title: Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol.
abstract: Nowadays, bisphosphonates are considered the drugs of choice for the treatment of several bone disorders. Their exact mechanism of action is not clear but recently it has been reported that the aminobisphosphonates inhibit cholesterol biosynthesis and that this might be relevant for their actions on bone osteoclasts. The study includes 87 postmenopausal women with moderate to severe osteoporosis. The patients were randomly assigned to intravenous (iv) infusion of 50 mg of the aminobisphosphonate Neridronate dissolved in 100 ml of saline solution every 2 months for a year (44 patients). The remaining 43 served as controls. At the time of each infusion blood samples were obtained for the evaluation of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), and total and bone alkaline phosphatase (AP). Free deoxypyridinoline (f-DPD) was measured in fasting urine specimens. In the control group no significant changes were observed throughout the study period for any of the biochemical variables. In the Neridronate-treated patients both bone AP and f-DPD excretion fell significantly by 15-20%. In these patients serum total cholesterol and serum triglycerides showed marginal decreases, which were occasionally significant. LDL-C and Apo B fell by 5-6% and these changes were statistically significant at most time points. Apo A-I and HDL-C rose progressively with time. At the 12th month, HDL-C rose 17-18% (p < 0.0001) above the baseline values. Similar findings were obtained in four postmenopausal women given high iv doses of Pamidronate or Alendronate. In conclusion aminobisphophonates, at least when given iv, induce remarkable and unexpected effects on lipid metabolism with a final profile that might be clinically relevant.
authors.affiliation: Department of Rheumatology, University of Verona, Valeggio S/M, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Adami
authors.forename: V
authors.initials: V
authors.lastname: Braga
authors.forename: G
authors.initials: G
authors.lastname: Guidi
authors.forename: D
authors.initials: D
authors.lastname: Gatti
authors.forename: D
authors.initials: D
authors.lastname: Gerardi
authors.forename: E
authors.initials: E
authors.lastname: Fracassi
mesh_terms: D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007527:Isoenzymes / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D000077268:Pamidronate; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood
chemical_list: D000596:Amino Acids; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004164:Diphosphonates; D007527:Isoenzymes; D014280:Triglycerides; C053389:6-amino-1-hydroxyhexane-1,1-diphosphonate; C036020:deoxypyridinoline; D002784:Cholesterol; D000469:Alkaline Phosphatase; D000077268:Pamidronate; D019386:Alendronate