Cardiovascular risk assessment in osteoporotic patients using osteoprotegerin as a reliable predictive biochemical marker

Barbu,Carmen  G.; Arsene,Andreea  L.; Florea,Suzana; Albu,Alice; Sirbu,Anca; Martin,Sorina; Nicolae,Alina  C.; Burcea‑Dragomiroiu,George  T.A.; Popa,Daniela  E.; Velescu,Bruno  S.; Dumitrescu,Ion  B.; Mitrea,Niculina; Draganescu,Doina; Lupuliasa,Dumitru; Spandidos,Demetrios  A.; Tsatsakis,Aristides  M.; Dragoi,Cristina  M.; Fica,Simona

doi:10.3892/mmr.2017.7376

Cardiovascular risk assessment in osteoporotic patients using osteoprotegerin as a reliable predictive biochemical marker

Authors:
- Carmen G. Barbu
- Andreea L. Arsene
- Suzana Florea
- Alice Albu
- Anca Sirbu
- Sorina Martin
- Alina C. Nicolae
- George T.A. Burcea‑Dragomiroiu
- Daniela E. Popa
- Bruno S. Velescu
- Ion B. Dumitrescu
- Niculina Mitrea
- Doina Draganescu
- Dumitru Lupuliasa
- Demetrios A. Spandidos
- Aristides M. Tsatsakis
- Cristina M. Dragoi
- Simona Fica
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Affiliations: Elias Hospital, Department of Endocrinology, Faculty of Medicine, ‘Carol Davila’University of Medicine and Pharmacy, 011461 Bucharest, Romania, Department of General and Pharmaceutical Microbiology, Faculty of Pharmacy, ‘Carol Davila’ University of Medicine and Pharmacy, 020956 Bucharest, Romania, Department of Biochemistry, Faculty of Pharmacy, ‘Carol Davila’ University of Medicine and Pharmacy, 020956 Bucharest, Romania, Department of Drug Control, Faculty of Pharmacy, ‘Carol Davila’ University of Medicine and Pharmacy, 020956 Bucharest, Romania, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, ‘Carol Davila’ University of Medicine and Pharmacy, 020956 Bucharest, Romania, Department of Pharmaceutical Physics and Informatics, Faculty of Pharmacy, ‘Carol Davila’ University of Medicine and Pharmacy, 020956 Bucharest, Romania, Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, ‘Carol Davila’ University of Medicine and Pharmacy, 020956 Bucharest, Romania, Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion 71003, Crete, Greece, Laboratory of Toxicology, Medical School, University of Crete, Heraklion 71003, Crete, Greece
Published online on: August 28, 2017 https://doi.org/10.3892/mmr.2017.7376
Pages: 6059-6067
Copyright: © Barbu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoprotegerin (OPG), a member of the tumour necrosis factor receptor (TNFR) superfamily of proteins known to be involved in a large number of biological systems, plays a pivotal role in bone remodelling. In addition to the roles of OPG in bone metabolism, it has been reported to be associated with a high cardiovascular risk in patients with metabolic syndrome. In most cases, the exact functions of OPG remain to be established; however, the widespread expression of OPG suggests that this molecule may have multiple biological activities, mainly in the cardiometabolic environment. The aim of this study was to evaluate the value of OPG as a predictive marker for cardiovascular and metabolic risk in osteoporotic patients. The study group comprised patients with osteoporosis, in order to evaluate the association between OPG serum levels and cardiovascular pathology. Our results revealed significant correlations between classical biochemical bone and metabolic parameters, such as osteocalcin and parathyroid hormone with lipid and glucose biomarkers, sustaining the crosstalk between calcium and bone parameters and cardiovascular risk. The OPG serum level proved to have a significant and independent predictive value for metabolic syndrome (MetS) as a cardiovascular risk standard in osteoporotic patients. The OPG serum levels were increased in patients with MetS as a protective response against the atherosclerotic lesions. The serum levels of 25‑hydroxy vitamin D had significant and independent predictive value for cardiovascular and metabolic risk in our subjects, sustaining the active role of vitamin D beyond the area of bone metabolism.

