TABLE 5.

The effects of GGOH in vivo model of BRONJ.

Authors (years)	Study design	Major findings
Nagaoka et al. (2015)	Model: Male C57BL/6J mice of 6 weeks were injected with zoledronate (250 μg/kg) and LPS (250 μg/kg) (i.p.) twice a week. First maxillary molar was extracted after 2 weeks.	GGOH and GGPP ↑ bone mineral density, bone volume and TRAP + cells at the tooth-extracted socket caused by zoledronate + LPS.
	Treatment: GGOH (250 μg/kg) or GGPP (250 μg/kg) were injected together with zoledronate and LPS after tooth extraction for 4 weeks
Koneski et al. (2018)	Model: Male Wistar rats were given zoledronate (0.06 mg/kg) for 5 weeks and underwent first mandibular molar extraction	GGOH ↓ inflammation of soft tissue and bone defect
	Treatment: GGOH solution at the extraction socket at 5 mM for the last 2 weeks	Less rats treated with GGOH shows osteonecrosis in tissue adjacent to the extraction
		GGOH improves vascularity, tissue granulation, osteoblast lining and epithelial coverage and ↓ empty bone lacunae
Chen et al. (2021)	Model: male C57BL/6J mice (4 weeks old) were given zoledronate (250 μg/kg) twice a week (i.p.). One week after zoledronate treatment, the first maxillary molar was extracted	GGOH restores efferocytosis of macrophages on apoptotic cells by upregulating Rac1 homeostasis and expression in the membrane
	Treatment: GGOH (250 μg/kg) were injected twice a week together with zoledronate acid after tooth extraction for 4 weeks	GGOH ↓ osteocytic apoptosis at the alveolar crest and improved bone healing of sockets (new woven bone, periosteum at alveolar crest) in mice

Abbreviation↓, decrease; ↑, increase; i.p., intraperitoneal; GGPP, geranylgeranyl pyrophosphate; GGOH, geranylgeraniol; LPS, lipopolysaccharide.