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Considering zoledronate toxicity in surgical wounds and the capacity of calcium phosphate synthetic compounds to adsorb it, the aim of this work was to demonstrate and elucidate the mechanism underlying this adsorption. Methods: Four different calcium phosphate synthetic bone substitutes were used in this study: AdBone\u00ae BCP (0.5\u20131 mm), Guidor\u00ae easy-graft (0.5\u20131 mm), Maxresorb\u00ae (0.5\u20131 mm) and Maxresorb\u00ae (0.8\u20131.5 mm). The materials were incubated in aqueous zoledronate solutions. Samples of the solutions obtained after 1, 2, 3, 6, 24, 48, 72 and 120 h of conditioning were then analyzed by spectrophotometry to measure their absorbance and subsequently characterized by micro-elemental analysis. Results: All four materials demonstrated time-dependent zoledronate adsorption. AdBone\u00ae BCP achieved the most rapid and sustained sequestration, reaching 80% reduction at 24 h and stabilizing at 85% from 72 h onwards without re-release. Maxresorb\u00ae formulations showed comparable kinetics through 72 h (70\u201375%) but exhibited partial re-release at 120 h. Guidor\u00ae easy-graft showed negligible adsorption through the first 24 h, consistent with the physical barrier effect of its PLGA coating. Spectrophotometric findings were independently confirmed by elemental analysis. Conclusions: This work confirms zoledronate adsorption by calcium phosphate synthetic biomaterials. Among the tested materials, AdBone\u00ae BCP demonstrated the most favorable adsorption profile, with kinetics well matched to the critical window of alveolar wound healing. These findings support the use of biphasic calcium phosphate bone substitutes as a local strategy to reduce free zoledronate bioavailability at the surgical site, potentially lowering the risk of MRONJ in patients undergoing dentoalveolar procedures under bisphosphonate therapy.<\/jats:p>","DOI":"10.3390\/ph19081281","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:01:35Z","timestamp":1786640495000},"page":"1281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential Zoledronate Adsorption by Commercially Available Biphasic Calcium Phosphate Bone Substitutes"],"prefix":"10.3390","volume":"19","author":[{"given":"Siri","family":"Paulo","sequence":"first","affiliation":[{"name":"Institute of Endodontics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0689-6007","authenticated-orcid":false,"given":"Mafalda","family":"Laranjo","sequence":"additional","affiliation":[{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), University of Coimbra, 3000-354 Coimbra, Portugal"},{"name":"Institute of Biophysics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4185-7871","authenticated-orcid":false,"given":"Ana Margarida","family":"Abrantes","sequence":"additional","affiliation":[{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), University of Coimbra, 3000-354 Coimbra, Portugal"},{"name":"Institute of Biophysics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Jorge","family":"Teixo","sequence":"additional","affiliation":[{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), University of Coimbra, 3000-354 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8244-139X","authenticated-orcid":false,"given":"Diogo A.","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Mendes-Abreu","sequence":"additional","affiliation":[{"name":"Centro Hospitalar e Universit\u00e1rio de Coimbra, 3004-561 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Pedro","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Centro Hospitalar e Universit\u00e1rio de Coimbra, 3004-561 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-1650","authenticated-orcid":false,"given":"Maria Filomena","family":"Botelho","sequence":"additional","affiliation":[{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), University of Coimbra, 3000-354 Coimbra, Portugal"},{"name":"Institute of Biophysics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5968-6161","authenticated-orcid":false,"given":"Manuel Marques","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Institute of Endodontics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), University of Coimbra, 3000-354 Coimbra, Portugal"},{"name":"Laboratory for Evidence-Based Sciences and Precision Dentistry, University Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Mechanical Engineering, Materials and Processes-CEMMPRE, Chemical Engineering Department, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arm\u00e9nio","family":"Serra","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Faculty of Sciences and Technology, University of Coimbra, 3030-790 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ctrv.2011.09.003","article-title":"Direct and Indirect Anticancer Activity of Bisphosphonates: A Brief Review of Published Literature","volume":"38","author":"Gnant","year":"2012","journal-title":"Cancer Treat. