Associations of Trabecular and Cortical Volumetric Bone Mineral Density With Coronary Artery Calcification Score: The Swedish Cardiopulmonary Bioimage Study Pilot Study | Cardiology | JAMA Cardiology | JAMA Network
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Figure.  Associations of Trabecular and Cortical Bone Mineral Density With Coronary Artery Calcification Score (CACS)
Associations of Trabecular and Cortical Bone Mineral Density With Coronary Artery Calcification Score (CACS)

A, Odds ratios (OR) and 95% confidence intervals are represented for the risk of CACS greater than 0 per 1-SD increase in trabecular bone volumetric bone mineral density (Tb.vBMD; blue dots) or cortical vBMD (Ct.vBMD, orange dots) in the global cohort (n = 1060) or in sex-stratified populations (n = 519 men and n = 539 women) using base or full logistic regression models (n = 1021 all, n = 503 men, and n = 518 women). The combined base logistic model was adjusted for age, sex, and body mass index (and menopausal status in women), while the full model was further adjusted for smoking status, diabetes, hypertension, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, physical activity, and family history of cardiovascular event. B, OR and 95% confidence intervals represent the risk of CACS greater than 0 in individuals with Ct.vBMD/Tb.vBMD ratio greater than the median (8.32) using base and full logistic regression models (same number as is A).

Table.  Participant Characteristicsa
Participant Characteristicsa
1.
Chan  JJ, Cupples  LA, Kiel  DP, O’Donnell  CJ, Hoffmann  U, Samelson  EJ.  QCT volumetric bone mineral density and vascular and valvular calcification: the Framingham study.   J Bone Miner Res. 2015;30(10):1767-1774. doi:10.1002/jbmr.2530PubMedGoogle ScholarCrossref
2.
Ahmadi  N, Mao  SS, Hajsadeghi  F,  et al.  The relation of low levels of bone mineral density with coronary artery calcium and mortality.   Osteoporos Int. 2018;29(7):1609-1616. doi:10.1007/s00198-018-4524-7PubMedGoogle ScholarCrossref
3.
Brommage  R, Ohlsson  C.  Translational studies provide insights for the etiology and treatment of cortical bone osteoporosis.   Best Pract Res Clin Endocrinol Metab. 2018;32(3):329-340. doi:10.1016/j.beem.2018.02.006PubMedGoogle ScholarCrossref
4.
Ekblom-Bak  E, Ekblom  Ö, Fagman  E,  et al.  Fitness attenuates the prevalence of increased coronary artery calcium in individuals with metabolic syndrome.   Eur J Prev Cardiol. 2018;25(3):309-316. doi:10.1177/2047487317745177PubMedGoogle ScholarCrossref
5.
Sigurdsson  G, Aspelund  T, Chang  M,  et al.  Increasing sex difference in bone strength in old age: the Age, Gene/Environment Susceptibility-Reykjavik study (AGES-REYKJAVIK).   Bone. 2006;39(3):644-651. doi:10.1016/j.bone.2006.03.020PubMedGoogle ScholarCrossref
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Research Letter
October 14, 2020

Associations of Trabecular and Cortical Volumetric Bone Mineral Density With Coronary Artery Calcification Score: The Swedish Cardiopulmonary Bioimage Study Pilot Study

Author Affiliations
  • 1Center for Bone and Arthritis Research, Institute of Medicine, Department of Internal Medicine and Clinical Nutrition, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
  • 2Lariboisière Hospital, Department of Rheumatology, Université de Paris, Paris, France
  • 3Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden
  • 4Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  • 5Institute of Clinical Sciences, Department of Radiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  • 6Department of Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden
  • 7Region Västra Götaland, Department of Drug Treatment, Sahlgrenska University Hospital, Gothenburg, Sweden
JAMA Cardiol. 2021;6(2):238-240. doi:10.1001/jamacardio.2020.4880

The link between osteoporosis and cardiovascular diseases has been extensively reported, and previous studies show an inverse association between trabecular bone volumetric bone mineral density (Tb.vBMD) in the spine and coronary artery calcification score (CACS).1,2 However, the association between cortical vBMD (Ct.vBMD) in the long bones and CACS may differ from the association for Tb.vBMD because the 2 bone compartments are largely differentially regulated.3

Methods

To compare the associations of Tb.vBMD and Ct.vBMD with CACS, we used the cross-sectional population-based Swedish Cardiopulmonary Bioimage Study (SCAPIS) pilot cohort, consisting of randomly selected participants aged 50 to 64 years.4 Coronary artery calcification score expressed as Agatston score,4 Tb.vBMD in the vertebral body of the 12th thoracic vertebra,5 and Ct.vBMD at the right midshaft femur5 were all assessed in 1060 participants (519 men and 541 women) using computed tomography (Table). Institutional ethical review board approval was obtained, and written consent was obtained for all patients. A 2-sided P value less than .05 was considered significant.

Results

The association between Tb.vBMD and Ct.vBMD was modest (variance explained r2 = 11%), demonstrating that these parameters may provide substantial nonoverlapping information for prediction of CACS. In combined models also adjusted for cardiovascular risk factors (full model in the Figure), Tb.vBMD was independently inversely associated with CACS greater than 0 (per SD increase, odds ratio [OR], 0.79; 95% CI, 0.67 to 0.94), while Ct.vBMD was independently directly associated with CACS greater than 0 (per SD increase, OR, 1.24; 95% CI, 1.05 to 1.46). Sex-stratified analyses revealed that these associations were only significant in women (Figure, A).

