BoneKEy Reports | BoneKEy Watch

Therapeutic doses of clopidogrel increase fracture risk


Clopidogrel, a widely used P2Y12 inhibitor that helps to prevent coronary artery disease in high-risk patients, is suspected to block some of the pathways involved in bone metabolism. Previous animal studies have suggested a link between clopidogrel and bone loss but this is the first large human population study to assess fracture risk in patients taking the drug.

Data were collected from 77 503 patients from a Danish cohort who took clopidogrel between 1996 and 2008. The rate of fractures in this group was compared with 232 510 age- and gender-matched controls. Analysis showed that clopidogrel use did affect fracture risk, but its impact varied with dose and the gender of the recipient.

Generally, a low dose reduced the fracture risk in men, whereas higher doses (i.e. prescription level) significantly increased the chance of sustaining an osteoporotic fracture at the hip, forearm or spine, in both men and women. Women taking lower defined daily doses (0.10–0.39) were at increased risk of all fractures, including hip fractures.

Editor's comment: Following on from mouse experiments showing that clopidogrel causes bone loss (see BoneKEy Watch August 2012), this large, epidemiological survey confirms an association between long-term clopidogrel use and increased fracture risk. These observations may have important consequences for determining the most appropriate anti-aggregant therapy in osteoporotic patients. They also suggest that the fracture risk associated with newer platelet inhibitors, which are even more potent, should be investigated.

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