Bisphosphonates (BPs) are the most used bone-specific anti-resorptive agents, often chosen as first-line
therapy in several
bone diseases characterized by an imbalance between osteoblast-mediated bone production and osteoclast-mediated
bone resorption. BPs target the
farnesyl pyrophosphate synthase (FPPS) in osteoclasts, reducing
bone resorption. Lately, there has been an increasing interest in BPs direct pro-survival/pro-mineralizing properties in osteoblasts and their
pain-relieving effects. Even so, molecular targets involved in these effects appear now largely elusive.
Ion channels are emerging players in bone homeostasis. Nevertheless, the effects of BPs on these
proteins have been poorly described. Here we reviewed the actions of BPs on
ion channels in musculoskeletal cells. In particular, the TRPV1 channel is essential for osteoblastogenesis. Since it is involved in bone
pain sensation, TRPV1 is a possible alternative target of BPs.
Ion channels are emerging targets and anti-target for
bisphosphonates.
Zoledronic acid can be the first selective musculoskeletal and vascular
KATP channel blocker targeting with high affinity the inward rectifier channels Kir6.1-SUR2B and Kir6.2-SUR2A. The action of this
drug against the overactive mutants of KCNJ9-ABCC9 genes observed in the
Cantu' Syndrome (CS) may improve the appropriate prescription in those CS patients affected by musculoskeletal disorders such as
bone fracture and bone
frailty.