<?xml version="1.0"?>
<doi_batch xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns="http://www.crossref.org/schema/4.4.0" xmlns:fr="http://www.crossref.org/fundref.xsd" xmlns:ct="http://www.crossref.org/clinicaltrials.xsd" xmlns:ai="http://www.crossref.org/AccessIndicators.xsd" xmlns:rel="http://www.crossref.org/relations.xsd" xmlns:jats="http://www.ncbi.nlm.nih.gov/JATS1" version="4.4.0" xsi:schemaLocation="http://www.crossref.org/schema/4.4.0 crossref4.4.0.xsd">
  <head>
    <doi_batch_id>TODENTJ-25-03-2019_TODENTJ-12-546</doi_batch_id>
    <timestamp>1553507420</timestamp>
    <depositor>
      <depositor_name>Bentham Open</depositor_name>
      <email_address>doi@benthamopen.net</email_address>
    </depositor>
    <registrant>Bentham Open</registrant>
  </head>
  <body>
    <journal>
      <journal_metadata language="en">
        <full_title>The Open Dentistry Journal</full_title>
        <abbrev_title>TODENTJ</abbrev_title>
        <issn media_type="print">1874-2106</issn>
      </journal_metadata>
      <journal_issue>
        <publication_date media_type="print">
          <month>7</month>
          <day>31</day>
          <year>2018</year>
        </publication_date>
        <journal_volume>
          <volume>12</volume>
        </journal_volume>
        <issue>1</issue>
      </journal_issue>
      <journal_article publication_type="full_text">
        <titles>
          <title>Evaluation of Effect of Low-Dose Methotrexate on Osseointegration of Implants: A Biomechanical Study on Dogs</title>
        </titles>
        <contributors>
          <person_name contributor_role="author" sequence="first">
            <given_name>Mohamad</given_name>
            <surname>Tavakoli</surname>
          </person_name>
          <person_name contributor_role="author" sequence="additional">
            <given_name>Jaber</given_name>
            <surname>Yaghini</surname>
          </person_name>
          <person_name contributor_role="author" sequence="additional">
            <given_name>Ahmad Moghare</given_name>
            <surname>abed</surname>
          </person_name>
          <person_name contributor_role="author" sequence="additional">
            <given_name>Meisam</given_name>
            <surname>Malekzadeh</surname>
          </person_name>
          <person_name contributor_role="author" sequence="additional">
            <given_name>Dina</given_name>
            <surname>Maleki</surname>
          </person_name>
        </contributors>
        <jats:abstract>
                <jats:sec>
                    <jats:title>Background:</jats:title>
                    <jats:p>Methotrexate (MTX) is an immunosuppressive drug, widely used in inflammatory disturbances including rheumatoid arthritis. However, there is no consensus regarding the effect of MTX on implant osseointegration.</jats:p>
                </jats:sec>
                <jats:sec>
                    <jats:title>Objective:</jats:title>
                    <jats:p>The purpose of this experimental study was to investigate the effect of low dose MTX on Bone-Implant Contact (BIC) of dogs.</jats:p>
                </jats:sec>
                <jats:sec>
                    <jats:title>Methods:</jats:title>
                    <jats:p>Six mandibular premolar teeth (bilateral) of 8 mature dogs were extracted. After 3 months of healing, 6 implants (bone level, resorbable blast media surface) were inserted into the mandible of each dog (3 in each side). Dogs were randomly divided into a study group (receiving 2.5 mg/week MTX orally, 3 times per week for 4 weeks) and a control group each containing 4 dogs. In the 1<jats:sup>st</jats:sup> week, postoperative BIC was evaluated in 4 dogs, two from each group. In the 4<jats:sup>th</jats:sup> week, reverse torque and BIC were evaluated in the remaining 4 dogs. Data were analyzed with two-way ANOVA test for 95% confidence interval.</jats:p>
                </jats:sec>
                <jats:sec>
                    <jats:title>Results:</jats:title>
                    <jats:p>The reverse torque test of the 4<jats:sup>th</jats:sup> week, showed a satisfying osseointegration. Histopathologic evaluation revealed that the BIC was significantly higher in the control group in comparison to the MTX group in the 1<jats:sup>st</jats:sup> and 4<jats:sup>th</jats:sup> week. In addition, the BIC of both groups were significantly increased in the 4<jats:sup>th</jats:sup> week in comparison to the 1<jats:sup>st</jats:sup> week in both groups.</jats:p>
                </jats:sec>
                <jats:sec>
                    <jats:title>Conclusion:</jats:title>
