{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:55:46Z","timestamp":1760151346155,"version":"build-2065373602"},"reference-count":128,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T00:00:00Z","timestamp":1647561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>A study was conducted to determine the effect of long-term supplementation with selenium and copper, administered at twice the level used in the standard diet of rats, on the content of selected elements in the femoral bones of healthy rats and rats with implanted LNCaP cancer cells. After an adaptation period, the animals were randomly divided into two experimental groups. The rats in the experimental group were implanted with prostate cancer cells. The rats in the control group were kept in the same conditions as those in the experimental group and fed the same diet, but without implanted cancer cells. The cancer cells (LNCaP) were intraperitoneally implanted in the amount of 1 \u00d7 106 (in PBS 0.4 mL) at the age of 90 days. The content of elements in the samples was determined by a quadrupole mass spectrometer with inductively coupled plasma ionization (ICP-MS). In the femoral bones of rats with implanted LNCaP cells, in the case of the standard diet and the copper-enriched diet, there was a marked decreasing trend in the content of the analysed elements relative to the control rats. This may indicate slow osteolysis taking place in the bone tissue. Contrasting results were obtained for the diet enriched with selenium; there was no significant reduction in the level of these elements, and there was even an increase in the concentrations of Fe and K in the bones of rats with implanted LNCaP cells. Particularly, numerous changes in the mineral composition of the bones were generated by enriching the diet with copper. The elements that most often underwent changes (losses) in the bones were cobalt, iron, manganese and molybdenum. The changes observed, most likely induced by the implantation of LNCaP cells, may indicate a disturbance of mineral homeostasis.<\/jats:p>","DOI":"10.3390\/nu14061285","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T21:34:27Z","timestamp":1647812067000},"page":"1285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effect of Copper and Selenium Supplementation on the Level of Elements in Rats\u2019 Femurs under Neoplastic Conditions"],"prefix":"10.3390","volume":"14","author":[{"given":"Dorota","family":"Skrajnowska","sequence":"first","affiliation":[{"name":"Department of Bromatology, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1806-7735","authenticated-orcid":false,"given":"Agata","family":"Jagielska","sequence":"additional","affiliation":[{"name":"Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5199-9681","authenticated-orcid":false,"given":"Anna","family":"Ruszczy\u0144ska","sequence":"additional","affiliation":[{"name":"Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakub","family":"Idkowiak","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentsk\u00e1 573, 53210 Pardubice, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1617-2352","authenticated-orcid":false,"given":"Barbara","family":"Bobrowska-Korczak","sequence":"additional","affiliation":[{"name":"Department of Bromatology, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jht.2011.08.003","article-title":"Specialized Connective Tissue: Bone, the Structural Framework of the Upper Extremity","volume":"25","author":"Weatherholt","year":"2012","journal-title":"J. Hand Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jtemb.2019.06.013","article-title":"Homeostatic Changes of Some Trace Elements in Geriatric Rats in the Condition of Oxidative Stress Induced by Aluminum and the Beneficial Role of Resveratrol","volume":"55","author":"Muselin","year":"2019","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1016\/j.biomaterials.2006.11.043","article-title":"FT-IR Imaging of Native and Tissue-Engineered Bone and Cartilage","volume":"28","author":"Boskey","year":"2007","journal-title":"Biomaterials"},{"key":"ref_4","first-page":"114","article-title":"Mechanical Basis of Bone Strength: Influence of Bone Material, Bone Structure and Muscle Action","volume":"17","author":"Hart","year":"2017","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1177\/0022034510377791","article-title":"Aging and Bone","volume":"89","author":"Boskey","year":"2010","journal-title":"J. Dent. Res."