Aortic Calcification Linked to Hip Fracture Risk

TORONTO — Aortic calcification was found to be an independent predictor of accelerated bone loss and hip fracture among postmenopausal women in a prospective epidemiologic study, Dr. Laszlo B. Tanko said at a world congress on osteoporosis.

Epidemiologic studies have suggested a link between cardiovascular disease and osteoporosis, two conditions that clearly are major contributors to morbidity and mortality in the elderly, but whether atherosclerosis is an independent contributor to fracture risk had not yet been determined, Dr. Tanko said. In the first long-term study addressing the questions of whether the severity and progression of aortic calcification might be associated with bone loss and fracture risk, Dr. Tanko and his colleagues from the Center for Clinical and Basic Research, Ballerup, Denmark, analyzed data from the Danish Prospective Epidemiological Risk Factors study.

In this study of 2,662 postmenopausal women, investigators identified classic cardiovascular risk factors in a baseline interview. They assessed aortic calcification using lateral x-rays and scored any calcification according to the Framingham system. Lumbar spine and total hip bone mineral density (BMD) were measured by dual-energy x-ray absorptiometry.

A total of 1,877 patients had normal aortic calcification scores (below 3) at baseline, while 785 had scores of 3 or higher. Mean score among those in the group with lower scores was 0.4, compared with 6.5 among those in the higher-scores group.

Those with advanced aortic calcification at baseline subsequently had annual rates of progression of atherosclerotic burden that were approximately 2.5 higher than did those with normal calcification at baseline, Dr. Tanko said at the meeting, which was sponsored by the International Osteoporosis Foundation.

BMD scores at baseline for lumbar spine and hip were significantly lower among women with advanced atherosclerosis, with means of 0.84 g/cm

These differences were independent of age and body mass index, he said.

Accelerated subsequent rates of bone loss were seen among women with advanced atherosclerosis but not among those who were normal at baseline.

But at the lumbar spine, increases in BMD, rather than decreases, were seen among the advanced atherosclerosis group. An explanation for this may lie in the fact that the local blood supply to the proximal femur is unilateral, delicate, and more vulnerable to impaired blood flow than is blood supply to the vertebrae. Vertebral blood supply is bilateral and more advanced in terms of compensating for arterial obstruction, Dr. Tanko said.

During the study follow-up period, which averaged 7.5 years, there were 431 incident vertebral fractures and 37 incident hip fractures. There also were 113 acute cardiovascular events.

On multivariate regression analysis, there was a slightly increased but not statistically significant risk (relative risk 1.2) of vertebral fractures among those with advanced aortic calcification at baseline. Hip fracture risk, however, was 2.3-fold increased among those with higher calcification, compared with those whose calcification scores were normal at baseline. Regression analysis also showed that women with higher calcification also had a 2.5-fold increased risk of a cardiovascular event.

“We can say that aortic calcification is an independent predictor of accelerated bone loss and incident fracture at the hip but not at the vertebra. We are tempted to speculate that antiatherogenic measures might help decrease not only cardiovascular disease but also might help prevent fractures,” Dr. Tanko said.

In the question and answer session following Dr. Tanko's presentation, an audience member asked if he had considered the possibility that both atherosclerosis and bone loss are associated with a single common factor such as a cytokine cascade, or whether the bone loss might be causing atherosclerosis.

Dr. Tanko acknowledged that although he could not exclude systemic factors such as the impact of proinflammatory cytokines, he believed that his findings more clearly demonstrate the direct impact of ischemic atherosclerotic vascular disease on local bone metabolism.

He recently wrote that the underlying mechanism linking osteoporosis and cardiovascular disease is not yet fully understood, but “it seems reasonable to presume that the independent association reflects either a direct contribution of ischemic vascular disease to bone turnover or common pathomechanisms acting simultaneously on both bone and vascular cells. As for the latter option, proinflammatory cytokines such as IL-6 and TNF-α are known to exert proatherogenic effects, but they may also enhance osteoclastogenesis and consequently increased bone resorption” (J. Intern. Med. 2006;259:598–605).

