{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:39:31Z","timestamp":1787067571986,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016070","name":"International Team for Implantology (ITI)","doi-asserted-by":"publisher","award":["1171_2016"],"award-info":[{"award-number":["1171_2016"]}],"id":[{"id":"10.13039\/501100016070","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Nitrogen-containing bisphosphonates lead to the depletion of geranylgeranyl pyrophosphate involved in the mevalonate pathway. The effect of geranylgeraniol (GGOH) on human osteoblast and osteoclast activities suppressed by zoledronate was investigated in this study. The effect of GGOH on human osteoblasts and osteoclasts subjected to treatment with zoledronate was analyzed by assessing cell viability, osteoclast differentiation, resorption ability, gene expression, and protein synthesis. Cell viability suppressed by bisphosphonates in osteoblasts and osteoprogenitor cells was restored with GGOH. Osteoclast differentiation was analyzed by vitronectin receptor immunofluorescence staining, and the addition of GGOH to zoledronate significantly increased osteoclast differentiation compared with zoledronate alone. A trend of reversal of osteoclast resorption by GGOH was observed; however, it was not significant in all groups. The expression of ALP, type 1 collagen, and RUNX2 in osteoblasts was recovered by the addition of GGOH. Only CALCR expression in osteoclasts was significantly recovered by GGOH addition in the zoledronate group. Although the activities of osteoblasts and osteoclasts were not entirely restored, the possibility that the topical application of GGOH in MRONJ patients or patients with dental problems and bisphosphonates might lessen the risk of development and recurrence of MRONJ is shown.<\/jats:p>","DOI":"10.3390\/life13061353","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T01:32:34Z","timestamp":1686274354000},"page":"1353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Geranylgeraniol Application in Human Osteoblasts and Osteoclasts for Reversal of the Effect of Bisphosphonates"],"prefix":"10.3390","volume":"13","author":[{"given":"Junho","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Oral & Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0653-2422","authenticated-orcid":false,"given":"Jung Soo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Korea University Anam Hospital, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeewan","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8665-5803","authenticated-orcid":false,"given":"Bilal","family":"Al-Nawas","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3296-7630","authenticated-orcid":false,"given":"Thomas","family":"Ziebart","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Hospital Giessen and Marburg of the Philipps University of Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9620-4814","authenticated-orcid":false,"given":"Yong-Dae","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Oral & Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.bone.2003.12.011","article-title":"A randomized clinical trial comparing oral alendronate and intravenous pamidronate for the treatment of Paget\u2019s disease of bone","volume":"34","author":"Walsh","year":"2004","journal-title":"Bone"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/jbmr.2999","article-title":"Outcome of Long-Term Bisphosphonate Therapy in McCune-Albright Syndrome and Polyostotic Fibrous Dysplasia","volume":"32","author":"Majoor","year":"2017","journal-title":"J. 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