},{"key":"ref_6","unstructured":"Dempster, D.W., Cauley, J.A., Bouxsein, M.L., and Cosman, F. (2021). Chapter 8\u2014The regulatory role of matrix proteins in mineralization of bone. Marcus and Feldman\u2019s Osteoporosis, Academic Press. [5th ed.]."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hernandez, R.K., Wade, S.W., Reich, A., Pirolli, M., Liede, A., and Lyman, G.H. (2018). Incidence of Bone Metastases in Patients with Solid Tumors: Analysis of Oncology Electronic Medical Records in the United States. BMC Cancer, 18.","DOI":"10.1186\/s12885-017-3922-0"},{"key":"ref_8","first-page":"487","article-title":"The Effect of Environmental Factors on Concentration of Trace Elements in Hip Joint Bones of Patients after Hip Replacement Surgery","volume":"20","author":"Lanocha","year":"2013","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s00244-008-9228-0","article-title":"Interactions between Concentrations of Chemical Elements in Human Femoral Heads","volume":"57","author":"Kwapulinski","year":"2009","journal-title":"Arch. Environ. Contam. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"610","DOI":"10.5604\/12321966.1232555","article-title":"Chemometric Evaluation of Concentrations of Trace Elements in Intervertebral Disc Tissue in Patient with Degenerative Disc Disease","volume":"24","author":"Kubaszewski","year":"2017","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.bone.2013.07.006","article-title":"Prostate Cancer Metastases Alter Bone Mineral and Matrix Composition Independent of Effects on Bone Architecture in Mice\u2014A Quantitative Study Using MicroCT and Raman Spectroscopy","volume":"56","author":"Bi","year":"2013","journal-title":"Bone"},{"key":"ref_12","first-page":"1262","article-title":"Bone Tissue Lesion in Oncological Disease (Literature Review and Own Research Data)","volume":"71","author":"Syniachenko","year":"2018","journal-title":"Wiadomo\u015bci Lek."},{"key":"ref_13","first-page":"181","article-title":"Microelements for Bone Boost: The Last but Not the Least","volume":"13","author":"Pepa","year":"2016","journal-title":"Clin. Cases Miner. Bone Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jtemb.2015.06.005","article-title":"Effects of Thirty Elements on Bone Metabolism","volume":"32","author":"Dermience","year":"2015","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1002\/pros.23022","article-title":"Heterogeneous Copper Concentrations in Cancerous Human Prostate Tissues","volume":"75","author":"Denoyer","year":"2015","journal-title":"Prostate"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3390\/nu5010097","article-title":"Selenium in Bone Health: Roles in Antioxidant Protection and Cell Proliferation","volume":"5","author":"Zeng","year":"2013","journal-title":"Nutrients"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4061","DOI":"10.1210\/jc.2012-2121","article-title":"Bone Turnover and Bone Mineral Density Are Independently Related to Selenium Status in Healthy Euthyroid Postmenopausal Women","volume":"97","author":"Hoeg","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"19213","DOI":"10.1038\/srep19213","article-title":"Selenium Exposure and Cancer Risk: An Updated Meta-Analysis and Meta-Regression","volume":"6","author":"Cai","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Beukhof, C.M., Medici, M., van den Beld, A.W., Hollenbach, B., Hoeg, A., Visser, W.E., de Herder, W.W., Visser, T.J., Schomburg, L., and Peeters, R.P. (2016). Selenium Status Is Positively Associated with Bone Mineral Density in Healthy Aging European Men. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152748"},{"key":"ref_20","first-page":"22","article-title":"Influence of copper (II) complex on the activity of selected oxidative enzymes","volume":"28","author":"Kubiak","year":"2010","journal-title":"Pol. Merkur. Lek. Organ Pol. Tow. Lek."