title: Bisphosphonates for cardiovascular risk reduction: A systematic review and meta-analysis.
abstract: Bisphosphonates might be effective in reducing cardiovascular events due to their ability to reduce calcification in arterial walls. We aimed to investigate the effects of treatment with bisphosphonates on the prevention of atherosclerotic processes and cardiovascular disease.
  
  
  
  Pubmed, Embase and the Cochrane Library were systematically reviewed by two independent investigators for randomized controlled studies published up to January 2016, in which the effect of bisphosphonates on arterial wall disease, cardiovascular events, cardiovascular mortality or all-cause mortality were reported. There was no restriction for the type of population used in the trials. Random-effects models were used to calculate the pooled estimates.
  
  
  
  61 trials reporting the effects of bisphosphonates on the outcomes of interest were included. Bisphosphonates had beneficial effects on arterial wall disease regarding arterial calcification (pooled mean percentage difference of 2 trials -11.52 (95% CI -16.51 to -6.52, p < 0.01, I(2) 13%), but not on arterial stiffness (pooled mean percentage difference of 2 trials -2.82; 95% CI -10.71-5.07; p = 0.48, I(2) 59%). No effect of bisphosphonate treatment on cardiovascular events was found (pooled RR of 20 trials 1.03; 95% CI 0.91-1.17, I(2) 16%), while a lower risk for cardiovascular mortality was observed in patients treated with bisphosphonates (pooled RR of 10 trials 0.81; 95% CI 0.64-1.02; I(2) 0%) although not statistically significant. Patients treated with bisphosphonates had a reduced risk of all-cause mortality (pooled RR of 48 trials 0.90; 95% CI 0.84-0.98; I(2) 53%).
  
  
  
  In this systematic review and meta-analysis it is shown that bisphosphonates reduce arterial wall calcification but have no effect on arterial stiffness or on cardiovascular events. Bisphosphonates tend to reduce the risk of cardiovascular mortality and reduce all-cause mortality in various patient groups, including osteoporosis and cancer patients.
authors: Department of Vascular Medicine, University Medical Center Utrecht, The Netherlands.
authors: Guido
authors: G
authors: Kranenburg
authors: Department of Vascular Medicine, University Medical Center Utrecht, The Netherlands.
authors: Jonas W
authors: JW
authors: Bartstra
authors: Department of Vascular Medicine, University Medical Center Utrecht, The Netherlands.
authors: Maaike
authors: M
authors: Weijmans
authors: Department of Radiology, University Medical Center Utrecht, The Netherlands.
authors: Pim A
authors: PA
authors: de Jong
authors: Department of Radiology, University Medical Center Utrecht, The Netherlands.
authors: Willem P
authors: WP
authors: Mali
authors: Department of Geriatric Medicine, University Medical Center Utrecht, The Netherlands.
authors: Harald J
authors: HJ
authors: Verhaar
authors: Department of Vascular Medicine, University Medical Center Utrecht, The Netherlands.
authors: Frank L J
authors: FLJ
authors: Visseren
authors: Department of Vascular Medicine, University Medical Center Utrecht, The Netherlands. Electronic address: W.Spiering@umcutrecht.nl.
authors: Wilko
authors: W
authors: Spiering
mesh_terms: D001158:Arteries / Q000503:physiopathology; D002114:Calcinosis / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D002319:Cardiovascular System / Q000187:drug effects; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000150:complications / Q000401:mortality; D010024:Osteoporosis / Q000150:complications / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D040242:Risk Reduction Behavior; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D004164:Diphosphonates
keywords: Arterial calcification; Arterial stiffness; Atherosclerosis; Bisphosphonates; Cardiovascular mortality; Mortality; cardiovascular events