{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:29:27Z","timestamp":1787020167812,"version":"build-2736575974"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Bonn"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cardiovasc Disord"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aortic valve stenosis (AVS) is the most common heart valve disease requiring intervention. Osteoporosis, affecting\u2009~\u200910% of those over 50, is linked to aortic valve calcification and increased AVS risk. However, its direct role in AVS development or progression remains unclear. Using a mouse model, we examined whether estrogen-deficiency-induced osteoporosis modifies early hemodynamic and histological remodeling of the aortic valve after mechanical injury, and whether zoledronic acid (ZA) treatment alters these processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Osteoporosis was induced in mice via bilateral ovariectomy (OVX), with sham-operated controls. To prevent bone loss, ZA or vehicle were administered weekly via intraperitoneal injection. Two weeks post-OVX, AVS was induced by mechanically injuring the aortic valve under echocardiographic guidance, with control procedures (CTR) in separate groups. After model validation, C57BL\/6J mice were assigned to six groups: WI Sham Vehicle, WI OVX Vehicle, WI OVX ZA, WI Sham ZA, CTR OVX Vehicle, and CTR OVX ZA. Echocardiography was performed at baseline and 2, 4, and 6 weeks post-injury. Bone density was assessed via micro-CT and histology, with peak aortic velocity as the primary endpoint. Mice were euthanized at 8 weeks for tissue analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      OVX induced a significant reduction in trabecular bone mineral density (TBM, 50.6%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0025). Treatment with ZA effectively reversed bone resorption in OVX mice (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and even enhanced trabecular structures compared to sham-operated animals (increase of TBM by 130%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Mechanical injury to the aortic valve successfully induced AVS, as evidenced by increased peak velocity (1294 vs. 2157\u00a0mm\/s,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and mean pressure gradient 2 weeks post-procedure (1.58 vs. 4.19 mmHg,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). However, neither OVX nor ZA treatment influenced the severity of AVS. Histological analyses confirmed aortic valve thickening following injury. Picrosirius red and CD68 staining revealed no differences in collagen content or immune cell infiltration of the aortic valve between osteoporotic and non-osteoporotic animals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>OVX-induced osteoporosis did not affect AVS severity after mechanical injury in our study. This suggests osteoporosis may not directly influence AVS in the early, pre-calcific stage that was studied in this model. However, to overcome limitations of the study, further studies with longer durations or refined models are needed to confirm these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12872-025-05037-4","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T03:30:34Z","timestamp":1753932634000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Aortic valve stenosis and osteoporosis: insights from a mouse