Abstract
Background
Bone turnover markers have a potential clinical use in describing bone remodeling and in predicting fractures.
Aims
In an elderly population ≥75 years with a fresh hip fracture, and in healthy controls, investigate bone turnover markers and their relation to each other, to vitamin D status and to bone mineral density (BMD).
Methods
In a cross-sectional study serum levels of dickkopf-1 (DKK-1), sclerostin (SOST), osteoprotegerin (OPG), osteopontin (OPN), osteocalcin, 25-hydroxyvitamin D (25(OH)D) were analyzed in 89 Swedish patients with a fresh hip fracture and in 82 healthy volunteers. Serum levels of bone markers were determined by Luminex technique.
Results
S-25-hydroxyvitamin D (S-25(OH)D) was decreased in patients compared to controls (48 ± 21 vs. 76 ± 25 nmol/L, p < 0.001). SOST, but none of the other bone turnover markers correlated with BMD (r = 0.50, p < 0.001). Compared with controls, higher levels of OPG (488 ± 1.4 vs. 191 ± 1.4 ng/L, p < 0.001), OPN (69 ± 1.7 vs. 19 ± 1.4 µg/L, p < 0.001), DKK-1 (273 ± 1.7 vs. 168 ± 1.7 ng/L, p < 0.001), and lower levels of osteocalcin (5.8 ± 3.5 vs. 9.5 ± 3.6 µg/L, p < 0.001), were found in the fracture group. Levels of OPG, DKK-1 and SOST in both groups were positively associated. S-25(OH)D concentration was not found to be strongly associated with any of the bone markers.
Conclusions
In contrast to findings in other studies, we found no strong correlation between 25(OH)D and the investigated bone markers. Both in patients with a fresh hip fracture and in healthy elderly, DKK-1, SOST and OPG appear to be associated. This suggests a relevance in these relationships meriting further investigation.
Similar content being viewed by others
References
Ioannidis G, Papaioannou A, Hopman WM, Akhtar-Danesh N, Anastassiades T, Pickard L, Kennedy CC, Prior JC, Olszynski WP, Davison KS, Goltzman D, Thabane L, Gafni A, Papadimitropoulos EA, Brown JP, Josse RG, Hanley DA, Adachi JD (2009) Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study. CMAJ 181:265–271. doi:10.1503/cmaj.081720
Haleem S, Lutchman L, Mayahi R, Grice JE, Parker MJ (2008) Mortality following hip fracture: trends and geographical variations over the last 40 years. Injury 39:1157–1163. doi:10.1016/j.injury.2008.03.022
Maier GS, Seeger JB, Horas K, Roth KE, Kurth AA, Maus U (2015) The prevalence of vitamin D deficiency in patients with vertebral fragility fractures. Bone Jt J 97:89–93. doi:10.1302/0301-620X.97B1.34558
Eastell R, Hannon RA (2008) Biomarkers of bone health and osteoporosis risk. Proc Nutr Soc 67:157–162. doi:10.1017/S002966510800699X
Garnero P, Delmas PD (2004) Contribution of bone mineral density and bone turnover markers to the estimation of risk of osteoporotic fracture in postmenopausal women. J Musculoskelet Neuronal Interact 4:50–63
Łukaszkiewicz J, Karczmarewicz E, Płudowski P Jaworski M, Czerwiński E, Lewiński A, Marcinowska-Suchowierska E, Milewicz A, Spaczyński M, Lorenc RS; EPOLOS Group (2008) Feasibility of simultaneous measurement of bone formation and bone resorption markers to assess bone turnover rate in postmenopausal women: an EPOLOS study. Med Sci Monit 14:PH65–PH70
Gerdhem P, Ivaska KK, Alatalo SL, Halleen JM, Hellman J, Isaksson A, Pettersson K, Väänänen HK, Akesson K, Obrant KJ (2004) Biochemical markers of bone metabolism and prediction of fracture in elderly women. J Bone Miner Res 19:386–393
