Lithium chloride stimulates bone formation in extraction socket repair in rats.

PURPOSE: Previous evidence shows that lithium chloride (LiCl), a suppressor of glycogen synthase kinase-3ß (GSK-3ß), may enhance bone formation in several medical and dental conditions. Thus, the purpose of the current study was to assess the effects of LiCl on extraction socket repair in rats. METHODS: Thirty rats were randomly assigned into a control group (administration of water; n = 15) or a LiCl group (administration of 150 mg/kg of LiCl; n = 15). LiCl and water were given every other day, starting at 7 days before the extraction of upper first molars until the end of each experiment period. Histological sections from five rats per group were obtained at 10, 20, and 30 days post-extractions. Histometrical analysis of newly formed bone (NB) and the levels of tartrate-resistant acid phosphatase (TRAP)-stained cells were evaluated at 10, 20, and 30 days post-extractions. Immunohistochemical staining for receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), bone sialoprotein (BSP), osteocalcin (OCN), and osteopontin (OPN) was assessed at 10 days post-extractions. RESULTS: The LiCl group had a greater proportion of NB than the control group at 20 days (P < 0.05). At 30 days, the rate of TRAP-stained cells was lower in the LiCl group than in the control group (P < 0.05). At 10 days, the LiCl group presented stronger staining for OPG, BSP, OPN, and OCN, when compared to the control group (P < 0.05). CONCLUSION: Systemic LiCl enhanced extraction socket repair, stimulated an overall increase in bone formation markers, and restricted the levels of TRAP in rats.

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.

Role of Metformin in Reversing the Negative Impact of Hyperglycemia on Bone Healing Around Implants Inserted in Type 2 Diabetic Rats.

PURPOSE: There is interest in establishing hypoglycemiant agents able to contain/revert the impact of diabetes mellitus on osseointegration. The purpose of this study was to assess the possible effect of metformin in reversing the negative effects of hyperglycemia on the healing of bone surrounding implants inserted in rats. MATERIALS AND METHODS: Rats (10 per group) were assigned to one of the following groups: DM group: type 2 diabetic rats deprived of metformin (M) treatment; MDM group: type 2 diabetic rats under M treatment (40 mg/kg/day, starting on the 15th day after implant placement); control group: nondiabetic rats without M treatment. At 30 days after streptozotocin injection, titanium implants were placed in tibiae. Animals were euthanized 30 days after implant surgery. Bone-to-implant contact (BIC), bone area (BA), and the number of receptor activator of nuclear factor κB ligand (RANKL)- and osteoprotegerin (OPG)-stained cells were assessed in cortical and medullary areas. RESULTS: The percentages of BIC and BA in the cortical bone were reduced in the DM and MDM groups compared with the control group (P < .05). The percentage of BA in the medullary region was reduced in the DM group compared with the control group (P < .05). The MDM group showed the greatest number of OPG-stained cells, while the DM group presented the greatest ratio of RANKL/OPG in the medullary area (P < .05). CONCLUSION: Metformin did not modulate the damaging effect of hyperglycemia on bone healing around implants at histometric levels, but increased the expression of OPG and decreased the RANKL/OPG ratio in the medullary area, yielding some molecular benefits in the osseointegration of implants under the hyperglycemic state.

Effects of metformin on bone healing around titanium implants inserted in non-diabetic rats.

OBJECTIVE: To evaluate the effects of metformin on bone healing around titanium implants inserted in non-diabetic rats. METHODS: Twenty Wistar rats were randomly assigned to one of the following groups: control group (n = 10): rats without metformin treatment; MT group (n = 10): rats treated with metformin (40 mg/kg/day by gavage). At thirty days after implant placement, animals were euthanized. Histometric measurements of bone-to-implant contact (BIC) and bone area (BA), in addition to immunohistochemical analysis of the number of cells stained for RANKL and OPG, were assessed in the cortical and medullary areas around implants. RESULTS: The percentages of BIC and BA in the cortical bone were significantly lower in the MT group than in the control group (P < 0.05). Furthermore, the medullary bone around the implants inserted in the metformin-treated animals exhibited an increased number of RANKL-stained cells than that around the implants inserted in the control animals (P < 0.05). CONCLUSIONS: Metformin negatively affected osseointegration by reducing the percentages of BIC and BA and increasing the expression of RANKL around titanium implants inserted in non-diabetic rats.