Bisphosphonate Use and Prevalence of Valvular and Vascular Calcification in Women MESA (The Multi-Ethnic Study of Atherosclerosis)

OBJECTIVES: The aim of this study was to determine whether nitrogen-containing bisphosphonate (NCBP) therapy is associated with the prevalence of cardiovascular calcification. Cardiovascular calcification correlates with atherosclerotic disease burden. Experimental data suggest that NCBP might limit cardiovascular calcification, which has implications for disease prevention.

METHODS: The relationship of NCBP use to the prevalence of aortic valve, aortic valve ring, mitral annulus, thoracic aorta, and coronary artery calcification (AVC, AVRC, MAC, TAC, and CAC, respectively) detected by computed tomography was assessed in 3,710 women within the MESA (Multi-Ethnic Study of Atherosclerosis) with regression modeling.

RESULTS: Analyses were age-stratified, because of a significant interaction between age and NCBP use (interaction p values: AVC p < 0.0001; AVRC p < 0.0001; MAC p = 0.002; TAC p < 0.0001; CAC p = 0.046). After adjusting for age; body mass index; demographic data; diabetes; smoking; blood pressure; cholesterol levels; and statin, hormone replacement, and renin-angiotensin inhibitor therapy, NCBP use was associated with a lower prevalence of cardiovascular calcification in women ≥65 years of age (prevalence ratio: AVC 0.68 [95% confidence interval (CI): 0.41 to 1.13]; AVRC 0.65 [95% CI: 0.51 to 0.84]; MAC 0.54 [95% CI: 0.33 to 0.93]; TAC 0.69 [95% CI: 0.54 to 0.88]; CAC 0.89 [95% CI: 0.78 to 1.02]), whereas calcification was more prevalent in NCBP users among the 2,181 women <65 years of age (AVC 4.00 [95% CI: 2.33 to 6.89]; AVRC 1.92 [95% CI: 1.42 to 2.61]; MAC 2.35 [95% CI: 1.12 to 4.84]; TAC 2.17 [95% CI: 1.49 to 3.15]; CAC 1.23 [95% CI: 0.97 to 1.57]).

CONCLUSIONS: Among women in the diverse MESA cohort, NCBPs were associated with decreased prevalence of cardiovascular calcification in older subjects but more prevalent cardiovascular calcification in younger ones. Further study is warranted to clarify these age-dependent NCBP effects.



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  1. Interesting data describing the relation between biphosphonates and cardiovascular calcifications! Note that the relation was age dependent, and that the relation with coronary artery calcifications was borderline significant (see CI). Exact pathophysiology is intriguing, but not completely clear.
    In the past, the association between drugs that change calcium metabolism and coronary calcifications was also shown in patients with chronic kidney disease receiving phosphate binders, see example:

    The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer.
    Russo D, Miranda I, Ruocco C, Battaglia Y, Buonanno E, Manzi S, Russo L, Scafarto A, Andreucci VE.
    Kidney Int. 2007 Nov;72(10):1255-61.
    PMID: 17805238

  2. Truly interesting study, that further helps understand the pathophysiology process of atherosclerosis and its link with bone metabolism.

    From the Discussion: “Among the proposed explanations for this paradox is that chronic inflammation in response to oxidized LDL modulates calcification differently in vascular tissue and in bone, resulting in tandem calcification of soft tissue and softening of calcified tissues.”

    Hasn’t Atorvastatin been shown to decrease inflammatory markers even in patients with normal cholesterol levels?

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