model"],"prefix":"10.1186","volume":"25","author":[{"given":"Hannah","family":"Billig","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamia","family":"Singer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Bourauel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A.","family":"Schildberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Masson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikola","family":"L\u00fcbbering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzel","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Perner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Stei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Niepmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Silaschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad","family":"Bakhtiary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Nickenig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Zimmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"issue":"4","key":"5037_CR1","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1161\/ATVBAHA.119.313067","volume":"40","author":"PR Goody","year":"2020","unstructured":"Goody PR, Hosen MR, Christmann D, Niepmann ST, Zietzer A, Adam M, et al. Aortic valve stenosis: from basic mechanisms to novel therapeutic targets. Arterioscler Thromb Vasc Biol. 2020;40(4):885\u2013900.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"7","key":"5037_CR2","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1093\/eurheartj\/ehab757","volume":"43","author":"S Kraler","year":"2021","unstructured":"Kraler S, Blaser MC, Aikawa E, Camici GG, L\u00fcscher TF. Calcific aortic valve disease: from molecular and cellular mechanisms to medical therapy. Eur Heart J. 2021;43(7):683\u201397.","journal-title":"Eur Heart J"},{"key":"5037_CR3","doi-asserted-by":"crossref","unstructured":"Dweck MR, Jenkins WSA, Vesey AT, Pringle MAH, Chin CWL, Malley TS et al. 18F-Sodium Fluoride uptake is a marker of active calcification and disease progression in patients with aortic stenosis. Circulation. 2014;7(2):371\u20138.","DOI":"10.1161\/CIRCIMAGING.113.001508"},{"issue":"2","key":"5037_CR4","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1161\/01.CIR.90.2.844","volume":"90","author":"CM Otto","year":"1994","unstructured":"Otto CM, Kuusisto J, Reichenbach DD, Gown AM, O\u2019Brien KD. Characterization of the early lesion of \u2018degenerative\u2019 valvular aortic stenosis. Histological and immunohistochemical studies. Circulation. 1994;90(2):844\u201353.","journal-title":"Circulation"},{"issue":"5","key":"5037_CR5","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.jacc.2015.05.066","volume":"66","author":"TA Pawade","year":"2015","unstructured":"Pawade TA, Newby DE, Dweck MR. Calcification in aortic stenosis: the skeleton key. J Am Coll Cardiol. 2015;66(5):561\u201377.","journal-title":"J Am Coll Cardiol"},{"issue":"17","key":"5037_CR6","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1161\/01.CIR.0000070591.21548.69","volume":"107","author":"NM Rajamannan","year":"2003","unstructured":"Rajamannan NM, Subramaniam M, Rickard D, Stock SR, Donovan J, Springett M, et al. Human aortic valve calcification is associated with an osteoblast phenotype. Circulation. 2003;107(17):2181\u20134.","journal-title":"Circulation"},{"issue":"11","key":"5037_CR7","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1161\/01.CIR.103.11.1522","volume":"103","author":"ER Mohler III","year":"2001","unstructured":"Mohler ER 3rd, Gannon F, Reynolds C, Zimmerman R, Keane MG, Kaplan FS. Bone formation and inflammation in cardiac valves. Circulation. 2001;103(11):1522\u20138.","journal-title":"Circulation"},{"issue":"1","key":"5037_CR8","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.yjmcc.2003.09.015","volume":"36","author":"JJ Kaden","year":"2004","unstructured":"Kaden JJ, Bickelhaupt S, Grobholz R, Haase KK, Sar\u03b9ko\u00e7 A, K\u03b9l\u03b9\u00e7 R, et al. Receptor activator of nuclear factor \u03baB ligand and osteoprotegerin regulate aortic valve calcification. J Mol Cell Cardiol. 