Table 5.

In vivo studies evaluating the impact of a combination of local and systemic statin administration on periodontal wound healing.

Local + systemic drug delivery
Reference	Experimental periodontitis induction model (i) Animal (ii) Method (iii) Site	Periodontitis treatment (i) Type of treatment (ii) Type and dose of statin (iii) Mode and time of statin delivery	Results	Periodontal considerations
[57]	Rats (male) EIP by ligature mandibular M1	Nonsurgical treatment (therapeutic) Atorvastatin Systemically (5 mg/kg in a volume of 0.5 mL) and locally (0.1 mg/kg in a volume of 0.05 mL) at a dose of 0.1 mg/kg in a volume of 0.05 mL	↗ alveolar bone area % ↗ VEGF ↘ MMP-9 ↘ alveolar bone and attachment loss Local application showed better results on periodontium healing	Atorvastatin increased the alveolar bone regeneration while decreasing the periodontal inflammation and attachment loss
[92]	Rats (female ovarectomized) EIP by ligatures Maxillary M1 and M2 bilaterally	Nonsurgical treatment (therapeutic) Simvastatin Local injection (0.8 mg/0.05 mL) Oral (25 mg/kg) For two months until euthanasia	↗ alveolar crest height (28% with local & oral and 27% with local) ↗ BV/TV ↗ trabecular thickness ↘ trabecular separation	Simvastatin reduced bone degradation when administered locally, systemically, or both locally and systemically together

The animals included in the studies are healthy unless stated otherwise. Treatment was considered (1) “preventative” when it started at least one day before the start of EIP/ACP induction, (ii) “protective” when it started the same day as that of EIP/ACP induction, and (iii) “therapeutic” when it started at least one day after the start of EIP/ACP induction.