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1	Suliburska J, Bogdanski P, Gajewska E, Kalmus G, Sobieska M and Samborski W: The association of insulin resistance with serum osteoprotegerin in obese adolescents. J Physiol Biochem. 69:847–853. 2013. View Article : Google Scholar : PubMed/NCBI
2	de Ciriza Perez C Villacampa: Osteoprotegerin: A promising biomarker in the metabolic syndrome - New perspectives. Biochem Anal Biochem. 5:1–3. 2016.
3	Fuentes E, Fuentes F, Vilahur G, Badimon L and Palomo I: Mechanisms of chronic state of inflammation as mediators that link obese adipose tissue and metabolic syndrome. Mediators Inflamm. 2013:1365842013. View Article : Google Scholar : PubMed/NCBI
4	Monseu M, Dubois S, Boursier J, Aubé C, Gagnadoux F, Lefthériotis G and Ducluzeau PH: Osteoprotegerin levels are associated with liver fat and liver markers in dysmetabolic adults. Diabetes Metab. 42:364–367. 2016. View Article : Google Scholar : PubMed/NCBI
5	Docea AO, Vassilopoulou L, Fragou D, Arsene AL, Fenga C, Kovatsi L, Petrakis D, Rakitskii VN, Nosyrevh AE, Izotovh BN, et al: CYP polymorphisms and pathological conditions related to chronic exposure to organochlorine pesticides. Toxicol Rep. 4:335–341. 2017. View Article : Google Scholar : PubMed/NCBI
6	Drăgoi CM, Nicolae AC, Grigore C, Dinu-Pîrvu CE and Arsene AL: Characteristics of glucose homeostasis and lipidic profile in a hamster metabolic syndrome model, after the co-administration of melatonin and irbesartan in a multiparticulate pharmaceutical formulationThe Second International Conference on Interdisciplinary Management of Diabetes Mellitus and its Complications, INTERDIAB 2016. 3–5–March. Diabetes Mellitus as Cardiovascular Disease, Ed.Niculescu, Bucharest: pp. 221–229. 2016;
7	Hernández AF, Parrón T, Tsatsakis AM, Requena M, Alarcón R and López-Guarnido O: Toxic effects of pesticide mixtures at a molecular level: Their relevance to human health. Toxicology. 307:136–145. 2013. View Article : Google Scholar : PubMed/NCBI
8	Mrema EJ, Rubino FM, Brambilla G, Moretto A, Tsatsakis AM and Colosio C: Persistent organochlorinated pesticides and mechanisms of their toxicity. Toxicology. 307:74–88. 2013. View Article : Google Scholar : PubMed/NCBI
9	Aguilera AA, Diaz GH, Barcelata ML, Guerrero OA and Ros RM: Effects of fish oil on hypertension, plasma lipids, and tumor necrosis factor-alpha in rats with sucrose-induced metabolic syndrome. J Nutr Biochem. 15:350–357. 2004. View Article : Google Scholar : PubMed/NCBI
10	Klöting N, Blüher M and Klöting I: The polygenetically inherited metabolic syndrome of WOKW rats is associated with insulin resistance and altered gene expression in adipose tissue. Diabetes Metab Res Rev. 22:146–154. 2006. View Article : Google Scholar : PubMed/NCBI
11	Augoulea A, Vrachnis N, Lambrinoudaki I, Dafopoulos K, Iliodromiti Z, Daniilidis A, Varras M, Alexandrou A, Deligeoroglou E and Creatsas G: Osteoprotegerin as a marker of atherosclerosis in diabetic patients. Int J Endocrinol. 2013:1820602013. View Article : Google Scholar : PubMed/NCBI
