The Cellular and Mitochondrial Consequences of Mevalonate Pathway Inhibition by Nitrogen-Containing Bisphosphonates: A Narrative Review
Nitrogen-containing bisphosphonates (N-BPs) are commonly used drugs in the treatment of bone diseases due to their potent inhibition of the mevalonate pathway, leading to disrupted protein prenylation and reduced osteoclast activity. Although N-BPs are effective in reducing bone resorption, increasi...
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2025-07-01
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| author | Adrianna Budzinska Wieslawa Jarmuszkiewicz |
| author_facet | Adrianna Budzinska Wieslawa Jarmuszkiewicz |
| author_sort | Adrianna Budzinska |
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| description | Nitrogen-containing bisphosphonates (N-BPs) are commonly used drugs in the treatment of bone diseases due to their potent inhibition of the mevalonate pathway, leading to disrupted protein prenylation and reduced osteoclast activity. Although N-BPs are effective in reducing bone resorption, increasing evidence indicates their side effects on various non-skeletal cells. The aim of this review is to synthesize the current knowledge on the cellular and molecular effects of N-BPs outside the skeletal system, with particular emphasis on their impact on mitochondrial function and energy metabolism. At the cellular level, N-BPs may reduce viability, modulate inflammatory responses, trigger apoptosis, disrupt cytoskeletal organization, and influence signaling and energy metabolism. N-BPs may also impair the prenylation of proteins essential for mitochondrial dynamics and quality control, and may disrupt Ca<sup>2+</sup> homeostasis. As we have shown in endothelial cells, by inhibiting the mevalonate pathway, N-BPs may lead to a reduction in key components of the mitochondrial respiratory chain, such as coenzyme Q (CoQ) and <i>a</i>-heme. These effects can contribute to impaired mitochondrial respiratory function, increased oxidative stress, and mitochondria-dependent apoptosis, affecting cellular energy metabolism and viability. These findings underscore the multifaceted impact of N-BPs beyond bone, emphasizing the importance of mitochondrial health and energy metabolism in understanding their broader biological effects and potential adverse outcomes. |
| format | Article |
| id | doaj-art-753b5638deab41a5b40a3519ce15838c |
| institution | DOAJ |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-753b5638deab41a5b40a3519ce15838c2025-08-20T03:07:58ZengMDPI AGPharmaceuticals1424-82472025-07-01187102910.3390/ph18071029The Cellular and Mitochondrial Consequences of Mevalonate Pathway Inhibition by Nitrogen-Containing Bisphosphonates: A Narrative ReviewAdrianna Budzinska0Wieslawa Jarmuszkiewicz1Laboratory of Mitochondrial Biochemistry, Department of Bioenergetics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Collegium Biologicum, Uniwersytetu Poznanskiego 6, 61-614 Poznan, PolandLaboratory of Mitochondrial Biochemistry, Department of Bioenergetics, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Collegium Biologicum, Uniwersytetu Poznanskiego 6, 61-614 Poznan, PolandNitrogen-containing bisphosphonates (N-BPs) are commonly used drugs in the treatment of bone diseases due to their potent inhibition of the mevalonate pathway, leading to disrupted protein prenylation and reduced osteoclast activity. Although N-BPs are effective in reducing bone resorption, increasing evidence indicates their side effects on various non-skeletal cells. The aim of this review is to synthesize the current knowledge on the cellular and molecular effects of N-BPs outside the skeletal system, with particular emphasis on their impact on mitochondrial function and energy metabolism. At the cellular level, N-BPs may reduce viability, modulate inflammatory responses, trigger apoptosis, disrupt cytoskeletal organization, and influence signaling and energy metabolism. N-BPs may also impair the prenylation of proteins essential for mitochondrial dynamics and quality control, and may disrupt Ca<sup>2+</sup> homeostasis. As we have shown in endothelial cells, by inhibiting the mevalonate pathway, N-BPs may lead to a reduction in key components of the mitochondrial respiratory chain, such as coenzyme Q (CoQ) and <i>a</i>-heme. These effects can contribute to impaired mitochondrial respiratory function, increased oxidative stress, and mitochondria-dependent apoptosis, affecting cellular energy metabolism and viability. These findings underscore the multifaceted impact of N-BPs beyond bone, emphasizing the importance of mitochondrial health and energy metabolism in understanding their broader biological effects and potential adverse outcomes.https://www.mdpi.com/1424-8247/18/7/1029mevalonate pathwaymitochondrianitrogen-containing bisphosphonates |
| spellingShingle | Adrianna Budzinska Wieslawa Jarmuszkiewicz The Cellular and Mitochondrial Consequences of Mevalonate Pathway Inhibition by Nitrogen-Containing Bisphosphonates: A Narrative Review Pharmaceuticals mevalonate pathway mitochondria nitrogen-containing bisphosphonates |
| title | The Cellular and Mitochondrial Consequences of Mevalonate Pathway Inhibition by Nitrogen-Containing Bisphosphonates: A Narrative Review |
| title_full | The Cellular and Mitochondrial Consequences of Mevalonate Pathway Inhibition by Nitrogen-Containing Bisphosphonates: A Narrative Review |
| title_fullStr | The Cellular and Mitochondrial Consequences of Mevalonate Pathway Inhibition by Nitrogen-Containing Bisphosphonates: A Narrative Review |
| title_full_unstemmed | The Cellular and Mitochondrial Consequences of Mevalonate Pathway Inhibition by Nitrogen-Containing Bisphosphonates: A Narrative Review |
| title_short | The Cellular and Mitochondrial Consequences of Mevalonate Pathway Inhibition by Nitrogen-Containing Bisphosphonates: A Narrative Review |
| title_sort | cellular and mitochondrial consequences of mevalonate pathway inhibition by nitrogen containing bisphosphonates a narrative review |
| topic | mevalonate pathway mitochondria nitrogen-containing bisphosphonates |
| url | https://www.mdpi.com/1424-8247/18/7/1029 |
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