Good bone quality linked to better CV health for UK adults
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Participants in the UK Biobank who had a higher bone speed of sound were more likely to have good cardiovascular health, according to a study published in The Journal of Bone and Mineral Research.
“Cardiovascular disease, in particular, ischemic heart disease, is an important global cause of morbidity and mortality. Osteoporosis is a growing public health problem, particularly in aging populations. These two conditions share a number of risk factors, such as older age, sedentary lifestyle and smoking,” Zahra Raisi-Estabragh, MBBS, PhD, a British Heart Foundation clinical research training fellow at Queen Mary University of London, told Healio. “Existing work suggests associations between the two conditions that extend beyond their common risk factors. Furthermore, limited biological studies have suggested potential mechanistic links between the two conditions. Understanding the interplay between ischemic heart disease and osteoporosis may provide insight into novel disease pathways and inform interventional and population health strategies.”
Raisi-Estabragh and colleagues at the MRC Lifecourse Epidemiology Unit (MRC LEU), University of Southampton, and the William Harvey Research Institute, NIHR Barts Biomedical Research Centre, QMU, analyzed data collected in the UK Biobank, a population study conducted among adults aged 40 to 69 years from 2006 to 2010 in the United Kingdom. Researchers collected data from participants who had a calcaneal quantitative ultrasound to measure bone speed of sound, with higher speed of sound values indicating better bone health.
Researchers used three metrics to determine CV health. The arterial stiffness index was calculated at baseline using finger photoplethysmography, with lower values indicating better CV health. Aortic distensibility was assessed with CV MRI, with higher values indicating better CV health. Researchers also compiled the number of incidents of myocardial infarction and ischemic heart disease mortality among participants during a follow-up duration of 7 to 12 years.
Complete bone speed of sound and arterial stiffness index data were available for 71,949 men and 87,593 women (mean age, 58 years; 91.9% white). In a fully adjusted model, higher speed of sound values were associated with lower arterial stiffness index, with similar values found for men and women and for premenopausal and postmenopausal women. Higher speed of sound was associated with greater aortic distensibility in the ascending aorta for women and in the descending aorta for men.
Mediators in the association differed for men and women. For men, alkaline phosphatase accounted for 7.5% of the association, phosphate accounted for 4.6% and vitamin D was responsible for 3.2%. For women, phosphate accounted for 13.2%, whereas alkaline phosphatase accounted for 9.6%. For men, C-reactive protein accounted for 6.1% of the effect, but the effect was reversed for women, accounting for –8.6%. Sex hormone-binding globulin had a similar effect for men (17.14%) and women (19.55%).
In crude models, a higher bone speed of sound was associated with a lower risk for MI and ischemic heart disease mortality in men. In a model adjusted for hypertension, hypercholesterolemia and diabetes, each one standard deviation increase in bone speed of sound was associated with a 14% lower risk for ischemic heart disease mortality for men (subdistribution HR = 0.86; 95% CI, 0.75-1). Women had a much weaker association between higher speed of sound and a lower risk for MI and reduced heart disease morality.
“We demonstrate, in the largest cohort ever studied, that poorer bone health is associated with poorer vascular health as measured by objective and validated methods, whilst accounting for classical cardiovascular risk factors. We also demonstrate the association of poorer bone health with greater risk of ischemic heart disease deaths. These relationships were consistent for men and women and were not modified by menopause status,” Raisi-Estabragh said.
The mechanisms driving the associations are complex and likely vary by sex, Raisi-Estabragh noted.
“The wealth of information available in the UK Biobank permitted a highly detailed analysis of the complex interactions between musculoskeletal and cardiovascular health, helping to elucidate potential underlying mechanisms and informing novel approaches to clinical risk assessment,” Nicholas Harvey, PhD, professor of rheumatology and clinical epidemiology at the MRC LEU, University of Southampton, who supervised the work, told Healio.
Perspective
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There has been a considerable body of observational data linking osteoporosis to cardiovascular disease. This study by Raisi-Estabragh and colleagues is notable for the largest number of subjects studied to date, and while the skeletal phenotyping was limited to calcaneal quantitative ultrasound, the vascular phenotyping was exquisite and included measures of arterial stiffness, aortic distensibility and cardiovascular outcomes. The findings reinforce a significant link between skeletal deterioration and CV measures, including CV mortality.
These findings are also relevant to an issue that is currently confronting clinicians, namely weighing the skeletal benefits vs. CV risks of treatment with the sclerostin antibody romosozumab-aqqg (Evenity, Amgen). As summarized elsewhere (Khosla S. Nat Rev Endocrinol. 2017;doi:10.1038/nrendo.2017.136), romosozumab is the most potent drug currently available to increase bone mass. However, two different studies have provided conflicting data regarding the CV risks associated with romosozumab therapy. In the FRAME trial (Cosman, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1607948), where only 18.3% of women had existing vertebral fractures, there was no increased risk for serious CV events associated with romosozumab treatment. By contrast, in the ARCH trial (Saag, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1708322), where 96.1% of women had existing vertebral fractures, romosozumab was associated with a 32% increase in serious CV events. Based on the study by Raisi-Estabragh et al, a logical explanation is that because of the link between osteoporosis and CVD, the women in the ARCH trial had a much greater existing burden of CVD and, hence, were more susceptible to any adverse CV effects of romosozumab.
Finally, although Raisi-Estabragh and colleagues searched for possible mediators using serum markers, clearly observational data such as this cannot provide evidence for causal links, which requires direct interventional as well as animal studies. Nonetheless, this study is important for its definitive findings and should spur investigators to further define the underlying mechanisms linking osteoporosis to CVD.
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