                    <jats:p>MTX has the potential to interfere with osseointegration process.</jats:p>
                </jats:sec>
            </jats:abstract>
        <publication_date>
          <month>7</month>
          <day>31</day>
          <year>2018</year>
        </publication_date>
        <pages>
          <first_page>546</first_page>
          <last_page>554</last_page>
        </pages>
        <publisher_item>
          <identifier id_type="sici">TODENTJ-12-546</identifier>
        </publisher_item>
        <crossmark>
          <crossmark_version>1</crossmark_version>
          <crossmark_policy>10.2174/crossmark_policy</crossmark_policy>
          <crossmark_domains>
            <crossmark_domain>
              <domain>opendentistryjournal.com</domain>
            </crossmark_domain>
            <crossmark_domain>
              <domain>benthamopen.com</domain>
            </crossmark_domain>
          </crossmark_domains>
          <crossmark_domain_exclusive>true</crossmark_domain_exclusive>
          <custom_metadata>
            <assertion name="review_status" label="Review Status" group_name="peer_review_details" group_label="Peer Review Details" order="0">Peer Reviewed</assertion>
            <assertion name="review_process" label="Review Process" group_name="peer_review_details" group_label="Peer Review Details" order="1">Single blind</assertion>
            <assertion name="screening_status" label="Screening Status" group_name="plagiarism_screening" group_label="Plagiarism Screening" order="0">Checked with iThenticate</assertion>
            <assertion name="received" label="Received" group_name="publication_history" group_label="Publication History" order="0">2018-4-14</assertion>
            <assertion name="revised" label="Revised" group_name="publication_history" group_label="Publication History" order="1">2018-6-20</assertion>
            <assertion name="accepted" label="Accepted" group_name="publication_history" group_label="Publication History" order="2">2018-7-16</assertion>
            <assertion name="published" label="Published" group_name="publication_history" group_label="Publication History" order="3">2018-7-31</assertion>
            <ai:program name="AccessIndicators">
              <ai:license_ref>https://creativecommons.org/licenses/by/4.0/legalcode</ai:license_ref>
            </ai:program>
          </custom_metadata>
        </crossmark>
        <doi_data>
          <doi>10.2174/1874210601812010546</doi>
          <timestamp>1553507420</timestamp>
          <resource>https://opendentistryjournal.com/VOLUME/12/PAGE/546/</resource>
          <collection property="crawler-based">
            <item crawler="google">
              <resource>https://opendentistryjournal.com/contents/volumes/V12/TODENTJ-12-546/TODENTJ-12-546.pdf</resource>
            </item>
            <item crawler="msn">
              <resource>https://opendentistryjournal.com/contents/volumes/V12/TODENTJ-12-546/TODENTJ-12-546.pdf</resource>
            </item>
            <item crawler="altavista">
              <resource>https://opendentistryjournal.com/contents/volumes/V12/TODENTJ-12-546/TODENTJ-12-546.pdf</resource>
            </item>
            <item crawler="yahoo">
              <resource>https://opendentistryjournal.com/contents/volumes/V12/TODENTJ-12-546/TODENTJ-12-546.pdf</resource>
            </item>
            <item crawler="scirus">
              <resource>https://opendentistryjournal.com/contents/volumes/V12/TODENTJ-12-546/TODENTJ-12-546.pdf</resource>
            </item>
            <item crawler="iParadigms">
              <resource>https://opendentistryjournal.com/contents/volumes/V12/TODENTJ-12-546/TODENTJ-12-546.pdf</resource>
            </item>
          </collection>
          <collection property="text-mining">
            <item>
              <resource mime_type="application/pdf">https://opendentistryjournal.com/contents/volumes/V12/TODENTJ-12-546/TODENTJ-12-546.pdf</resource>
            </item>
            <item>
              <resource mime_type="application/xml">https://opendentistryjournal.com/contents/volumes/V12/TODENTJ-12-546/TODENTJ-12-546.xml</resource>
            </item>
          </collection>
        </doi_data>
        <citation_list>
          <citation key="ref1">
            <journal_title>Periodontol. 2000</journal_title>
            <author>Bosshardt D.D.</author>
            <volume>73</volume>
            <first_page>22</first_page>
            <cYear>2017</cYear>
            <doi>10.1111/prd.12179</doi>
            <unstructured_citation>
                    Bosshardt DD, Chappuis V, Buser D. 