2004;36(1):57\u201366.","journal-title":"J Mol Cell Cardiol"},{"issue":"10","key":"5037_CR9","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1038\/nrrheum.2012.120","volume":"8","author":"CE Lampropoulos","year":"2012","unstructured":"Lampropoulos CE, Papaioannou I, D\u2019Cruz DP. Osteoporosis\u2014a risk factor for cardiovascular disease? Nat Rev Rheumatol. 2012;8(10):587\u201398.","journal-title":"Nat Rev Rheumatol"},{"issue":"25","key":"5037_CR10","doi-asserted-by":"publisher","first-page":"2428","DOI":"10.1161\/CIRCULATIONAHA.121.054823","volume":"143","author":"LL Demer","year":"2021","unstructured":"Demer LL, Tintut Y. Hearts of stone: calcific aortic stenosis and antiresorptive agents for osteoporosis. Circulation. 2021;143(25):2428\u201330.","journal-title":"Circulation"},{"issue":"16","key":"5037_CR11","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1093\/eurheartj\/ehq237","volume":"31","author":"J Hjortnaes","year":"2010","unstructured":"Hjortnaes J, Butcher J, Figueiredo J-L, Riccio M, Kohler RH, Kozloff KM, et al. Arterial and aortic valve calcification inversely correlates with osteoporotic bone remodelling: a role for inflammation. Eur Heart J. 2010;31(16):1975\u201384.","journal-title":"Eur Heart J"},{"issue":"11","key":"5037_CR12","doi-asserted-by":"publisher","first-page":"2520","DOI":"10.1002\/jbmr.2269","volume":"29","author":"NC Wright","year":"2014","unstructured":"Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, et al. The recent prevalence of osteoporosis and low bone mass in the united States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. 2014;29(11):2520\u20136.","journal-title":"J Bone Miner Res"},{"issue":"25","key":"5037_CR13","doi-asserted-by":"publisher","first-page":"2418","DOI":"10.1161\/CIRCULATIONAHA.121.053708","volume":"143","author":"TA Pawade","year":"2021","unstructured":"Pawade TA, Doris MK, Bing R, White AC, Forsyth L, Evans E, et al. Effect of denosumab or alendronic acid on the progression of aortic stenosis: a double-blind randomized controlled trial. Circulation. 2021;143(25):2418\u201327.","journal-title":"Circulation"},{"issue":"25","key":"5037_CR14","doi-asserted-by":"publisher","first-page":"e506","DOI":"10.1161\/CIR.0000000000000912","volume":"142","author":"SR El Khoudary","year":"2020","unstructured":"El Khoudary SR, Aggarwal B, Beckie TM, Hodis HN, Johnson AE, Langer RD, et al. Menopause transition and cardiovascular disease risk: implications for timing of early prevention: a scientific statement from the American heart association. Circulation. 2020;142(25):e506\u201332.","journal-title":"Circulation"},{"issue":"3","key":"5037_CR15","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s002239900419","volume":"62","author":"EI Barengolts","year":"1998","unstructured":"Barengolts EI, Berman M, Kukreja SC, Kouznetsova T, Lin C, Chomka EV. Osteoporosis and coronary atherosclerosis in asymptomatic postmenopausal women. Calcif Tissue Int. 1998;62(3):209\u201313.","journal-title":"Calcif Tissue Int"},{"issue":"1","key":"5037_CR16","doi-asserted-by":"publisher","first-page":"16006","DOI":"10.1038\/nrdp.2016.6","volume":"2","author":"BR Lindman","year":"2016","unstructured":"Lindman BR, Clavel M-A, Mathieu P, Iung B, Lancellotti P, Otto CM, et al. Calcific aortic stenosis. Nat Reviews Disease Primers. 2016;2(1):16006.","journal-title":"Nat Reviews Disease Primers"},{"issue":"1","key":"5037_CR17","first-page":"105","volume":"133","author":"MA Clynes","year":"2020","unstructured":"Clynes MA, Harvey NC, Curtis EM, Fuggle NR, Dennison EM, Cooper C. The epidemiology of osteoporosis. Br Med Bull. 2020;133(1):105\u201317.","journal-title":"Br Med Bull"},{"key":"5037_CR18","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.atherosclerosis.2021.08.031","volume":"335","author":"D Massera","year":"2021","unstructured":"Massera D, Buzkova P, Bortnick AE, Owens DS, Mao S, Li D, et al. Bone mineral density and long-term progression of aortic valve and mitral annular calcification: the Multi-Ethnic study of atherosclerosis. Atherosclerosis. 