Abstract
Importance of the field: Bisphosphonates (BPs), structurally similar to pyrophosphates and functionally superior in restraining osteoclast-induced bone resorption, have been widely used as clinical drugs in the treatment of osteoporosis, bone voids and associated inflammation. However, owing to their high aqueous solubility and the consequently high rate of loss during oral administration, the loading and targeting of BPs pose major challenges in practice. Alternative delivery routes such as nasal, subcutaneous/intramuscular injection have contributed little to improving the bioavailiability and efficacy of BPs. To improve and optimize the delivery efficiency and efficacy of BPs, numerous strategies have been developed and adopted. Studies on controlled release of BPs provide important information on the fabrication of BP delivery systems for in situ treatment. As BPs play an important therapeutic role in osteoporosis and similar diseases, it has become essential and vital to survey various reported fabrication methodologies of these systems and the consequential orthopedic treatments so as to keep abreast with advances in their clinical use.Areas covered in this review: Transplantable delivery systems for controlled release of BP are reviewed from literature published since 2000. The fabrication pathways and the release of BPs from various material systems are discussed in case studies. Recent progress in CaP models based on the strong and specific chelation between BPs and calcium phosphate crystals is highlighted.What the reader will gain: This review offers an outline of the advances in BP controlled release and delivery systems for orthopedic therapy.Take home message: Understanding the cutting-edge BP controlled release and delivery systems for in situ treatment is key to the successful design of a more promising and perfect delivery system for orthopedic therapy. Moreover, developing such delivery systems incorporating the numerous advantages of BPs and controlled release environment requires substantially more flexible models to control better the fate of BP drugs.
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