete in sex steroids, the OPG/RANKL system was not associated with BMD.

Khosla S (2001) Minireview: the OPG/RANKL/RANK system. Endocrinology 142:5050–5055CrossRefPubMed

Teitelbaum SL (2000) Bone resorption by osteoclasts. Science 289:1504–1508CrossRefPubMed

Vega D, Maalouf NM, Sakhaee K (2007) Clinical review: the role of receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/osteoprotegerin: clinical implications. J Clin Endocrinol Metab 92:4514–4521CrossRefPubMed

Abrahamsen B, Hjelmborg JV, Kostenuik P, Stilgren LS, Kyvik K, Adamu S, Brixen K, Langdahl BL (2005) Circulating amounts of osteoprotegerin and RANK ligand: genetic influence and relationship with BMD assessed in female twins. Bone 36:727–735CrossRefPubMed

Browner WS, Lui LY, Cummings SR (2001) Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J Clin Endocrinol Metab 86:631–637CrossRefPubMed

Han KO, Choi JT, Choi HA, Moon IG, Yim CH, Park WK, Yoon HK, Han IK (2005) The changes in circulating osteoprotegerin after hormone therapy in postmenopausal women and their relationship with oestrogen responsiveness on bone. Clin Endocrinol 62:349–353CrossRef

Indridason OS, Franzson L, Sigurdsson G (2005) Serum osteoprotegerin and its relationship with bone mineral density and markers of bone turnover. Osteoporos Int 16:417–423CrossRefPubMed

Khosla S, Arrighi HM, Melton LJ III, Atkinson EJ, O’Fallon WM, Dunstan C, Riggs BL (2002) Correlates of osteoprotegerin levels in women and men. Osteoporos Int 13:394–399CrossRefPubMed

Kim JG, Kim JH, Lee DO, Kim H, Kim JY, Suh CS, Kim SH, Choi YM (2008) Changes in the serum levels of osteoprotegerin and soluble receptor activator for nuclear factor kappaB ligand after estrogen–progestogen therapy and their relationships with changes in bone mass in postmenopausal women. Menopause 15:357–362CrossRefPubMed

10.

Kudlacek S, Schneider B, Woloszczuk W, Pietschmann P, Willvonseder R (2003) Serum levels of osteoprotegerin increase with age in a healthy adult population. Bone 32:681–686CrossRefPubMed

11.

Liu JM, Zhao HY, Ning G, Zhao YJ, Chen Y, Zhang Z, Sun LH, Xu MY, Chen JL (2005) Relationships between the changes of serum levels of OPG and RANKL with age, menopause, bone biochemical markers and bone mineral density in Chinese women aged 20–75. Calcif Tissue Int 76:1–6CrossRefPubMed

12.

Oh KW, Rhee EJ, Lee WY, Kim SW, Oh ES, Baek KH, Kang MI, Choi MG, Yoo HJ, Park SW (2004) The relationship between circulating osteoprotegerin levels and bone mineral metabolism in healthy women. Clin Endocrinol 61:244–249CrossRef

13.

Rogers A, Saleh G, Hannon RA, Greenfield D, Eastell R (2002) Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women. J Clin Endocrinol Metab 87:4470–4475CrossRefPubMed

14.

Szulc P, Hofbauer LC, Heufelder AE, Roth S, Delmas PD (2001) Osteoprotegerin serum levels in men: correlation with age, estrogen, and testosterone status. J Clin Endocrinol Metab 86:3162–3165CrossRefPubMed

15.

Uemura H, Yasui T, Miyatani Y, Yamada M, Hiyoshi M, Arisawa K, Irahara M (2008) Circulating profiles of osteoprotegerin and soluble receptor activator of nuclear factor kappaB ligand in post-menopausal women. J Endocrinol Investig 31:163–168

16.

Ueland T, Yndestad A, Oie E, Florholmen G, Halvorsen B, Froland SS, Simonsen S, Christensen G, Gullestad L, Aukrust P (2005) Dysregulated osteoprotegerin/RANK ligand/RANK axis in clinical and experimental heart failure. Circulation 111:2461–2468CrossRefPubMed

17.

Jørgensen HL, Kusk P, Madsen B, Fenger M, Lauritzen JB (2004) Serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter region are related to peripheral measures of bone mass and fracture odds ratios. J Bone Miner Metab 22:132–138CrossRefPubMed

18.

Yano K, Tsuda E, Washida N, Kobayashi F, Goto M, Harada A, Ikeda K, Higashio K, Yamada Y (1999) Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis. J Bone Miner Res 14:518–527CrossRefPubMed

19.