2021;335:126\u201334.","journal-title":"Atherosclerosis"},{"key":"5037_CR19","doi-asserted-by":"crossref","unstructured":"Pfister R, Michels G, Sharp SJ, Luben R, Wareham NJ, Khaw K-T. Inverse association between bone mineral density and risk of aortic stenosis in men and women in EPIC\u2013Norfolk prospective study. Int J Cardiol. 2015;178:29\u201330.","DOI":"10.1016\/j.ijcard.2014.10.065"},{"issue":"6","key":"5037_CR20","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1097\/00019501-200509000-00007","volume":"16","author":"Y Aksoy","year":"2005","unstructured":"Aksoy Y, Yagmur C, Tekin GO, Yagmur J, Topal E, Kekilli E, et al. Aortic valve calcification: association with bone mineral density and cardiovascular risk factors. Coron Artery Dis. 2005;16(6):379\u201383.","journal-title":"Coron Artery Dis"},{"issue":"6","key":"5037_CR21","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1111\/j.1365-2265.2009.03543.x","volume":"71","author":"HS Choi","year":"2009","unstructured":"Choi HS, Rhee Y, Hur NW, Chung N, Lee EJ, Lim S-K. Association between low bone mass and aortic valve sclerosis in Koreans. Clin Endocrinol. 2009;71(6):792\u20137.","journal-title":"Clin Endocrinol"},{"issue":"14","key":"5037_CR22","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1016\/j.jacc.2020.01.053","volume":"75","author":"L Tastet","year":"2020","unstructured":"Tastet L, Shen M, Capoulade R, Arsenault M, B\u00e9dard \u00c9, C\u00f4t\u00e9 N, et al. Bone mineral density and progression rate of calcific aortic valve stenosis. J Am Coll Cardiol. 2020;75(14):1725\u20136.","journal-title":"J Am Coll Cardiol"},{"issue":"10","key":"5037_CR23","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1002\/jbmr.2530","volume":"30","author":"JJ Chan","year":"2015","unstructured":"Chan JJ, Cupples LA, Kiel DP, O\u2019Donnell CJ, Hoffmann U, Samelson EJ. QCT volumetric bone mineral density and vascular and valvular calcification: the Framingham study. J Bone Miner Res. 2015;30(10):1767\u201374.","journal-title":"J Bone Miner Res"},{"issue":"4","key":"5037_CR24","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1161\/CIRCRESAHA.116.309306","volume":"120","author":"L Simard","year":"2017","unstructured":"Simard L, C\u00f4t\u00e9 N, Dagenais F, Mathieu P, Couture C, Trahan S, et al. Sex-Related discordance between aortic valve calcification and hemodynamic severity of aortic stenosis. Circul Res. 2017;120(4):681\u201391.","journal-title":"Circul Res"},{"key":"5037_CR25","doi-asserted-by":"crossref","unstructured":"Myasoedova V, Massaiu I, Moschetta D, Chiesa M, Valerio V, Bozzi M et al. Sex-specific cell types and molecular pathways drive fibro-calcific aortic valve stenosis. Cardiovasc. Res. 2022;118(Supplement_1):cvac066.141.","DOI":"10.1093\/cvr\/cvac066.141"},{"issue":"8","key":"5037_CR26","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1007\/s00392-019-01413-1","volume":"108","author":"ST Niepmann","year":"2019","unstructured":"Niepmann ST, Steffen E, Zietzer A, Adam M, Nordsiek J, Gyamfi-Poku I, et al. Graded murine wire-induced aortic valve stenosis model mimics human functional and morphological disease phenotype. Clin Res Cardiol. 2019;108(8):847\u201356.","journal-title":"Clin Res Cardiol"},{"issue":"1","key":"5037_CR27","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s00395-023-00980-9","volume":"118","author":"ST Niepmann","year":"2023","unstructured":"Niepmann ST, Willemsen N, Boucher AS, Stei M, Goody P, Zietzer A, et al. Toll-like receptor-3 contributes to the development of aortic valve stenosis. Basic Res Cardiol. 