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

  • Fernando de Souza Malta
  • Marcelo Henrique Napimoga
  • Letícia Macedo Marins
  • Tamires Szeremeske Miranda
  • Flavianny Bárbara de Oliveira
  • Aline Tany Posch
  • Magda Feres
  • Poliana Mendes DuarteEmail author
Original Article



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.


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).


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.


Ovariectomy Lithium chloride Alveolar bone loss RANK ligand Osteoprotegerin Osteocalcin Osteopontin 



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

Funding information

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.

Compliance with ethical standards

Conflict of interest

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).

Informed consent

This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

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784_2019_3067_MOESM2_ESM.docx (110 kb)
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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Fernando de Souza Malta
    • 1
  • Marcelo Henrique Napimoga
    • 2
  • Letícia Macedo Marins
    • 1
  • Tamires Szeremeske Miranda
    • 1
  • Flavianny Bárbara de Oliveira
    • 1
  • Aline Tany Posch
    • 2
  • Magda Feres
    • 1
  • Poliana Mendes Duarte
    • 1
    • 3
    Email author
  1. 1.Department of Periodontology, Dental Research DivisionGuarulhos UniversitySão PauloBrazil
  2. 2.Faculdade São Leopoldo MandicInstituto São Leopoldo MandicCampinasBrazil
  3. 3.Department of Periodontology, College of DentistryUniversity of FloridaGainesvilleUSA

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