                    Osseointegration of titanium, titanium alloy and zirconia dental implants: Current knowledge and open questions. 
                    Periodontol 2000  
                    2017; 
                    73
                    (1)
                    : 22-40.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref2">
            <journal_title>J. Periodontol.</journal_title>
            <author>Trisi P.</author>
            <volume>74</volume>
            <first_page>945</first_page>
            <cYear>2003</cYear>
            <doi>10.1902/jop.2003.74.7.945</doi>
            <unstructured_citation>
                    Trisi P, Lazzara R, Rebaudi A, Rao W, Testori T, Porter SS. 
                    Bone-implant contact on machined and dual acid-etched surfaces after 2 months of healing in the human maxilla. 
                    J Periodontol  
                    2003; 
                    74
                    (7)
                    : 945-56.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref3">
            <journal_title>Int. J. Nanomedicine</journal_title>
            <author>Tan N.</author>
            <volume>12</volume>
            <first_page>5433</first_page>
            <cYear>2017</cYear>
            <doi>10.2147/IJN.S138615</doi>
            <unstructured_citation>
                    Tan N, Liu X, Cai Y, et al. 
                    The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs. 
                    Int J Nanomedicine  
                    2017; 
                    12
                    : 5433-42.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref4">
            <unstructured_citation>
                    Yaghini J, Moghareh Abed A, Izadi M, Birang R, Torabinia N, Tavakoli M. 
                    Effect of short-term steroid use (prednisolone) on bone healing around implants: An experimental study on dogs OHDM  
                    2017; 
                    16
                    (2)
                    : 1-4.
                    
                </unstructured_citation>
          </citation>
          <citation key="ref5">
            <journal_title>J. Indian Prosthodont. Soc.</journal_title>
            <author>Parithimarkalaignan S.</author>
            <volume>13</volume>
            <first_page>2</first_page>
            <cYear>2013</cYear>
            <doi>10.1007/s13191-013-0252-z</doi>
            <unstructured_citation>
                    Parithimarkalaignan S, Padmanabhan TV. 
                    Osseointegration: An update. 
                    J Indian Prosthodont Soc  
                    2013; 
                    13
                    (1)
                    : 2-6.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref6">
            <journal_title>Int. Orthop.</journal_title>
            <author>Başarir K.</author>
            <volume>33</volume>
            <first_page>855</first_page>
            <cYear>2009</cYear>
            <doi>10.1007/s00264-007-0490-y</doi>
            <unstructured_citation>
                    Başarir K, Erdemli B, Can A, Erdemli E, Zeyrek T. 
                    Osseointegration in arthroplasty: Can simvastatin promote bone response to implants? 
