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Clodronate
Eugene McCloskey1, Alexander H Paterson2, Trevor Powles3
1Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK; Centre for Integrated Research in Musculoskeletal Ageing (CIMA), Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK.
Bone
|October 31, 2020
Summary
Clodronate, an early bisphosphonate, effectively treats bone diseases like Paget's and multiple myeloma by inducing osteoclast apoptosis. Its unique mechanism and formulations offer significant clinical utility in various cancers and inflammatory conditions.
Area of Science:
- Pharmacology
- Oncology
- Immunology
Background:
- Clodronate, a first-generation bisphosphonate, exhibits potent anti-resorptive properties and a distinct mechanism of action compared to nitrogen-containing bisphosphonates.
- Its intracellular metabolism yields AppCCl2p, leading to mitochondrial dysfunction, impaired energy metabolism, and osteoclast apoptosis.
Purpose of the Study:
- To review the clinical utility and evolving applications of clodronate.
- To highlight its efficacy in treating various bone-related disorders and its role in macrophage depletion.
Main Methods:
- Review of pre-clinical studies utilizing liposomal clodronate for macrophage depletion in disease models.
- Analysis of clinical studies evaluating oral and injectable clodronate formulations for various oncological and bone conditions.
Main Results:
- Clodronate demonstrates significant clinical success in Paget's disease, hypercalcaemia, multiple myeloma, and breast cancer.
- Liposomal clodronate is a preferred agent for macrophage depletion in pre-clinical research.
- Oral clodronate exhibits a three-fold higher gastro-intestinal absorption rate compared to nitrogen-containing bisphosphonates.
Conclusions:
- Clodronate is a clinically valuable bisphosphonate with established efficacy in multiple bone-related diseases.
- Ongoing research explores novel therapeutic applications for clodronate in diverse medical and veterinary fields.
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