Baron R, Rawadi G (2007) Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 148:2635–2643
Dovjak P, Dorfer S, Föger-Samwald U, Kudlacek S, Marculescu R, Pietschmann P (2014) Serum levels of sclerostin and dickkopf-1: effects of age, gender and fracture status. Gerontology 60:493–501. doi:10.1159/000358303
Rogers A, Eastell R (2005) Circulating osteoprotegerin and receptor activator for nuclear factor kappa B ligand: clinical utility in metabolic bone disease assessment. J Clin Endocrinol Metab 90:6323–6362
Chang IC, Chiang TI, Yeh KT, Lee H, Cheng YW (2010) Increased serum osteopontin is a risk factor for osteoporosis in menopausal women. Osteoporos Int 21:1401–1409. doi:10.1007/s00198-009-1107-7
Hind K, Oldroyd B, Truscott JG (2010) In vivo precision of the GE Lunar iDXA densitometer for the measurement of total-body, lumbar spine, and femoral bone mineral density in adults. J Clin Densitom 13:413–417. doi:10.1016/j.jocd.2010.06.002
Baron R, Rawadi G (2007) Wnt signaling and the regulation of bone mass. Curr Osteoporos Rep 5(2):73–80
Pinzone JJ, Hall BM, Thudi NK, Vonau M, Qiang YW, Rosol TJ, Shaughnessy JD Jr (2009) The role of dickkopf-1 in bone development, homeostasis, and disease. Blood 113(3):517–525. doi:10.1182/blood-2008-03-145169
Gatti D, Viapiana O, Fracassi E, Idolazzi L, Dartizio C, Povino MR, Adami S, Rossini M (2012) Sclerostin and DKK1 in postmenopausal osteoporosis treated with denosumab. J Bone Miner Res 27:2259–2263. doi:10.1002/jbmr.1681
Papapoulos S (2011) Targeting sclerostin as potential treatment of osteoporosis. Ann Rheum Dis 70:i119–i122
Staehling-Hampton K, Proll S, Paeper BW, Zhao L, Charmley P, Brown A, Gardner JC, Galas D, Schatzman RC, Beighton P, Papapoulos S, Hamersma H, Brunkow ME (2002) A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12–q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet 110:144–152
Ardawi MS, Al-Kadi HA, Rouzi AA, Qari MH (2011) Determinants of serum sclerostin in healthy pre- and postmenopausal women. J Bone Miner Res 26:2812–2822. doi:10.1002/jbmr.1681
Sarahrudi K, Thomas A, Albrecht C, Aharinejad S (2012) Strongly enhanced levels of sclerostin during human fracture healing. J Orthop Res 30:1549–1555. doi:10.1002/jor.22129
Hampson G, Edwards S, Conroy S, Blake GM, Fogelman I, Frost ML (2013) The relationship between inhibitors of the Wnt signalling pathway (dickkopf-1(DKK1) and sclerostin), bone mineral density, vascular calcification and arterial stiffness in post-menopausal women. Bone 56:42–47. doi:10.1016/j.bone.2013.05.010
Mödder UI, Clowes JA, Hoey K, Peterson JM, McCready L, Oursler MJ, Riggs BL, Khosla S (2011) Regulation of circulating sclerostin levels by sex steroids in women and in men. J Bone Miner Res 26:27–34. doi:10.1002/jbmr.128
Thambiah S, Roplekar R, Manghat P, Fogelman I, Fraser WD, Goldsmith D, Hampson G (2012) Circulating sclerostin and dickkopf-1 (DKK1) in predialysis chronic kidney disease (CKD): relationship with bone density and arterial stiffness. Calcif Tissue Int 90:473–480. doi:10.1007/s00223-012-9595-4
Padhi D, Jang G, Stouch B, Fang L, Posvar E (2011) Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 26:19–26. doi:10.1002/jbmr.173