Based on these findings, we hypothesized that the ratio between Ct.vBMD and Tb.vBMD might be a risk marker for coronary artery calcification. A high Ct.vBMD/Tb.vBMD ratio was indeed associated with an increased risk of CACS greater than 0 (greater than vs less than the median, OR, 1.46; 95% CI, 1.08 to 1.99; full model; CACS 0 = referent). Sex-stratified analyses revealed that this association was significant in women but not men (Figure, B). The Ct.vBMD/Tb.vBMD ratio was also associated with CACS greater than 100 (OR, 1.87; 95% CI, 1.12 to 3.11; full model; CACS 0 = referent).

Discussion

The finding of an inverse association between Tb.vBMD in the spine and CACS greater than 0 confirms previous studies,1,2 while the observation of a direct association between Ct.vBMD in a long bone and CACS is novel. Previous analyses of cortical vBMD defined as the outer 1-mm bone of the vertebral body did not show a significant association with CACS in the Framingham study,1 but this cortical bone compartment is not representative of the cortical bone of long bones. The opposite directions of the associations for trabecular and cortical vBMD with CACS may be explained by the known difference in the regulation of trabecular and cortical bone.3 Because of its greater surface area, trabecular bone is more rapidly lost than cortical bone when remodeling becomes unbalanced. In addition, the regulation of the 2 bone compartments by hormones, growth factors, and medications differs substantially.3 It has been proposed that the established inverse link between trabecular vBMD and CACS could be mediated via inflammation, estrogen status, and/or lipids and that this link is more pronounced in women.1 One may speculate that the direct independent association between Ct.vBMD and CACS depends on partly similar mechanisms that regulate cortical bone mineralization and coronary artery calcification. The main limitation of this study is its cross-sectional design. Validation in independent cohorts should be performed to determine whether the cortical to trabecular vBMD ratio, integrating information from both bone compartments, may be used as a risk marker for coronary artery disease in women.

Conclusions

To our knowledge, this study provides the first demonstration of opposite associations for trabecular and cortical vBMD with CACS, suggesting a differential role of trabecular and cortical vBMD on the risk of coronary artery calcification, mainly in women. We propose that distinct pathophysiologic mechanisms exist for the trabecular vs cortical bone in the bone-vascular axis.

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Article Information

Corresponding Author: Claes Ohlsson, MD, PhD, Centre for Bone and Arthritis Research, Klin Farm Laboratory, Vita Stråket 11, SE-41345 Gothenburg, Sweden (claes.ohlsson@medic.gu.se).

Accepted for Publication: August 17, 2020.

Published Online: October 14, 2020. doi:10.1001/jamacardio.2020.4880

Author Contributions: Dr Ohlsson had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Funck-Brentano, Brandberg, Ohlsson.

Acquisition, analysis, or interpretation of data: Funck-Brentano, Grahnemo, Hjelmgren, Brandberg, Bergström.

Drafting of the manuscript: Funck-Brentano, Hjelmgren, Ohlsson.

Critical revision of the manuscript for important intellectual content: Funck-Brentano, Grahnemo, Hjelmgren, Brandberg, Bergström.

Statistical analysis: Funck-Brentano, Grahnemo, Hjelmgren, Ohlsson.

Obtained funding: Bergström, Ohlsson.

Administrative, technical, or material support: Funck-Brentano, Hjelmgren, Brandberg, Bergström.

Supervision: Brandberg, Bergström, Ohlsson.

Conflict of Interest Disclosures: Dr Brandberg reported grants from Heart and Lung foundation during the conduct of the study. Dr Ohlsson reported grants from the Swedish Research Council, the Swedish state under the agreement between Swedish government and the country councils, the ALF-agreement, the Lundberg Foundation, the Knut and Alice Wallenberg Foundation, and the Novo Nordisk Foundation during the conduct of the study. No other disclosures were reported.

Funding/Support: The main funding body of The Swedish Cardiopulmonary Bioimage Study (SCAPIS) is the Swedish Heart and Lung Foundation. The study is also funded by the Knut and Alice Wallenberg Foundation, the Swedish Research Council and VINNOVA (Sweden’s Innovation agency). In addition, the SCAPIS Pilot study received support from the Sahlgrenska Academy at University of Gothenburg and Region Västra Götaland.

Additional Contributions: We thank the participants in this study and the staff at the SCAPIS test center in Gothenburg.

References
1.
Chan  JJ, Cupples  LA, Kiel  DP, O’Donnell  CJ, Hoffmann  U, Samelson  EJ.  QCT volumetric bone mineral density and vascular and valvular calcification: the Framingham study.   J Bone Miner Res. 2015;30(10):1767-1774. doi:10.1002/jbmr.2530PubMedGoogle ScholarCrossref
2.
Ahmadi  N, Mao  SS, Hajsadeghi  F,  et al.  The relation of low levels of bone mineral density with coronary artery calcium and mortality.   Osteoporos Int. 2018;29(7):1609-1616. doi:10.1007/s00198-018-4524-7PubMedGoogle ScholarCrossref
3.
Brommage  R, Ohlsson  C.  Translational studies provide insights for the etiology and treatment of cortical bone osteoporosis.   Best Pract Res Clin Endocrinol Metab. 2018;32(3):329-340. doi:10.1016/j.beem.2018.02.006PubMedGoogle ScholarCrossref
4.
Ekblom-Bak  E, Ekblom  Ö, Fagman  E,  et al.  Fitness attenuates the prevalence of increased coronary artery calcium in individuals with metabolic syndrome.   Eur J Prev Cardiol. 2018;25(3):309-316. doi:10.1177/2047487317745177PubMedGoogle ScholarCrossref
5.
Sigurdsson  G, Aspelund  T, Chang  M,  et al.  Increasing sex difference in bone strength in old age: the Age, Gene/Environment Susceptibility-Reykjavik study (AGES-REYKJAVIK).   Bone. 2006;39(3):644-651. doi:10.1016/j.bone.2006.03.020PubMedGoogle ScholarCrossref
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