Background and Purpose Because of increased life expectancy, most postmenopausal women today suffer from osteoporosis and atherosclerotic diseases, which are currently considered unrelated diseases. Our study was aimed at analyzing relations between bone mineral density (BMD) and ultrasonographic assessment of carotid wall characteristics.
Methods The relation of carotid atherosclerosis to BMD was examined in 30 postmenopausal women aged 67 to 85 years. High-resolution B-mode ultrasonography was performed, and the severity of carotid atherosclerosis was determined by plaque score. BMD was measured by dual-energy x-ray absorptiometry.
Results The correlation of plaque score with low total BMD was r=.549 (P<.002). Multiple linear regression analysis indicated significant correlation of plaque score with total cholesterol level and low total BMD.
Conclusions Our results suggest a relation between carotid atherosclerosis, one of the major causes of ischemic cerebrovascular diseases, and osteoporosis.
Atherosclerosis and osteoporosis are currently considered unrelated diseases. As age advances, osteoporosis is more frequently found in women than men; atherosclerosis is an illness predominantly affecting men. A parallel relation has been noted between spinal osteoporosis and aortic calcification due to atherosclerosis.1 2 (Pathological calcification of the arterial wall is an underlying feature of atherosclerosis.) Because of increased life expectancy, many postmenopausal women today suffer from osteoporosis and atherosclerotic diseases, such as coronary heart disease and cerebrovascular disease.
Extracranial carotid atherosclerosis is one of the major causes of cerebrovascular diseases.3 In our present investigation, we performed high-resolution real-time B-mode ultrasonography to determine the extent of carotid atherosclerosis and quantified the results by use of a scoring system. We then evaluated the relation between osteoporosis and carotid atherosclerosis.
Subjects and Methods
The study surveys, which were ultrasonographic assessments of the carotid arteries and evaluations of BMD, were carried out from July 1994 to April 1995. Thirty postmenopausal women aged 67 to 85 (mean±SD, 75.3±5.5) years from a private, upper-middle-class senior citizens residence participated in this study. All subjects underwent a health examination to screen for age-related diseases (arteriosclerotic disease, hypertension, diabetes mellitus, hypercholesterolemia, and heart diseases). None of the subjects had diseases that interfered with the activities of normal daily life. Informed consent was obtained from each subject.
In all subjects, carotid B-mode imaging was performed with a 7.5-MHz transducer with an axial resolution of less than 0.4 mm (EUB-555, Hitachi, Japan). The subject was seated comfortably, and scanning of the extracranial carotid arteries in the neck was performed bilaterally in three different longitudinal projections and in the transverse projection. Severity of carotid atherosclerosis was evaluated by plaque score. This score, through use of the scoring system method of Handa and colleagues,3 was computed by summing the maximum thickness (in millimeters) of the intima-media complex (plaque thickness) of both sides of the carotid arteries. All ultrasound examinations were performed by a single sonographer (O.U.), who was blinded to the BMD readings. The mean coefficient of variation for the difference between plaque scores obtained in repeated examinations performed by the same examiner was less than 8%.
Total BMD, defined as the total BMC divided by the area (g/cm2), was measured by use of dual-energy x-ray absorptiometry (XR-26 x-ray bone densitometer, Norland). Lumbar spine BMD (L2-L4) was also measured.
Data are expressed as mean±SD. The relation between the plaque score and BMD was evaluated by linear regression analysis. Multiple linear regression analysis was used to assess the correlation among BMD, carotid lesion, and risk factors (age, hypertension, and hypercholesterolemia).
Subjects were considered hypertensive if they were taking antihypertensive agents or if blood pressure measured in our institute was >160 mm Hg systolic or >95 mm Hg diastolic (n=12). Subjects were considered diabetic if they were being treated for diabetes with oral hypoglycemic agents or insulin or if the glycosylated hemoglobin (HbA1c) level was >7.0% (n=1). Subjects were considered hypercholesterolemic if they were taking antihypercholesterolemic agents or their serum cholesterol level was >220 mg/dL (n=13). The atherogenic index was calculated as the ratio of (total cholesterol−HDL cholesterol) to HDL cholesterol. Only one subject was a moderate drinker (up to 10 g alcohol per day) or a smoker. The characteristics of subjects are shown in Table 1⇓.
