Acute myocardial infarction and atherosclerosis of the coronary arteries in patients treated with drugs against osteoporosis: calcium in the vessels and not the bones?

We studied the association between bisphosphonate use and risk of acute myocardial infarction (AMI) or atherosclerosis of the coronary vessels using a nationwide retrospective cohort from Denmark. All users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) comprised the exposed group and three age- and gender-matched controls from the general population (n = 310,683), the unexposed group. The main outcomes were occurrence of AMI or atherosclerosis of the coronary vessels. An excess risk of AMI was seen in users of alendronate compared to the unexposed. However, an inverse dose-response relationship was seen, with an increased risk in those with low adherence (≤0.66 DDD, HR = 1.50, 95% CI 1.24-1.82) and a nonsignificantly decreased risk in those who were adherent to the drug (≥1 DDD, HR = 0.80, 95% CI 0.59-1.09; P for trend <0.01). For etidronate and raloxifene, no excess risk was present and no dose-response relationship was seen. For atherosclerosis of the coronary vessels, a similar trend as for AMI was seen for alendronate but a protective effect was present at high doses (≥1 DDD, HR = 0.58, 95% CI 0.49-0.70). For etidronate, an increased risk of atherosclerosis was seen at all doses, with no dose-response relationship. For raloxifene, no excess of atherosclerosis was observed. At high doses of alendronate a decreased risk of atherosclerosis of the coronary vessels was seemingly present, whereas at low doses an increased risk was present. The finding may be spurious due to the "healthy user" effect, but a causal relationship cannot be excluded.