Jemtland R, Holden M, Reppe S, Olstad OK, Reinholt FP, Gautvik VT, Refvem H, Frigessi A, Houston B, Gautvik KM (2011) Molecular disease map of bone characterizing the postmenopausal osteoporosis phenotype. J Bone Miner Res 26:1793–1801. doi:10.1002/jbmr.396
MacDonald BT, Tamai K, He X (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17:9–26. doi:10.1016/j.devcel.2009.06.016
Butler JS, Murray DW, Hurson CJ, O’Brien J, Doran PP, O’Byrne JM (2011) The role of Dkk1 in bone mass regulation: correlating serum Dkk1 expression with bone mineral density. J Orthop Res 29:414–418. doi:10.1002/jor.21260
Register TC, Hruska KA, Divers J, Bowden DW, Palmer ND, Carr JJ, Wagenknecht LE, Hightower RC, Xu J, Smith SC, Dietzen DJ, Langefeld CD, Freedman BI (2012) Plasma dickkopf1 (DKK1) concentrations negatively associate with atherosclerotic calcified plaque in African–Americans with type 2 diabetes. J Clin Endocrinol Metab 98:E60–E65. doi:10.1210/jc.2012-3038
Viapiana O, Fracassi E, Troplini S, Idolazzi L, Rossini M, Adami S, Gatti D (2013) Sclerostin and DKK1 in primary hyperparathyroidism. Calcif Tissue Int 92:324–329. doi:10.1007/s00223-012-9665-7
Cho EH, Cho KH, Lee HA, Kim SW (2013) High serum osteopontin levels are associated with low bone mineral density in postmenopausal women. J Korean Med Sci 28:1496–1499. doi:10.3346/jkms.2013.28.10.1496
Fodor D, Bondor C, Albu A, Simon SP, Craciun A, Muntean L (2013) The value of osteopontin in the assessment of bone mineral density status in postmenopausal women. J Investig Med 61:15–21. doi:10.231/JIM.0b013e3182761264
Sypniewska G, Sobanska I, Pater A, Kedziora-Kornatowska K, Nowacki W (2010) Does serum osteoprotegerin level relate to fragility fracture in elderly women with low vitamin D status? Med Sci Monit 16:CR96–CR101
Kearns AE, Khosla S, Kostenuik P (2008) RANKL and OPG: regulation of bone remodeling in health and disease. Endocrine Rev 29:155–192
Köttstorfer J, Thomas A, Gregori M, Kecht M, Kaiser G, Eipeldauer S, Sarahrudi K (2014) Are OPG and RANKL involved in human fracture healing? J Orthop Res 32:1557–1561. doi:10.1002/jor.22723
Wang XF, Zhang YK, Yu ZS, Zhou JL (2013) The role of the serum RANKL/OPG ratio in the healing of intertrochanteric fractures in elderly patients. Mol Med Rep 7:1169–1172. doi:10.3892/mmr.2013.1335
Barton RN, Weijers JW, Horan MA (1993) Increased rates of cortisol production and urinary free cortisol excretion in elderly women 2 weeks after proximal femur fracture. Eur J Clin Invest 23:171–176
Acknowledgments
This work was supported by a grant from the Kamprad Family Foundation for Entrepreneurship, Research & Charity. We are also indebted to nurses Anna Pettersson, Agneta Hallengren and to Ulrika Lönnbom for excellent assistance.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflicts of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Rights and permissions
About this article
Cite this article
Wanby, P., Nobin, R., Von, SP. et al. Serum levels of the bone turnover markers dickkopf-1, sclerostin, osteoprotegerin, osteopontin, osteocalcin and 25-hydroxyvitamin D in Swedish geriatric patients aged 75 years or older with a fresh hip fracture and in healthy controls. J Endocrinol Invest 39, 855–863 (2016). https://doi.org/10.1007/s40618-015-0421-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40618-015-0421-5