Lithium chloride assuages bone loss in experimental periodontitis in estrogen-deficient rats

Objectives Evidence shows that lithium, a medication commonly used for bipolar disorder treatment, presents bone anabolic activity. This study evaluated the effects of lithium chloride on periodontitis-induced bone loss (BL) and on intact alveolar bone during estrogen sufficiency and deficiency. Materials and methods Rats (24/group) received sham surgery plus water (estrogen-sufficient group), ovariectomy plus water (estrogen-deficient group), sham surgery plus lithium chloride (150 mg/kg/every other day) (lithium/estrogen-sufficient group), or ovariectomy plus lithium chloride (lithium/estrogen-deficient group). One first mandibular molar received ligature, while the contralateral molar was left unligated. BL and trabecular bone area (TBA) were assessed in the furcation bone at 10, 20, and 30 days after ligature placement. Histochemical staining for TRAP and immunohistochemical staining for osteocalcin, osteopontin, osteoprotegerin, and RANKL were evaluated at 30 days after ligature placement. Results At 10 days, the estrogen-deficient group presented the highest BL (0.115 ± 0.026), while the lithium/estrogen-deficient group (0.048 ± 0.024) presented the lowest BL in the ligated teeth ( p < 0.05). At 20 and 30 days, the estrogen-deficient group exhibited significantly higher BL than all the other groups ( p < 0.05). The ligated teeth of the lithium/estrogen-sufficient group presented the highest TBA while those of the estrogen-deficient group presented the lowest TBA at 10 and 30 days ( p < 0.05). Unligated teeth of lithium-treated groups had stronger staining for osteocalcin and osteopontin than the estrogen-deficient group ( p < 0.05). Ligated and unligated teeth of the estrogen-deficient group exhibited lower expression of osteoprotegerin than the other groups ( p < 0.05). Lithium-treated groups exhibited generally higher staining of RANKL than the untreated groups ( p < 0.05). Unligated teeth in both estrogen-sufficient groups presented lower TRAP expression than both estrogen-deficient groups ( p < 0.05). Conclusions Lithium chloride reduced ligature-induced BL in estrogen-deficient rats and yielded an overall greater trabecular area and overexpression of bone markers in alveolar bone under normal and deficient estrogen states. Clinical relevance Lithium chloride may be a promising agent to assuage alveolar bone loss related to periodontitis, especially in osteoporotic conditions.