Sclerostin and Cardiovascular Disease

Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den Ende J, Willems P, Paes-Alves AF, Hill S, Bueno M, Ramos FJ, Tacconi P, Dikkers FG, Stratakis C, Lindpaintner K, Vickery B, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet. 2001;10:537–43.

Article  CAS  PubMed  Google Scholar 

Brunkow ME, Gardner JC, Van Ness J, Paper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo PJ, Fu Y-H, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan JT. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Gen. 2001;68:577–89.

Article  CAS  Google Scholar 

Galea GL, Lanyon LE, Price JS. Sclerostin's role in bone's adaptive response to mechanical loading. Bone. 2017;96:38–44.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, Hofbauer LC, Lau E, Lewiecki EM, Miyauchi A, Zerbini CA, Milmont CE, Chen L, Maddox J, Meisner PD, Libanati C, Grauer A. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375:1532–43.

Article  CAS  PubMed  Google Scholar 

•• Saag KG, Petersen J, Grauer A. Romosozumab versus alendronate and fracture risk in women with osteoporosis. N Engl J Med. 2018;378:195–6. This trial was the first indication that sclerostin inhibition might exert clinically relevant effects on risk of myocardial infarction and stroke

PubMed  Google Scholar 

Koos R, Brandenburg V, Mahnken AH, Schneider R, Dohmen G, Autschbach R, Marx N, Kramann R. Sclerostin as a potential novel biomarker for aortic valve calcification: an in-vivo and ex-vivo study. J Heart Valve Dis. 2013;22:317–25.

PubMed  Google Scholar 

Zhu D, Mackenzie NC, Millan JL, Farquharson C, MacRae VE. The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells. PLoS One. 2011;6:e19595.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bundy K, Boone J, Simpson CL. Wnt signaling in vascular calcification. Front Cardiovasc Med. 2021;8:708470.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Krishna SM, Seto SW, Jose RJ, Li J, Morton SK, Biros E, Wang Y, Nsengiyumva V, Lindeman JH, Loots GG, Rush CM, Craig JM, Golledge J. Wnt signaling pathway inhibitor sclerostin inhibits angiotensin II-induced aortic aneurysm and atherosclerosis. Arterioscler Thromb Vasc Biol. 2017;37:553–66.

Article  CAS  PubMed  Google Scholar 

• De Mare A, Opdebeeck B, Neven E, D'Haese PC, Verhulst A. Sclerostin protects against vascular calcification development in mice. J Bone Miner Res. 2022;37:687–99. This study suggests that sclerostin protects against vascular calcification, based on findings of increased vascular calcification in sclerostin knockout mice

Article  PubMed  Google Scholar 

Bisson SK, Ung RV, Picard S, Valade D, Agharazii M, Lariviere R, Mac-Way F. High calcium, phosphate and calcitriol supplementation leads to an osteocyte-like phenotype in calcified vessels and bone mineralisation defect in uremic rats. J Bone Miner Metab. 2019;37:212–23.

Article  CAS  PubMed  Google Scholar 

Turk JR, Deaton AM, Yin J, Stolina M, Felx M, Boyd G, Bienvenu JG, Varela A, Guillot M, Holdsworth G, Wolfreys A, Dwyer D, Kumar SV, de Koning EM, Qu Y, Engwall M, Locher K, Ward LD, Glaus C, et al. Nonclinical cardiovascular safety evaluation of romosozumab, an inhibitor of sclerostin for the treatment of osteoporosis in postmenopausal women at high risk of fracture. Regul Toxicol Pharmacol. 2020;115:104697.

Article  CAS  PubMed  Google Scholar 

Golledge J, Thanigaimani S. Role of sclerostin in cardiovascular disease. Arterioscler Thromb Vasc Biol. 2022;42:e187–202.

Article  CAS  PubMed  Google Scholar 

Frysz M, Gergei I, Scharnagl H, Smith GD, Zheng J, Lawlor DA, Herrmann M, Maerz W, Tobias JH. Circulating Sclerostin Levels Are Positively Related to Coronary Artery Disease Severity and Related Risk Factors. J Bone Miner Res. 2022;37:273–84.

Article  CAS  PubMed  Google Scholar 

Gregson CL, Poole KE, McCloskey EV, Duncan EL, Rittweger J, Fraser WD, Smith GD, Tobias JH. Elevated circulating Sclerostin concentrations in individuals with high bone mass, with and without LRP5 mutations. J Clin Endocrinol Metab. 2014;99:2897–907.

CAS  PubMed  PubMed Central  Google Scholar 

Zheng J, Maerz W, Gergei I, Kleber M, Drechsler C, Wanner C, Brandenburg V, Reppe S, Gautvik KM, Medina-Gomez C, Shevroja E, Gilly A, Park YC, Dedoussis G, Zeggini E, Lorentzon M, Henning P, Lerner UH, Nilsson KH, et al. Mendelian randomization analysis reveals a causal influence of circulating sclerostin levels on bone mineral density and fractures. J Bone Miner Res. 2019;34:1824–36.

Article  CAS  PubMed  Google Scholar 

Veronese N, Stubbs B, Crepaldi G, Solmi M, Cooper C, Harvey NC, Reginster JY, Rizzoli R, Civitelli R, Schofield P, Maggi S, Lamb SE. Relationship between low bone mineral density and fractures with incident cardiovascular disease: a systematic review and meta-analysis. J Bone Miner Res. 2017;32:1126–35.

