title: The anti-osteoporotic and anti-atherogenic effects of alendronate and simvastatin in ovariectomized rats fed high fat diet: A comparative study of combination therapy versus monotherapy.
abstract: OBJECTIVE
  Epidemiological studies suggest a possible link between osteoporosis and cardiovascular diseases. Mevalonate pathway was pointed to as a part of this link. This study was done to investigate the effects of Alendronate (Al) and Simvastatin (Sim), both act on the mevalonate pathway, on osteoporosis, dyslipidemia and atherosclerotic changes in ovariectomized (OVX) rats fed high fat diet (HFD).
  
  
  METHODS
  60 female albino rats were equally divided into 5 groups: control sham, OVX-HFD untreated, OVX -HFD treated with Al (3mg/kg/d) or/and Sim (6mg/kg/d). Treatments were taken for 4 weeks by oral gavage and were started 8 weeks after ovariectomy.
  
  
  RESULTS
  OVX-HFD untreated group exhibited a significant negative alteration in lipid profile and on different bone markers e.g. alkaline phosphatase, hydroxyproline and osteocalcin. A significant increase in body weights and on serum levels of TNFα, iNOS and leptin were also found compared to control sham group. Vascular reactivity studies revealed a significant decrease in effective concentration 50 of phenylephrine and in acetylcholine% of relaxation and a significant increase in maximum contractile response of phenylephrine. The atherosclerotic and osteoporotic changes were further confirmed histopathologically. Treatment of OVX-HFD with Al or/and Sim significantly improved these deleterious effects compared to OVX-HFD untreated group. Comparing the combination therapy versus the mono-therapy exhibited a significant improvement in different tested parameters which came in favor of the combination therapy.
  
  
  CONCLUSIONS
  Al and Sim have anti-osteoporotic, anti-dyslipidemic and anti-atherosclerotic beneficial effects. Their combination has more promising effects in treatment of osteoporosis, dyslipidemia and atherosclerosis.
authors.affiliation: Pharmacology Department, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
authors.forename: Maha Tarek
authors.initials: MT
authors.lastname: Mohamed
authors.affiliation: Pharmacology Department, Faculty of Medicine, Ain-Shams University, Cairo, Egypt. Electronic address: sallyabuelezz@yahoo.com.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Abuelezz
authors.affiliation: Histology Department, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
authors.forename: Suzi Sobhy
authors.initials: SS
authors.lastname: Atalla
authors.affiliation: Pharmacology Department, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
authors.forename: Lobna Fouad Abd
authors.initials: LFA
authors.lastname: El Aziz
authors.affiliation: Pharmacology Department, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
authors.forename: Sonia Salib
authors.initials: SS
authors.lastname: Gorge
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D003131:Combined Modality Therapy / Q000379:methods; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D015675:Osteocalcin / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D010052:Ovariectomy / Q000379:methods; D051381:Rats; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D015675:Osteocalcin; D019821:Simvastatin; D000469:Alkaline Phosphatase; D019386:Alendronate
keywords: Alendronate; Athrosclerosis; Osteoporosis; Ovariectomized high fat diet; Simvastatin