2023;118(1):6.","journal-title":"Basic Res Cardiol"},{"key":"5037_CR28","doi-asserted-by":"publisher","first-page":"7582716","DOI":"10.1155\/2017\/7582716","volume":"2017","author":"M Suzuki","year":"2017","unstructured":"Suzuki M, Millecamps M, Naso L, Ohtori S, Mori C, Stone LS. Chronic osteoporotic pain in mice: cutaneous and deep musculoskeletal pain are partially independent of bone resorption and differentially sensitive to Pharmacological interventions. J Osteoporos. 2017;2017:7582716.","journal-title":"J Osteoporos"},{"key":"5037_CR29","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.bone.2014.06.023","volume":"66","author":"M-T Haider","year":"2014","unstructured":"Haider M-T, Holen I, Dear TN, Hunter K, Brown HK. Modifying the osteoblastic niche with Zoledronic acid in vivo\u2014Potential implications for breast cancer bone metastasis. Bone. 2014;66:240\u201350.","journal-title":"Bone"},{"issue":"18","key":"5037_CR30","doi-asserted-by":"publisher","first-page":"5829","DOI":"10.1158\/1078-0432.CCR-09-0426","volume":"15","author":"S Pozzi","year":"2009","unstructured":"Pozzi S, Vallet S, Mukherjee S, Cirstea D, Vaghela N, Santo L, et al. High-Dose Zoledronic acid impacts bone remodeling with effects on osteoblastic lineage and bone mechanical properties. Clin Cancer Res. 2009;15(18):5829\u201339.","journal-title":"Clin Cancer Res"},{"issue":"4","key":"5037_CR31","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/S0002-9149(00)00959-0","volume":"86","author":"F Antonini-Canterin","year":"2000","unstructured":"Antonini-Canterin F, Pavan D, Burelli C, Cassin M, Cervesato E, Nicolosi GL. Validation of the ejection fraction-velocity ratio: a new simplified function-corrected index for assessing aortic stenosis severity. Am J Cardiol. 2000;86(4):427\u201333.","journal-title":"Am J Cardiol"},{"key":"5037_CR32","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.toxlet.2022.04.005","volume":"362","author":"S Liu","year":"2022","unstructured":"Liu S, Zhao J, Tian W-s, Wang J-c, Wang H-w. Zhou B-h. Estrogen deficiency aggravates fluorine ion-induced renal fibrosis via the TGF-\u03b21\/Smad signaling pathway in rats. Toxicol Lett. 2022;362:26\u201337.","journal-title":"Toxicol Lett"},{"issue":"2","key":"5037_CR33","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1080\/13813455.2019.1676262","volume":"128","author":"NI Hussien","year":"2022","unstructured":"Hussien NI, E-kH I, M. SS, and, Shoman AA. Chronic oestrogen deficiency induced by ovariectomy May cause lung fibrosis through activation of the renin-angiotensin system in rats. Arch Physiol Biochem. 2022;128(2):290\u20139.","journal-title":"Arch Physiol Biochem"},{"key":"5037_CR34","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/bs.apha.2017.08.002","volume":"81","author":"X Wang","year":"2018","unstructured":"Wang X, Khalil RA. Matrix metalloproteinases, vascular remodeling, and vascular disease. Adv Pharmacol. 2018;81:241\u2013330.","journal-title":"Adv Pharmacol"},{"issue":"1","key":"5037_CR35","doi-asserted-by":"publisher","first-page":"139","DOI":"10.3892\/ijmm.2016.2582","volume":"38","author":"Y Komatsu","year":"2016","unstructured":"Komatsu Y, Ibi M, Chosa N, Kyakumoto S, Kamo M, Shibata T, et al. Zoledronic acid suppresses transforming growth factor-\u03b2-induced fibrogenesis by human gingival fibroblasts. Int J Mol Med. 2016;38(1):139\u201347.","journal-title":"Int J Mol Med"},{"issue":"4","key":"5037_CR36","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1166\/jbt.2017.1567","volume":"7","author":"C Ge","year":"2017","unstructured":"Ge C, Li Q, Li X, Shu Y, Lu R, Zou X, et al. Zoledronic acid inhibits TGF-\u03b21-Induced the proliferation, migration and EMT through Smad pathway in human gingival fibroblasts. J Biomaterials Tissue Eng. 2017;7(4):319\u201326.","journal-title":"J Biomaterials Tissue Eng"},{"issue":"6","key":"5037_CR37","doi-asserted-by":"publisher","first-page":"H1080","DOI":"10.1152\/ajpheart.00157.2022","volume":"322","author":"JE Joll","year":"2022","unstructured":"Joll JE, Bersi MR, Nyman JS, Merryman WD. Evaluation of early bilateral ovariectomy in mice as a model of left heart disease. Am J Physiol Heart Circ Physiol. 