Abstract
BackgroundDiabetes induces long bone loss and aggravation of periodontitis-induced alveolar bone loss. Simvastatin (SIM), which is a lipid-lowering agent is known to have an anabolic effect on bone. Therefore, we investigated effect of SIM on tibial and alveolar bone loss in type 1 diabetic rats with periodontitis.MethodsRats were divided into control (C), diabetes with periodontitis (DP), and diabetes with periodontitis treated with SIM (DPS) groups. DP and DPS groups were intravenously injected with streptozotocin (50 mg/kg), and C group was injected with citrate buffer. Seven days later (day 0), periodontitis was induced by ligatures of mandibular first molars. DP and DPS groups were orally administered vehicle or SIM (30 mg/kg) from day 0 to days 3, 10, or 20. Alveolar and tibial bone loss was measured using histological and m-CT analysis alone or in combination. Osteoclast number and sclerostin-positive osteocytes in tibiae were evaluated by tartrate-resistant acid phosphatase and immunohistochemical staining, respectively. Glucose, triglyceride (TG), cholesterol (CHO), and low-density lipoprotein (LDL) were evaluated.ResultsConsistent with diabetes induction, the DP group showed higher glucose and TG levels at all timepoints and higher CHO levels on day 20 than C group. Compared to the DP group, the DPS group exhibited reduced levels of glucose (day 3), TG (days 10 and 20), CHO, and LDL levels (day 20). Bone loss analysis revealed that the DP group had lower bone volume fraction, bone mineral density, bone surface density, and trabecular number in tibiae than C group at all timepoints. Interestingly, the DPS group exhibited elevation of these indices at early stages compared to the DP group. The DPS group showed reduction of osteoclasts (day 3) and sclerostin-positive osteocytes (days 3 and 20) compared with the DP group. There was no difference in alveolar bone loss between DP and DPS groups.ConclusionsThese results suggest that SIM attenuates tibial, but not alveolar bone loss in type 1 diabetic rats with periodontitis. Moreover, attenuation of tibial bone loss by SIM may be related to inhibition of osteoclast formation and reduction of sclerostin expression.
Highlights
Diabetes induces long bone loss and aggravation of periodontitis-induced alveolar bone loss
After acclimation for 1 week, rats were randomly assigned to three groups: control group (C), diabetes with periodontitis group (DP), or diabetes with periodontitis treated with Simv‐ astatin (SIM) group (DPS)
Serum TG, CHO, and low-density lipoprotein (LDL) levels are reduced with SIM treatment TG level was higher in the DP group than the C group during the experimental period but was lower in the DPS group than the DP group on days 10 and 20 (Fig. 2a)
Summary
Diabetes induces long bone loss and aggravation of periodontitis-induced alveolar bone loss. Simv‐ astatin (SIM), which is a lipid-lowering agent is known to have an anabolic effect on bone. We investigated effect of SIM on tibial and alveolar bone loss in type 1 diabetic rats with periodontitis. SIM has anti-inflammatory, angiogenic, and bone anabolic actions, which have generated interest. Periodontitis is an inflammatory disease that induces alveolar bone loss. SIM treatment has a beneficial effect on alveolar bone level [5,6,7,8]. SIM treatment resulted in improved radiographic defect depth in periodontitis patients [1, 9, 10]. SIM treatment prevents alveolar bone loss in ovariectomized rats with periodontitis [11] and recovers cyclosporine A-induced
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