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.drup.2005.07.001","article-title":"Metastases and Their Microenvironments: Linking Pathogenesis and Therapy","volume":"8","author":"Sierra","year":"2005","journal-title":"Drug Resist. Updates"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100470","DOI":"10.1016\/j.jbo.2023.100470","article-title":"Management of Bone Metastasis with Zoledronic Acid: A Systematic Review and Bayesian Network Meta-Analysis","volume":"39","author":"Lorange","year":"2023","journal-title":"J. Bone Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1038\/sj.bjc.6604382","article-title":"Risks and Benefits of Bisphosphonates","volume":"98","author":"Coleman","year":"2008","journal-title":"Br. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"115390","DOI":"10.1016\/j.bone.2020.115390","article-title":"Zoledronate","volume":"137","author":"Reid","year":"2020","journal-title":"Bone"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/jbmr.1494","article-title":"The Effect of 3 versus 6 Years of Zoledronic Acid Treatment of Osteoporosis: A Randomized Extension to the HORIZON-Pivotal Fracture Trial (PFT)","volume":"27","author":"Black","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1177\/1759720X13477714","article-title":"Bisphosphonate Drug Holiday: Who, When and How Long","volume":"5","author":"Diab","year":"2013","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.joms.2022.02.008","article-title":"American Association of Oral and Maxillofacial Surgeons\u2019 Position Paper on Medication-Related Osteonecrosis of the Jaws\u20142022 Update","volume":"80","author":"Ruggiero","year":"2022","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6551954","DOI":"10.1155\/mi\/6551954","article-title":"Taohong Siwu Decoction Regulates MSC-Mediated H-Type Angiogenesis to Accelerate Bone Fracture Healing Through VHL\/HIF-1\u03b1 Ubiquitination","volume":"2026","author":"Li","year":"2026","journal-title":"Mediat. Inflamm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.ijom.2015.01.026","article-title":"Treatment Strategies and Outcomes of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) with Characterization of Patients: A Systematic Review","volume":"44","author":"Fliefel","year":"2015","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1016\/j.jcms.2019.06.004","article-title":"Gingival Fibroblasts and Medication-Related Osteonecrosis of the Jaw: Results by Real-Time and Wound Healing in Vitro Assays","volume":"47","author":"Yuan","year":"2019","journal-title":"J. Cranio-Maxillofac. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s00784-017-2163-6","article-title":"The Effects of Ozone Application on Genotoxic Damage and Wound Healing in Bisphosphonate-Applied Human Gingival Fibroblast Cells","volume":"22","author":"Akdeniz","year":"2018","journal-title":"Clin. Oral Investig."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bullock, G., Miller, C.A., McKechnie, A., and Hearnden, V. (2021). A Review Into the Effects of Pamidronic Acid and Zoledronic Acid on the Oral Mucosa in Medication-Related Osteonecrosis of the Jaw. Front. Oral Health, 2.","DOI":"10.3389\/froh.2021.822411"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.2147\/DDDT.S456811","article-title":"Inflammation Can Be a High-Risk Factor for Mucosal Nonunion of MRONJ by Regulating SIRT1 Signaling When Treated with an Oncologic Dose of Zoledronate","volume":"18","author":"Zhu","year":"2024","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Paulo, S., Laranjo, M., Abrantes, A.M., Casalta-Lopes, J., Santos, K., Gon\u00e7alves, A.C., Paula, A.B., Marto, C.M., Sarmento-Ribeiro, A.B., and Carrilho, E. (2019). Synthetic Calcium Phosphate Ceramics as a Potential Treatment for Bisphosphonate-Related Osteonecrosis of the Jaw. Materials, 12.","DOI":"10.3390\/ma12111840"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bullock, G., Miller, C., McKechnie, A., and Hearnden, V. (2020). Synthetic Hydroxyapatite Inhibits Bisphosphonate Toxicity to the Oral Mucosa in Vitro. Materials, 13.","DOI":"10.3390\/ma13092086"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1248\/bpb.20.1183","article-title":"Osteotropic Drug Delivery System (ODDS) Based on Bisphosphonic Prodrug. V. Biological Disposition and Targeting Characteristics of Osteotropic Estradiol","volume":"20","author":"Fujisaki","year":"1997","journal-title":"Biol. Pharm. Bull."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3109\/10611869808995866","article-title":"Osteotropic Drug Delivery System (ODDS) Based on Bisphosphonic Prodrug. I.v. Effects of Osteotropic Estradiol on Bone Mineral Density and Uterine Weight in Ovariectomized Rats","volume":"5","author":"Fujisaki","year":"1998","journal-title":"J. Drug Target."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1002\/adma.200306340","article-title":"Chemically Modified Calcium Phosphates as Novel Materials for Bisphosphonate Delivery","volume":"16","author":"Josse","year":"2004","journal-title":"Adv. Mater."