2022;322(6):H1080\u20135.","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"22","key":"5037_CR38","doi-asserted-by":"publisher","first-page":"2938","DOI":"10.1161\/CIRCULATIONAHA.107.743161","volume":"117","author":"LL Demer","year":"2008","unstructured":"Demer LL, Tintut Y, Vascular Calcification. Circulation. 2008;117(22):2938\u201348.","journal-title":"Circulation"},{"issue":"1","key":"5037_CR39","first-page":"364310","volume":"2011","author":"KL Sider","year":"2011","unstructured":"Sider KL, Blaser MC, Simmons CA. Animal models of calcific aortic valve disease. Int J Inflamm. 2011;2011(1):364310.","journal-title":"Int J Inflamm"},{"issue":"2","key":"5037_CR40","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1007\/s00223-021-00930-4","volume":"112","author":"SD Vasikaran","year":"2023","unstructured":"Vasikaran SD, Miura M, Pikner R, Bhattoa HP, Cavalier E, the IOFIJCoBM. Practical considerations for the clinical application of bone turnover markers in osteoporosis. Calcif Tissue Int. 2023;112(2):148\u201357.","journal-title":"Calcif Tissue Int"},{"issue":"7","key":"5037_CR41","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1002\/jbmr.141","volume":"25","author":"ML Bouxsein","year":"2010","unstructured":"Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, M\u00fcller R. Guidelines for assessment of bone microstructure in rodents using micro\u2013computed tomography. J Bone Miner Res. 2010;25(7):1468\u201386.","journal-title":"J Bone Miner Res"},{"issue":"1","key":"5037_CR42","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.amjcard.2009.02.051","volume":"104","author":"AH Skolnick","year":"2009","unstructured":"Skolnick AH, Osranek M, Formica P, Kronzon I. Osteoporosis treatment and progression of aortic stenosis. Am J Cardiol. 2009;104(1):122\u20134.","journal-title":"Am J Cardiol"},{"issue":"16","key":"5037_CR43","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1016\/j.jacc.2012.01.024","volume":"59","author":"O Aksoy","year":"2012","unstructured":"Aksoy O, Cam A, Goel SS, Houghtaling PL, Williams S, Ruiz-Rodriguez E, et al. Do bisphosphonates slow the progression of aortic stenosis? J Am Coll Cardiol. 2012;59(16):1452\u20139.","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"5037_CR44","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1161\/CIRCRESAHA.116.310262","volume":"121","author":"G Chinetti-Gbaguidi","year":"2017","unstructured":"Chinetti-Gbaguidi G, Daoudi M, Rosa M, Vinod M, Louvet L, Copin C, et al. Human alternative macrophages populate calcified areas of atherosclerotic lesions and display impaired RANKL-Induced osteoclastic bone resorption activity. Circ Res. 2017;121(1):19\u201330.","journal-title":"Circ Res"},{"issue":"2","key":"5037_CR45","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.ejvs.2015.10.004","volume":"51","author":"JM Davaine","year":"2016","unstructured":"Davaine JM, Quillard T, Chatelais M, Guilbaud F, Brion R, Guyomarch B, et al. Bone like arterial calcification in femoral atherosclerotic lesions: prevalence and role of osteoprotegerin and pericytes. Eur J Vasc Endovasc Surg. 2016;51(2):259\u201367.","journal-title":"Eur J Vasc Endovasc Surg"},{"issue":"2","key":"5037_CR46","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1002\/jbmr.2043","volume":"29","author":"EJ Samelson","year":"2013","unstructured":"Samelson EJ, Miller PD, Christiansen C, Daizadeh NS, Grazette L, Anthony MS, et al. RANKL Inhibition with denosumab does not influence 3-Year progression of aortic calcification or incidence of adverse cardiovascular events in postmenopausal women with osteoporosis and high cardiovascular risk. J Bone Miner Res. 2013;29(2):450\u20137.","journal-title":"J Bone Miner Res"},{"key":"5037_CR47","doi-asserted-by":"crossref","unstructured":"Abdoun K, Tastet L, B\u00e9dard E, Arsenault M, Pibarot P, Clavel M-A. Effect of early menopause and hormone replacement therapy on aortic stenosis progression. Can J Cardiol. 2025;41(7):1418\u201327.","DOI":"10.1016\/j.cjca.2025.01.024"},{"issue":"4","key":"5037_CR48","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1016\/j.jacc.2005.09.049","volume":"47","author":"M-C Drolet","year":"2006","unstructured":"Drolet M-C, Roussel E, Deshaies Y, Couet J, Arsenault M. A high fat\/high carbohydrate diet induces aortic valve disease in C57BL\/6J mice. J Am Coll Cardiol. 2006;47(4):850\u20135.","journal-title":"J Am Coll Cardiol"},{"key":"5037_CR49","doi-asserted-by":"crossref","unstructured":"Wen D, Hu L, Shan J, Zhang H, Hu L, Yuan A et al. Mechanical injury accentuates lipid deposition in ApoE\u2013\/\u2013 mice and advance aortic valve stenosis: a novel modified aortic valve stenosis model. Front Cardiovasc Med. 2023;10:1119746.","DOI":"10.3389\/fcvm.2023.1119746"},{"issue":"2","key":"5037_CR50","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1161\/ATVBAHA.113.302610","volume":"34","author":"S Honda","year":"2014","unstructured":"Honda S, Miyamoto T, Watanabe T, Narumi T, Kadowaki S, Honda Y, Arteriosclerosis, et al. Thromb Vascular Biology. 2014;34(2):270\u20138.","journal-title":"Thromb Vascular Biology"},{"issue":"4","key":"5037_CR51","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1002\/ame2.12393","volume":"7","author":"N Qian","year":"2024","unstructured":"Qian N, Wang Y, Hu W, Cao N, Qian Y, Chen J, et al. A novel mouse model of calcific aortic valve stenosis. Anim Models Experimental Med. 2024;7(4):523\u201332.","journal-title":"Anim Models Experimental Med"},{"issue":"16","key":"5037_CR52","doi-asserted-by":"publisher","first-page":"e15433","DOI":"10.14814\/phy2.15433","volume":"10","author":"M-A Fleury","year":"2022","unstructured":"Fleury M-A, Annabi M-S, Voisine M, Hervault M, Boilard A-J, Shen M, et al. Impact of sex and sex hormones on pathophysiology and progression of aortic stenosis in a murine model. Physiological Rep. 2022;10(16):e15433.","journal-title":"Physiological Rep"},{"issue":"7","key":"5037_CR53","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1359\/JBMR.050307","volume":"20","author":"ML Bouxsein","year":"2005","unstructured":"Bouxsein ML, Myers KS, Shultz KL, Donahue LR, Rosen CJ, Beamer WG. Ovariectomy-induced bone loss varies among inbred strains of mice. J Bone Min Res. 2005;20(7):1085\u201392.","journal-title":"J Bone Min Res"},{"key":"5037_CR54","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.ejphar.2015.03.028","volume":"759","author":"T Komori","year":"2015","unstructured":"Komori T. Animal models for osteoporosis. Eur J Pharmacol. 2015;759:287\u201394.","journal-title":"Eur J Pharmacol"},{"issue":"2","key":"5037_CR55","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1210\/endrev\/bnab028","volume":"43","author":"PR Ebeling","year":"2021","unstructured":"Ebeling PR, Nguyen HH, Aleksova J, Vincent AJ, Wong P, Milat F. Secondary osteoporosis. Endocr Rev. 2021;43(2):240\u2013313.","journal-title":"Endocr Rev"},{"key":"5037_CR56","unstructured":"Rosen CJ. The epidemiology and pathogenesis of osteoporosis. South Dartmouth: MDText.com; 2000."