Heavy calcification of the aortic wall (red arrows) at its site of bifurcation. Courtesy Dr. Laszlo B. Tanko

TORONTO — Aortic calcification was found to be an independent predictor of accelerated bone loss and hip fracture among postmenopausal women in a prospective epidemiologic study, Dr. Laszlo B. Tanko said at a world congress on osteoporosis.

Epidemiologic studies have suggested a link between cardiovascular disease and osteoporosis, two conditions that clearly are major contributors to morbidity and mortality in the elderly, but whether atherosclerosis is an independent contributor to fracture risk had not yet been determined, Dr. Tanko said. In the first long-term study addressing the questions of whether the severity and progression of aortic calcification might be associated with bone loss and fracture risk, Dr. Tanko and his colleagues from the Center for Clinical and Basic Research, Ballerup, Denmark, analyzed data from the Danish Prospective Epidemiological Risk Factors study.

In this study of 2,662 postmenopausal women, investigators identified classic cardiovascular risk factors in a baseline interview. They assessed aortic calcification using lateral x-rays and scored any calcification according to the Framingham system. Lumbar spine and total hip bone mineral density (BMD) were measured by dual-energy x-ray absorptiometry.

A total of 1,877 patients had normal aortic calcification scores (below 3) at baseline, while 785 had scores of 3 or higher. Mean score among those in the group with lower scores was 0.4, compared with 6.5 among those in the higher-scores group.

Those with advanced aortic calcification at baseline subsequently had annual rates of progression of atherosclerotic burden that were approximately 2.5 higher than did those with normal calcification at baseline, Dr. Tanko said at the meeting, which was sponsored by the International Osteoporosis Foundation.

BMD scores at baseline for lumbar spine and hip were significantly lower among women with advanced atherosclerosis, with means of 0.84 g/cm

These differences were independent of age and body mass index, he said.

Accelerated subsequent rates of bone loss were seen among women with advanced atherosclerosis but not among those who were normal at baseline.

But at the lumbar spine, increases in BMD, rather than decreases, were seen among the advanced atherosclerosis group. An explanation for this may lie in the fact that the local blood supply to the proximal femur is unilateral, delicate, and more vulnerable to impaired blood flow than is blood supply to the vertebrae. Vertebral blood supply is bilateral and more advanced in terms of compensating for arterial obstruction, Dr. Tanko said.

During the study follow-up period, which averaged 7.5 years, there were 431 incident vertebral fractures and 37 incident hip fractures. There also were 113 acute cardiovascular events.

On multivariate regression analysis, there was a slightly increased but not statistically significant risk (relative risk 1.2) of vertebral fractures among those with advanced aortic calcification at baseline. Hip fracture risk, however, was 2.3-fold increased among those with higher calcification, compared with those whose calcification scores were normal at baseline. Regression analysis also showed that women with higher calcification also had a 2.5-fold increased risk of a cardiovascular event.

“We can say that aortic calcification is an independent predictor of accelerated bone loss and incident fracture at the hip but not at the vertebra. We are tempted to speculate that antiatherogenic measures might help decrease not only cardiovascular disease but also might help prevent fractures,” Dr. Tanko said.

In the question and answer session following Dr. Tanko's presentation, an audience member asked if he had considered the possibility that both atherosclerosis and bone loss are associated with a single common factor such as a cytokine cascade, or whether the bone loss might be causing atherosclerosis.

Dr. Tanko acknowledged that although he could not exclude systemic factors such as the impact of proinflammatory cytokines, he believed that his findings more clearly demonstrate the direct impact of ischemic atherosclerotic vascular disease on local bone metabolism.

He recently wrote that the underlying mechanism linking osteoporosis and cardiovascular disease is not yet fully understood, but “it seems reasonable to presume that the independent association reflects either a direct contribution of ischemic vascular disease to bone turnover or common pathomechanisms acting simultaneously on both bone and vascular cells. As for the latter option, proinflammatory cytokines such as IL-6 and TNF-α are known to exert proatherogenic effects, but they may also enhance osteoclastogenesis and consequently increased bone resorption” (J. Intern. Med. 2006;259:598–605).