},{"key":"ref_21","first-page":"110","article-title":"In vitro study of the effects of copper ion on osteoclastic resorption in various dental mineralized tissues","volume":"42","author":"Li","year":"2007","journal-title":"Zhonghua Kou Qiang Yi Xue Za Zhi Zhonghua Kouqiang Yixue Zazhi Chin. J. Stomatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1007\/s00204-014-1355-y","article-title":"Copper: Toxicological Relevance and Mechanisms","volume":"88","author":"Gaetke","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s10534-011-9430-9","article-title":"Systems Biology Approach to Wilson\u2019s Disease","volume":"24","author":"Burkhead","year":"2011","journal-title":"Biometals"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jtemb.2010.11.004","article-title":"Risks and Benefits of Copper in Light of New Insights of Copper Homeostasis","volume":"25","author":"Olivares","year":"2011","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1159\/000341976","article-title":"Copper, Zinc, and Cu\/Zn Ratio in Transitional Cell Carcinoma of the Bladder","volume":"89","author":"Golabek","year":"2012","journal-title":"Urol. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.mad.2015.01.004","article-title":"Serum Copper to Zinc Ratio: Relationship with Aging and Health Status","volume":"151","author":"Malavolta","year":"2015","journal-title":"Mech. Ageing Dev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1743-7075-11-30","article-title":"Prostate Cancer and the Influence of Dietary Factors and Supplements: A Systematic Review","volume":"11","author":"Mandair","year":"2014","journal-title":"Nutr. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1677\/erc.0.0110255","article-title":"Copper Deficiency as an Anti-Cancer Strategy","volume":"11","author":"Goodman","year":"2004","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s12011-012-9488-4","article-title":"Selenium Protects Bone Marrow Stromal Cells against Hydrogen Peroxide-Induced Inhibition of Osteoblastic Differentiation by Suppressing Oxidative Stress and ERK Signaling Pathway","volume":"150","author":"Liu","year":"2012","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1016\/j.bbagen.2009.03.014","article-title":"Selenoproteins and Human Health: Insights from Epidemiological Data","volume":"1790","author":"Rayman","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0891-5849(01)00610-4","article-title":"Oxidative stress modulates osteoblastic differentiation of vascular and bone cells","volume":"31","author":"Mody","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/S0736-0266(00)00079-6","article-title":"Osteosarcoma cell apoptosis induced by selenium","volume":"19","author":"Hiraoka","year":"2001","journal-title":"J. Orthop. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Yang, T., Lee, S.J., Park, K.C., Park, S.H., Chung, J., and Lee, S. (2022). The Effects of Selenium on Bone Health: From Element to Therapeutics. Molecules, 27.","DOI":"10.3390\/molecules27020392"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6323","DOI":"10.1210\/jc.2005-0794","article-title":"Circulating osteoprotegerin and receptor activator for nuclear factor (B ligand: Clinical utility in metabolic bone disease assessment","volume":"90","author":"Rogers","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1001\/jama.292.4.490","article-title":"Clinical implications of the osteoprotegerin\/RANKL\/RANK system for bone and vascular diseases","volume":"292","author":"Hofbauer","year":"2004","journal-title":"JAMA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.1002\/pmic.201000306","article-title":"Identification of osteocyte-selective proteins","volume":"10","author":"Guo","year":"2010","journal-title":"Proteomics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.bbrc.2012.01.005","article-title":"Antioxidants, like coenzyme Q10, selenite, and curcumin, inhibited osteoclast differentiation by suppressing reactive oxygen species generation","volume":"418","author":"Moon","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1634\/stemcells.2005-0117","article-title":"Selenium supplementation restores the antioxidative capacity and prevents cell damage in bone marrow stromal cells in vitro","volume":"24","author":"Ebert","year":"2006","journal-title":"Stem Cells"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.3945\/jn.111.157040","article-title":"Selenium Deficiency Decreases Antioxidative Capacity and Is Detrimental to Bone Microarchitecture in Mice","volume":"142","author":"Cao","year":"2012","journal-title":"J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/aje\/kwj005","article-title":"Antioxidant Intake and Risk of Osteoporotic Hip Fracture in Utah: An Effect Modified by Smoking Status","volume":"163","author":"Zhang","year":"2006","journal-title":"Am. J. Epidemiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s12011-017-0964-8","article-title":"Zinc: The Other Suspected Environmental Factor in Kashin-Beck Disease in Addition to Selenium","volume":"179","author":"Wang","year":"2017","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1155\/2010\/354189","article-title":"The Antioxidant Enzyme GPX1 Gene Polymorphisms Are Associated with Low BMD and Increased Bone Turnover Markers","volume":"29","author":"Mlakar","year":"2010","journal-title":"Dis. Markers"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.mehy.2011.07.042","article-title":"From Selenoprotein to Endochondral Ossification: A Novel Mechanism with MicroRNAs Potential in Bone Related Diseases?","volume":"77","author":"Sun","year":"2011","journal-title":"Med. Hypotheses"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.joca.2008.10.007","article-title":"The Role of Plasma Cytokine Levels, CRP and Selenoprotein S Gene Variation in OA","volume":"17","author":"Bos","year":"2009","journal-title":"Osteoarthr. Cartil."},{"key":"ref_45","first-page":"e036612","article-title":"Selenium and bone health: A protocol for a systematic review and metaanalysis","volume":"10","author":"Wang","year":"2020","journal-title":"BMJ"},{"key":"ref_46","first-page":"1886","article-title":"Association between dietary antioxidant quality score (DAQs) and bone mineral density in Spanish women","volume":"27","author":"Rivas","year":"2012","journal-title":"Nutr. Hosp."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1017\/S0007114514002773","article-title":"Associations between the dietary intake of antioxidant nutrients and the risk of hip fracture in elderly Chinese: A case-control study","volume":"112","author":"Sun","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1359\/jbmr.1999.14.1.129","article-title":"Smoking, antioxidant vitamins, and the risk of hip fracture","volume":"14","author":"Melhus","year":"1999","journal-title":"J. Bone Miner. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1093\/ajcn\/82.3.581","article-title":"Lack of a relation between vitamin and mineral antioxidants and bone mineral density: Results from the women\u2019s health Initiative","volume":"82","author":"Wolf","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s12011-011-9109-7","article-title":"Plasma selenium, zinc, copper and lipid levels in postmenopausal Turkish women and their relation with osteoporosis","volume":"144","author":"Arikan","year":"2011","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1080\/09637480701780724","article-title":"Nutrition and lifestyle in relation to bone health and body weight in Croatian postmenopausal women","volume":"60","author":"Ilich","year":"2009","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_52","first-page":"19250","article-title":"Correlation between bone mineral density and serum trace element contents of elderly males in Beijing urban area","volume":"8","author":"Wang","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s12011-009-8363-4","article-title":"Correlation analysis between bone mineral density and serum element contents of postmenopausal women in Xi\u2019an urban area","volume":"131","author":"Liu","year":"2009","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e212","DOI":"10.1016\/S2666-7568(21)00051-9","article-title":"Effect of selenium supplementation on musculoskeletal health in older women: A randomised, double-blind, placebo-controlled trial","volume":"2","author":"Walsh","year":"2021","journal-title":"Lancet Healthy Longev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"E110","DOI":"10.1017\/S0029665121002330","article-title":"Effect of selenium supplementation on biomarkers of bone turnover","volume":"80","author":"Perri","year":"2021","journal-title":"Proc. Nutr. Soc."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1001\/jama.2008.864","article-title":"Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)","volume":"301","author":"Lippman","year":"2009","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"217","DOI":"10.7326\/0003-4819-147-4-200708210-00175","article-title":"Effects of Long-Term Selenium Supplementation on the Incidence of Type 2 Diabetes: A Randomized Trial","volume":"147","author":"Stranges","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3389\/fonc.2011.00023","article-title":"Targeting apoptosis signaling pathways for anticancer therapy","volume":"1","author":"Fulda","year":"2011","journal-title":"Front. