{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:42:21Z","timestamp":1792885341522,"version":"4.5.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017834","name":"University of Connecticut Health Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017834","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000078","name":"Division of Materials Research","doi-asserted-by":"publisher","award":["2044870"],"award-info":[{"award-number":["2044870"]}],"id":[{"id":"10.13039\/100000078","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007710","name":"University of Connecticut","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017673","name":"National GEM Consortium","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017673","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Bone disease is highly prevalent in patients with chronic kidney disease (CKD), leading to an increased risk of bone fractures. This is due in part to metabolic acid-induced bone dissolution. Bisphosphonates (BPPs) are a potential treatment for inhibiting bone dissolution; however, there are limited studies observing the use of BPPs on acidotic patients. We aimed to determine efficacy of BPPs on maintaining bone health and pH regulation in acid-exposed mice. Using a diet-induced murine model of metabolic acidosis, we examined bone structure, composition, and mechanics as well as blood gases for three groups: control, acidosis, and acidosis + bisphosphonates (acidosis+BPP). Acidosis was induced for 14 days and alendronate was administered every 3 days for the acidosis+BPP group. The administration of BPP had little to no effect on bone structure, mechanics, and composition of the acidosis bones. However, administration of BPP did cause the mice to develop more severe acidosis than the acidosis only group. Overall, we discovered that BPPs may exacerbate acidosis symptoms by inhibiting the release of buffering ions from bone. Therefore, we propose that BPP administration should be carefully considered for those with CKD and that alkali supplementation could help minimize acidifying effects.<\/jats:p>","DOI":"10.1371\/journal.pone.0291649","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T17:36:00Z","timestamp":1694799360000},"page":"e0291649","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Administration of alendronate exacerbates ammonium chloride-induced acidosis in mice"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3306-7220","authenticated-orcid":true,"given":"Mikayla","family":"Moody","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tannin A.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchir","family":"Trivedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5187-4427","authenticated-orcid":true,"given":"Alix","family":"Deymier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,9,15]]},"reference":[{"key":"pone.0291649.ref001","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1002\/jbmr.1916","article-title":"Rapid cortical bone loss in patients with chronic kidney disease","volume":"28","author":"T.L. 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Med"},{"key":"pone.0291649.ref006","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1097\/MNH.0000000000000585","article-title":"Bisphosphonate therapy in CKD: the current state of affairs, Curr","volume":"29","author":"M.J. Damasiewicz","year":"2020","journal-title":"Opin. Nephrol. Hypertens"},{"key":"pone.0291649.ref007","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1007\/s00198-016-3861-7","article-title":"Efficacy and safety of osteoporosis medications in a rat model of late-stage chronic kidney disease accompanied by secondary hyperparathyroidism and hyperphosphatemia","volume":"28","author":"M. Ota","year":"2017","journal-title":"Osteoporos. Int"},{"key":"pone.0291649.ref008","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/nrneph.2010.33","article-title":"Metabolic acidosis: pathophysiology, diagnosis and management","volume":"6","author":"J.A. Kraut","year":"2010","journal-title":"Nat. Rev. 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Liu","year":"2023","journal-title":"Metabolites"},{"key":"pone.0291649.ref012","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.actbio.2020.11.033","article-title":"Effects of acidosis on the structure, composition, and function of adult murine femurs","volume":"121","author":"A.K. Peterson","year":"2021","journal-title":"Acta Biomater"},{"key":"pone.0291649.ref013","article-title":"Physiochemical dissolutions governs early modifications in acid-exposed murine bone with long-term recovery, Orthop","volume":"22","author":"M. Moody","year":"2023","journal-title":"Rheumatol. Open Access J"},{"key":"pone.0291649.ref014","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1210\/endo-119-1-119","article-title":"Effect of pH on bone resorption by rat osteoclasts in vitro","volume":"119","author":"T.R. Arnett","year":"1986","journal-title":"Endocrinology"},{"key":"pone.0291649.ref015","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/8756-3282(95)00486-6","article-title":"Modulation of the resorptive activity of rat osteoclasts by small changes in extracellular pH near the physiological range","volume":"18","author":"T.R. Arnett","year":"1996","journal-title":"Bone"},{"key":"pone.0291649.ref016","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.4065\/83.9.1032","article-title":"Bisphosphonates: Mechanism of Action and Role in Clinical Practice, Mayo Clin","volume":"83","author":"M.T. Drake","year":"2008","journal-title":"Proc. Mayo Clin"},{"key":"pone.0291649.ref017","unstructured":"National Research Council (US) Committee for the Update of the Guide for theCare and Use of Laboratory Animals, Guide for the Care and Use of Laboratory Animals, 8th ed., National Academies Press (US), Washington (DC), 2011. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK54050\/ (accessed January 24, 2023)."},{"key":"pone.0291649.ref018","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1007\/s11999-010-1692-y","article-title":"Raman Assessment of Bone Quality","volume":"469","author":"M.D. Morris","year":"2011","journal-title":"Clin. Orthop"},{"key":"pone.0291649.ref019","doi-asserted-by":"crossref","first-page":"7464","DOI":"10.1039\/D1AN01560E","article-title":"Compositional assessment of bone by Raman spectroscopy","volume":"146","author":"M. Unal","year":"2021","journal-title":"Analyst"},{"key":"pone.0291649.ref020","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.bone.2010.08.023","article-title":"BoneJ: Free and extensible bone image analysis in ImageJ","volume":"47","author":"M. Doube","year":"2010","journal-title":"Bone"},{"key":"pone.0291649.ref021","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1681\/ASN.2017040422","article-title":"Metabolic Acidosis and Subclinical Metabolic Acidosis in CKD, J","volume":"29","author":"K.L. Raphael","year":"2018","journal-title":"Am. Soc. Nephrol"},{"key":"pone.0291649.ref022","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.xkme.2021.03.012","article-title":"Eubicarbonatemic Hydrogen Ion Retention and CKD Progression","volume":"3","author":"N.E. Madias","year":"2021","journal-title":"Kidney Med"},{"key":"pone.0291649.ref023","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0272-6386(97)90045-7","article-title":"The clinical spectrum of chronic metabolic acidosis: homeostatic mechanisms produce significant morbidity","volume":"29","author":"R.J. Alpern","year":"1997","journal-title":"Am. J. Kidney Dis. Off. J. Natl. Kidney Found"},{"key":"pone.0291649.ref024","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1053\/j.ajkd.2015.08.028","article-title":"Metabolic Acidosis of CKD: An Update","volume":"67","author":"J.A. Kraut","year":"2016","journal-title":"Am. J. Kidney Dis"},{"key":"pone.0291649.ref025","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/ndt\/gfy054","article-title":"Hypercalcemia: etiology and management, Nephrol","volume":"33","author":"A.D. Renaghan","year":"2018","journal-title":"Dial. Transplant"},{"key":"pone.0291649.ref026","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1152\/ajplegacy.1960.198.5.1126","article-title":"Changes in bone sodium during acute acidosis in the rat","volume":"198","author":"W.H. Bergstrom","year":"1960","journal-title":"Am. J. Physiol.-Leg. Content"},{"key":"pone.0291649.ref027","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1359\/JBMR.050817","article-title":"Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: a pooled analysis of nine clinical trials","volume":"20","author":"P.D. Miller","year":"2005","journal-title":"J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res"},{"key":"pone.0291649.ref028","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/jdi.12944","article-title":"Alendronate improves fasting plasma glucose and insulin sensitivity, and decreases insulin resistance in prediabetic osteopenic postmenopausal women: A randomized triple\u2010blind clinical trial","volume":"10","author":"M. Karimi Fard","year":"2019","journal-title":"J. Diabetes Investig"},{"key":"pone.0291649.ref029","article-title":"The Use of Alendronate Is Associated with a Decreased Incidence of Type 2 Diabetes Mellitus\u2014A Population-Based Cohort Study in Taiwan","volume":"10","author":"D.-C. Chan","year":"2015","journal-title":"PLoS ONE"},{"key":"pone.0291649.ref030","first-page":"247","article-title":"Metabolic Acidosis-Induced Insulin Resistance and Cardiovascular Risk, Metab. Syndr","volume":"9","author":"G. Souto","year":"2011","journal-title":"Relat. Disord"},{"key":"pone.0291649.ref031","doi-asserted-by":"crossref","first-page":"E328","DOI":"10.1152\/ajpendo.1979.236.4.E328","article-title":"Glucose intolerance following chronic metabolic acidosis in man","volume":"236","author":"R.A. DeFronzo","year":"1979","journal-title":"Am. J. Physiol.-Endocrinol. Metab"},{"key":"pone.0291649.ref032","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/0026-0495(92)90185-D","article-title":"Insulin resistance in obesity is associated with elevated basal lactate levels and diminished lactate appearance following intravenous glucose and insulin","volume":"41","author":"J. Lovejoy","year":"1992","journal-title":"Metabolism"},{"key":"pone.0291649.ref033","doi-asserted-by":"crossref","DOI":"10.1136\/bmjdrc-2021-002300","article-title":"Management of type 2 diabetes in chronic kidney disease","volume":"9","author":"J.L. Triozzi","year":"2021","journal-title":"BMJ Open Diabetes Res. 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