                    Int Orthop  
                    2009; 
                    33
                    (3)
                    : 855-9.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref7">
            <journal_title>Int. J. Oral Maxillofac. Surg.</journal_title>
            <author>Clementini M.</author>
            <volume>43</volume>
            <first_page>323</first_page>
            <cYear>2014</cYear>
            <doi>10.1016/j.ijom.2013.11.012</doi>
            <unstructured_citation>
                    Clementini M, Rossetti PH, Penarrocha D, Micarelli C, Bonachela WC, Canullo L. 
                    Systemic risk factors for peri-implant bone loss: A systematic review and meta-analysis. 
                    Int J Oral Maxillofac Surg  
                    2014; 
                    43
                    (3)
                    : 323-34.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref8">
            <journal_title>Int. J. Oral Maxillofac. Implants</journal_title>
            <author>Sugerman P.B.</author>
            <volume>17</volume>
            <first_page>191</first_page>
            <cYear>2002</cYear>
            <unstructured_citation>
                    Sugerman PB, Barber MT. 
                    Patient selection for endosseous dental implants: Oral and systemic considerations. 
                    Int J Oral Maxillofac Implants  
                    2002; 
                    17
                    (2)
                    : 191-201.
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref9">
            <journal_title>J. Periodontol.</journal_title>
            <author>Pablos A.B.</author>
            <volume>79</volume>
            <first_page>300</first_page>
            <cYear>2008</cYear>
            <doi>10.1902/jop.2008.070301</doi>
            <unstructured_citation>
                    Pablos AB, Ramalho SA, König B Jr, Furuse C, de Araújo VC, Cury PR. 
                    Effect of meloxicam and diclofenac sodium on peri-implant bone healing in rats. 
                    J Periodontol  
                    2008; 
                    79
                    (2)
                    : 300-6.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref10">
            <journal_title>Clin. Oral Implants Res.</journal_title>
            <author>Sakakura C.E.</author>
            <volume>18</volume>
            <first_page>34</first_page>
            <cYear>2007</cYear>
            <doi>10.1111/j.1600-0501.2006.01253.x</doi>
            <unstructured_citation>
                    Sakakura CE, Marcantonio E Jr, Wenzel A, Scaf G. 
                    Influence of cyclosporin A on quality of bone around integrated dental implants: A radiographic study in rabbits. 
                    Clin Oral Implants Res  
                    2007; 
                    18
                    (1)
                    : 34-9.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref11">
            <journal_title>Lancet</journal_title>
            <author>McInnes I.B.</author>
            <volume>389</volume>
            <first_page>2328</first_page>
            <cYear>2017</cYear>
            <doi>10.1016/S0140-6736(17)31472-1</doi>
            <unstructured_citation>
                    McInnes IB, Schett G. 
                    Pathogenetic insights from the treatment of rheumatoid arthritis. 
                    Lancet  
                    2017; 
                    389
                    (10086)
                    : 2328-37.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref12">
            <journal_title>Int. J. Clin. Rheumatol.</journal_title>
            <author>Kaltsonoudis E.</author>
            <volume>7</volume>
            <first_page>179</first_page>
            <cYear>2012</cYear>
            <doi>10.2217/ijr.12.10</doi>
            <unstructured_citation>
                    Kaltsonoudis E, Papagoras C, Droso A. 
                    Current and future role of methotrexate in the therapeutic armamentarium for rheumatoid arthritis. 
                    Int J Clin Rheumatol  
                    2012; 
                    7
                    (2)
                    : 179-89.
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref13">
            <journal_title>Arthritis Rheum.</journal_title>
            <author>May K.P.</author>
            <volume>37</volume>
            <first_page>201</first_page>
            <cYear>1994</cYear>
            <doi>10.1002/art.1780370208</doi>
            <unstructured_citation>
                    May KP, West SG, McDermott MT, Huffer WE. 
                    The effect of low-dose methotrexate on bone metabolism and histomorphometry in rats. 