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1007\/s00204-013-1034-4","article-title":"Oxidative stress: The mitochondria dependent and mitochondria independent pathways of apoptosis","volume":"87","author":"Sinha","year":"2013","journal-title":"Arch. Toxicol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.tox.2015.04.003","article-title":"Regulated necrosis and its implications in toxicology","volume":"333","author":"Aki","year":"2015","journal-title":"Toxicology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e2708","DOI":"10.1097\/MD.0000000000002708","article-title":"Association between Cd Exposure and Risk of Prostate Cancer","volume":"95","author":"Yuan","year":"2016","journal-title":"Medicine"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1007\/s00775-010-0675-5","article-title":"Correlation of Concentrations of Selected Trace Elements with Gleason Grade of Prostate Tissues","volume":"15","author":"Banas","year":"2010","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_63","first-page":"470","article-title":"Selenium as Marker for Cancer Risk and Prevention","volume":"84","author":"Lener","year":"2012","journal-title":"Pol. Przegl. Chir."},{"key":"ref_64","first-page":"62","article-title":"Androgen Action in Prostate Function and Disease","volume":"6","author":"Banerjee","year":"2018","journal-title":"Am. J. Clin. Exp. Urol."},{"key":"ref_65","first-page":"1171","article-title":"Selenium Effects on Prostate Cell Growth","volume":"9","author":"Menter","year":"2000","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1007\/s00204-010-0595-8","article-title":"Selenium: A Double-Edged Sword for Defense and Offence in Cancer","volume":"84","author":"Chovanec","year":"2010","journal-title":"Arch. Toxicol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1590\/S1516-89132005000200009","article-title":"Selenium Protective Activity against Aflatoxin B1 Adverse Affects on Drosophila Melanogaster","volume":"48","author":"Uysal","year":"2005","journal-title":"Braz. Arch. Biol. Technol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/BF02898024","article-title":"Serum Selenium Level and Other Risk Factors for Breast Cancer among Patients in a Malaysian Hospital","volume":"12","author":"Rejali","year":"2007","journal-title":"Environ. Health Prev. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1002\/ijc.30875","article-title":"Selenium and Breast Cancer Risk: A Prospective Nested Case\u2013Control Study on Serum Selenium Levels, Smoking Habits and Overweight","volume":"141","author":"Sandsveden","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"9104","DOI":"10.1038\/s41598-020-64073-6","article-title":"Prognosis of Prostate Cancer and Bone Metastasis Pattern of Patients: A SEER-Based Study and a Local Hospital Based Study from China","volume":"10","author":"Liu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2013.07.036","article-title":"Selection of Bone Metastasis Seeds by Mesenchymal Signals in the Primary Tumor Stroma","volume":"154","author":"Zhang","year":"2013","journal-title":"Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nrc3055","article-title":"Cancer to Bone: A Fatal Attraction","volume":"11","author":"Weilbaecher","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"61","DOI":"10.4137\/CGM.S12769","article-title":"The Osteoblastic and Osteoclastic Interactions in Spinal Metastases Secondary to Prostate Cancer","volume":"6","author":"Dushyanthen","year":"2013","journal-title":"Cancer Growth Metastasis"},{"key":"ref_74","first-page":"4239","article-title":"Advances in Cancer Pain from Bone Metastasis","volume":"9","author":"Zhu","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.eucr.2018.11.001","article-title":"Hypercalcemia Due to Parathyroid Hormone-Related Peptide Secreted by Neuroendocrine Dedifferentiated Prostate Cancer","volume":"22","author":"Ando","year":"2018","journal-title":"Urol. Case Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"554078","DOI":"10.3389\/fendo.2021.554078","article-title":"Endocrinology of the Aging Prostate: Current Concepts","volume":"12","author":"Cannarella","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_77","first-page":"1","article-title":"Benign Prostatic Hyperplasia: Epidemiology, Economics and Evaluation","volume":"22","author":"Vuichoud","year":"2015","journal-title":"Can. J. Urol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"9575","DOI":"10.7314\/APJCP.2014.15.22.9575","article-title":"Epidemiology, Etiology, Diagnosis and Treatment of Prostate Cancer","volume":"15","author":"Daniyal","year":"2014","journal-title":"Asian Pac. J. Cancer Prev. APJCP"},{"key":"ref_79","unstructured":"(2021, September 02). Cancer Today. Available online: http:\/\/gco.iarc.fr\/today\/home."