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.drudis.2010.05.003","article-title":"Calcium Phosphate Biomaterials as Bone Drug Delivery Systems: A Review","volume":"15","author":"Verron","year":"2010","journal-title":"Drug Discov. Today"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bigi, A., Boanini, E., Bigi, A., and Boanini, E. (2018). Calcium Phosphates as Delivery Systems for Bisphosphonates. J. Funct. Biomater., 9.","DOI":"10.3390\/jfb9010006"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.jct.2016.02.005","article-title":"Thermodynamic Study of the Interaction between Calcium and Zoledronic Acid by Calorimetry","volume":"97","author":"Sauzet","year":"2016","journal-title":"J. Chem. Thermodyn."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.actamat.2012.10.039","article-title":"Bioceramics for Drug Delivery","volume":"61","author":"Arcos","year":"2013","journal-title":"Acta Mater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115401","DOI":"10.1016\/j.colsurfb.2025.115401","article-title":"Injectable Carbon Nanotube-Reinforced Calcium Phosphate Bone Cements with High-Strength and Improved Osteogenesis for Bone Regeneration","volume":"260","author":"Wu","year":"2026","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Paulo, S., Laranjo, M., Paula, A., Abrantes, A.M., Martins, J., Marto, C.M., Coelho, A., Casalta-Lopes, J., Carvalho, L., and Carrilho, E. (2020). Calcium Phosphate Ceramics Can Prevent Bisphosphonate-Related Osteonecrosis of the Jaw. Materials, 13.","DOI":"10.3390\/ma13081955"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mikai, A., Ono, M., Tosa, I., Nguyen, H.T.T., Hara, E.S., Nosho, S., Kimura-Ono, A., Nawachi, K., Takarada, T., and Kuboki, T. (2020). BMP-2\/\u03b2-TCP Local Delivery for Bone Regeneration in MRONJ-Like Mouse Model. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197028"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16510","DOI":"10.1038\/s41598-022-20128-4","article-title":"Beta Tricalcium Phosphate, Either Alone or in Combination with Antimicrobial Photodynamic Therapy or Doxycycline, Prevents Medication-Related Osteonecrosis of the Jaw","volume":"12","author":"Hadad","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Tanaka, Y., Aung, K.T., Ono, M., Mikai, A., Dang, A.T., Hara, E.S., Tosa, I., Ishibashi, K., Ono-Kimura, A., and Nawachi, K. (2021). Suppression of Bone Necrosis around Tooth Extraction Socket in a MRONJ-like Mouse Model by E-RhBMP-2 Containing Artificial Bone Graft Administration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312823"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sacco, R., Sartoretto, S.C., de Brito Resende, R.F., de Albuquerque Calasans-Maia, J., Rossi, A.M., de Souza Lima, V.H., de Almeida Barros Mour\u00e3o, C.F., Granjeiro, J.M., Yates, J., and Calasans-Maia, M.D. (2022). The Use of Hydroxyapatite Loaded with Doxycycline (HADOX) in Dentoalveolar Surgery as a Risk-Reduction Therapeutic Protocol in Subjects Treated with Different Bisphosphonate Dosages. Medicina, 59.","DOI":"10.3390\/medicina59010046"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1177\/19433875211048367","article-title":"The Role of Bone Grafts in Preventing Medication-Related Osteonecrosis of the Jaw: Histomorphometric, Immunohistochemical, and Clinical Evaluation in Animal Model","volume":"15","author":"Balbas","year":"2022","journal-title":"Craniomaxillofac. Trauma Reconstr."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Dang, A.T., Ono, M., Wang, Z., Tosa, I., Hara, E.S., Mikai, A., Kitagawa, W., Yonezawa, T., Kuboki, T., and Oohashi, T. (2024). Local E-RhBMP-2\/\u03b2-TCP Application Rescues Osteocyte Dendritic Integrity and Reduces Microstructural Damage in Alveolar Bone Post-Extraction in MRONJ-like Mouse Model. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126648"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16032","DOI":"10.1038\/s41598-023-43315-3","article-title":"Impact of Beta-Tricalcium Phosphate on Preventing Tooth Extraction-Triggered Bisphosphonate-Related Osteonecrosis of the Jaw in Rats","volume":"13","author":"Funayama","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/xrs.2490","article-title":"Nitrogen Determination by SEM-EDS and Elemental Analysis","volume":"42","author":"Gazulla","year":"2013","journal-title":"X-Ray Spectrom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s10853-014-8685-2","article-title":"Performing Elemental Microanalysis with High Accuracy and High Precision by Scanning Electron Microscopy\/Silicon Drift Detector Energy-Dispersive X-Ray Spectrometry (SEM\/SDD-EDS)","volume":"50","author":"Newbury","year":"2015","journal-title":"J. Mater. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00198-007-0540-8","article-title":"Mechanisms of Action of Bisphosphonates: Similarities and Differences and Their Potential Influence on Clinical Efficacy","volume":"19","author":"Russell","year":"2008","journal-title":"Osteoporos. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.4065\/83.9.1032","article-title":"Bisphosphonates: Mechanism of Action and Role in Clinical Practice","volume":"83","author":"Drake","year":"2008","journal-title":"Mayo Clin. Proc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S8756-3282(99)00116-7","article-title":"Bisphosphonates: From the Laboratory to the Clinic and Back Again","volume":"25","author":"Russell","year":"1999","journal-title":"Bone"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.2174\/138161210793563635","article-title":"Bisphosphonates: Molecular Mechanisms of Action and Effects on Bone Cells, Monocytes and Macrophages","volume":"16","author":"Roelofs","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.bone.2010.11.008","article-title":"Biochemical and Molecular Mechanisms of Action of Bisphosphonates","volume":"49","author":"Rogers","year":"2011","journal-title":"Bone"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.addr.2012.01.008","article-title":"Calcium Phosphate Cements as Drug Delivery Materials","volume":"64","author":"Ginebra","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.actbio.2011.11.017","article-title":"Calcium Phosphate Ceramic Systems in Growth Factor and Drug Delivery for Bone Tissue Engineering: A Review","volume":"8","author":"Bose","year":"2012","journal-title":"Acta Biomater."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.addr.2012.07.009","article-title":"How Smart Do Biomaterials Need to Be? A Translational Science and Clinical Point of View","volume":"65","author":"Holzapfel","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7776","DOI":"10.1016\/j.biomaterials.2010.06.047","article-title":"In Vivo Bone Augmentation in an Osteoporotic Environment Using Bisphosphonate-Loaded Calcium de Fi Cient Apatite","volume":"31","author":"Verron","year":"2010","journal-title":"Biomaterials"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1054\/ijom.2002.0292","article-title":"Early Bone Healing Events in the Human Extraction Socket","volume":"31","author":"Devlin","year":"2002","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1007\/s10856-014-5218-0","article-title":"Adsorption on Apatitic Calcium Phosphates for Drug Delivery: Interaction with Bisphosphonate Molecules","volume":"25","author":"Pascaud","year":"2014","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_46","first-page":"813","article-title":"Influence of PH on Osteoclasts Treated with Zoledronate and Alendronate","volume":"23","author":"Arnett","year":"2018","journal-title":"Clin. Oral Investig."},{"key":"ref_47","first-page":"114","article-title":"The Healing Socket and Socket Regeneration","volume":"29","author":"Steiner","year":"2008","journal-title":"Compend. Contin. Educ. Dent."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"015005","DOI":"10.1088\/1748-6041\/7\/1\/015005","article-title":"The Chemical Composition of Synthetic Bone Substitutes Influences Tissue Reactions in Vivo: Histological and Histomorphometrical Analysis of the Cellular Inflammatory Response to Hydroxyapatite, Beta-Tricalcium Phosphate and Biphasic Calcium Phosphate Ceramics","volume":"7","author":"Ghanaati","year":"2012","journal-title":"Biomed. Mater."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4252","DOI":"10.1007\/s10853-017-1880-1","article-title":"Ab Initio Investigation of Adsorption Characteristics of Bisphosphonates on Hydroxyapatite (001) Surface","volume":"53","author":"Ri","year":"2018","journal-title":"J. Mater. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ijpharm.2013.01.031","article-title":"Drug Carriers in Osteoporosis: Preparation, Drug Encapsulation and Applications","volume":"445","author":"Miladi","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1016\/S0142-9612(00)00101-0","article-title":"Synthetic Biodegradable Polymers as Orthopedic Devices","volume":"21","author":"Middleton","year":"2000","journal-title":"Biomaterials"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1016\/j.biomaterials.2004.05.019","article-title":"Novel Biomaterials for Bisphosphonate Delivery","volume":"26","author":"Josse","year":"2005","journal-title":"Biomaterials"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1600-0714.1987.tb00674.x","article-title":"Evaluation of PH Changes in Inflammation of the Subcutaneous Air Pouch Lining in the Rat, Induced by Carrageenan, Dextran and Staphylococcus Aureus","volume":"16","year":"1987","journal-title":"J. Oral Pathol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hazehara-Kunitomo, Y., Hara, E.S., Ono, M., Aung, K.T., Komi, K., Pham, H.T., Akiyama, K., Okada, M., Oohashi, T., and Matsumoto, T. (2019). Acidic Pre-Conditioning Enhances the Stem Cell Phenotype of Human Bone Marrow Stem\/Progenitor Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051097"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/8\/1281\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T04:17:19Z","timestamp":1786767439000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/8\/1281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":54,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ph19081281"],"URL":"https:\/\/doi.org\/10.3390\/ph19081281","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]}}}