As shown in the Figure⇓, there was a significant linear correlation (r=.549; P<.002) between plaque score and low total BMD. Lumbar spine BMD was not significantly associated with plaque score. We also examined the associations among plaque score, age, hypertension, total cholesterol, atherogenic index, and total BMD. Multiple linear regression analysis indicated significant correlation of plaque score with age, total cholesterol level, and low total BMD. Hypertension and atherogenic index were not significantly associated with carotid atherosclerosis in the postmenopausal women in our study (Table 2⇓).
Some studies1 2 have suggested a relation between spinal osteoporosis and aortic calcification due to atherosclerosis. The mechanism of this apparent calcium shift from bone to soft tissue remains to be elucidated. Osteoporosis has been ascribed to prolonged calcium deficiency leading to secondary hyperparathyroidism. The increase in atherosclerosis among women as they develop osteoporosis suggests that the two illnesses may be more closely related than previously realized. It has been suggested4 that the use of vitamin D as a food supplement coincides with epidemic onsets of atherosclerosis and osteoporosis and that excess vitamin D induces both conditions in humans and laboratory animals. Nordin et al5 studied the effects of six different treatment regimens on 95 postmenopausal women with unequivocally wedged or compressed vertebrae. Three treatments (calcium, estrogens, and 1α-OHD3 plus hormones) appear to be useful. Vitamin D (10 000 to 50 000 IU/d) and 1α-OHD3 (1 to 2 μg/d) resulted in increased bone calcium resorption. The amount of vitamin D that may increase the incidence of cardiovascular degeneration was estimated in one epidemiological study to be 30 μg (1200 IU)/d.6 Fifteen patients in our study had been treated with 1α-OHD3 (0.25 to 1.0 μg/d). There were no significant differences in plaque score and total BMD between the untreated and treated patients (plaque score, 3.38±3.08 versus 3.34±4.59; total BMD, 0.740±0.084 versus 0.739±0.075 g/cm2).
Laroche et al7 studied by dual-energy x-ray absorptiometry the BMC of both legs in 18 men presenting with symptomatic arterial disease of the lower limbs. The mean BMC of the leg more severely affected by arterial disease was significantly lower than that of the leg less affected. They suggest that demineralization seems to be related to a direct local effect of atherosclerosis and not to associated general risk factors (eg, tobacco consumption, sedentary lifestyle, lower body-build index). It is tempting to suggest that systemic atherosclerosis is reflected in carotid atherosclerosis and is responsible for osteoporosis.
Broulik and Kapitola8 demonstrated that women with osteoporosis had higher cholesterol levels than control subjects and that BMD in cigarette smokers was significantly lower than in nonsmokers and was not associated with low body weight. Hypercholesterolemia and tobacco consumption are known risk factors for atherosclerosis,3 9 and the link between these risk factors and osteoporosis could well be arterial disease.
Sato et al10 showed that many hemiplegic stroke patients have hypovitaminosis D and osteopenia. A combination of sunlight deprivation due to immobilization (which is caused by cerebral arteriosclerosis) together with decreased dietary intake of vitamin D may be responsible for osteoporosis in subjects with severe carotid atherosclerosis. Our results suggest a relation between osteoporosis and atherosclerosis.
Selected Abbreviations and Acronyms
|BMC||=||bone mineral content|
|BMD||=||bone mineral density|
- Received February 12, 1997.
- Revision received May 28, 1997.
- Accepted May 28, 1997.
- Copyright © 1997 by American Heart Association
Dent CE, Engelbrecht HE, Godfrey RC. Osteoporosis of lumbar vertebrae and calcification of abdominal aorta in women living in Durban. Br Med J. 1968;4:76-79.
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Nordin BE, Horsman A, Crilly RG, Marshall DH, Simpson M. Treatment of spinal osteoporosis in postmenopausal women. Br Med J. 1980;280:451-455.
Linden V. Vitamin D and myocardial infarction. Br Med J. 1974;3:647-650.
Sato Y, Maruoka H, Oizumi K, Kikuyama M. Vitamin D deficiency and osteopenia in the hemiplegic limbs of the stroke patients. Stroke. 1996;27:2183-2187.