The contribution of serum osteoprotegerin to bone mass and vertebral fractures in postmenopausal women (original) (raw)
Abstract
Regulation of osteoclastic activity is critical for understanding bone loss associated with the postmenopausal period. In vitro and animal studies have revealed the role of OPG as a decoy receptor that neutralizes the effect of RANKL on the differentiation and activation of osteoclasts. However, the role of the OPG-RANKL system in postmenopausal osteoporosis is controversial. Thus, the aim of this study was to investigate the relationship among circulating levels of OPG, RANKL, bone turnover markers (BTM), bone mineral density (BMD) and vertebral fractures in postmenopausal women. We determined anthropometric parameters, circulating OPG and RANKL, BTM, estradiol, BMD by dual X-ray absorptiometry at the lumbar spine (LS) and femoral neck (FN), and pre-existing vertebral fractures in 206 ambulatory postmenopausal women of a mean age of 62 years (SD 7). Circulating OPG was significantly related to age ( r =0.158; P =0.023), years since menopause ( r =0.167; P =0.016) and BMD (LS Z-score: r =0.240; P =0.001, FN Z-score: r =0.156; P =0.025). Over half of the women had undetectable RANKL ( n =113; 54.9%). There were no significant differences in clinical variables, BTM or BMD among women with detectable vs. undetectable RANKL. OPG was found to be independently associated with osteoporosis (OR: 2.9, 1.4–5.9) and prevalent vertebral fractures (OR: 2.5, 1.2–5.4). We conclude that serum OPG levels are independently associated with bone mass and prevalent vertebral fractures in postmenopausal women.
Access this article
Subscribe and save
- Get 10 units per month
- Download Article/Chapter or eBook
- 1 Unit = 1 Article or 1 Chapter
- Cancel anytime Subscribe now
Buy Now
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Instant access to the full article PDF.
Similar content being viewed by others
References
- Hofbauer LC, Khosla S, Dunstan CR, Lacey D, Boyle WJ, Riggs BL (2000) The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res 15:2–12
CAS PubMed Google Scholar - Yasuda H, Shima N, Nakagawa N et al (1998) Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139:1329-1337
Article PubMed Google Scholar - Akatsu T, Murakami T, Ono K et al (1998) Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy. Bone 23:495-498
Article Google Scholar - Bekker PJ, Holloway D, Nakanishi A, Arrighi HM, Leese PT, Dunstan CR (2001) The effect of a single dose of osteoprotegerin in postmenopausal women. J Bone Miner Res 16:348-360
CAS PubMed Google Scholar - Bekker PJ, Holoway DL, Rasmussen AS, et al (2004) A single-dose placebo-controlled study of AMG 162, fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 19:1059–1066
CAS PubMed Google Scholar - 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 140:4367-4370
Article CAS PubMed Google Scholar - Schevde NK, Bendixen A, Dienger KM, Pike JW (2000) Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression. Proc Natl Acad Sci USA 977:829–834
Google Scholar - Simonet WS, Lacey DL, Dunstan CR et al (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309-319
Article CAS PubMed Google Scholar - Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL (2003) Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest 111:1221–1230
Article CAS PubMed Google Scholar - Yano K, Tsuda E, Washida N et al (1999) Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis. J Bone Miner Res 14:518–527
CAS PubMed Google Scholar - Khosla S, Arrighi HM, Melton III LJ et al (2002) Correlates of osteoprotegerin levels in women and men. Osteoporos Int 13:394–399
Article CAS PubMed Google Scholar - 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 86:631–637
Article CAS PubMed Google Scholar - 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 87:4470–4475
Article CAS PubMed Google Scholar - Kudlacek S, Schneider B, Woloszczuk W, Pietschmann P, Willvonseder R (2004) Serum levels of osteoprotegerin increase with age in a healthy adult population. Bone 32:681–686
Article Google Scholar - Schett G, Stefan K, Redlich K et al (2004) Soluble RANKL and risk of nontraumatic fracture. JAMA 291:1108–1113
Article CAS PubMed Google Scholar - Pennisi P, Signorelli SS, Riccobene S et al (2004) Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels. Osteoporos Int 15:389–395
Article Google Scholar - Rinaldi S, Déchaud H, Biessy C et al (2001) Reliability and validity of commerciallyavailable, direct radioimmunoassays for measurements of blood androgens and estrogens in postmenopausal women. Cancer Epidemiol Biomark Prev 10:757–765
