Top

20-11-2023 | Acromegaly | Original Article

Assessment of osteoprotegerin and RANKL levels and several cardiovascular risk scoring systems in acromegaly

Authors: Gokcen Unal Kocabas, Banu Sarer Yurekli, Ilgin Yildirim Simsir, Su Ozgur, Murat Aksit, Giray Bozkaya

Published in: Hormones

Abstract

Purpose

The OPG/RANKL (osteoprotegerin/receptor activator of nuclear factor kappa-B) system, which plays a crucial role in bone metabolism, is also associated with vascular calcification. Acromegaly is characterized by excessive secretion of growth hormone and insulin-like growth factor, and studies have demonstrated an elevated risk of cardiovascular disease in individuals with acromegaly. In this study, our objective was to investigate the relationship between OPG/RANKL and various cardiovascular risk scoring systems.

Methods

We recruited 44 consecutive acromegaly patients and 41 healthy controls with a similar age and gender distribution for this study.

Results

While RANKL levels were significantly higher in the acromegaly group compared to the controls, OPG levels were not found to be significantly different between the two groups. Furthermore, within the acromegaly group, RANKL levels were significantly higher in patients with active acromegaly compared to those with controlled acromegaly.

Osteoprotegerin levels showed a positive correlation with the Framingham risk score (FRS) in the acromegaly group. Linear regression analysis revealed an association of OPG with FRS (adjusted R² value of 21.7%).

Conclusion

OPG and RANKL may serve as potential markers for assessment of cardiovascular calcification and prediction of the cardiovascular risk status in acromegalic patients.

Zhang L, Zeng F, Jiang M, Han M, Huang B (2022) Roles of osteoprotegerin in endocrine and metabolic disorders through receptor activator of nuclear factor kappa-B ligand/receptor activator of nuclear factor kappa-B signaling. Front Cell Dev Biol 10:1005681. https://doi.org/10.3389/fcell.2022.1005681 CrossRefPubMedPubMedCentral

Monseu M, Dubois S, Boursier J, Aube C, Gagnadoux F, Leftheriotis G, Ducluzeau PH (2016) Osteoprotegerin levels are associated with liver fat and liver markers in dysmetabolic adults. Diabetes Metab 42:364–367. https://doi.org/10.1016/j.diabet.2016.02.004 CrossRefPubMed

Harper E, Forde H, Davenport C, Rochfort KD, Smith D, Cummins PM (2016) Vascular calcification in type-2 diabetes and cardiovascular disease: Integrative roles for OPG, RANKL and TRAIL. Vascul Pharmacol 82:30–40. https://doi.org/10.1016/j.vph.2016.02.003 CrossRefPubMed

Callegari A, Coons ML, Ricks JL, Yang HL, Gross TS, Huber P, Rosenfeld ME, Scatena M (2013) Bone marrow- or vessel wall-derived osteoprotegerin is sufficient to reduce atherosclerotic lesion size and vascular calcification. Arterioscler Thromb Vasc Biol 33:2491–2500. https://doi.org/10.1161/ATVBAHA.113.301755 CrossRefPubMed

Harsha MM, Tewari S, Gupta SK, Khanna R, Kumar S, Garg N, Kapoor A, Goel PK (2021) Acromegaly: cardiovascular risk factors, cardiovascular manifestations and early vascular alterations in relation to disease activity. Indian Heart J 73:499–502. https://doi.org/10.1016/j.ihj.2021.05.005 CrossRefPubMedPubMedCentral

Rubin J, Ackert-Bicknell CL, Zhu L, Fan X, Murphy TC, Nanes MS, Marcus R, Holloway L, Beamer WG, Rosen CJ (2002) IGF-I regulates osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand in vitro and OPG in vivo. J Clin Endocrinol Metab 87:4273–4279. https://doi.org/10.1210/jc.2002-020656 CrossRefPubMed

Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, Wass JA, Endocrine S (2014) Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 99:3933–3951. https://doi.org/10.1210/jc.2014-2700 CrossRefPubMed

Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97:1837–1847. https://doi.org/10.1161/01.cir.97.18.1837 CrossRefPubMed

Lloyd-Jones DM, Huffman MD, Karmali KN, Sanghavi DM, Wright JS, Pelser C, Gulati M, Masoudi FA, Goff DC Jr (2017) Estimating longitudinal risks and benefits from cardiovascular preventive therapies among medicare patients: the Million Hearts Longitudinal ASCVD Risk Assessment Tool: a special report from the American Heart Association and American College of Cardiology. J Am Coll Cardiol 69:1617–1636. https://doi.org/10.1016/j.jacc.2016.10.018 CrossRefPubMed

10.

Ulloque-Badaracco JR, Hernandez-Bustamante EA, Alarcon-Braga EA, Mosquera-Rojas MD, Campos-Aspajo A, Salazar-Valdivia FE, Valdez-Cornejo VA, Benites-Zapata VA, Herrera-Anazco P, Valenzuela-Rodriguez G, Hernandez AV (2022) Atherogenic index of plasma and coronary artery disease: a systematic review. Open Med (Wars) 17:1915–1926. https://doi.org/10.1515/med-2022-0590 CrossRefPubMed

11.

Ozer FF, Dagdelen S, Erbas T (2018) Relation of RANKL and OPG levels with bone resorption in patients with acromegaly and prolactinoma. Horm Metab Res 50:562–567. https://doi.org/10.1055/a-0630-1529 CrossRefPubMed

12.

Zhao HY, Liu JM, Ning G, Zhao YJ, Chen Y, Sun LH, Zhang LZ, Xu MY, Chen JL (2008) Relationships between insulin-like growth factor-I (IGF-I) and OPG, RANKL, bone mineral density in healthy Chinese women. Osteoporos Int 19:221–226. https://doi.org/10.1007/s00198-007-0440-y CrossRefPubMed

13.

Constantin T, Tangpricha V, Shah R, Oyesiku NM, Ioachimescu OC, Ritchie J, Ioachimescu AG (2017) Calcium and bone turnover markers in acromegaly: a prospective, controlled study. J Clin Endocrinol Metab 102:2416–2424. https://doi.org/10.1210/jc.2016-3693 CrossRefPubMed

14.

Jawiarczyk-Przybylowska A, Halupczok-Zyla J, Syrycka J, Zembska A, Kuliczkowska-Plaksej J, Bolanowski M (2022) Trabecular bone score and osteoprotegerin as useful tools in the assessment of bone deterioration in acromegaly. Front Endocrinol (Lausanne) 13:862845. https://doi.org/10.3389/fendo.2022.862845 CrossRefPubMed

15.

Goluke NMS, Schoffelmeer MA, De Jonghe A, Emmelot-Vonk MH, De Jong PA, Koek HL (2022) Serum biomarkers for arterial calcification in humans: a systematic review. Bone Rep 17:101599. https://doi.org/10.1016/j.bonr.2022.101599 CrossRefPubMedPubMedCentral

16.

Rochette L, Meloux A, Rigal E, Zeller M, Cottin Y, Vergely C (2019) The role of osteoprotegerin and its ligands in vascular function. Int J Mol Sci 20:705. https://doi.org/10.3390/ijms20030705 CrossRefPubMedPubMedCentral

17.

Colao A, Ferone D, Marzullo P, Lombardi G (2004) Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 25:102–152. https://doi.org/10.1210/er.2002-0022 CrossRefPubMed

18.

Orme SM, McNally RJ, Cartwright RA, Belchetz PE (1998) Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab 83:2730–2734. https://doi.org/10.1210/jcem.83.8.5007 CrossRefPubMed

19.

