ORLANDO — Bisphosphonate therapy was associated with a reduced prevalence of cardiovascular calcification in older women but a paradoxical increased prevalence in women under age 65 years, compared with bisphosphonate nonusers in the Multi-Ethnic Study of Atherosclerosis.
Since MESA is an observational study, this novel finding has to be considered hypothesis generating rather than definitive. It's unclear whether the unexpectedly higher prevalence of cardiovascular calcification in younger bisphosphonate users in MESA is the result of their likely shorter duration of treatment, differential drug effects, age-related differences in the pathogenesis of calcification, indication bias related to osteoporosis, or even chance, Dr. Sammy Elmariah said at the annual scientific sessions of the American Heart Association.
Replication of these new MESA findings should be sought in other large data sets, added Dr. Elmariah of Mount Sinai School of Medicine, New York.
MESA is an ongoing National Heart, Lung, and Blood Institute–funded longitudinal study of an ethnically diverse group of 6,814 men and women aged 45-84 years in six U.S. communities. All were free of cardiovascular symptoms at baseline.
Dr. Elmariah and his coworkers analyzed baseline data on bisphosphonate use and cardiovascular calcification in 3,636 participating women, 2,181 of whom were under age 65. MESA included 214 women on baseline bisphosphonate therapy. Cardiovascular calcification was assessed via multidetector row helical CT or electron-beam CT.
Among women aged 65 or older, bisphosphonate use was associated with a significantly lower prevalence of cardiovascular calcification at nearly all anatomic sites assessed.
For example, aortic valve calcification was 33% less common in the older bisphosphonate users than in nonusers in multivariate analyses adjusted for age, body mass index, ethnicity, socioeconomic variables, cardiovascular risk factors, statins, and hormone replacement therapy. Aortic valve ring calcification was 35% less common. Calcification of the mitral annulus was 46% less common in older bisphosphonate users, and thoracic aorta calcification was 32% less prevalent.
The only anatomic site where calcification wasn't significantly less common in older bisphosphonate users than nonusers was in the coronary arteries, where the adjusted 10% reduction in favor of bisphosphonate users fell short of statistical significance, Dr. Elmariah said.
The story was very different in women under 65 years of age. Younger bisphosphonate users were an adjusted four times more likely to have aortic valve calcification than were bisphosphonate nonusers, 1.9-times more likely to have aortic valve ring calcification, and 2.4 times more likely to have calcification of the mitral annulus. They also had 2.2-fold and 1.2-fold higher rates of calcification of the thoracic aorta and coronary arteries. All of these differences achieved statistical significance.
When the women were grouped in 10-year age subsets, a gradual reduction in the adjusted prevalence of cardiovascular calcification accompanied increasing age among bisphosphonate users.
The increased prevalence of cardiovascular calcification in younger bisphosphonate users came as a surprise in light of the known pharmacologic actions of the nitrogen-containing bisphosphonates, including several statin-like effects, according to Dr. Elmariah.
Dr. Elmariah's work was funded by the New York Academy of Medicine, the GlaxoSmithKline Research & Education Foundation for Cardiovascular Disease, and the NHLBI.
Calcification (arrows) was increased in younger bisphosphonate users.
Source ©2009 Elsevier Inc.