},{"issue":"3","key":"5037_CR57","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1093\/cvr\/cvac099","volume":"119","author":"J Gehlen","year":"2022","unstructured":"Gehlen J, Stundl A, Debiec R, Fontana F, Krane M, Sharipova D, et al. Elucidation of the genetic causes of bicuspid aortic valve disease. Cardiovascular Res. 2022;119(3):857\u201366.","journal-title":"Cardiovascular Res"},{"issue":"8","key":"5037_CR58","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1093\/eurheartj\/ehz591","volume":"41","author":"S Mas-Peiro","year":"2019","unstructured":"Mas-Peiro S, Hoffmann J, Fichtlscherer S, Dorsheimer L, Rieger MA, Dimmeler S, et al. Clonal haematopoiesis in patients with degenerative aortic valve stenosis undergoing transcatheter aortic valve implantation. Eur Heart J. 2019;41(8):933\u20139.","journal-title":"Eur Heart J"},{"issue":"9","key":"5037_CR59","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1093\/ehjci\/jeab079","volume":"22","author":"KD Boudoulas","year":"2021","unstructured":"Boudoulas KD, Triposkiadis F, Boudoulas H. Aortic stenosis: a complex entity with multiple coexistent abnormalities. Eur Heart J Cardiovasc Imaging. 2021;22(9):983\u20135.","journal-title":"Eur Heart J - Cardiovasc Imaging"},{"key":"5037_CR60","doi-asserted-by":"crossref","unstructured":"B\u00fcttner P, Feistner L, Lurz P, Thiele H, Hutcheson JD, Schlotter F. Dissecting calcific aortic valve disease\u2014the role, etiology, and drivers of valvular fibrosis. Front Cardiovasc Med. 2021;8:660797.","DOI":"10.3389\/fcvm.2021.660797"},{"issue":"6","key":"5037_CR61","first-page":"396","volume":"99","author":"GW Eveborn","year":"2013","unstructured":"Eveborn GW, Schirmer H, Heggelund G, Lunde P, Rasmussen K. The evolving epidemiology of valvular aortic stenosis. Troms\u00f8 Study Heart. 2013;99(6):396\u2013400.","journal-title":"Troms\u00f8 Study Heart"},{"key":"5037_CR62","doi-asserted-by":"crossref","unstructured":"Iqbal F, Schlotter F, Becker-Greene D, Lupieri A, Goettsch C, Hutcheson JD et al. Sortilin enhances fibrosis and calcification in aortic valve disease by inducing interstitial cell heterogeneity. Eur Heart J. 2023;44(10):885\u201398.","DOI":"10.1093\/eurheartj\/ehac818"}],"container-title":["BMC Cardiovascular Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12872-025-05037-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12872-025-05037-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12872-025-05037-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T15:23:26Z","timestamp":1760369006000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccardiovascdisord.biomedcentral.com\/articles\/10.1186\/s12872-025-05037-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["5037"],"URL":"https:\/\/doi.org\/10.1186\/s12872-025-05037-4","relation":{},"ISSN":["1471-2261"],"issn-type":[{"value":"1471-2261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,31]]},"assertion":[{"value":"17 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2025","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this article was revised: Affiliation for the authors Christoph Bourauel, Frank A. Schildberg, and Miriam Silaschi were incorrectly listed as members of the Department of Cardiology, University Hospital Bonn and it has been updated.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal procedures were conducted in accordance with institutional and national guidelines for the care and use of laboratory animals. The study protocol was approved by the Landesamt f\u00fcr Natur, Umwelt und Verbraucherschutz Nordrhein-Westfalen (LANUV) under the approval number TV 81-02.04.2022.A042.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical trial number"}}],"article-number":"562"}}