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

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Abstract

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.

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Acknowledgments

The authors thank Nadir Severina de Freitas for the help with the immunohistochemistry.

Funding

This study was funded by the São Paulo State Research Foundation (São Paulo, São Paulo, Brazil, no. 2016/23614-2). Research productivity fellowship to Poliana Mendes Duarte and Marcelo Henrique Napimoga from the National Council for Scientific and Technological Development.

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Authors and Affiliations

  1. Department of Periodontology, Dental Research Division, Guarulhos University, São Paulo, Brazil

    Fernando de Souza Malta, Letícia Macedo Marins, Tamires Szeremeske Miranda, Flavianny Bárbara de Oliveira, Magda Feres & Poliana Mendes Duarte

  2. Faculdade São Leopoldo Mandic, Instituto São Leopoldo Mandic, Área de Imunologia, Campinas, SP, Brazil

    Marcelo Henrique Napimoga & Aline Tany Posch

  3. Department of Periodontology, College of Dentistry, University of Florida, 1600 SW Archer Rd., Room D10-6, Gainesville, FL, 32610, USA

    Poliana Mendes Duarte

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  1. Fernando de Souza Malta
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Correspondence to Poliana Mendes Duarte.

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The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The study protocol and the manuscript were performed according to the ‘NC3Rs ARRIVE Guidelines, Animal Research: Reporting of In Vivo Experiments. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. The Institutional Committee for Animal Care and Use at Guarulhos University (Guarulhos, São Paulo, Brazil) approved the study protocol (028/16).

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de Souza Malta, F., Napimoga, M.H., Marins, L.M. et al. Lithium chloride assuages bone loss in experimental periodontitis in estrogen-deficient rats. Clin Oral Invest 24, 2025–2036 (2020). https://doi.org/10.1007/s00784-019-03067-9

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