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21332","article-title":"Cancer Statistics","volume":"66","author":"Siegel","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1023\/A:1015599831232","article-title":"Prostate Carcinoma Skeletal Metastases: Cross-Talk between Tumor and Bone","volume":"20","author":"Keller","year":"2001","journal-title":"Cancer Metastasis Rev."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Wong, S.K., Mohamad, N.-V., Giaze, T.R., Chin, K.-Y., Mohamed, N., and Ima-Nirwana, S. (2019). Prostate Cancer and Bone Metastases: The Underlying Mechanisms. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102587"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s12011-018-1583-8","article-title":"The Impact of Trace Minerals on Bone Metabolism","volume":"188","year":"2019","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e372972","DOI":"10.1100\/2012\/372972","article-title":"Atomic Mineral Characteristics of Indonesian Osteoporosis by High-Resolution Inductively Coupled Plasma Mass Spectrometry","volume":"2012","author":"Noor","year":"2012","journal-title":"Sci. World J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1159\/000177774","article-title":"Impaired Mechanical Strength of Bone in Experimental Copper Deficiency","volume":"37","author":"Jonas","year":"1993","journal-title":"Ann. Nutr. Metab."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Rondanelli, M., Faliva, M.A., Infantino, V., Gasparri, C., Iannello, G., Perna, S., Riva, A., Petrangolini, G., Tartara, A., and Peroni, G. (2021). Copper as Dietary Supplement for Bone Metabolism: A Review. Nutrients, 13.","DOI":"10.3390\/nu13072246"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3556","DOI":"10.1002\/jbm.a.35032","article-title":"Effects of Cu-Doped 45S5 Bioactive Glass on the Lipid Peroxidation-Associated Growth of Human Osteoblast-like Cells in Vitro","volume":"102","author":"Milkovic","year":"2014","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_88","unstructured":"National Research Council (US) (1995). Subcommittee on Laboratory Animal Nutrition. Nutrient Requirements of Laboratory Animals: Fourth Revised Edition, National Academies Press (US)."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s00775-014-1216-4","article-title":"The Mammalian Molybdenum Enzymes of MARC","volume":"20","author":"Ott","year":"2015","journal-title":"J. Biol. Inorg. Chem. JBIC"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.chemosphere.2016.08.142","article-title":"Exploratory Analysis of the Potential Relationship between Urinary Molybdenum and Bone Mineral Density among Adult Men and Women from NHANES 2007\u20132010","volume":"164","author":"Lewis","year":"2016","journal-title":"Chemosphere"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/(SICI)1099-1263(199905\/06)19:3<185::AID-JAT555>3.0.CO;2-Z","article-title":"Assessment of Molybdenum Toxicity in Humans","volume":"19","author":"Vyskocil","year":"1999","journal-title":"J. Appl. Toxicol. JAT"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e5464373","DOI":"10.1155\/2016\/5464373","article-title":"Nutritional Aspects of Essential Trace Elements in Oral Health and Disease: An Extensive Review","volume":"2016","author":"Bhattacharya","year":"2016","journal-title":"Scientifica"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/BF01321835","article-title":"Molybdenum-Induced Changes in the Epiphyseal Growth Plate","volume":"53","author":"Parry","year":"1993","journal-title":"Calcif. Tissue Int."},{"key":"ref_94","first-page":"107","article-title":"Physiological and Genotoxic Effects of Molybdenum-Induced Copper Deficiency in Cattle","volume":"46","author":"Picco","year":"2012","journal-title":"Agrociencia"},{"key":"ref_95","first-page":"200","article-title":"The Importance of Mineral Elements for Humans, Domestic Animals and Plants\u2014A Review","volume":"4","author":"Soetan","year":"2010","journal-title":"Afr. J. Food Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.mam.2005.07.003","article-title":"Nutritional Aspects of Manganese Homeostasis","volume":"26","author":"Aschner","year":"2005","journal-title":"Mol. Asp. Med."