On 2014 Mar 29, David Keller commented:

Further evidence linking bisphosphonate therapy with acute myocardial infarctions

Further evidence of a possible association of bisphosphonate therapy with acute myocardial infarction has emerged. Pittman and colleagues reported that bisphosphonate use was associated with an increased risk of incident acute myocardial infarction (AMI) in their observational study of elderly veterans with a history of osteoporotic fractures (1), and that “the timing of AMI correlated closely with the timing of bisphosphonate therapy initiation”. We now have at least three studies linking bisphosphonates, such as zoledronic acid, with adverse cardiac events. I agree with Pittman and colleagues that "further analysis and confirmation of these findings by prospective clinical trials is required".

1: Pittman CB, Davis LA, Zeringue AL, Caplan L, Wehmeier KR, Scherrer JF, Xian H, Cunningham FE, McDonald JR, Arnold A, Eisen SA. Myocardial infarction risk among patients with fractures receiving bisphosphonates. Mayo Clin Proc. 2014 Jan;89(1):43-51. doi: 10.1016/j.mayocp.2013.08.021. PubMed PMID: 24388021.

On 2014 Feb 11, David Keller commented:

In the interest of transparency, I submitted the above comments to the New England Journal of Medicine shortly after they published the results of this study. My letter was not published, but I was contacted by a physician employed by the sponsoring pharmaceutical company who offered to schedule a teleconference with me. I told him that I would prefer that he answer my comments in writing. He answered that he would arrange for a colleague to contact me, but I was never contacted. I shall invite him to reply in this forum.

On 2014 Feb 10, David Keller commented:

Boonen and colleagues report that annual intravenous infusion of 5 mg of zoledronic acid was associated with significantly more myocardial infarctions than placebo in men over age 50 with osteoporosis [P=0.03], but state that “none of the events were considered by the investigator to be related to the study drug”. Given that this study was manufacturer-funded, I would like to see a more detailed explanation of how it was determined that zoledronic acid played no role in raising the risk of M.I. An earlier study of a similar regimen of zoledronic acid versus placebo for treating postmenopausal osteoporosis found that serious atrial fibrillation occurred more frequently in the zoledronic acid group [P<0.001] (1). Given that we now have at least two studies demonstrating significantly increased rates of adverse cardiac outcomes with zoledronic acid infusion, the possibility that we are witnessing the emergence of a faint cardiac safety signal must be addressed by more than vague reassurances.

1) Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR; HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3;356(18):1809-22. PubMed PMID: 17476007

On 2014 Feb 10, David Keller commented:

Boonen and colleagues report that annual intravenous infusion of 5 mg of zoledronic acid was associated with significantly more myocardial infarctions than placebo in men over age 50 with osteoporosis [P=0.03], but state that “none of the events were considered by the investigator to be related to the study drug”. Given that this study was manufacturer-funded, I would like to see a more detailed explanation of how it was determined that zoledronic acid played no role in raising the risk of M.I. An earlier study of a similar regimen of zoledronic acid versus placebo for treating postmenopausal osteoporosis found that serious atrial fibrillation occurred more frequently in the zoledronic acid group [P<0.001] (1). Given that we now have at least two studies demonstrating significantly increased rates of adverse cardiac outcomes with zoledronic acid infusion, the possibility that we are witnessing the emergence of a faint cardiac safety signal must be addressed by more than vague reassurances.

1) Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR; HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3;356(18):1809-22. PubMed PMID: 17476007