2024 Volume 33 Issue 2 Pages 69-78
Fluvastatin (Flu) is a hydroxymethylglutaryl-CoA reductase inhibitor that reportedly has cholesterol-lowering and wound-healing effects, and has been shown to inhibit the onset of medication-related osteonecrosis of the jaw (MRONJ). However, measures are needed to prevent MRONJ caused by bone exposure during tooth extraction. Here, we examined the ability of locally applied, Flu-containing atelocollagen beads, which serve as a scaffold for sustained drug release, to prevent the onset of MRONJ in rats. MRONJ modeling was induced by the administration of an intravenous injection of zoledronic acid (ZOL) and extraction of the right maxillary M1 tooth from 8-week-old male rats. The rats were divided into three groups (n = 6 per group): the Flu group, which received local application of atelocollagen beads containing 1.5 mg/ml Flu to the tooth extraction socket; a phosphate-buffered saline control group; and an untreated control group. Macroscopic examination revealed that, in the Flu group, the bone exposure width of the tooth extraction socket was reduced and the mucosal covering was improved compared with the control groups. Histological examination of bone sections demonstrated that the numbers of empty bone lacunae were significantly reduced in the Flu group, suggesting an improvement in osteonecrosis. Immunohistological staining of bone sections showed ZOL-mediated elevations in osteoprotegerin (OPG) production and inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) expression in the control groups, whereas the Flu group showed elevations in both OPG and RANKL expression and higher numbers of vascular endothelial growth factor-positive cells. Furthermore, tartrate-resistant acid phosphate/alkaline phosphatase staining results were suggestive of improved bone remodeling function in the Flu group. These findings suggested that the sustained release of Flu from atelocollagen beads, applied locally at the tooth extraction socket, inhibited the onset of MRONJ and may be useful to prevent osteonecrosis of the jaw.
