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Erschienen in: Osteoporosis International 4/2005

01.04.2005 | Original Article

Serum osteoprotegerin and its relationship with bone mineral density and markers of bone turnover

verfasst von: Olafur S. Indridason, Leifur Franzson, Gunnar Sigurdsson

Erschienen in: Osteoporosis International | Ausgabe 4/2005

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Abstract

Introduction: The purpose of this study was to compare age-related differences in osteoprotegerin (OPG) in relationship with BMD and the serum bone markers osteocalcin (OC), collagen crosslinks (CTX), and tartrate-resistant acid phosphatase 5b (TRACP-5b). Methods: Data were derived from a cross-sectional study on bone health in a random sample of community-dwelling adults aged 30 to 85 years in the Reykjavik area in Iceland. All subjects had whole body, hip, and lumbar spine BMD measured (by DXA), gave blood samples, and answered a thorough questionnaire on medications and medical history. We assessed relationships using the Spearman correlation coefficient, partial correlation, and multivariable linear regression. Men and women were analyzed separately. Results: Of 2,310 subjects invited over 2 years, 1,630 participated. After excluding individuals with diseases and medications affecting bone metabolism, 517 women (age 56.1 ± 16.9 years) and 491 men (age 58.7 ± 14.9 years) remained for analysis. OPG increased steadily with age in both genders without a gender difference. In women, BMD at all sites declined steadily after age 50. In men, BMD remained relatively stable until age 70, after which it declined significantly. After controlling for age, BMI, and other confounding variables, OPG showed only a borderline positive relationship with whole body BMD in men (P=0.10), but the relationship was nonsignificant in women. In multivariable models, OPG was inversely related to TRACP-5b (P=0.002) and positively with OC (P=0.007), the OC/TRACP-5b (P=0.001) and OC/CTX (P=0.02) ratios in women. Among men, multivariable models showed a positive association between OPG and OC (P=0.05) and OC/TRACP-5b (P<0.009). Conclusions: We conclude that serum OPG levels are associated with a profile of bone turnover markers favoring bone formation, suggesting that OPG may be protective against age-related bone loss. Longitudinal studies are needed to address that issue.
Literatur
1.
Zurück zum Zitat Warming L, Hassager C, Christiansen C (2002) Changes in bone mineral density with age in men and women: a longitudinal study. Osteoporos Int 13:105–112CrossRefPubMed Warming L, Hassager C, Christiansen C (2002) Changes in bone mineral density with age in men and women: a longitudinal study. Osteoporos Int 13:105–112CrossRefPubMed
2.
Zurück zum Zitat Nguyen TV, Center JR, Eisman JA (2000) Osteoporosis in elderly men and women: effects of dietary calcium, physical activity, and body mass index. J Bone Miner Res 15:322–331PubMed Nguyen TV, Center JR, Eisman JA (2000) Osteoporosis in elderly men and women: effects of dietary calcium, physical activity, and body mass index. J Bone Miner Res 15:322–331PubMed
3.
Zurück zum Zitat Hernandez CJ, Beaupre GS, Carter DR (2003) A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis. Osteoporos Int 14:843–847CrossRefPubMed Hernandez CJ, Beaupre GS, Carter DR (2003) A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis. Osteoporos Int 14:843–847CrossRefPubMed
4.
Zurück zum Zitat Center JR, Nguyen TV, Sambrook PN, Eisman JA (1999) Hormonal and biochemical parameters in the determination of osteoporosis in elderly men. J Clin Endocrinol Metab 84:3626–3635CrossRefPubMed Center JR, Nguyen TV, Sambrook PN, Eisman JA (1999) Hormonal and biochemical parameters in the determination of osteoporosis in elderly men. J Clin Endocrinol Metab 84:3626–3635CrossRefPubMed
5.
