{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:42:33Z","timestamp":1785426153756,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022881","name":"American River Nutrition","doi-asserted-by":"crossref","award":["FF-2024-261"],"award-info":[{"award-number":["FF-2024-261"]}],"id":[{"id":"10.13039\/100022881","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100022881","name":"American River Nutrition","doi-asserted-by":"crossref","award":["FF-2024-262"],"award-info":[{"award-number":["FF-2024-262"]}],"id":[{"id":"10.13039\/100022881","id-type":"DOI","asserted-by":"crossref"}]},{"award":["FF-2024-261"],"award-info":[{"award-number":["FF-2024-261"]}],"id":[{"id":"https:\/\/ror.org\/03ntmq932","id-type":"ROR","asserted-by":"publisher"}]},{"award":["FF-2024-262"],"award-info":[{"award-number":["FF-2024-262"]}],"id":[{"id":"https:\/\/ror.org\/03ntmq932","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Geranylgeraniol (GGOH), an isoprenoid intermediate of the mevalonate pathway, regulates bone cell viability and function, particularly by mitigating cellular toxicity induced by nitrogen-containing bisphosphonates (N-BPs). Despite this, its role in osteoporosis remains underexplored. This scoping review synthesises evidence on the effects of GGOH in in vitro and in vivo models of osteoporosis. Methods: PubMed, Scopus, and Ovid were searched using GGOH- and osteoporosis-related terms. Primary studies evaluating GGOH exposure in cellular or animal osteoporosis models were eligible. Twenty-nine studies met the inclusion criteria. Results: In vitro findings demonstrate that GGOH reverses N-BP-induced depletion of geranylgeranyl pyrophosphate, restoring protein prenylation which is essential for osteoclast and osteoblast survival, cytoskeletal organisation, and differentiation. GGOH reduced osteoclast apoptosis, restored nuclear factor of activated T-cells 1 and carbonic anhydrase II expression, and prevented N-BP-associated suppression of bone resorption. In osteoblasts and mesenchymal stem cells, GGOH improved viability, upregulated osteogenic markers including runt-related transcription factor 2, alkaline phosphatase, collagen type I, and bone morphogenetic proteins, and rescued mineralisation impaired by alendronate or zoledronate. Independent of N-BPs, GGOH exerted divergent effects on osteoclasts, by inhibiting osteoclastogenesis or promoting retinoic acid receptor-mediated bone resorption and attenuating zoledronate protection in vascular calcification settings in a model-specific manner. In vivo, dietary GGOH supplementation improved trabecular and cortical bone parameters and reduced serum C-terminal telopeptide of type I collagen in obese mice, indicating suppression of bone resorption. Conclusions: Overall, although GGOH shows osteoprotective potential, its capacity to antagonise N-BP efficacy limits systemic co-administration. Current evidence suggests that local delivery may warrant future investigation as a strategy to mitigate N-BP-induced skeletal toxicity. However, studies evaluating bone tissue exposure, pharmacokinetics, and clinically achievable concentrations are required before this approach can be translated.<\/jats:p>","DOI":"10.3390\/ph19071117","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:18:31Z","timestamp":1784553511000},"page":"1117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Geranylgeraniol as a Modulator of Mevalonate Pathway Disruption: A Scoping Review of Cellular Mechanisms and Skeletal Outcomes in Osteoporosis Models"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-4592","authenticated-orcid":false,"given":"Sophia Ogechi","family":"Ekeuku","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Farhan Abed","family":"Al Salman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6254-5132","authenticated-orcid":false,"given":"Nur Vaizura","family":"Mohamad","sequence":"additional","affiliation":[{"name":"Centre for Drug & Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1184-4551","authenticated-orcid":false,"given":"Sok Kuan","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6628-1552","authenticated-orcid":false,"given":"Kok-Yong","family":"Chin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.9734\/jpri\/2024\/v36i117603","article-title":"Emerging Protein and Peptide Therapeutics for Osteoporosis: Advances in Anabolic and Catabolic Treatments","volume":"36","author":"Kuril","year":"2024","journal-title":"J. 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