The Role of Geranylgeraniol in Managing Bisphosphonate-Related Osteonecrosis of the Jaw
Medication-related osteonecrosis of the jaw (ONJ) is a rare but significant adverse side effect of antiresorptive drugs. Bisphosphonate-related ONJ (BRONJ) is the most prevalent condition due to the extensive use of the drug in cancer and osteoporosis treatment. Nitrogen-containing bisphosphonates s...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.878556/full |
| _version_ | 1811234768821420032 |
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| author | Kok-Yong Chin Sophia Ogechi Ekeuku Anne Trias |
| author_facet | Kok-Yong Chin Sophia Ogechi Ekeuku Anne Trias |
| author_sort | Kok-Yong Chin |
| collection | DOAJ |
| description | Medication-related osteonecrosis of the jaw (ONJ) is a rare but significant adverse side effect of antiresorptive drugs. Bisphosphonate-related ONJ (BRONJ) is the most prevalent condition due to the extensive use of the drug in cancer and osteoporosis treatment. Nitrogen-containing bisphosphonates suppress osteoclastic resorption by inhibiting farnesyl pyrophosphate synthase in the mevalonate pathway, leading to deficiency of the substrate for GTPase prenylation. The bone remodelling process is uncoupled, subsequently impairing bone healing and causing ONJ. Targeted administration of geranylgeraniol (GGOH) represents a promising approach to mitigate BRONJ because GGOH is a substrate for GTPase prenylation. In the current review, the in vitro effects of GGOH on osteoclasts, osteoblasts and other related cells of the jaw are summarised. We also present and appraise the current in vivo evidence of GGOH in managing BRONJ in animal models. Lastly, several considerations of using GGOH in the clinical management of BRONJ are highlighted. As a conclusion, GGOH is a promising topical agent to manage BRONJ, pending more research on an effective delivery system and validation from a clinical trial. |
| first_indexed | 2024-04-12T11:41:09Z |
| format | Article |
| id | doaj.art-bdf90a5373f8411eac24b9ca49088e27 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T11:41:09Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-bdf90a5373f8411eac24b9ca49088e272022-12-22T03:34:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-05-011310.3389/fphar.2022.878556878556The Role of Geranylgeraniol in Managing Bisphosphonate-Related Osteonecrosis of the JawKok-Yong Chin0Sophia Ogechi Ekeuku1Anne Trias2Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, MalaysiaDepartment of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, MalaysiaAmerican River Nutrition, Hadley, MA, United StatesMedication-related osteonecrosis of the jaw (ONJ) is a rare but significant adverse side effect of antiresorptive drugs. Bisphosphonate-related ONJ (BRONJ) is the most prevalent condition due to the extensive use of the drug in cancer and osteoporosis treatment. Nitrogen-containing bisphosphonates suppress osteoclastic resorption by inhibiting farnesyl pyrophosphate synthase in the mevalonate pathway, leading to deficiency of the substrate for GTPase prenylation. The bone remodelling process is uncoupled, subsequently impairing bone healing and causing ONJ. Targeted administration of geranylgeraniol (GGOH) represents a promising approach to mitigate BRONJ because GGOH is a substrate for GTPase prenylation. In the current review, the in vitro effects of GGOH on osteoclasts, osteoblasts and other related cells of the jaw are summarised. We also present and appraise the current in vivo evidence of GGOH in managing BRONJ in animal models. Lastly, several considerations of using GGOH in the clinical management of BRONJ are highlighted. As a conclusion, GGOH is a promising topical agent to manage BRONJ, pending more research on an effective delivery system and validation from a clinical trial.https://www.frontiersin.org/articles/10.3389/fphar.2022.878556/fullangiogenesisbonegingival fibroblastosteoblastsosteoclasts |
| spellingShingle | Kok-Yong Chin Sophia Ogechi Ekeuku Anne Trias The Role of Geranylgeraniol in Managing Bisphosphonate-Related Osteonecrosis of the Jaw Frontiers in Pharmacology angiogenesis bone gingival fibroblast osteoblasts osteoclasts |
| title | The Role of Geranylgeraniol in Managing Bisphosphonate-Related Osteonecrosis of the Jaw |
| title_full | The Role of Geranylgeraniol in Managing Bisphosphonate-Related Osteonecrosis of the Jaw |
| title_fullStr | The Role of Geranylgeraniol in Managing Bisphosphonate-Related Osteonecrosis of the Jaw |
| title_full_unstemmed | The Role of Geranylgeraniol in Managing Bisphosphonate-Related Osteonecrosis of the Jaw |
| title_short | The Role of Geranylgeraniol in Managing Bisphosphonate-Related Osteonecrosis of the Jaw |
| title_sort | role of geranylgeraniol in managing bisphosphonate related osteonecrosis of the jaw |
| topic | angiogenesis bone gingival fibroblast osteoblasts osteoclasts |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.878556/full |
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