Zurück zum Zitat Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R et al (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319CrossRefPubMed Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R et al (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319CrossRefPubMed
6.
Zurück zum Zitat Aubin JE, Bonnelye E (2000) Osteoprotegerin and its ligand: a new paradigm for regulation of osteoclastogenesis and bone resorption. Osteoporos Int 11:905–913CrossRefPubMed Aubin JE, Bonnelye E (2000) Osteoprotegerin and its ligand: a new paradigm for regulation of osteoclastogenesis and bone resorption. Osteoporos Int 11:905–913CrossRefPubMed
7.
Zurück zum Zitat Yano K, Tsuda E, Washida N, Kobayashi F, Goto M, Harada A et al (1999) Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis. J Bone Miner Res 14:518–527PubMed Yano K, Tsuda E, Washida N, Kobayashi F, Goto M, Harada A et al (1999) Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis. J Bone Miner Res 14:518–527PubMed
8.
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
9.
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
10.
Zurück zum Zitat Fahrleitner-Pammer A, Dobnig H, Piswanger-Soelkner C, Bonelli C, Dimai HP, Leb G et al (2003) Osteoprotegerin serum levels in women: correlation with age, bone mass, bone turnover and fracture status. Wien Klin Wochenschr 115:291–297PubMed Fahrleitner-Pammer A, Dobnig H, Piswanger-Soelkner C, Bonelli C, Dimai HP, Leb G et al (2003) Osteoprotegerin serum levels in women: correlation with age, bone mass, bone turnover and fracture status. Wien Klin Wochenschr 115:291–297PubMed
11.
Zurück zum Zitat Jung K, Lein M, Hosslin K, Grosse A, Roth S, Possinger K et al (2002) Osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) in the serum of healthy adults. Int J Biol Markers 17:177–181PubMed Jung K, Lein M, Hosslin K, Grosse A, Roth S, Possinger K et al (2002) Osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) in the serum of healthy adults. Int J Biol Markers 17:177–181PubMed
12.
Zurück zum Zitat Khosla S, Arrighi HM, Melton LJ 3rd, Atkinson EJ, O’Fallon WM, Dunstan C et al (2002) Correlates of osteoprotegerin levels in women and men. Osteoporos Int 13:394–399CrossRefPubMed Khosla S, Arrighi HM, Melton LJ 3rd, Atkinson EJ, O’Fallon WM, Dunstan C et al (2002) Correlates of osteoprotegerin levels in women and men. Osteoporos Int 13:394–399CrossRefPubMed
13.
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
14.
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
15.
Zurück zum Zitat Fahrleitner A, Prenner G, Leb G, Tscheliessnigg KH, Piswanger-Solkner C, Obermayer-Pietsch B et al (2003) Serum osteoprotegerin is a major determinant of bone density development and prevalent vertebral fracture status following cardiac transplantation. Bone 32:96–106CrossRefPubMed Fahrleitner A, Prenner G, Leb G, Tscheliessnigg KH, Piswanger-Solkner C, Obermayer-Pietsch B et al (2003) Serum osteoprotegerin is a major determinant of bone density development and prevalent vertebral fracture status following cardiac transplantation. Bone 32:96–106CrossRefPubMed
16.
Zurück zum Zitat Schett G, Kiechl S, Redlich K, Oberhollenzer F, Weger S, Egger G et al (2004) Soluble RANKL and risk of nontraumatic fracture. JAMA 291:1108–1113CrossRefPubMed Schett G, Kiechl S, Redlich K, Oberhollenzer F, Weger S, Egger G et al (2004) Soluble RANKL and risk of nontraumatic fracture. JAMA 291:1108–1113CrossRefPubMed
17.
Zurück zum Zitat Minisola S, Dionisi S, Pacitti MT, Paglia F, Carnevale V, Scillitani A et al (2002) Gender differences in serum markers of bone resorption in healthy subjects and patients with disorders affecting bone. Osteoporos Int 13:171–175CrossRefPubMed Minisola S, Dionisi S, Pacitti MT, Paglia F, Carnevale V, Scillitani A et al (2002) Gender differences in serum markers of bone resorption in healthy subjects and patients with disorders affecting bone. Osteoporos Int 13:171–175CrossRefPubMed
18.
