Zoledronate but not denosumab suppresses macrophagic differentiation of THP-1 cells. An aetiologic model of bisphosphonate-related osteonecrosis of the jaw (BRONJ)

Abstract

This is the first real-time study providing evidence for a dose-dependent immunosuppressive effect of zoledronate in contrast to denosumab on local macrophages.

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

“…Several publications have reported that N‐BPs can modulate the differentiation/function of immune cells with consequences on the inflammatory response. Macrophages (Hoefert et al, ) and T‐lymphocytes (Kalyan, Quabius, Wiltfang, Mönig, & Kabelitz, ) appear to be the most commonly‐affected immune cells but an impact on dendritic cells (Bringmann et al, ) and neutrophil granulocytes (Hagelauer, Pabst, Ziebart, Ulbrich, & Walter, ) has also been reported. The fact that patients treated with a combination of N‐BPs and immune modulator drugs such as Adalimumab (Preidl et al, ), Sunitinib (Hoefert & Eufinger, ), and aromatase inhibitors (Kourie et al, ) are evidence of enhanced frequency of BRONJ compared to patients treated simply that enforces the idea that immune modulation by N‐BPs may be implicated in the occurrence of side effects.…”

Plasticity of Myeloid Cells during Oral Barrier Wound Healing and the Development of Bisphosphonate-related Osteonecrosis of the Jaw

“…In bisphosphonate-treated rodent models, tooth extraction is associated with the development of osteonecrosis in the jawbone and prolonged chronic inflammation in oral barrier tissue (30,31). It has been indicated that bisphosphonates can be taken up by myeloid cells such as macrophages (32,33), dendritic cells (34), and neutrophils (35,36) and modulate their viability, migration, and function. This study addressed whether bisphosphonate-induced myeloid cell dysfunction might contribute to the pathological oral barrier immunity leading to the development of ONJ.…”

Surgery Combined with LPRF in Denosumab Osteonecrosis of the Jaw: Case Report

“…The search for medications with the same therapeutic effectiveness as the BP (bisphosphonates) but with fewer side effects has resulted in the discovery of Denosumab, which is a human monoclonal antibody to the receptor activator of nuclear factor kappa-B that inhibits the development and activity of osteoclasts by blocking the binding of RANKL to RANK, decreasing bone resorption, and increasing bone density (1,2).…”

“…This antiresorptive agent is a human monoclonal antibody of nuclear factor kappa-B ligand (RANKL) that inhibits the development and activity of osteoclasts by blocking the binding of RANKL to RANK, decreasing bone resorption and increasing bone density (1)(2)(3).…”