BoneKEy Reports | BoneKEy Watch
Clopidogrel (Plavix) could have a negative effect on bone health
DOI:10.1038/bonekey.2012.172
Clopidogrel (Plavix), which selectively blocks the P2Y12 receptor, is being used increasingly in stroke and heart attack prevention due to its ability to inhibit platelet aggregation. In this study Syberg et al. assessed the drug's impact on bone health; they first confirmed that both osteoblasts and osteoclasts express the P2Y12 receptor and then demonstrated that clopidogrel inhibited the formation of mineralized bone nodules in a dose-dependent manner.
The drug decreased the level of osteoblast proliferation and reduced the viability of mature osteoblasts. After 14 days of treatment with a low dose of clopidogrel (10 μM), activity of alkaline phosphatase decreased by 70% or more, collagen formation was reduced by 40% and adipocyte formation had gone up significantly. An even smaller dose (1 μM) was enough to inhibit osteoclast formation, resorptive activity and viability.
Ovariectomised mice treated with oral clopidrogel at a dose of 1 mg/kg daily for 4 weeks showed a reduction in whole body and femoral bone mineral density compared to controls. Trabecular bone volume in the tibia was 24% lower and in the femur 18% lower. Trabecular thickness and cortical bone remained unchanged, but trabecular number fell by 20% and was accompanied by a 15% increase in trabecular separation.
Editor's comment: The evidence that the anti-aggregant clopidogrel reduces osteoblastic and osteoclastic functions in vitro and increases bone loss in mice raises important clinical questions as such a large number of patients are now taking this medicine.
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