Abstract
Summary
Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with whole-body bone mineral density (WBMD) in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young.
Introduction
This study aims to investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during ‘healthy’ ageing.
Methods
WBMD and fasting plasma concentrations of dickkopf-1, fibroblast growth factor-23, osteocalcin, osteoprotegerin, osteopontin and sclerostin were measured in 272 older subjects (69 to 81 years; 52% female) and 171 younger subjects (18–30 years; 53% female).
Results
WBMD was lower in old than young. Circulating osteocalcin was lower in old compared with young, while dickkopf-1, osteoprotegerin and sclerostin were higher in old compared with young. These circulating factors were each positively associated with WBMD in the older adults and the relationships remained after adjustment for covariates (r values ranging from 0.174 to 0.254, all p < 0.01). In multivariate regression, the body mass index, circulating sclerostin and whole-body lean mass together accounted for 13.8% of the variation with WBMD in the older adults. In young adults, dickkopf-1 and body mass index together accounted for 7.7% of variation in WBMD.
Conclusion
Circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin are positively associated with WBMD in community-dwelling older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young.
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References
Genant HK et al (1999) Interim report and recommendations of the World Health Organization task-force for osteoporosis. Osteoporos Int 10(4):259–264
Hofbauer LC et al (1999) Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 140(9):4367–4370
Ferron M et al (2010) Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142(2):296–308
Kamiya N (2012) The role of BMPs in bone anabolism and their potential targets SOST and DKK1. Curr Mol Pharmacol 5(2):153–163
Gaudio A et al (2010) Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab 95(5):2248–2253
Ke HZ et al (2012) Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr rev 33(5):747–783
Takei Y, Minamizaki T, Yoshiko Y (2015) Functional diversity of fibroblast growth factors in bone formation. Int J Endocrinol 2015:729352
Standal T, Borset M, Sundan A (2004) Role of osteopontin in adhesion, migration, cell survival and bone remodeling. Exp Oncol 26(3):179–184
McPhee JS et al (2013) Physiological and functional evaluation of healthy young and older men and women: design of the European MyoAge study. Biogerontology 14(3):325–337
Monroe DG et al (2012) Update on Wnt signaling in bone cell biology and bone disease. Gene 492(1):1–18
Brunetti G et al (2016) Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-alpha. Osteoporos Int 27(7):2355–2365
Roforth MM et al (2014) Effects of age on bone mRNA levels of sclerostin and other genes relevant to bone metabolism in humans. Bone 59:1–6
Butler JS et al (2011) The role of Dkk1 in bone mass regulation: correlating serum Dkk1 expression with bone mineral density. J Orthop res 29(3):414–418
Szulc P et al (2013) Correlates of bone microarchitectural parameters and serum sclerostin levels in men: the STRAMBO study. J Bone Miner res 28(8):1760–1770
Garnero P et al (2013) Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study. Osteoporos Int 24(2):489–494
Polyzos SA et al (2012) Serum sclerostin levels positively correlate with lumbar spinal bone mineral density in postmenopausal women—the six-month effect of risedronate and teriparatide. Osteoporos Int 23(3):1171–1176
Thorson S et al (2013) Sclerostin and bone strength in women in their 10th decade of life. J Bone Miner res 28(9):2008–2016
Schett G et al (2003) Osteoprotegerin protects against generalized bone loss in tumor necrosis factor-transgenic mice. Arthritis Rheum 48(7):2042–2051
Weitzmann MN (2013) The role of inflammatory cytokines, the RANKL/OPG axis, and the immunoskeletal interface in physiological bone turnover and osteoporosis. Scientifica (Cairo) 2013:125705
Jabbar S et al (2011) Osteoprotegerin, RANKL and bone turnover in postmenopausal osteoporosis. J Clin Pathol 64(4):354–357
Oh KW et al (2005) Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system are associated with bone metabolism in middle-aged males. Clin Endocrinol 62(1):92–98
Rogers A et al (2002) Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women. J Clin Endocrinol Metab 87(10):4470–4475
Liu JM et al (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):1–6
Samelson EJ et al (2008) Increased plasma osteoprotegerin concentrations are associated with indices of bone strength of the hip. J Clin Endocrinol Metab 93(5):1789–1795
Stern A et al (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(5):555–562
Modder UI et al (2011) Regulation of circulating sclerostin levels by sex steroids in women and in men. J Bone Miner res 26(1):27–34
Modder UI et al (2011) Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner res 26(2):373–379
Mazziotti G et al (2006) Increased serum osteoprotegerin values in long-lived subjects: different effects of inflammation and bone metabolism. Eur J Endocrinol 154(3):373–377
Moester MJ et al (2010) Sclerostin: current knowledge and future perspectives. Calcif Tissue Int 87(2):99–107
Atalay S et al (2012) Diagnostic utility of osteocalcin, undercarboxylated osteocalcin, and alkaline phosphatase for osteoporosis in premenopausal and postmenopausal women. Ann lab med 32(1):23–30
Mora S et al (2015) Sclerostin and DKK-1: two important regulators of bone metabolism in HIV-infected youths. Endocrine 49(3):783–790
Fan B et al (2010) Does standardized BMD still remove differences between Hologic and GE-Lunar state-of-the-art DXA systems? Osteoporos Int 21(7):1227–1236
Acknowledgements
This project was supported by funding from European Union FP7 (‘MYOAGE’, #223576) and Medical Research Council (MR/K025252/1).
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Coulson, J., Bagley, L., Barnouin, Y. et al. Circulating levels of dickkopf-1, osteoprotegerin and sclerostin are higher in old compared with young men and women and positively associated with whole-body bone mineral density in older adults. Osteoporos Int 28, 2683–2689 (2017). https://doi.org/10.1007/s00198-017-4104-2
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DOI: https://doi.org/10.1007/s00198-017-4104-2
Keywords
- DKK1
- MYOAGE
- Osteoporosis
- Osteoprotegerin
- Sclerostin