},{"key":"ref_97","first-page":"34","article-title":"The Effects on Bone Cells of Metal Ions Released from Orthopaedic Implants. A Review","volume":"10","author":"Sansone","year":"2013","journal-title":"Clin. Cases Miner. Bone Metab."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"756","DOI":"10.3109\/17453674.2010.537806","article-title":"Cobalt Ions Induce Chemokine Secretion in a Variety of Systemic Cell Lines","volume":"81","author":"Devitt","year":"2010","journal-title":"Acta Orthop."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1002\/jbm.b.33734","article-title":"The Biological Response to Orthopaedic Implants for Joint Replacement: Part I: Metals","volume":"105","author":"Gibon","year":"2017","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1002\/jor.20837","article-title":"Cobalt Ions Induce Chemokine Secretion in Primary Human Osteoblasts","volume":"27","author":"Queally","year":"2009","journal-title":"J. Orthop. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2174\/1874325001004010221","article-title":"Significance of Elevated Blood Metal Ion Levels in Patients with Metal-on-Metal Prostheses: An Evaluation of Oxidative Stress Markers","volume":"4","author":"Tkaczyk","year":"2010","journal-title":"Open Orthop. J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1002\/jbm.a.32688","article-title":"Effect of Chromium and Cobalt Ions on the Expression of Antioxidant Enzymes in Human U937 Macrophage-like Cells","volume":"94A","author":"Tkaczyk","year":"2010","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3897","DOI":"10.1007\/s00018-015-1978-z","article-title":"2-Oxoglutarate-Dependent Dioxygenases Are Sensors of Energy Metabolism, Oxygen Availability, and Iron Homeostasis: Potential Role in the Regulation of Aging Process","volume":"72","author":"Salminen","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00394-011-0212-5","article-title":"Severe Nutritional Iron-Deficiency Anaemia Has a Negative Effect on Some Bone Turnover Biomarkers in Rats","volume":"51","author":"Campos","year":"2012","journal-title":"Eur. J. Nutr."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fphar.2017.00077","article-title":"Clinical Impact and Cellular Mechanisms of Iron Overload-Associated Bone Loss","volume":"8","author":"Jeney","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1093\/jn\/124.7.1060","article-title":"Spinal Bone Loss in Postmenopausal Women Supplemented with Calcium and Trace Minerals","volume":"124","author":"Strause","year":"1994","journal-title":"J. Nutr."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/(SICI)1520-670X(1996)9:3<87::AID-JTRA1>3.0.CO;2-E","article-title":"Copper Supplementation and the Maintenance of Bone Mineral Density in Middle-Aged Women","volume":"9","author":"Mcllrath","year":"1996","journal-title":"J. Trace Elem. Exp. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/sj.ejcn.1600763","article-title":"Effect of Dietary Copper Intakes on Biochemical Markers of Bone Metabolism in Healthy Adult Males","volume":"53","author":"Baker","year":"1999","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1017\/S0007114511002352","article-title":"Reported Zinc, but Not Copper, Intakes Influence Whole-Body Bone Density, Mineral Content and T Score Responses to Zinc and Copper Supplementation in Healthy Postmenopausal Women","volume":"106","author":"Nielsen","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.tox.2011.03.001","article-title":"Advances in Metal-Induced Oxidative Stress and Human Disease","volume":"283","author":"Jomova","year":"2011","journal-title":"Toxicology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.juro.2007.05.145","article-title":"Advanced but Not Localized Prostate Cancer Is Associated with Increased Oxidative Stress","volume":"178","author":"Yossepowitch","year":"2007","journal-title":"J. Urol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/pcan.2013.13","article-title":"Oxidative Stress in Prostate Cancer: Changing Research Concepts towards a Novel Paradigm for Prevention and Therapeutics","volume":"16","author":"Paschos","year":"2013","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"6082","DOI":"10.1158\/0008-5472.CAN-04-0838","article-title":"Growth