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Relationship between circulating serum osteoprotegerin and total receptor activator of nuclear κ-B ligand levels, triglycerides, and coronary calcification in postmenopausal women

Poornima, Indu G. MD1,2; Mackey, Rachel H. PhD, MPH3; Buhari, Alhaji M. MA, MSIE3; Cauley, Jane A. DrPH3; Matthews, Karen A. PhD4; Kuller, Lewis H. MD, DrPH3

doi: 10.1097/GME.0000000000000127
Original Articles

Objective This study evaluates the relationship of blood osteoprotegerin (OPG) and receptor activator of nuclear κ-B ligand (RANKL) levels with coronary artery calcium (CAC) and cardiovascular risk factors in two studies of postmenopausal women. OPG, a marker of bone turnover, and its ligand, RANKL, may contribute to cardiovascular disease risk.

Methods We tested the hypothesis that serum OPG and RANKL levels were associated with CAC and cardiovascular disease risk factors among postmenopausal women in the Women On the Move through Activity and Nutrition Study (WOMAN Study; n = 86; mean [SD], age 58 [2.9] y) and replicated our findings in the Healthy Women Study (HWS; n = 205; mean [SD] age, 61 [2.3] y). Serum OPG, total RANKL, and CAC were measured at baseline and 48 months in the WOMAN Study and on the eighth postmenopausal visit in the HWS.

Results In the WOMAN Study, higher OPG was associated with higher CAC, and higher total RANKL was associated with lower CAC and triglycerides. In the HWS, higher total RANKL was also associated with lower CAC and triglycerides. In logistic regression models adjusted for body mass index and triglycerides, the odds ratios (95% CIs) for CAC per unit increase in OPG were 1.78 (1.17-2.73) for the WOMAN Study and 1.02 (0.84-1.24) for the HWS, and the odds ratios (95% CIs) for CAC per unit increase in log total RANKL were 0.86 (0.64-1.17) for the WOMAN Study and 0.83 (0.72-0.96) for the HWS.

Conclusions The inverse association of total RANKL with CAC and triglycerides is a new finding and may have important implications given the increasing use of drugs that modify total RANKL and its receptor, receptor activator of nuclear κ-B.

Supplemental Digital Content is available in the text.

From the 1Division of Cardiology, Allegheny General Hospital, Pittsburgh, PA; 2Drexel University College of Medicine, Philadelphia, PA; 3Department of Epidemiology, Graduate School of Public Health, and 4Department of Psychiatry, Epidemiology, and Psychology, University of Pittsburgh, Pittsburgh, PA.

Received July 15, 2013; revised and accepted September 11, 2013.

Funding/support: This study was supported by a grant from the Allegheny Heart Institute.

Financial disclosure/conflicts of interest: None reported.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (

Address correspondence to: Indu G. Poornima, MD, Division of Cardiology, Allegheny General Hospital, 320 East North Avenue, Pittsburgh, PA 15212. E-mail:

© 2014 by The North American Menopause Society.