Table 1.

Effect of antiresorptive medication on macrophages’ activity.

Bisphosphonates	Cellular Activity	Polarization	Protein Expression
THP1 cells	(↓) viability [33,52,53] (↓) migration [54] (↓) phagocytosis [54]	(↑) M1 (–) M2 [55] (↑) M1 (↓) M2 [16]	(↑) MMP9 (–) MMP2 [52]
RAW264.7 cells	(↓) viability [56] (↑) apoptosis [57] (↓) migration [58]		(↑) IL1 [59,60] (↑) (IL1b, IL6, TNFα,NO) [40]
BMDMs		(↑) M1 (↓) M2 [16]	(↑) (IL1b, IL6, TNFα) [61] (↑) IL1b [62] (↑) IL6 [63]
Mouse MRONJ models		(↑) M1 [16] (↑) M1\(↓) M2 [22] (↓) M2 [64]	(↑) (IL6, IL1b, caspase1) [60,62]
Human MRONJ tissue	(↓) differentiation [34]	(↑) M1 (↓) M2 [35] (↑) M1 [65]	(↑) IL6 (↓) IL10 [35]
Denosumab/ anti-RANKL
THP1 cells	(–) viability [33]
BMDMs	(–) viability [66] (–) number [67]		(–) IL10 (–)TGFb [67]
Mouse MRONJ models	(↓) wound healing [66,67] (–) differentiation [68,69] (↓) functionality [70]	(–) M1 (–) M2 [64] (↑) M1 (↑↑) * M2 [67]
Human MRONJ tissue		(↑) M1 (↓) M2 [35]	(↑) IL6 (↓) IL10 [35]

(↑ upregulation, ↓ downregulation, – neutral); * when mAb was discontinued; BMDM, Bone marrow-derived macrophages.