                    Arthritis Rheum  
                    1994; 
                    37
                    (2)
                    : 201-6.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref14">
            <journal_title>J. Rheumatol.</journal_title>
            <author>El Miedany Y.M.</author>
            <volume>25</volume>
            <first_page>2083</first_page>
            <cYear>1998</cYear>
            <unstructured_citation>
                    El Miedany YM, Abubakr IH, El Baddini M. 
                    Effect of low dose methotrexate on markers of bone metabolism in patients with rheumatoid arthritis. 
                    J Rheumatol  
                    1998; 
                    25
                    (11)
                    : 2083-7.
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref15">
            <journal_title>J. Rheumatol.</journal_title>
            <author>Cranney A.B.</author>
            <volume>28</volume>
            <first_page>2395</first_page>
            <cYear>2001</cYear>
            <unstructured_citation>
                    Cranney AB, McKendry RJ, Wells GA, et al. 
                    The effect of low dose methotrexate on bone density. 
                    J Rheumatol  
                    2001; 
                    28
                    (11)
                    : 2395-9.
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref16">
            <journal_title>Clinics (São Paulo)</journal_title>
            <author>Carvas J.B.</author>
            <volume>66</volume>
            <first_page>1055</first_page>
            <cYear>2011</cYear>
            <doi>10.1590/S1807-59322011000600023</doi>
            <unstructured_citation>
                    Carvas JB, Pereira RMR, Bonfá E, et al. 
                    No deleterious effect of low dose methotrexate on titanium implant osseointegration in a rabbit model. 
                    Clinics (São Paulo)  
                    2011; 
                    66
                    (6)
                    : 1055-9.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref17">
            <journal_title>Curr. Opin. Rheumatol.</journal_title>
            <author>Braun J.</author>
            <volume>21</volume>
            <first_page>216</first_page>
            <cYear>2009</cYear>
            <doi>10.1097/BOR.0b013e328329c79d</doi>
            <unstructured_citation>
                    Braun J, Rau R. 
                    An update on methotrexate. 
                    Curr Opin Rheumatol  
                    2009; 
                    21
                    (3)
                    : 216-23.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref18">
            <journal_title>Rheumatology</journal_title>
            <author>Hider S.L.</author>
            <volume>46</volume>
            <first_page>1520</first_page>
            <cYear>2007</cYear>
            <doi>10.1093/rheumatology/kem147</doi>
            <unstructured_citation>
                    Hider SL, Bruce IN, Thomson W. 
                    The pharmacogenetics of methotrexate. 
                    Rheumatology  
                    2007; 
                    46
                    (10)
                    : 1520-4.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref19">
            <journal_title>Clin. Exp. Rheumatol.</journal_title>
            <author>Benedek T.G.</author>
            <volume>28</volume>
            <first_page>S3</first_page>
            <cYear>2010</cYear>
            <unstructured_citation>
                    Benedek TG. 
                    Methotrexate: From its introduction to non-oncologic therapeutics to anti-TNF-α. 
                    Clin Exp Rheumatol  
                    2010; 
                    28
                    (5)
                    (Suppl. 61)
                    : S3-8.
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref20">
            <journal_title>Head Face Med.</journal_title>
            <author>Annussek T.</author>
            <volume>8</volume>
            <first_page>26</first_page>
            <cYear>2012</cYear>
            <doi>10.1186/1746-160X-8-26</doi>
            <unstructured_citation>
                    Annussek T, Kleinheinz J, Thomas S, Joos U, Wermker K. 
                    Short time administration of antirheumatic drugs - methotrexate as a strong inhibitor of osteoblast’s proliferation in vitro. 
                    Head Face Med  
                    2012; 
                    8
                    : 26.
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref21">
            <journal_title>Am. J. Orthod.</journal_title>
            <author>Roberts W.E.</author>
            <volume>86</volume>
            <first_page>95</first_page>
            <cYear>1984</cYear>
            <doi>10.1016/0002-9416(84)90301-4</doi>
            <unstructured_citation>
                    Roberts WE, Smith RK, Zilberman Y, Mozsary PG, Smith RS. 