Zurück zum Zitat Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J (2000) The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int 11[Suppl 6]:S2–S17 Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J (2000) The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int 11[Suppl 6]:S2–S17
20.
Zurück zum Zitat Kurland ES, Cosman F, McMahon DJ, Rosen CJ, Lindsay R, Bilezikian JP (2000) Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 85:3069–3076CrossRefPubMed Kurland ES, Cosman F, McMahon DJ, Rosen CJ, Lindsay R, Bilezikian JP (2000) Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 85:3069–3076CrossRefPubMed
21.
Zurück zum Zitat Rubin MR, Bilezikian JP (2003) New anabolic therapies in osteoporosis. Endocrinol Metab Clin North Am 32:285–307PubMed Rubin MR, Bilezikian JP (2003) New anabolic therapies in osteoporosis. Endocrinol Metab Clin North Am 32:285–307PubMed
22.
Zurück zum Zitat Eastell R, Robins SP, Colwell T, Assiri AM, Riggs BL, Russell RG (1993) Evaluation of bone turnover in type I osteoporosis using biochemical markers specific for both bone formation and bone resorption. Osteoporos Int 3:255–260PubMed Eastell R, Robins SP, Colwell T, Assiri AM, Riggs BL, Russell RG (1993) Evaluation of bone turnover in type I osteoporosis using biochemical markers specific for both bone formation and bone resorption. Osteoporos Int 3:255–260PubMed
23.
Zurück zum Zitat Kleerekoper M (2001) The effect of fracture or disease on biochemical markers of bone remodelling. In: Eastell R, Baumann M, Hoyle R, Wieczorek L (eds) (2001) Bone markers—biochemical and clinical perspectives. Dunitz, London, pp 123–130 Kleerekoper M (2001) The effect of fracture or disease on biochemical markers of bone remodelling. In: Eastell R, Baumann M, Hoyle R, Wieczorek L (eds) (2001) Bone markers—biochemical and clinical perspectives. Dunitz, London, pp 123–130
24.
Zurück zum Zitat Sodergard R, Backstrom T, Shanbhag V, Carstensen H (1982) Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J Steroid Biochem 16:801–810CrossRefPubMed Sodergard R, Backstrom T, Shanbhag V, Carstensen H (1982) Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J Steroid Biochem 16:801–810CrossRefPubMed
25.
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 16:348–360PubMed 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 16:348–360PubMed
26.
Zurück zum Zitat Marcus R, Holloway L, Wells B, Greendale G, James MK, Wasilauskas C et al (1999) The relationship of biochemical markers of bone turnover to bone density changes in postmenopausal women: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. J Bone Miner Res 14:1583–1595PubMed Marcus R, Holloway L, Wells B, Greendale G, James MK, Wasilauskas C et al (1999) The relationship of biochemical markers of bone turnover to bone density changes in postmenopausal women: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. J Bone Miner Res 14:1583–1595PubMed
27.
Zurück zum Zitat Siddiqi A, Burrin JM, Noonan K, James I, Wood DF, Price CP et al (1997) A longitudinal study of markers of bone turnover in Graves’ disease and their value in predicting bone mineral density. J Clin Endocrinol Metab 82:753–759CrossRefPubMed Siddiqi A, Burrin JM, Noonan K, James I, Wood DF, Price CP et al (1997) A longitudinal study of markers of bone turnover in Graves’ disease and their value in predicting bone mineral density. J Clin Endocrinol Metab 82:753–759CrossRefPubMed
28.
Zurück zum Zitat Sigurdsson G, Franzson L, Steingrimsdottir L, Sigvaldason H (2000) The association between parathyroid hormone, vitamin D and bone mineral density in 70-year-old Icelandic women. Osteoporos Int 11:1031–1035CrossRefPubMed Sigurdsson G, Franzson L, Steingrimsdottir L, Sigvaldason H (2000) The association between parathyroid hormone, vitamin D and bone mineral density in 70-year-old Icelandic women. Osteoporos Int 11:1031–1035CrossRefPubMed
29.
