{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:22:36Z","timestamp":1789474956814,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2016 2612"],"award-info":[{"award-number":["PICT 2016 2612"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005363","name":"University of Buenos Aires","doi-asserted-by":"publisher","award":["UBACyT 2020 0020190100015BA"],"award-info":[{"award-number":["UBACyT 2020 0020190100015BA"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Antihistamines and glucocorticoids (GCs) are often used together in the clinic to treat several inflammation-related situations. Although there is no rationale for this association, clinical practice has assumed that, due to their concomitant anti-inflammatory effects, there should be an intrinsic benefit to their co-administration. In this work, we evaluated the effects of the co-treatment of several antihistamines on dexamethasone-induced glucocorticoid receptor transcriptional activity on the expression of various inflammation-related genes in A549 and U937 cell lines. Our results show that all antihistamines potentiate GCs\u2019 anti-inflammatory effects, presenting ligand-, cell- and gene-dependent effects. Given that treatment with GCs has strong adverse effects, particularly on bone metabolism, we also examined the impact of antihistamine co-treatment on the expression of bone metabolism markers. Using MC3T3-E1 pre-osteoblastic cells, we observed that, though the antihistamine azelastine reduces the expression of dexamethasone-induced bone loss molecular markers, it potentiates osteoblast apoptosis. Our results suggest that the synergistic effect could contribute to reducing GC clinical doses, ineffective by itself but effective in combination with an antihistamine. This could result in a therapeutic advantage, as the addition of an antihistamine may reinforce the wanted effects of GCs, while related adverse effects could be diminished or at least mitigated. By modulating the patterns of gene activation\/repression mediated by GR, antihistamines could enhance only the desired effects of GCs, allowing their effective dose to be reduced. Further research is needed to correctly determine the clinical scope, benefits, and potential risks of this therapeutic strategy.<\/jats:p>","DOI":"10.3390\/cells10113026","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T10:33:09Z","timestamp":1636108389000},"page":"3026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Antihistamines Potentiate Dexamethasone Anti-Inflammatory Effects. Impact on Glucocorticoid Receptor-Mediated Expression of Inflammation-Related Genes"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3844-577X","authenticated-orcid":false,"given":"Carlos Daniel","family":"Zappia","sequence":"first","affiliation":[{"name":"Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Instituto de Investigaciones Farmacol\u00f3gicas (ININFA), Universidad de Buenos Aires, Buenos Aires 1113, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Torralba-Agu","sequence":"additional","affiliation":[{"name":"Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Instituto de Investigaciones Farmacol\u00f3gicas (ININFA), Universidad de Buenos Aires, Buenos Aires 1113, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliana","family":"Echeverria","sequence":"additional","affiliation":[{"name":"Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Instituto de Investigaciones Farmacol\u00f3gicas (ININFA), Universidad de Buenos Aires, Buenos Aires 1113, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos P.","family":"Fitzsimons","sequence":"additional","affiliation":[{"name":"Center for Neuroscience, Faculty of Science, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Instituto de Investigaciones Farmacol\u00f3gicas (ININFA), Universidad de Buenos Aires, Buenos Aires 1113, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Monczor","sequence":"additional","affiliation":[{"name":"Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Instituto de Investigaciones Farmacol\u00f3gicas (ININFA), Universidad de Buenos Aires, Buenos Aires 1113, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic Inflammation in the Etiology of Disease across the Life Span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Buttorff, C., Ruder, T., and Bauman, M. (2017). Multiple Chronic Conditions in the United States, RAND Corporation.","DOI":"10.7249\/TL221"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/sj.bjp.0706736","article-title":"How corticosteroids control inflammation: Quintiles prize lecture 2005","volume":"148","author":"Barnes","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.pharmthera.2011.12.004","article-title":"Maps and legends: The quest for dissociated ligands of the glucocorticoid receptor","volume":"134","author":"Clark","year":"2012","journal-title":"Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.steroids.2009.09.002","article-title":"The human glucocorticoid receptor: Molecular basis of biologic function","volume":"75","author":"Nicolaides","year":"2010","journal-title":"Steroids"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1056\/NEJMra050541","article-title":"Antiinflammatory action of glucocorticoids\u2014New mechanisms for old drugs","volume":"353","author":"Rhen","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2005.06.029","article-title":"Molecular determinants of crosstalk between nuclear receptors and toll-like receptors","volume":"122","author":"Ogawa","year":"2005","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/sj.emboj.7600919","article-title":"The GRIP1:IRF3 Interaction as a target for glucocorticoid receptor-mediated immunosuppression","volume":"25","author":"Reily","year":"2006","journal-title":"EMBO J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.coph.2010.04.007","article-title":"Targeting inflammation using selective glucocorticoid receptor