                    Osseous adaptation to continuous loading of rigid endosseous implants. 
                    Am J Orthod  
                    1984; 
                    86
                    (2)
                    : 95-111.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref22">
            <journal_title>Int. J. Oral Maxillofac. Implants</journal_title>
            <author>Johansson C.</author>
            <volume>2</volume>
            <first_page>69</first_page>
            <cYear>1987</cYear>
            <unstructured_citation>
                    Johansson C, Albrektsson T. 
                    Integration of screw implants in the rabbit: A 1-year follow-up of removal torque of titanium implants. 
                    Int J Oral Maxillofac Implants  
                    1987; 
                    2
                    (2)
                    : 69-75.
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref23">
            <journal_title>Clin. Oral Implants Res.</journal_title>
            <author>Johansson C.B.</author>
            <volume>2</volume>
            <first_page>24</first_page>
            <cYear>1991</cYear>
            <doi>10.1034/j.1600-0501.1991.020103.x</doi>
            <unstructured_citation>
                    Johansson CB, Albrektsson T. 
                    A removal torque and histomorphometric study of commercially pure niobium and titanium implants in rabbit bone. 
                    Clin Oral Implants Res  
                    1991; 
                    2
                    (1)
                    : 24-9.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref24">
            <journal_title>Eur. Cell. Mater.</journal_title>
            <author>Pearce A.I.</author>
            <volume>13</volume>
            <first_page>1</first_page>
            <cYear>2007</cYear>
            <doi>10.22203/eCM.v013a01</doi>
            <unstructured_citation>
                    Pearce AI, Richards RG, Milz S, Schneider E, Pearce SG. 
                    Animal models for implant biomaterial research in bone: A review. 
                    Eur Cell Mater  
                    2007; 
                    13
                    (13)
                    : 1-10.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref25">
            <journal_title>Mod. Rheumatol.</journal_title>
            <author>Suematsu A.</author>
            <volume>17</volume>
            <first_page>17</first_page>
            <cYear>2007</cYear>
            <doi>10.3109/s10165-006-0531-1</doi>
            <unstructured_citation>
                    Suematsu A, Tajiri Y, Nakashima T, et al. 
                    Scientific basis for the efficacy of combined use of antirheumatic drugs against bone destruction in rheumatoid arthritis. 
                    Mod Rheumatol  
                    2007; 
                    17
                    (1)
                    : 17-23.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref26">
            <journal_title>Mod. Rheumatol.</journal_title>
            <author>Torikai E.</author>
            <volume>16</volume>
            <first_page>350</first_page>
            <cYear>2006</cYear>
            <doi>10.3109/s10165-006-0517-z</doi>
            <unstructured_citation>
                    Torikai E, Kageyama Y, Takahashi M, Nagano A. 
                    The effect of methotrexate on bone metabolism markers in patients with rheumatoid arthritis. 
                    Mod Rheumatol  
                    2006; 
                    16
                    (6)
                    : 350-4.
                    
                    
                    
                </unstructured_citation>
          </citation>
          <citation key="ref27">
            <journal_title>J. Rheumatol.</journal_title>
            <author>Uehara R.</author>
            <volume>28</volume>
            <first_page>251</first_page>
            <cYear>2001</cYear>
            <unstructured_citation>
                    Uehara R, Suzuki Y, Ichikawa Y. 
                    Methotrexate (MTX) inhibits osteoblastic differentiation in vitro: Possible mechanism of MTX osteopathy. 
                    J Rheumatol  
                    2001; 
                    28
                    (2)
                    : 251-6.
                    
                    
                </unstructured_citation>
          </citation>
        </citation_list>
      </journal_article>
    </journal>
  </body>
</doi_batch>