Zurück zum Zitat Vidal NO, Brandstrom H, Jonsson KB, Ohlsson C (1998) Osteoprotegerin mRNA is expressed in primary human osteoblast-like cells: down-regulation by glucocorticoids. J Endocrinol 159:191–195PubMed Vidal NO, Brandstrom H, Jonsson KB, Ohlsson C (1998) Osteoprotegerin mRNA is expressed in primary human osteoblast-like cells: down-regulation by glucocorticoids. J Endocrinol 159:191–195PubMed
30.
Zurück zum Zitat Hofbauer LC, Hicok KC, Chen D, Khosla S (2002) Regulation of osteoprotegerin production by androgens and anti-androgens in human osteoblastic lineage cells. Eur J Endocrinol 147:269–273PubMed Hofbauer LC, Hicok KC, Chen D, Khosla S (2002) Regulation of osteoprotegerin production by androgens and anti-androgens in human osteoblastic lineage cells. Eur J Endocrinol 147:269–273PubMed
31.
Zurück zum Zitat Brandstrom H, Jonsson KB, Ohlsson C, Vidal O, Ljunghall S, Ljunggren O (1998) Regulation of osteoprotegerin mRNA levels by prostaglandin E2 in human bone marrow stroma cells. Biochem Biophys Res Commun 247:338–341CrossRefPubMed Brandstrom H, Jonsson KB, Ohlsson C, Vidal O, Ljunghall S, Ljunggren O (1998) Regulation of osteoprotegerin mRNA levels by prostaglandin E2 in human bone marrow stroma cells. Biochem Biophys Res Commun 247:338–341CrossRefPubMed
32.
Zurück zum Zitat Lee SK, Lorenzo JA (1999) Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology 140:3552–3561CrossRefPubMed Lee SK, Lorenzo JA (1999) Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology 140:3552–3561CrossRefPubMed
33.
Zurück zum Zitat Hofbauer LC, Dunstan CR, Spelsberg 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 250:776–781CrossRefPubMed Hofbauer LC, Dunstan CR, Spelsberg 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 250:776–781CrossRefPubMed
34.
Zurück zum Zitat Brandstrom H, Jonsson KB, Vidal O, Ljunghall S, Ohlsson C, Ljunggren O (1998) Tumor necrosis factor-alpha and -beta upregulate the levels of osteoprotegerin mRNA in human osteosarcoma MG-63 cells. Biochem Biophys Res Commun 248:454–457CrossRefPubMed Brandstrom H, Jonsson KB, Vidal O, Ljunghall S, Ohlsson C, Ljunggren O (1998) Tumor necrosis factor-alpha and -beta upregulate the levels of osteoprotegerin mRNA in human osteosarcoma MG-63 cells. Biochem Biophys Res Commun 248:454–457CrossRefPubMed
35.
Zurück zum Zitat Viereck V, Grundker C, Blaschke S, Niederkleine B, Siggelkow H, Frosch KH et al (2003) Raloxifene concurrently stimulates osteoprotegerin and inhibits interleukin-6 production by human trabecular osteoblasts. J Clin Endocrinol Metab 88:4206–4213CrossRefPubMed Viereck V, Grundker C, Blaschke S, Niederkleine B, Siggelkow H, Frosch KH et al (2003) Raloxifene concurrently stimulates osteoprotegerin and inhibits interleukin-6 production by human trabecular osteoblasts. J Clin Endocrinol Metab 88:4206–4213CrossRefPubMed
36.
Zurück zum Zitat Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL (1999) Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 140:4367–4370CrossRefPubMed Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL (1999) Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 140:4367–4370CrossRefPubMed
37.
Zurück zum Zitat Fazzalari NL, Kuliwaba JS, Atkins GJ, Forwood MR, Findlay DM (2001) The ratio of messenger RNA levels of receptor activator of nuclear factor kappaB ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis. J Bone Miner Res 16:1015–1027PubMed Fazzalari NL, Kuliwaba JS, Atkins GJ, Forwood MR, Findlay DM (2001) The ratio of messenger RNA levels of receptor activator of nuclear factor kappaB ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis. J Bone Miner Res 16:1015–1027PubMed
Metadaten
Titel
Serum osteoprotegerin and its relationship with bone mineral density and markers of bone turnover
verfasst von
Olafur S. Indridason
Leifur Franzson
Gunnar Sigurdsson
Publikationsdatum
01.04.2005
Verlag
Springer-Verlag
Erschienen in
Osteoporosis International / Ausgabe 4/2005
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-004-1699-x

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