Bisphosphonates: therapeutics potential and recent advances in drug delivery

Abstract

Context: Bisphosphonates (BPs) are widely used for prevention and treatment of osteoporosis. BPs are known as gold standard for osteoporosis (OP) treatment due to their positive results in clinical studies. But some serious side effects are associated with BPs like gastrointestinal adverse effect i.e. esophagitis and ulcer of esophagus. Oral bioavailability (BA) of BPs ranges from 0.6 to 1% due to poor absorption through gastrointestinal tract (GIT). Objective: The main objective of this review is to explore the role of novel drug delivery systems (DDSs) for the delivering of BPs and minimizing the drawbacks associated with them. Methods: The current review is focusing on classification, mechanism of action, and limitations of BPs, and is also dwelling on the use of novel DDSs like nanoparticles, liposomes, topical, transdermal systems, implants, bisphosphonate osteotropic DDS (BP-ODDS), microspheres, and calcium phosphate cements (CPCs) for BPs. This review also gives a critically reviewed compilation of the various in vitro and in vivo studies conducted till date. Conclusion: On the basis of the exhaustive literature, it has been found that the novel DDS minimizes the side effects associated with BPs and enhances the BA. The advance drug delivery has a greater impact on reducing the undesirable effects and increasing the BA of BPs.

The underlying pathophysiology and therapeutic approaches for osteoporosis

“…Chemically, bisphosphonates are inorganic pyrophosphatase, which inhibit the dissolution of HA crystals and inhibit calcification and HA breakdown . These are considered a gold standard for fracture prevention across the world .…”

“…Thus, targeted delivery system to attain higher drug delivery efficiency, improved therapeutic efficacy in target cells/tissue, and minimize off‐target effects can be achieved with the help of nanoformulations . Controlled drug release is another aspect of nonomedicines, which can overcome the problem of premature degradation of drug, for example, the oral administration of bisphosphonates has been associated with mucosal damage and erosive esophagitis …”

Paradoxical side effects of bisphosphonates on the skeleton: What do we know and what can we do?

“…Limiting the use of systemic diffusion of active N‐BPs with local administration is the leitmotiv of these strategies. Implants covered with BPs (Fazil, Baboota, Sahni, Ameeduzzafar, & Ali, ) and sponges (Yang et al, ) or matrices (Jakobsen et al, ) full of N‐BPs have been shown to be an efficient strategy for minimizing side effects. An alternative strategy was using carriers for local delivery of active N‐BPs (Fazil et al, ).…”

Efficacy of Denosumab for Osteoporosis in Three Female Patients with Osteogenesis Imperfecta

“…Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor κB ligand (RANKL) that blocks its binding to RANK (Fazil et al 2015). Through the inhibition of RANKL, the drug has been shown to decrease bone resorption, increase BMD, and reduce the risk of fractures in postmenopausal women with osteoporosis (Lewiecki et al 2007;Bone et al 2011;McClung et al 2012).…”