Heavy calcification of the aortic wall (red arrows) at its site of bifurcation. Courtesy Dr. Laszlo B. Tanko

TORONTO — Aortic calcification was found to be an independent predictor of accelerated bone loss and hip fracture among postmenopausal women in a prospective epidemiologic study, Dr. Laszlo B. Tanko said at a world congress on osteoporosis.

Epidemiologic studies have suggested a link between cardiovascular disease and osteoporosis, two conditions that clearly are major contributors to morbidity and mortality in the elderly, but whether atherosclerosis is an independent contributor to fracture risk had not yet been determined, Dr. Tanko said. In the first long-term study addressing the questions of whether the severity and progression of aortic calcification might be associated with bone loss and fracture risk, Dr. Tanko and his colleagues from the Center for Clinical and Basic Research, Ballerup, Denmark, analyzed data from the Danish Prospective Epidemiological Risk Factors study.

In this study of 2,662 postmenopausal women, investigators identified classic cardiovascular risk factors in a baseline interview. They assessed aortic calcification using lateral x-rays and scored any calcification according to the Framingham system. Lumbar spine and total hip bone mineral density (BMD) were measured by dual-energy x-ray absorptiometry.

A total of 1,877 patients had normal aortic calcification scores (below 3) at baseline, while 785 had scores of 3 or higher. Mean score among those in the group with lower scores was 0.4, compared with 6.5 among those in the higher-scores group.

Those with advanced aortic calcification at baseline subsequently had annual rates of progression of atherosclerotic burden that were approximately 2.5 higher than did those with normal calcification at baseline, Dr. Tanko said at the meeting, which was sponsored by the International Osteoporosis Foundation.

BMD scores at baseline for lumbar spine and hip were significantly lower among women with advanced atherosclerosis, with means of 0.84 g/cm

These differences were independent of age and body mass index, he said.

Accelerated subsequent rates of bone loss were seen among women with advanced atherosclerosis but not among those who were normal at baseline.

But at the lumbar spine, increases in BMD, rather than decreases, were seen among the advanced atherosclerosis group. An explanation for this may lie in the fact that the local blood supply to the proximal femur is unilateral, delicate, and more vulnerable to impaired blood flow than is blood supply to the vertebrae. Vertebral blood supply is bilateral and more advanced in terms of compensating for arterial obstruction, Dr. Tanko said.

During the study follow-up period, which averaged 7.5 years, there were 431 incident vertebral fractures and 37 incident hip fractures. There also were 113 acute cardiovascular events.

On multivariate regression analysis, there was a slightly increased but not statistically significant risk (relative risk 1.2) of vertebral fractures among those with advanced aortic calcification at baseline. Hip fracture risk, however, was 2.3-fold increased among those with higher calcification, compared with those whose calcification scores were normal at baseline. Regression analysis also showed that women with higher calcification also had a 2.5-fold increased risk of a cardiovascular event.

“We can say that aortic calcification is an independent predictor of accelerated bone loss and incident fracture at the hip but not at the vertebra. We are tempted to speculate that antiatherogenic measures might help decrease not only cardiovascular disease but also might help prevent fractures,” Dr. Tanko said.

In the question and answer session following Dr. Tanko's presentation, an audience member asked if he had considered the possibility that both atherosclerosis and bone loss are associated with a single common factor such as a cytokine cascade, or whether the bone loss might be causing atherosclerosis.

Dr. Tanko acknowledged that although he could not exclude systemic factors such as the impact of proinflammatory cytokines, he believed that his findings more clearly demonstrate the direct impact of ischemic atherosclerotic vascular disease on local bone metabolism.

He recently wrote that the underlying mechanism linking osteoporosis and cardiovascular disease is not yet fully understood, but “it seems reasonable to presume that the independent association reflects either a direct contribution of ischemic vascular disease to bone turnover or common pathomechanisms acting simultaneously on both bone and vascular cells. As for the latter option, proinflammatory cytokines such as IL-6 and TNF-α are known to exert proatherogenic effects, but they may also enhance osteoclastogenesis and consequently increased bone resorption” (J. Intern. Med. 2006;259:598–605).

Heavy calcification of the aortic wall (red arrows) at its site of bifurcation. Courtesy Dr. Laszlo B. Tanko