Oh KW, Rhee EJ, Lee WY, Kim SW, Baek KH, Kang MI, Yun EJ, Park CY, Ihm SH, Choi MG, Yoo HJ, Park SW (2005) Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system are associated with bone metabolism in middle-aged males. Clin Endocrinol 62:92–98CrossRef

20.

Samelson EJ, Broe KE, Demissie S, Beck TJ, Karasik D, Kathiresan S, Kiel DP (2008) Increased plasma osteoprotegerin concentrations are associated with indices of bone strength of the hip. J Clin Endocrinol Metab 93:1789–1795CrossRefPubMed

21.

Mezquita-Raya P, de la Higuera M, Garcia DF, Alonso G, Ruiz-Requena ME, de Dios LJ, Escobar-Jimenez F, Munoz-Torres M (2005) The contribution of serum osteoprotegerin to bone mass and vertebral fractures in postmenopausal women. Osteoporos Int 16:1368–1374CrossRefPubMed

22.

Schett G, Kiechl S, Redlich K, Oberhollenzer F, Weger S, Egger G, Mayr A, Jocher J, Xu Q, Pietschmann P, Teitelbaum S, Smolen J, Willeit J (2004) Soluble RANKL and risk of nontraumatic fracture. JAMA 291:1108–1113CrossRefPubMed

23.

Stern A, Laughlin GA, Bergstrom J, Barrett-Connor E (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 156:555–562CrossRefPubMed

24.

Jørgensen L, Joakimsen O, Mathiesen EB, Ahmed L, Berntsen GK, Fønnebø V, Joakimsen R, Njølstad I, Schirmer H, Jacobsen BK (2006) Carotid plaque echogenicity and risk of nonvertebral fractures in women: a longitudinal population-based study. Calcif Tissue Int 79:207–213CrossRefPubMed

25.

Berntsen GK, Tollan A, Magnus JH, Søgaard AJ, Ringberg T, Fønnebø V (1999) The Tromsø Study: artifacts in forearm bone densitometry—prevalence and effect. Osteoporos Int 10:425–432CrossRefPubMed

26.

Berntsen GK, Fønnebø V, Tollan A, Søgaard AJ, Joakimsen RM, Magnus JH (2000) The Tromsø Study: determinants of precision in bone densitometry. J Clin Epidemiol 53:1104–1112CrossRef

27.

Emaus N, Berntsen GK, Joakimsen R, Fønnebø V (2005) Bone mineral density measures in longitudinal studies: the choice of phantom is crucial for quality assessment. The Tromsø Study, a population-based study. Osteoporos Int 16:1597–1603CrossRefPubMed

28.

Ueland T, Brixen K, Mosekilde L, Mosekilde L, Flyvbjerg A, Bollerslev J (2003) Age-related changes in cortical bone content of insulin-like growth factor binding protein (IGFBP)-3, IGFBP-5, osteoprotegerin, and calcium in postmenopausal osteoporosis: a cross-sectional study. J Clin Endocrinol Metab 88:1014–1018CrossRefPubMed

29.

Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312:1254–1259PubMed

30.

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

31.

McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ (2006) Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354:821–831CrossRefPubMed

32.

Min H, Morony S, Sarosi I, Dunstan CR, Capparelli C, Scully S, Van G, Kaufman S, Kostenuik PJ, Lacey DL, Boyle WJ, Simonet WS (2000) Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis. J Exp Med 192:463–474CrossRefPubMed

33.

Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Gwyneth V, Itie A, Khoo W, Wakeham A, Dunstan CR, Lacey DL, Mak TW, Boyle WJ, Penninger JM (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397:315–323CrossRefPubMed

34.

Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176CrossRefPubMed

Title: Bone loss in relation to serum levels of osteoprotegerin and nuclear factor-κB ligand: the Tromsø Study
Authors: L. Jørgensen
A. Vik
N. Emaus
J. Brox
J.-B. Hansen
E. Mathiesen
P. Vestergaard
Publication date: 01-06-2010
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 6/2010
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-009-1035-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Bone loss in relation to serum levels of osteoprotegerin and nuclear factor-κB ligand: the Tromsø 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 6/2010

Longitudinal changes in femur bone mineral density after spinal cord injury: effects of slice placement and peel method

Compromised bone strength index in the hemiparetic distal tibia epiphysis among chronic stroke patients: the association with cardiovascular function, muscle atrophy, mobility, and spasticity

Hip structural geometry and incidence of hip fracture in postmenopausal women: what does it add to conventional bone mineral density?

The effects of strontium ranelate on biochemical markers of bone turnover and their relationship with bone mineral density

Bone mineral density reference ranges for Australian men: Geelong Osteoporosis Study

Measurement uncertainty for the analysis of serum 25-hydroxyvitamin D