Effects of strontium ranelate on ligature-induced periodontitis in estrogen-deficient and estrogen-sufficient rats.

BACKGROUND AND OBJECTIVES: Strontium ranelate is a medication indicated for the treatment of osteoporosis that presents concomitant anti-resorptive and osteoanabolic dual biological activity. However, the effects of strontium ranelate on alveolar bone have been poorly explored. Furthermore, to date, there are no data on the effects of this medication on alveolar bone loss (BL) during conditions of estrogen deficiency. Therefore, the aim of this study was to evaluate the effects of strontium ranelate on ligature-induced periodontitis in estrogen-deficient and estrogen-sufficient rats. METHODS: Ninety-six rats were assigned to one of the following groups: sham-surgery + water (estrogen-sufficient; n = 24); ovariectomy + water (estrogen-deficient; n = 24), sham-surgery + strontium ranelate (ranelate/estrogen-sufficient; n = 24) and; ovariectomy + strontium ranelate (ranelate/estrogen-deficient; n = 24). The rats received strontium ranelate or water from the 14th day after ovariectomy until the end of the experiment. On the 21st day after ovariectomy, one first mandibular molar received a ligature, while the contralateral tooth was left unligated. Eight rats per group were killed at 10, 20, and 30 days after ligature placement. Bone loss (BL) and trabecular bone area (TBA) were analyzed in the furcation area of ligated and unligated teeth at all experimental times by histometry. Tartrate-resistant acid phosphatase (TRAP) positive cells and immunohistochemical staining for osteocalcin (OCN), osteopontin (OPN), osteoprotegerin (OPG), and receptor activator of NF-КB ligand (RANKL) were assessed in the ligated teeth at 30 days after ligature placement. RESULTS: At 10 and 30 days, ligated teeth of the estrogen-deficient group exhibited higher BL, when compared to all other groups (P < .05). At 10 days, TBAs were higher in the unligated teeth of strontium ranelate-treated groups, when compared to those of untreated groups (P < .05). At 30 days, the ligated teeth of the estrogen-deficient group exhibited lower TBA than the other groups (P < .05). There were no differences among groups regarding the number of TRAP-stained cells (P < .05). The strontium ranelate-treated groups exhibited lower expressions of OCN and RANKL than the untreated groups (P < .05). The estrogen-sufficient group presented higher staining for OPG than both treated and untreated estrogen-deficient groups (P < .05). CONCLUSIONS: Strontium ranelate prevented ligature-induced BL in an estrogen-deficiency condition and, to a certain extent, increased TBA in the presence and absence of periodontal collapse in states of estrogen deficiency and estrogen sufficiency. Furthermore, strontium ranelate also affected the expression of bone markers, appearing to have acted predominantly as an anti-resorptive agent.

Strontium ranelate increases osteoblast activity.

Strontium ranelate (SR) is the first generation of a new class of medication for osteoporosis, which is capable of inducing bone formation and, to a certain extent, inhibiting bone resorption. The aim of this study was to evaluate the in vitro effects of SR on osteoblastic cell cultures. MC3TE-E1 cells were seeded in 24-well plates at a density of 2×10(4) cells/well and exposed to SR at 0.05, 0.1, and 0.5mM. The following parameters were assayed: 1) Cell proliferation by hemocytometer counting after 24, 48 and 72h, 2) Cell viability by MTT assay after 24, 48 and 72h, 3) Type I Collagen and Osteopontin (OPN) quantification by Western Blotting, ELISA, and Real Time PCR after 48h, 3) Immunolocalization of fibronectin (FN) by epifluorescence, and 4) matrix mineralization by Alizarin Red staining after 14days. After 24, 48 and 72h, the cell proliferation and viability were not affected by SR at 0.05 and 0.1mM (p>0.05). However, cell cultures exposed to SR at 0.5mM exhibited a decrease in both cell proliferation and cell viability in all time points assayed (p<0.05). High levels of protein and mRNA for Type I Collagen and OPN were detected in cultures exposed to SR, particularly at 0.5mM (p<0.05). SR allowed the expression of FN in osteoblastic cell cultures as observed by epifluorescence analysis. The mineralized bone-like nodule formation was affected in a concentration-dependent manner by SR, with large bone-like nodules being detected in osteoblastic cell cultures exposed to SR at 0.5mM. In conclusion, these results suggest that SR can accelerate acquisition of the osteoblastic phenotype, which explains, at least in part, the rebalancing of bone turnover in favor of bone formation.