and Survival Mechanisms Associated with Perineural Invasion in Prostate Cancer","volume":"64","author":"Ayala","year":"2004","journal-title":"Cancer Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/ijc.10866","article-title":"Serum Selenium and Risk of Prostate Cancer in U.S. Blacks and Whites","volume":"103","author":"Vogt","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e5944","DOI":"10.1097\/MD.0000000000005944","article-title":"Serum Selenium Levels and Prostate Cancer Risk: A MOOSE-Compliant Meta-Analysis","volume":"96","author":"Cui","year":"2017","journal-title":"Medicine"},{"key":"ref_116","first-page":"1431","article-title":"The Association between Selenium and Prostate Cancer: A Systematic Review and Meta-Analysis","volume":"19","author":"Sayehmiri","year":"2018","journal-title":"Asian Pac. J. Cancer Prev. APJCP"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/pros.22573","article-title":"Phase 3 Clinical Trial Investigating the Effect of Selenium Supplementation in Men at High-Risk for Prostate Cancer","volume":"73","author":"Algotar","year":"2013","journal-title":"Prostate"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1001\/jama.2011.1437","article-title":"Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)","volume":"306","author":"Klein","year":"2011","journal-title":"JAMA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.3390\/nu5041122","article-title":"Selenium and Prostate Cancer Prevention: Insights from the Selenium and Vitamin E Cancer Prevention Trial (SELECT)","volume":"5","author":"Nicastro","year":"2013","journal-title":"Nutrients"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"S40","DOI":"10.1301\/00296640260130722","article-title":"Micronutrient Malnutrition, Infection, and Immunity: An Overview","volume":"60","author":"Bhaskaram","year":"2002","journal-title":"Nutr. Rev."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1093\/jn\/132.4.674","article-title":"Selenite and Selenomethionine Promote HL-60 Cell Cycle Progression","volume":"132","author":"Zeng","year":"2002","journal-title":"J. Nutr."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"39428","DOI":"10.1074\/jbc.M305542200","article-title":"Cell Death Caused by Selenium Deficiency and Protective Effect of Antioxidants","volume":"278","author":"Saito","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1017\/S0007114509990195","article-title":"Acute Effects of Calcium Carbonate, Calcium Citrate and Potassium Citrate on Markers of Calcium and Bone Metabolism in Young Women","volume":"102","author":"Karp","year":"2009","journal-title":"Br. J. Nutr."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1210\/jc.2004-2451","article-title":"Effects of Potassium Alkali and Calcium Supplementation on Bone Turnover in Postmenopausal Women","volume":"90","author":"Sakhaee","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"256","DOI":"10.3109\/13685538.2013.819326","article-title":"Arsenic Exposure Associated with Decreased Bone Mineralization in Male","volume":"17","author":"Akbal","year":"2014","journal-title":"Aging Male"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.3899\/jrheum.100234","article-title":"Musculoskeletal Complications of Hereditary Hemochromatosis: A Case-Control Study","volume":"37","author":"Richette","year":"2010","journal-title":"J. Rheumatol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e288","DOI":"10.1016\/j.lpm.2017.05.037","article-title":"Genetic Hemochromatosis: Pathophysiology, Diagnostic and Therapeutic Management","volume":"46","author":"Brissot","year":"2017","journal-title":"Presse Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1002\/jbmr.1692","article-title":"Iron Overload Accelerates Bone Loss in Healthy Postmenopausal Women and Middle-Aged Men: A 3-Year Retrospective Longitudinal Study","volume":"27","author":"Kim","year":"2012","journal-title":"J. Bone Miner. Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/6\/1285\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:38:49Z","timestamp":1760135929000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/6\/1285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,18]]},"references-count":128,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["nu14061285"],"URL":"https:\/\/doi.org\/10.3390\/nu14061285","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2022,3,18]]}}}