Department of Periodontology, Dental Research Division, Guarulhos University, São Paulo, Brazil.
Faculdade São Leopoldo Mandic, Instituto São Leopoldo Mandic, Área de Imunologia, Campinas, SP, Brazil.
Clin Oral Investig. 2020 Jun;24(6):2025-2036. doi: 10.1007/s00784-019-03067-9. Epub 2019 Sep 11.
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.
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.
Lithium chloride may be a promising agent to assuage alveolar bone loss related to periodontitis, especially in osteoporotic conditions.
有证据表明,常用于治疗双相情感障碍的药物锂具有促进骨合成代谢的作用。本研究旨在评估氯化锂对牙周炎诱导的骨丢失(BL)以及在雌激素充足和缺乏时完整牙槽骨的影响。
将大鼠(每组 24 只)分为假手术+水(雌激素充足组)、卵巢切除术+水(雌激素缺乏组)、假手术+氯化锂(150mg/kg/隔日)(锂+雌激素充足组)或卵巢切除术+氯化锂(锂+雌激素缺乏组)。一只第一下颌磨牙结扎,对侧磨牙不结扎。结扎后 10、20 和 30 天,在分叉骨处评估 BL 和小梁骨面积(TBA)。结扎后 30 天,通过 TRAP 组织化学染色和骨钙素、骨桥蛋白、骨保护素和 RANKL 的免疫组织化学染色进行评估。
在 10 天时,雌激素缺乏组的 BL 最高(0.115±0.026),而锂+雌激素缺乏组(0.048±0.024)结扎牙的 BL 最低(p<0.05)。在 20 和 30 天时,雌激素缺乏组的 BL 明显高于其他组(p<0.05)。锂+雌激素充足组结扎牙的 TBA 最高,而雌激素缺乏组结扎牙的 TBA 最低(p<0.05)。在 10 和 30 天时,锂处理组的未结扎牙的骨钙素和骨桥蛋白染色强于雌激素缺乏组(p<0.05)。与其他组相比,雌激素缺乏组结扎牙和未结扎牙的骨保护素表达较低(p<0.05)。锂处理组的 RANKL 染色普遍高于未处理组(p<0.05)。在雌激素充足的两组中,未结扎牙的 TRAP 表达均低于雌激素缺乏的两组(p<0.05)。
氯化锂可减少雌激素缺乏大鼠结扎诱导的 BL,并在正常和雌激素缺乏状态下使牙槽骨的小梁面积总体增加和骨标志物表达上调。
氯化锂可能是一种有前途的药物,可减轻与牙周炎相关的牙槽骨丢失,尤其是在骨质疏松症的情况下。