A cohort study of the effects of serum osteoprotegerin and osteoprotegerin gene polymorphisms on cardiovascular mortality in elderly women

Summary Objective  To investigate the role of serum osteoprotegerin (OPG) and OPG gene polymorphisms in relation to cardiovascular (CV) and all-cause mortality in elderly women. Background  The OPG/RANK/RANKL plays a vital role in bone cell biology. It has also been detected in myocardial tissue and atherosclerotic plaques. In some population studies, OPG and OPG gene polymorphisms have been associated with CV disease risk. Design, measurements and results  In an 8·5-year cohort population study of 1333 postmenopausal women mean age 75·2 ± 2·7 years, serum OPG concentrations above the median were associated with an increased risk of all-cause [odds ratio (OR) 1·39 (1·04–1·85)], and in particular CV mortality [OR 1·83 (1·10–3·05)], before and after adjusting for age, BMI, treated hypertension, diabetes, hypercholesterolemia, previous HRT use, calcium supplementation and smoking. Genotyping the OPG gene did not provide further information on the association between OPG and CV risk or mortality events. Conclusions  Raised osteoprotegerin appears to be an independent risk factor for total and CV death and thus has potential as a useful biomarker of risk as well as a potential target for therapeutic intervention.