Ghotbi Elena, Subhas Nikhil, Bancks Michael P, Elmariah Sammy, Halperin Jonathan L, Bluemke David A, Kestenbaum Bryan R, Barr R Graham, Post Wendy S, Budoff Matthew, Lima João A C, Demehri Shadpour
Department of Radiology and Radiologic Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Division of Public Health Sciences, Department of Epidemiology & Prevention, Wake Forest University School of Medicine, Winston-Salem, NC 27109, USA.
Diagnostics (Basel). 2025 Jul 7;15(13):1727. doi: 10.3390/diagnostics15131727.
Bisphosphonates may influence vascular calcification and atheroma formation via farnesyl pyrophosphate synthase inhibition in the mevalonate pathway regulating bone and lipid metabolism. However, the clinical impact of NCB use on cardiovascular outcomes remains uncertain, largely due to methodological heterogeneity in prior studies. We aimed to evaluate the association between nitrogen-containing bisphosphonate (NCB) therapy and coronary artery calcium (CAC) progression, as well as the incidence of cardiovascular disease (CVD) and coronary heart disease (CHD) events. From 6814 participants in MESA Exam 1, we excluded males (insufficient male NCB users in the MESA cohort), pre-menopausal women, baseline NCB users, and users of hormone replacement therapy, raloxifene, or calcitonin. Among 166 NCB initiators and 1571 non-users with available CAC measurements, propensity score matching was performed using the available components of FRAX, namely age, race, BMI, LDL cholesterol, alcohol, smoking, and steroid use, and baseline CAC yielded 165 NCB initiators matched to 473 non-users (1:3 ratio). Linear mixed-effects models evaluated CAC progression, and Cox models analyzed incident CVD and CHD events. In the overall cohort, NCB use was not significantly associated with CAC progression (annual change: -0.01 log Agatston units; 95% CI: -0.05 to 0.01). However, among participants with a baseline estimated glomerular filtration rate (eGFR) < 65 mL/min/1.73 m, NCB use was associated with attenuated CAC progression compared with non-users (-0.06 log Agatston units/year; 95% CI: -0.12 to -0.007). No significant association was observed between NCB use and incident CVD events in the overall cohort (HR: 0.90; 95% CI: 0.60-1.36) or within kidney function subgroups. Incident NCB use among postmenopausal women with mild or no CAC at baseline was associated with reduced CAC progression only in women with impaired kidney function. However, this association did not correspond to a decreased risk of subsequent cardiovascular events, suggesting that the observed imaging benefit may not translate into meaningful clinical association.
双膦酸盐可能通过抑制甲羟戊酸途径中的法尼基焦磷酸合酶来影响血管钙化和动脉粥样硬化形成，该途径调节骨骼和脂质代谢。然而，使用含氮双膦酸盐（NCB）对心血管结局的临床影响仍不确定，这主要是由于既往研究中方法学的异质性。我们旨在评估含氮双膦酸盐（NCB）治疗与冠状动脉钙化（CAC）进展之间的关联，以及心血管疾病（CVD）和冠心病（CHD）事件的发生率。在MESA Exam 1的6814名参与者中，我们排除了男性（MESA队列中男性NCB使用者不足）、绝经前女性、基线NCB使用者以及激素替代疗法、雷洛昔芬或降钙素使用者。在166名NCB起始使用者和1571名有可用CAC测量值的非使用者中，使用FRAX的可用成分（即年龄、种族、BMI、低密度脂蛋白胆固醇、酒精、吸烟和类固醇使用情况）进行倾向评分匹配，基线CAC使165名NCB起始使用者与473名非使用者匹配（1:3比例）。线性混合效应模型评估CAC进展，Cox模型分析CVD和CHD事件的发生率。在整个队列中，使用NCB与CAC进展无显著关联（年度变化：-0.01阿加斯顿单位对数；95%CI：-0.05至0.01）。然而，在基线估计肾小球滤过率（eGFR）<65 mL/min/1.73 m²的参与者中，与非使用者相比，使用NCB与CAC进展减缓相关（-0.06阿加斯顿单位对数/年；95%CI：-0.12至-0.007）。在整个队列中（HR：0.90；95%CI：0.60-1.36）或肾功能亚组中，未观察到使用NCB与CVD事件发生率之间的显著关联。基线时轻度或无CAC的绝经后女性中，开始使用NCB仅在肾功能受损的女性中与CAC进展减缓相关。然而，这种关联并不对应于随后心血管事件风险的降低，这表明观察到的影像学益处可能无法转化为有意义的临床关联。