Article  PubMed  Google Scholar 

Bovijn J, Krebs K, Chen CY, Boxall R, Censin JC, Ferreira T, Pulit SL, Glastonbury CA, Laber S, Millwood IY, Lin K, Li L, Chen Z, Milani L, Smith GD, Walters RG, Magi R, Neale BM, Lindgren CM, Holmes MV. Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics. Sci Transl Med. 2020;12(549):eaay6570.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lewiecki EM, Blicharski T, Goemaere S, Lippuner K, Meisner PD, Miller PD, Miyauchi A, Maddox J, Chen L, Horlait S. A phase III randomized placebo-controlled trial to evaluate efficacy and safety of romosozumab in men with osteoporosis. J Clin Endocrinol Metab. 2018;103:3183–93.

Article  PubMed  Google Scholar 

European Medicines Agency Assessment report on Evenity, available from: https://www.ema.europa.eu/en/documents/assessment-report/evenity-epar-public-assessment-report_en.pdf.

Reid IR, Horne AM, Mihov B, Stewart A, Garratt E, Bastin S, Gamble GD. Effects of zoledronate on cancer, cardiac events, and mortality in osteopenic older women. J Bone Miner Res. 2020;35:20–7.

Article  CAS  PubMed  Google Scholar 

Cummings SR, Lui LY, Eastell R, Allen IE. Association between drug treatments for patients with osteoporosis and overall mortality rates: a meta-analysis. JAMA Intern Med. 2019;179(11):1491–500.

Article  PubMed  PubMed Central  Google Scholar 

Takeuchi Y. Romosozumab and cardiovascular safety in Japan. Osteoporos Sarcopenia. 2021;7:89–91.

Article  PubMed  PubMed Central  Google Scholar 

Kawaguchi H. Serious Adverse events with romosozumab use in japanese patients: need for clear formulation of contraindications worldwide. J Bone Miner Res. 2020;35:994–5.

Article  PubMed  Google Scholar 

• Vestergaard Kvist A, Faruque J, Vallejo-Yague E, Weiler S, Winter EM, Burden AM. Cardiovascular safety profile of romosozumab: a pharmacovigilance analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS). J Clin Med. 2021;10 This pharmacovigilance study identified a potential safety signal for increased major cardiovascular events particularly in Japan

Sebastian A, Loots GG. Genetics of Sost/SOST in sclerosteosis and van Buchem disease animal models. Metabolism. 2018;80:38–47.

Article  CAS  PubMed  Google Scholar 

Holdsworth G, Staley JR, Hall P, van Koeverden I, Vangjeli C, Okoye R, Boyce RW, Turk JR, Armstrong M, Wolfreys A, Pasterkamp G. Sclerostin downregulation globally by naturally occurring genetic variants, or locally in atherosclerotic plaques, does not associate with cardiovascular events in humans. J Bone Miner Res. 2021;36(7):1326–39.

Article  CAS  PubMed  Google Scholar 

• Zheng J, Wheeler E, Pietzner M, Andlauer T, Yau MS, Hartley AE, Brumpton BM, Rasheed H, Kemp JP, Frysz M, Robinson J, Reppe S, Prijatelj V, Gautvik KM, Falk L, Maerz W, Gergei I, Peyser PA, Kavousi M, et al. Lowering of circulating sclerostin may increase risk of atherosclerosis and its risk factors: evidence from a genome-wide association meta-analysis followed by Mendelian randomization. Arthritis Rheumatol. (In Press). 2023; https://doi.org/10.1002/art.42538. This Mendelian Randomisation study suggested that genetically determined decreases in circulating sclerostin lead to an increased risk of myocardial infarction, coronary artery calcification, and CVD risk factors such as hypertension and type II diabetes

Kemp JP, Morris JA, Medina-Gomez C, Forgetta V, Warrington NM, Youlten SE, Zheng J, Gregson CL, Grundberg E, Trajanoska K, Logan JG, Pollard AS, Sparkes PC, Ghirardello EJ, Allen R, Leitch VD, Butterfield NC, Komla-Ebri D, Adoum AT, et al. Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis. Nat Genet. 2017;49:1468–75.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zheng HF, Forgetta V, Hsu YH, Estrada K, Rosello-Diez A, Leo PJ, Dahia CL, Park-Min KH, Tobias JH, Kooperberg C, Kleinman A, Styrkarsdottir U, Liu CT, Uggla C, Evans DS, Nielson CM, Walter K, Pettersson-Kymmer U, McCarthy S, et al. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature. 2015;526:112–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ishibashi H, Crittenden DB, Miyauchi A, Libanati C, Maddox J, Fan M, Chen L, Grauer A. Romosozumab increases bone mineral density in postmenopausal Japanese women with osteoporosis: a phase 2 study. Bone. 2017;103:209–15.

Article  CAS  PubMed  Google Scholar 

Hartiala JA, Han Y, Jia Q, Hilser JR, Huang P, Gukasyan J, Schwartzman WS, Cai Z, Biswas S, Tregouet DA, Smith NL, Seldin M, Pan C, Mehrabian M, Lusis AJ, Bazeley P, Sun YV, Liu C, Quyyumi AA, et al. Genome-wide analysis identifies novel susceptibility loci for myocardial infarction. Eur Heart J. 2021;42:919–33.

Article  CAS  PubMed  PubMed Central  Google Scholar 

留言 (0)

沒有登入
gif