Abdominal Aortic Calcification, Bone Mineral Density, and Fractures: A Systematic Review and Meta-analysis of Observational Studies

Abstract

Background Abdominal aortic calcification (AAC) has been inconsistently associated with skeletal health. We aimed to investigate the association of AAC with bone mineral density (BMD) and fracture risk by pooling the findings of observational studies. Methods Medline, EMBASE, Web of Science and Google Scholar were searched (August 2021). All clinical studies that assessed the association between AAC and BMD or fracture were included. AAC was categorized into any/advanced (all higher reported groups) vs no/less advanced (lowest reported group). Pooled standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CI) were determined for BMD and fracture, respectively, using random-effects models. Results Of 2,192 articles screened, 86 (61,553 participants) were included in the review, while 42 provided data for meta-analysis. AAC was associated with lower BMD at the total hip [SMD=-1.05 (95%CI: -1.47 to -0.63); 16 studies], femoral neck [-0.25 (-0.46 to - 0.04); 10] and lumbar spine [-0.67 (-1.21 to -0.12); 20]. AAC was associated with a greater risk of any fracture [RR= 1.73 (95%CI: 1.48 to 2.02); 27]. AAC was also associated with vertebral, non-vertebral and hip fractures. In dose-response analysis, the highest AAC group had greater risks of any, vertebral and non-vertebral fractures. Conclusions AAC is associated with lower BMD and increased fracture risk at multiple sites, underscoring the potential importance of vascular disease on skeletal health. Detection of AAC at the time of BMD testing may provide clinicians with prognostic information about bone health to enhance osteoporosis screening programs and fracture risk prediction.

Machine-Learning Assessed Abdominal Aortic Calcification is Associated with Long-Term Fall and Fracture Risk in Community-Dwelling Older Australian Women

“…[11] Overall, falls and fracture risk estimates using ML-AAC24 appear consistent with manually assessed AAC, which aligns with the good levels of agreement reported between the ML-AAC24 and AAC scored by trained imaging specialists. [13] We and others have shown that the presence and extent of manually assessed AAC is associated with impaired musculoskeletal health, [7,8,11] increased risk for all-cause mortality and cardiac events, [6] as well as late-life dementia hospitalizations and deaths. [25] Recently, we reported that women with higher ML-AAC24 had increased risk of all-cause mortality and CVD-related mortality.…”

“…[11] In support of the current results showing poorer bone health with moderate to extensive ML-AAC24, a meta-analysis of 30 studies showed that those with any/advanced AAC had lower BMD at the total hip, femoral neck, and lumbar spine. [11] Overall, falls and fracture risk estimates using ML-AAC24 appear consistent with manually assessed AAC, which aligns with the good levels of agreement reported between the ML-AAC24 and AAC scored by trained imaging specialists. [13] We and others have shown that the presence and extent of manually assessed AAC is associated with impaired musculoskeletal health, [7,8,11] increased risk for all-cause mortality and cardiac events, [6] as well as late-life dementia hospitalizations and deaths.…”

“…The potential mechanisms underlying the observed relationships between AAC and falls and fracture risk have been discussed. [7,8,11] Briefly, this may relate to impaired blood flow to the skeleton distal to the abdominal aorta negatively influencing BMD, which may contribute to increasing fracture risk. Vascular disease may also contribute to increased falls propensity, and subsequent fracture, via various mechanisms.…”

“…[24] There are also shared genetic and environmental risk factors for muscle, bone, and vascular health. [7,8,11] However, the potential mechanisms require further investigation. Although moderate to extensive ML-AAC24 was associated with incident self-reported clinical fractures, it was not associated with incident fracture-related hospitalizations.…”

“…[2,3] More extensive AAC is associated with an increased risk of cardiovascular disease (CVD) and related events, CVD and all-cause mortality, [4][5][6] as well as lower BMD, poorer muscle strength, and increased risk for injurious falls and fracture. [7][8][9][10][11] A major limitation for the clinical assessment of AAC is that it needs to be manually scored by a trained expert, a time-consuming task that limits the possibility for AAC assessment to be scaled and incorporated into routine clinical assessment, especially as part of osteoporosis screening. To address this limitation, machine learning (ML) approaches have been investigated to automate the identification of AAC and AAC-24 scoring from lateral spine images.…”