Geranylgeraniol as a Modulator of Mevalonate Pathway Disruption: A Scoping Review of Cellular Mechanisms and Skeletal Outcomes in Osteoporosis Models
Abstract
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…
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Evidence Hub reads this as a review, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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