12	Bernardi S, Fabris B, Thomas M, Toffoli B, Tikellis C, Candido R, Catena C, Mulatero P, Barbone F, Radillo O, et al: Osteoprotegerin increases in metabolic syndrome and promotes adipose tissue proinflammatory changes. Mol Cell Endocrinol. 394:13–20. 2014. View Article : Google Scholar : PubMed/NCBI
13	Bjerre M: Osteoprotegerin (OPG) as a biomarker for diabetic cardiovascular complications. Springerplus. 2:6582013. View Article : Google Scholar : PubMed/NCBI
14	Gordin D, Soro-Paavonen A, Thomas MC, Harjutsalo V, Saraheimo M, Bjerre M, Forsblom C, Flyvbjerg A and Groop PH; FinnDiane Study Group, : Osteoprotegerin is an independent predictor of vascular events in Finnish adults with type 1 diabetes. Diabetes Care. 36:1827–1833. 2013. View Article : Google Scholar : PubMed/NCBI
15	Guo C, Hu F, Zhang S, Wang Y and Liu H: Association between osteoprotegerin gene polymorphisms and cardiovascular disease in type 2 diabetic patients. Genet Mol Biol. 36:177–182. 2013. View Article : Google Scholar : PubMed/NCBI
16	Montagnana M, Lippi G, Danese E and Guidi GC: The role of osteoprotegerin in cardiovascular disease. Ann Med. 45:254–264. 2013. View Article : Google Scholar : PubMed/NCBI
17	Baud'huin M, Duplomb L, Teletchea S, Lamoureux F, Ruiz-Velasco C, Maillasson M, Redini F, Heymann MF and Heymann D: Osteoprotegerin: Multiple partners for multiple functions. Cytokine Growth Factor Rev. 24:401–409. 2013. View Article : Google Scholar : PubMed/NCBI
18	Chen Z, Xue J, Shen T, Mu S and Fu Q: Curcumin alleviates glucocorticoid-induced osteoporosis through the regulation of the Wnt signaling pathway. Int J Mol Med. 37:329–338. 2016. View Article : Google Scholar : PubMed/NCBI
19	Ndip A, Wilkinson FL, Jude EB, Boulton AJ and Alexander MY: RANKL-OPG and RAGE modulation in vascular calcification and diabetes: Novel targets for therapy. Diabetologia. 57:2251–2260. 2014. View Article : Google Scholar : PubMed/NCBI
20	Xiong J, Piemontese M, Thostenson JD, Weinstein RS, Manolagas SC and O'Brien CA: Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency. Bone. 66:146–154. 2014. View Article : Google Scholar : PubMed/NCBI
21	Zhang Y, Shao J, Wang Z, Yang T, Liu S, Liu Y, Fan X and Ye W: Aqueous extract of pomegranate seed attenuates glucocorticoid-induced bone loss and hypercalciuria in mice: A comparative study with alendronate. Int J Mol Med. 38:491–498. 2016. View Article : Google Scholar : PubMed/NCBI
22	Bischoff-Ferrari HA and Staehelin HB: Importance of vitamin D and calcium at older age. Int J Vitam Nutr Res. 78:286–292. 2008. View Article : Google Scholar : PubMed/NCBI
23	O'Brien EA, Williams JH and Marshall MJ: Osteoprotegerin is produced when prostaglandin synthesis is inhibited causing osteoclasts to detach from the surface of mouse parietal bone and attach to the endocranial membrane. Bone. 28:208–214. 2001. View Article : Google Scholar : PubMed/NCBI
24	Nan R, Grigorie D, Cursaru A, Șucaliuc A, Drăguț R, Rusu E, Mușat M and Radulian G: Bisphosphonates - A good choice for women with type 2 diabetes and postmenopausal osteoporosis? Farmacia. 64:257–261. 2016.
25	Cima LN and Fica S: The use of anabolic therapy in patients with betathalassemia major-induced osteoporosis - review of the literature. Farmacia. 65:167–172. 2017.
