title: Low-dose combination of alendronate and atorvastatin reduces ligature-induced alveolar bone loss in rats.
abstract: OBJECTIVE
  Atorvastatin (ATV) has bone anabolic properties, and alendronate (ALD) is an important antiresorptive drug. This study aimed to evaluate the effects of the combination of ALD and ATV on ligature-induced alveolar bone loss in rats.
  
  
  METHODS
  Periodontitis was induced by ligature in 78 Wistar rats. Groups of six rats prophylactically received 0.9% saline (SAL), ALD (0.01 or 0.25 mg/kg subcutaneously) or ATV (0.3 or 27 mg/kg by gavage). Then, groups of six rats received the combination of ALD+ATV (0.25 mg/kg + 27 mg/kg, 0.01 mg/kg + 0.3 mg/kg, 0.25 mg/kg + 0.3 mg/kg or 0.01 mg/kg + 27 mg/kg) prophylactically. An extra group of six rats received therapeutic SAL or a lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) therapeutically. Three extra groups of six rats each received SAL or a lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) prophylactically or therapeutically for histometric and immunohistochemical analyses. The rats were killed on day 11 after ligature placement, and the maxillae were removed and processed for macroscopic, histomorphometric and TRAP immunohistochemical analyses. Gingival samples were collected to evaluate myeloperoxidase (MPO) activity. Blood samples were collected to measure serum bone-specific alkaline phosphatase (BALP) and transaminase levels and for hematological studies. Rats were weighed daily.
  
  
  RESULTS
  All combined therapies prevented alveolar bone loss when compared with SAL or low doses of monotherapy (ALD or ATV) (p < 0.05). The lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively), administered either prophylactically (39.0%) or therapeutically (53.5%), prevented alveolar bone loss. Decreases in bone and cementum resorption, in leukocyte infiltration and in immunostaining for TRAP and MPO activity corroborated the morphometric findings. The lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) prevented BALP reduction (p < 0.05) and did not alter the level of serum transaminases. Moreover, the lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) also reduced neutrophilia and lymphomonocytosis and did not cause weight loss when compared with administration of SAL.
  
  
  CONCLUSIONS
  The lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) demonstrated a protective effect on alveolar bone loss.
authors.affiliation: Department of Clinical Dentistry, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: P
authors.initials: P
authors.lastname: Goes
authors.forename: I M
authors.initials: IM
authors.lastname: Melo
authors.forename: L M C M
authors.initials: LM
authors.lastname: Silva
authors.forename: N M B
authors.initials: NM
authors.lastname: Benevides
authors.forename: N M N
authors.initials: NM
authors.lastname: Alencar
authors.forename: R A
authors.initials: RA
authors.lastname: Ribeiro
authors.forename: V
authors.initials: V
authors.lastname: Lima
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000410:Alanine Transaminase / Q000097:blood; D019386:Alendronate / Q000008:administration & dosage*; D000469:Alkaline Phosphatase / Q000097:blood; D016301:Alveolar Bone Loss / Q000517:prevention & control*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D000069059:Atorvastatin; D001835:Body Weight; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D003739:Dental Cementum / Q000187:drug effects; D005881:Gingiva / Q000201:enzymology; D006538:Heptanoic Acids / Q000008:administration & dosage*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007263:Infusions, Parenteral; D007279:Injections, Subcutaneous; D007527:Isoenzymes / Q000032:analysis; D007960:Leukocyte Disorders / Q000517:prevention & control; D007962:Leukocytes / Q000187:drug effects; D007964:Leukocytosis / Q000517:prevention & control; D008297:Male; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D009195:Peroxidase / Q000032:analysis; D011758:Pyrroles / Q000008:administration & dosage*; D017208:Rats, Wistar; D012391:Root Resorption / Q000517:prevention & control; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D050071:Bone Density Conservation Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007527:Isoenzymes; D011758:Pyrroles; D000069059:Atorvastatin; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D019386:Alendronate
keywords: alendronate; alveolar bone loss; atorvastatin; inflammation