Google Scholar - Diaz Curiel M, Carrasco de la Peña JL, Honorato Perez J, Perez Cano R, Rapado A, Ruiz Martinez I (1997) Study of bone mineral density in lumbar spine and femoral neck in a Spanish population. Multicentre Research Project on Osteoporosis. Osteoporos Int 7:59–64
CAS Google Scholar - Orwoll ES, Oviatt SK, Mann T (1990) The impact of osteophytic and vascular calcifications on vertebral mineral density measurements in men. J Clin Endocrinol Metab 70:1202–1207
CAS PubMed Google Scholar - Report of a WHO Study Group. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. World Health Organ Tech Rep Ser 843:1–129
- Cook GJ, Lodge MA, Blake GM, Marsden PK, Fogelman I (2000) Differences in skeletal kinetics between vertebral and humeral bone measured by 18Ffluoride positron emission tomography in postmenopausal women. J Bone Miner Res 15:763–769
Google Scholar - Naylor KE, Rogers A, Fraser RB, Hall V, Eastell R, Blumsohn A (2003) Serum osteoprotegerin as a determinant of bone metabolism in a longitudinal study of human pregnancy and lactation. J Clin Endocrinol Metab 88:5361–5365
Article CAS PubMed Google Scholar - Hegedus D, Ferencz V, Lakatos PL et al (2002) Decreased bone density, elevated serum osteoprotegerin, and b-cross-laps in Wilson disease. J Bone Miner Res 17:1961–1967
Google Scholar - Szalay F, Hegedus D, Lakatos PL et al (2003) High serum osteoprotegerin and low RANKL in primary biliary cirrhosis. J Hepatol 38:395–400
Article Google Scholar - Hofbauer LC, Schoppet M, Schüller P, Viereck V, Michael Christ M (2004) Effects of oral contraceptives on circulating osteoprotegerin and soluble RANK ligand serum levels in healthy young women. Clin Endocrinol 60:14–219
Google Scholar - Bord S, Ireland DC, Beavan SR, Compston JE (2003) The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts. Bone 32:136–141
Article Google Scholar - Seck T, Diel I, Bismar H, Ziegler R, Pfeilschifter J (2001) Serum parathyroid hormone, but no menopausal status, is associated with the expression of osteoprotegerin and RANKL mRNA in human bone samples. Eur J Endocrinol 145:199–205
Article Google Scholar - Riggs BL, Sundeep K, Melton LJ III (2002) Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev 23:279–302
Article CAS PubMed Google Scholar - Looker AC, Bauer DC, Chesnut CH III, et al (2000) Clinical use of biochemical markers of bone remodelling: current status and future directions. Osteoporosis Int 11:467–480
Article Google Scholar
Acknowledgments
This study was supported by a grant from Eli Lilly & Co. (Spain), FIS (no. PI021089), Red de Centros de Metabolismo y Nutricion (C03/08) and the Hospital Clínico Foundation. We would like to express our gratitude to Prof. Andrew F. Stewart for his critical review of this manuscript.
Author information
Authors and Affiliations
- Bone Metabolic Unit of the Endocrinology Division, University Hospital San Cecilio, Plaza Isabel La Católica 2, 18009, Granada, Spain
Pedro Mezquita-Raya, Magdalena de la Higuera, Diego Fernández García, Guillermo Alonso, Fernando Escobar-Jiménez & Manuel Muñoz-Torres - Biochemistry Division, University Hospital San Cecilio, Granada, Spain
María Estrella Ruiz-Requena - Biostatistics Department, University School of Medicine, Granada, Spain
Juan de Dios Luna
Authors
- Pedro Mezquita-Raya
You can also search for this author inPubMed Google Scholar - Magdalena de la Higuera
You can also search for this author inPubMed Google Scholar - Diego Fernández García
You can also search for this author inPubMed Google Scholar - Guillermo Alonso
You can also search for this author inPubMed Google Scholar - María Estrella Ruiz-Requena
You can also search for this author inPubMed Google Scholar - Juan de Dios Luna
You can also search for this author inPubMed Google Scholar - Fernando Escobar-Jiménez
You can also search for this author inPubMed Google Scholar - Manuel Muñoz-Torres
You can also search for this author inPubMed Google Scholar
Corresponding author
Correspondence toManuel Muñoz-Torres.
Rights and permissions
About this article
Cite this article
Mezquita-Raya, P., de la Higuera, M., García, D.F. et al. The contribution of serum osteoprotegerin to bone mass and vertebral fractures in postmenopausal women.Osteoporos Int 16, 1368–1374 (2005). https://doi.org/10.1007/s00198-005-1844-1
- Received: 28 July 2004
- Accepted: 17 December 2004
- Published: 12 February 2005
- Issue Date: November 2005
- DOI: https://doi.org/10.1007/s00198-005-1844-1