modulators","volume":"10","author":"Haegeman","year":"2010","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nri2748","article-title":"Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells","volume":"10","author":"Glass","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1124\/mol.107.038794","article-title":"Separating transrepression and transactivation: A distressing divorce for the glucocorticoid receptor?","volume":"72","author":"Newton","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_12","first-page":"503","article-title":"Dissociated glucocorticoid receptor ligands: Compounds with an improved therapeutic index","volume":"6","author":"Rehwinkel","year":"2005","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1096\/fj.11-192112","article-title":"Glucocorticoid Receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages","volume":"26","author":"Kleiman","year":"2012","journal-title":"FASEB J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1172\/JCI28034","article-title":"Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy","volume":"117","author":"Tuckermann","year":"2007","journal-title":"J. Clin. Invest."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1172\/JCI60006","article-title":"Glucocorticoid receptor dimerization induces MKP1 to protect against TNF-induced inflammation","volume":"122","author":"Vandevyver","year":"2012","journal-title":"J. Clin. Invest."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"pe44","DOI":"10.1126\/scisignal.141pe44","article-title":"Acetylation of MKP-1 and the control of inflammation","volume":"1","author":"Chi","year":"2008","journal-title":"Sci. Signal"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4805","DOI":"10.1096\/fj.12-216382","article-title":"Mechanisms of the anti-inflammatory effects of glucocorticoids: Genomic and nongenomic interference with MAPK signaling pathways","volume":"26","author":"Ayroldi","year":"2012","journal-title":"FASEB J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1210\/en.2012-2045","article-title":"New insights into the anti-inflammatory mechanisms of glucocorticoids: An emerging role for glucocorticoid-receptor-mediated transactivation","volume":"154","author":"Vandevyver","year":"2013","journal-title":"Endocrinology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/nrendo.2013.183","article-title":"Glucocorticoid sensitivity in health and disease","volume":"9","author":"Quax","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1002\/jbmr.1688","article-title":"Selective Glucocorticoid receptor modulation maintains bone mineral density in mice","volume":"27","author":"Thiele","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1007\/s11914-007-0024-y","article-title":"The RANKL\/RANK\/OPG pathway","volume":"5","author":"Boyce","year":"2007","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/S8756-3282(02)00737-8","article-title":"Glucocorticoid-Induced osteopenia in the mouse as assessed by histomorphometry, microcomputed tomography, and biochemical markers","volume":"30","author":"McLaughlin","year":"2002","journal-title":"Bone"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1210\/endo.140.10.7034","article-title":"Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: Potential paracrine mechanisms of glucocorticoid-induced osteoporosis","volume":"140","author":"Hofbauer","year":"1999","journal-title":"Endocrinology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17476","DOI":"10.1038\/srep17476","article-title":"Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways","volume":"5","author":"Zappia","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00531","DOI":"10.1002\/prp2.531","article-title":"Azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model","volume":"7","author":"Zappia","year":"2019","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00530","DOI":"10.1002\/prp2.530","article-title":"Therapeutic utility of glucocorticoids and antihistamines cotreatment. Rationale and perspectives","volume":"7","author":"Zappia","year":"2019","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/325365a0","article-title":"Glucocorticoid receptor mutants that are constitutive activators of transcriptional enhancement","volume":"325","author":"Godowski","year":"1987","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3685","DOI":"10.4049\/jimmunol.0902230","article-title":"Gene-specific repression of proinflammatory cytokines in stimulated human macrophages by nuclear I\u03baB\u03b1","volume":"185","author":"Ghosh","year":"2010","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"32978","DOI":"10.1074\/jbc.M605935200","article-title":"Lipopolysaccharide-induced Cyclooxygenase-2 expression in human U937 macrophages is phosphatidic acid Phosphohydrolase-1-Dependent","volume":"281","author":"Grkovich","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0006-291X(88)80835-0","article-title":"The transcription of the interleukin 1 Beta Gene is induced with PMA and inhibited with dexamethasone in U937 cells","volume":"156","author":"Nishida","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5899","DOI":"10.1073\/pnas.0510996103","article-title":"Coordinated binding of NF-KappaB family members in the response of human cells to lipopolysaccharide","volume":"103","author":"Schreiber","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sharif, O., Bolshakov, V.N., Raines, S., Newham, P., and Perkins, N.D. (2007). Transcriptional profiling of the LPS induced NF-KappaB response in macrophages. BMC Immunol., 8.","DOI":"10.1186\/1471-2172-8-1"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.22203\/eCM.v024a01","article-title":"In search of an osteoblast cell model for in vitro research","volume":"24","author":"Czekanska","year":"2012","journal-title":"Eur. Cell. Mater."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"34431","DOI":"10.1074\/jbc.M400738200","article-title":"Mepyramine, a histamine H1 receptor inverse agonist, binds preferentially to a G protein-coupled form of the receptor and sequesters G protein","volume":"279","author":"Fitzsimons","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1124\/mol.60.5.1133","article-title":"Histamine H(1)-receptor activation of nuclear factor-Kappa B: Roles for G beta gamma- and G alpha(q\/11)-subunits in constitutive and agonist-mediated signaling","volume":"60","author":"Bakker","year":"2001","journal-title":"Mol. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1124\/jpet.106.118869","article-title":"In vitro pharmacology of clinically used central nervous system-active drugs as inverse H(1) receptor agonists","volume":"322","author":"Bakker","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"173913","DOI":"10.1016\/j.ejphar.2021.173913","article-title":"Biased agonism at histamine H1 receptor: Desensitization, internalization and MAPK activation triggered by antihistamines","volume":"896","author":"Burghi","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ejphar.2013.06.027","article-title":"Antihistaminergics and inverse agonism: Potential therapeutic applications","volume":"715","author":"Monczor","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1210\/en.2008-0863","article-title":"Kinetic complexity of the global response to glucocorticoid receptor action","volume":"150","author":"John","year":"2009","journal-title":"Endocrinology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1101\/gad.1564207","article-title":"Cell- and gene-specific regulation of primary target genes by the androgen receptor","volume":"21","author":"Bolton","year":"2007","journal-title":"Genes Dev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.molcel.2013.08.037","article-title":"Distinct properties of cell-type-specific and shared transcription factor binding sites","volume":"52","author":"Gertz","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13845","DOI":"10.1073\/pnas.2336092100","article-title":"Target-specific utilization of transcriptional regulatory surfaces by the glucocorticoid receptor","volume":"100","author":"Rogatsky","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"So, A.Y.-L., Chaivorapol, C., Bolton, E.C., Li, H., and Yamamoto, K.R. (2007). Determinants of cell- and gene-specific transcriptional regulation by the glucocorticoid receptor. PLoS Genet., 3.","DOI":"10.1371\/journal.pgen.0030094"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1677\/jme.0.0230255","article-title":"Nuclear receptors: Coactivators, Corepressors and chromatin remodeling in the control of transcription","volume":"23","author":"Collingwood","year":"1999","journal-title":"J. Mol. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3389\/fphar.2019.00214","article-title":"A model of glucocorticoid receptor interaction with coregulators predicts transcriptional regulation of target genes","volume":"10","author":"Monczor","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.mad.2004.06.010","article-title":"Mechanisms of glucocorticoid receptor signaling during inflammation","volume":"125","author":"Smoak","year":"2004","journal-title":"Mech. Ageing Dev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1365-2249.2007.03484.x","article-title":"Suppression of lipopolysaccharide- and tumour necrosis factor-alpha-induced interleukin (IL)-8 expression by glucocorticoids involves changes in IL-8 promoter acetylation","volume":"150","author":"Tsaprouni","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1101\/gad.827900","article-title":"The glucocorticoid receptor inhibits NF\u03baB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain","volume":"14","author":"Nissen","year":"2000","journal-title":"Genes Dev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6891","DOI":"10.1128\/MCB.20.18.6891-6903.2000","article-title":"Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1beta-induced histone H4 acetylation on lysines 8 and 12","volume":"20","author":"Ito","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1210\/me.2008-0257","article-title":"A novel mitogen-activated protein kinase phosphatase-1 and glucocorticoid receptor (GR) interacting protein-1-dependent combinatorial mechanism of gene transrepression by GR","volume":"23","author":"Cho","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"963","DOI":"10.4049\/jimmunol.163.2.963","article-title":"Lipopolysaccharide modulates cyclooxygenase-2 Transcriptionally and posttranscriptionally in human macrophages independently from endogenous IL-1 Beta and TNF-Alpha","volume":"163","author":"Tiraloche","year":"1999","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0163-7258(02)00297-8","article-title":"Mechanisms involved in the side effects of glucocorticoids","volume":"96","author":"Asadullah","year":"2002","journal-title":"Pharmacol. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.rdc.2015.08.005","article-title":"Glucocorticoid-induced osteoporosis","volume":"42","author":"Whittier","year":"2016","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1210\/er.2018-00097","article-title":"Glucocorticoids and bone: Consequences of Endogenous and exogenous excess and replacement therapy","volume":"39","author":"Hardy","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.2353\/ajpath.2009.080871","article-title":"Histamine promotes osteoclastogenesis through the differential expression of histamine receptors on osteoclasts and osteoblasts","volume":"174","author":"Baroukh","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"555","DOI":"10.2131\/jts.32.555","article-title":"A comparative study of histamine activities on differentiation of osteoblasts and osteoclasts","volume":"32","author":"Ikawa","year":"2007","journal-title":"J. Toxicol. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/j.amjmed.2008.06.036","article-title":"Antihistamine therapy and bone mineral density: Analysis in a population-based US sample","volume":"121","author":"Kinjo","year":"2008","journal-title":"Am. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"887","DOI":"10.5604\/17322693.1064029","article-title":"Histamine in regulation of bone remodeling processes","volume":"67","author":"Wiercigroch","year":"2013","journal-title":"Postepy Hig. Med. 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