Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol

Nowadays, bisphosphonates are considered the drugs of choice for the treatm ent of several bone disorders. Their exact mechanism of action is not clear but recently it has been reported that the aminobisphosphonates inhibit ch olesterol 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 mi of saline solution every 2 months for a year (44 patients). The rem aining 43 served as controls. At the time of each infusion blood samples we re obtained for the evaluation of total cholesterol, triglycerides, high-de nsity lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholester ol (LDL-C), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), and tot al and bone alkaline phosphatase (AP). Free deoxypyridinoline (f-DPD) was m easured in fasting urine specimens. In the control group no significant cha nges were observed throughout the study period for any of the biochemical v ariables. In the Neridronate-treated patients both bone AP and f-DPD excret ion fell significantly by 15-20 %. In these patients serum total cholestero l and serum triglycerides showed marginal decreases, which were occasionall y significant. LDL-C and Apo B fell by 5-6% and these changes were statisti cally 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 ba seline values. Similar findings were obtained in four postmenopausal women given high iv doses of Pamidronate or Alendronate. In conclusion aminobisph ophonates, at least when given iv, induce remarkable and unexpected effects on lipid metabolism with a final profile that might be clinically relevant .