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Erschienen in: Osteoporosis International 6/2010

01.06.2010 | Original Article

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

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

Erschienen in: Osteoporosis International | Ausgabe 6/2010

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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.
Literatur
1.
3.
Zurück zum Zitat 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 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
4.
Zurück zum Zitat 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 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
5.
Zurück zum Zitat 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 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
6.
Zurück zum Zitat 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 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
7.
Zurück zum Zitat 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 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
8.
Zurück zum Zitat 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 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
9.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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
Metadaten
Titel
Bone loss in relation to serum levels of osteoprotegerin and nuclear factor-κB ligand: the Tromsø Study
verfasst von
L. Jørgensen
A. Vik
N. Emaus
J. Brox
J.-B. Hansen
E. Mathiesen
P. Vestergaard
Publikationsdatum
01.06.2010
Verlag
Springer-Verlag
Erschienen in
Osteoporosis International / Ausgabe 6/2010
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-009-1035-6

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