Significance of bisphosphonates on angiogenesis in vivo and their effect under geranyl-geraniol addition — could it alter the treatment of bisphosphonate-associated necrosis of the jaw?

Are secondary effects of bisphosphonates on the vascular system of bone contributing to increased risk for atypical femoral fractures in osteoporosis?

“…[ 57,60 ] Thus, BP can potentially influence the functioning of EC cells during such treatment, directly or indirectly. Furthermore, BP can affect the activity and functionality of EC in vitro [ 19,61,62 ] and in vivo in a mouse model. [ 63 ] Interestingly, the nitrogen‐containing BP pamidronate and zoledronate affected the EC the greatest. [ 19 ] The effect of zoledronic acid on human EC has been reported to be reversed by exposure of the cells to epidermal growth factor, [ 64 ] and platelet‐derived growth factor‐BB [ 65 ] and extracellular vesicles (EV) from adipose tissue [ 66 ] were reported to reverse the effects of zoledronic acid on angiogenesis in rat models.…”

Bisphosphonate-Modified Functional Supramolecular Hydrogel Promotes Periodontal Bone Regeneration by Osteoclast Inhibition

“…Therefore, it is speculated that short-term or topical application of low doses of BP analogs can avoid the above adverse effects . Indeed, to achieve ideal bone repair, increasing studies have been implemented in recent years using BPs in combination with biomaterials for local application in bone tissue engineering, which not only effectively avoids the side effects associated with systemic application of BPs but also allows the formation of functional tissue engineering biomaterials to promote bone regeneration through their high osteoaffinity and the ability to inhibit bone resorption of BPs …”

“…14 Indeed, to achieve ideal bone repair, increasing studies have been implemented in recent years using BPs in combination with biomaterials for local application in bone tissue engineering, 15 which not only effectively avoids the side effects associated with systemic application of BPs but also allows the formation of functional tissue engineering biomaterials to promote bone regeneration through their high osteoaffinity and the ability to inhibit bone resorption of BPs. 16 In this study, a well-studied, biocompatible hydrogel, Nap-Gly-Phe-Phe (NapGFF), was chosen to facilely prepare the supramolecular hydrogel (Figure 1). Then, NapGFF (Nap) was covalently combined with alendronate (Alen), a medicine for osteoporosis, to form an acidic amphiphilic peptide gelator and was self-assembled into a supramolecular hydrogel, Nap-Alen.…”