26	Lee CJ, Wang JH, Chen ML, Yang CF, Chen YC and Hsu BG: Serum osteoprotegerin is associated with arterial stiffness assessed according to the cardio-ankle vascular index in hypertensive patients. J Atheroscler Thromb. 22:304–312. 2015. View Article : Google Scholar : PubMed/NCBI
27	Pérez de Ciriza C, Moreno M, Restituto P, Bastarrika G, Simón I, Colina I and Varo N: Circulating osteoprotegerin is increased in the metabolic syndrome and associates with subclinical atherosclerosis and coronary arterial calcification. Clin Biochem. 47:272–278. 2014. View Article : Google Scholar : PubMed/NCBI
28	Yu G, Ji X, Jin J and Bu S: Association of serum and vitreous concentrations of osteoprotegerin with diabetic retinopathy. Ann Clin Biochem. 52:232–236. 2015. View Article : Google Scholar : PubMed/NCBI
29	Zhu M, Fang X, Zhou S, Li W and Guan S: Indirect co culture of vascular smooth muscle cells with bone marrow mesenchymal stem cells inhibits vascular calcification and downregulates the Wnt signaling pathways. Mol Med Rep. 13:5141–5148. 2016. View Article : Google Scholar : PubMed/NCBI
30	Wang ST, Xu JM, Wang M, Chen FL and Ding G: Increased plasma osteoprotegerin concentrations in type 1 diabetes with albuminuria. Clin Nephrol. 79:192–198. 2013. View Article : Google Scholar : PubMed/NCBI
31	Borman P, Babaoğlu S, Gur G, Bingol S and Bodur H: Bone mineral density and bone turnover in patients with psoriatic arthritis. Clin Rheumatol. 27:443–447. 2008. View Article : Google Scholar : PubMed/NCBI
32	Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R and Reginster JY: Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF): European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 24:23–57. 2013. View Article : Google Scholar : PubMed/NCBI
33	Christgau S, Rosenquist C, Alexandersen P, Bjarnason NH, Ravn P, Fledelius C, Herling C, Qvist P and Christiansen C: Clinical evaluation of the Serum CrossLaps One Step ELISA, a new assay measuring the serum concentration of bone-derived degradation products of type I collagen C-telopeptides. Clin Chem. 44:2290–2300. 1998.PubMed/NCBI
34	Grădinaru D, Mitrea N, Margină D, Arsene AL, Gruia V, Drăgoi C, Nicolae A, Borşa C and Gherasim P: Evaluation of serum osteocalcin in eldery patients with type-2 diabetes mellitus. Farmacia. 57:331–338. 2009.
35	Hamann KL and Lane NE: Parathyroid hormone update. Rheum Dis Clin North Am. 32:703–719. 2006. View Article : Google Scholar : PubMed/NCBI
36	Henriksen K, Karsdal MA and Martin TJ: Osteoclast-derived coupling factors in bone remodeling. Calcif Tissue Int. 94:88–97. 2014. View Article : Google Scholar : PubMed/NCBI
37	Starup-Linde J, Eriksen SA, Lykkeboe S, Handberg A and Vestergaard P: Biochemical markers of bone turnover in diabetes patients - a meta-analysis, and a methodological study on the effects of glucose on bone markers. Osteoporos Int. 25:1697–1708. 2014. View Article : Google Scholar : PubMed/NCBI
38	Kamineni V, Latha AP and Ramathulasi K: Association between serum 25-hydroxyvitamin D levels and bone mineral density in normal postmenopausal women. J Midlife Health. 7:163–168. 2016.PubMed/NCBI
39	Rasheed N Wael, Barbu CG, Florea S, Branceanu G, Fica S, Mitrea N, Dragoi CM, Nicolae AC and Arsene AL: Biochemical markers of calcium and bone metabolism in the monitoring of osteoporosis treatment. Farmacia. 62:728–736. 2014.
40	Ohta H, Uemura Y, Nakamura T, Fukunaga M, Ohashi Y, Hosoi T, Mori S, Sugimoto T, Itoi E, Orimo H, et al Adequate Treatment of Osteoporosis (A-TOP) Research Group, : Serum 25-hydroxyvitamin D level as an independent determinant of quality of life in osteoporosis with a high risk for fracture. Clin Ther. 36:225–235. 2014. View Article : Google Scholar : PubMed/NCBI
41	Zugravu CA, Soptica F, Tarcea M and Cucu A: Pertinence of vitamin D supplementation in the adult Romanian population. Farmacia. 64:467–472. 2016.
42	Heaney RP: The vitamin D requirement in health and disease. J Steroid Biochem Mol Biol. 97:13–19. 2005. View Article : Google Scholar : PubMed/NCBI
43	Holick MF: Vitamin D: A millenium perspective. J Cell Biochem. 88:296–307. 2003. View Article : Google Scholar : PubMed/NCBI