Risedronate Directly Inhibits Osteoclast Differentiation and Inflammatory Bone Loss

Abstract

Risedronate, a nitrogen-containing bisphosphonate, is widely used in the clinical field for the treatment of osteoporosis. Risedronate is known to exert its effects through binding to hydroxyapatite in bone tissue, inhibiting osteoclastic activity, and inducing apoptosis of osteoclasts. The purpose of this study was to determine the effects of risedronate on osteoclast differentiation in vitro and on an inflammatory bone loss model in vivo. Risedronate inhibited osteoclast differentiation in co-culture of bone marrow cells (BMCs) and osteoblasts, and suppressed receptor activator of nuclear factor (NF)-k kB ligand (RANKL)-mediated osteoclast differentiation from bone marrow-derived macrophages (BMMs) in a dose-dependent manner without toxicity. Risedronate significantly inhibited expression of c-Fos and nuclear factor of activated T cells (NFAT) c1 induced by RANKL. To examine the effect of risedronate on bone loss in vivo, we used a mouse model of lipopolysaccharide (LPS)-mediated bone loss. Micro-CT analysis of the femurs showed that LPS treatment caused bone loss. However, bone loss was significantly attenuated in mice administered with risedronate. Taken together, we conclude that risedronate exerts beneficial effects on osteoporosis by inhibiting osteoclast differentiation both directly and indirectly. In infectious conditions, the inhibitory effect of risedronate on bone erosion was excellent. Thus risedronate could be a treatment option for osteoporosis caused by inflammatory and infectious conditions.

Systemic treatment with strontium ranelate promotes tibial fracture healing in ovariectomized rats

“…Brennan et al [37] have recently reported that osteoblasts played key roles in the mechanisms of action of SR with increased secretion of OPG and diminished RANKL availability, which led to stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption. However, bisphosphonates produced its antiresorptive effect on osteoclasts directly and intensively, resulting in significantly decrease of osteoclast formation and function, even leading to apoptosis of osteoclast [38,39]. However, special attention should be paid to the anabolic action of SR.…”

Zoledronic acid inhibits RANK expression and migration of osteoclast precursors during osteoclastogenesis

“…In contrast, a recent study has shown that risedronate suppresses RANKL-induced osteoclastogenesis in co-cultures of mouse bone marrow cells (BMCs) with osteoblasts (Kwak et al 2009). Furthermore, fluorescent labeled risedronate analogs uptake by CD14-positive bone marrow monocytes such as osteoclast precursors (Roelofs et al 2010).…”

Dental Implant Surface Enhancement and Osseointegration

“…Bisphosphates are antiresorptive agents that have beneficial effects for the patients on preventing further bone loss, and their effects on increasing the bone mass is modest (Kwak et al, 2009, Yoshinari et al, 2002. It has been shown that bisphosphonate incorporated on to titanium implants increased bone density locally in the peri-implant region (Josse et al, 2005) with the effect of the antiresorptive drug limited to the vicinity of the implant.…”