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While XLH is associated with dental implant\u2010related complications, no clinical or preclinical studies have investigated socket healing. XLH secondarily disrupts local mineral metabolism by increasing levels of the mineralization inhibitors, osteopontin (OPN) and inorganic pyrophosphate (PP\n                      <jats:sub>i<\/jats:sub>\n                      ). Tissue\u2010nonspecific alkaline phosphatase (TNAP) promotes mineralization by dephosphorylating OPN and hydrolyzing PP\n                      <jats:sub>i<\/jats:sub>\n                      . In this proof\u2010of\u2010principle study, we hypothesized that alveolar bone socket healing defects in the\n                      <jats:italic>Hyp<\/jats:italic>\n                      mouse model of XLH would be improved by exogenous TNAP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Maxillary first molars were extracted from wild\u2010type (WT) and\n                      <jats:italic>Hyp<\/jats:italic>\n                      mice at 6\u2009weeks, and collagen gel \u00b1 mineral\u2010targeted TNAP (TNAP\u2010Fc\u2010D\n                      <jats:sub>10<\/jats:sub>\n                      ; asfotase alfa) was placed in sockets. Submucosal injections of TNAP\u2010Fc\u2010D\n                      <jats:sub>10<\/jats:sub>\n                      or saline were delivered at 7 and 14\u2009days post\u2010procedure (dpp) in some mice. Maxillae were collected at 21 dpp for micro\u2010computed tomography, histology, and RT\u2010qPCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Untreated\n                      <jats:italic>Hyp<\/jats:italic>\n                      mice showed impaired socket healing compared to WT mice in bone volume and density. TNAP delivered at the time of extraction was unable to improve healing in\n                      <jats:italic>Hyp<\/jats:italic>\n                      mice. However, additional local TNAP delivery increased both alveolar bone volume and density in\n                      <jats:italic>Hyp<\/jats:italic>\n                      mice. Histology indicated repeated TNAP increased both woven and mature bone in\n                      <jats:italic>Hyp<\/jats:italic>\n                      mouse sockets. Immunostaining for osteopontin and bone sialoprotein suggested partial resolution of osteoid accumulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      TNAP enhanced socket healing in\n                      <jats:italic>Hyp<\/jats:italic>\n                      mice, overcoming inherent bone healing defects in XLH. These results provide new insights into bone healing with implications beyond alveolar bone in XLH.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jre.70044","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T21:10:28Z","timestamp":1759957828000},"page":"309-322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeted Alkaline Phosphatase Therapy Enhances Alveolar Bone Healing in X\u2010Linked Hypophosphatemia in Mice"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1848-0335","authenticated-orcid":false,"given":"Aonjittra","family":"Phanrungsuwan","sequence":"first","affiliation":[{"name":"Division of Biosciences, College of Dentistry The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bella","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Division of Biosciences, College of Dentistry The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1547-2671","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Mill\u00e1n","sequence":"additional","affiliation":[{"name":"Sanford Children's Health Research Center Sanford Burnham Prebys Medical Discovery Institute  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3444-0576","authenticated-orcid":false,"given":"Brian L.","family":"Foster","sequence":"additional","affiliation":[{"name":"Division of Biosciences, College of Dentistry The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010023\u201002882\u20104"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0031\u20103955(05)70485\u20105"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgz203"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE\u201008\u20100818"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE\u201015\u20100515"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ15\u20100275"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2023.116791"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.340"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.adaj.2024.05.016"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.688309"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41405\u2010024\u201000223\u20106"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198\u2010021\u201005997\u20101"},{"key":"e_1_2_12_14_1","volume-title":"GeneReviews((R))","author":"Laurent M. 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