Bogazzi F, Battolla L, Spinelli C, Rossi G, Gavioli S, Di Bello V, Cosci C, Sardella C, Volterrani D, Talini E, Pepe P, Falaschi F, Mariani G, Martino E (2007) Risk factors for development of coronary heart disease in patients with acromegaly: a five-year prospective study. J Clin Endocrinol Metab 92:4271–4277. https://doi.org/10.1210/jc.2007-1213 CrossRefPubMed

20.

Akutsu H, Kreutzer J, Wasmeier G, Ropers D, Rost C, Mohlig M, Wallaschofski H, Buchfelder M, Schofl C (2010) Acromegaly per se does not increase the risk for coronary artery disease. Eur J Endocrinol 162:879–886. https://doi.org/10.1530/EJE-09-0945 CrossRefPubMed

21.

Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM, Lauer MS, Post WS, Raggi P, Redberg RF, Rodgers GP, Shaw LJ, Taylor AJ, Weintraub WS, American College of Cardiology Foundation Clinical Expert Consensus Task F, Society of Atherosclerosis I, Prevention, Society of Cardiovascular Computed T (2007) ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol 49:378–402. https://doi.org/10.1016/j.jacc.2006.10.001 CrossRefPubMed

22.

Arad Y, Goodman KJ, Roth M, Newstein D, Guerci AD (2005) Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study. J Am Coll Cardiol 46:158–165. https://doi.org/10.1016/j.jacc.2005.02.088 CrossRefPubMed

23.

Greenland P, LaBree L, Azen SP, Doherty TM, Detrano RC (2004) Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA 291:210–215. https://doi.org/10.1001/jama.291.2.210 CrossRefPubMed

24.

Ragonese M, Alibrandi A, Di Bella G, Salamone I, Puglisi S, Cotta OR, Torre ML, Ferrau F, Ruggeri RM, Trimarchi F, Cannavo S (2014) Cardiovascular events in acromegaly: distinct role of Agatston and Framingham score in the 5-year prediction. Endocrine 47:206–212. https://doi.org/10.1007/s12020-013-0115-8 CrossRefPubMed

25.

Semb AG, Ueland T, Aukrust P, Wareham NJ, Luben R, Gullestad L, Kastelein JJ, Khaw KT, Boekholdt SM (2009) Osteoprotegerin and soluble receptor activator of nuclear factor-kappaB ligand and risk for coronary events: a nested case-control approach in the prospective EPIC-Norfolk population study 1993–2003. Arterioscler Thromb Vasc Biol 29:975–980. https://doi.org/10.1161/ATVBAHA.109.184101 CrossRefPubMed

26.

Venuraju SM, Yerramasu A, Corder R, Lahiri A (2010) Osteoprotegerin as a predictor of coronary artery disease and cardiovascular mortality and morbidity. J Am Coll Cardiol 55:2049–2061. https://doi.org/10.1016/j.jacc.2010.03.013 CrossRefPubMed

Title: Assessment of osteoprotegerin and RANKL levels and several cardiovascular risk scoring systems in acromegaly
Authors: Gokcen Unal Kocabas
Banu Sarer Yurekli
Ilgin Yildirim Simsir
Su Ozgur
Murat Aksit
Giray Bozkaya
Publication date: 20-11-2023
Publisher: Springer International Publishing
Keyword: Acromegaly
Published in: Hormones
Print ISSN: 1109-3099
Electronic ISSN: 2520-8721
DOI: https://doi.org/10.1007/s42000-023-00509-8

Webinar | 08-11-2023 | 18:00 (CET)

Keynote Webinar | Spotlight on Diet and Diabetes

Watch now

An expert-led symposium exploring the prevention and management of type 2 diabetes through dietary interventions. Highlights include discussion of the recent EASD guidelines, therapeutic diets, food types and processing, plus psychological factors that influence patient success, and the drivers of healthy eating and diabetes control.

Prof. Mike Lean

Prof. Falko Sniehotta

Keynote Webinar | Spotlight on Diet and Diabetes

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Keynote Webinar | Spotlight on Diet and Diabetes