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Detection of Vascular Disease Risk in Women by Panoramic Radiography
1 Department of Oral and Maxillofacial Radiology, Hiroshima University Dental Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan; Correspondence: *corresponding author, akiro{at}hiroshima-u.ac.jp
Low bone mineral density and rapid bone loss of the skeleton are associated with mortality risk from vascular diseases in post-menopausal women. Panoramic radiographic measurements are considered as indicators of skeletal bone mineral density or bone turnover. We hypothesize that such measurements may be associated with vascular disease risk in post-menopausal women. Associations of mandibular cortical shape and width on panoramic radiographs with skeletal bone mineral density and risk factors related to vascular diseases were investigated in 87 post-menopausal women. Cortical shape was associated with skeletal bone mineral density, low-density lipoprotein cholesterol, apolipoprotein B, resting heart rate, and endothelial dysfunction. Cortical width was associated with skeletal bone mineral density, low-density lipoprotein cholesterol, and apolipoprotein A1. Dentists may be able to refer women with increased risk of vascular diseases, as well as low bone mineral density, to medical professionals for further examination by panoramic findings.
Key Words: panoramic radiograph • menopause • women • vascular disease • detection
Both osteoporosis and vascular diseases such as cardiovascular disease and stroke are significant health burdens worldwide, resulting in substantial morbidity, incremental medical costs, and increased risk of mortality. Several investigators have demonstrated that low bone mineral density or rapid bone loss may be associated with increased risk of mortality from vascular disease in post-menopausal women (Browner et al., 1991, 1993; Barengolts et al., 1998; Johansson et al., 1998; von der Recke et al, 1999; Kado et al., 2000; Jorgensen et al., 2001; van der Klift et al., 2002). Possible pathways linking low bone mineral density with vascular disease in women include low estrogen exposure throughout life. Recent studies in Finland (Klemetti et al., 1994), Japan (Taguchi et al., 1996, 2003), the United Kingdom (Devlin and Horner, 2002; Horner et al., 2002), and the United States (Bollen et al., 2000) suggest that mandibular cortical shape and width on panoramic radiographs may be useful in identifying women with low bone mineral density or high risk of osteoporotic fracture. Association between low bone mineral density and vascular disease risk implies that panoramic radiographic measurements may also be useful in identifying women with increased risk for vascular disease. Carotid calcification identified on panoramic radiographs was reported to be a powerful marker for subsequent vascular events (Cohen et al., 2002). However, carotid calcification indicates the development, or the final stage, of vascular disease (Ross, 1999). Little is known as to whether panoramic radiographic measurements are markers for the initial stage of vascular disease in which no aggressive management can improve the vascular function and reduce the future mortality risk. Since the early stage of vascular disease, namely, endothelial dysfunction, can be improved by medications such as low-dose estrogen (Sanada et al., 2003) and exercise (Goto et al., 2003), we used the term "no aggressive management". The aim of our study was therefore to investigate the relationships among panoramic radiographic measurements, bone mineral density of the spine and the hip, and subclinical risk factors for vascular disease in post-menopausal women.
Subjects Of 652 women who visited our clinic for bone mineral assessment between 1996 and 2002, 87 Japanese post-menopausal women aged 46 to 68 yrs (mean ± SD, 54.6 ± 5.1) were recruited for this study. Twenty-seven women had had a hysterectomy, eight had unilateral oophorectomy, and 14 bilateral oophorectomy. Exclusion criteria were: absence of consent for panoramic radiographs and questionnaire, tobacco use, use of medications that affect bone and lipid metabolisms, presence of metabolic bone diseases, diabetes, clinical manifestations of atherosclerosis, cancers with bone metastasis, significant renal impairment, liver disorders, bone-destructive lesions in the mandible, non-vertebral osteoporotic fractures, and vertebral osteoporotic fracture on x-ray at bone mineral assessment. All subjects reported no menstruation for at least 1 yr. Informed consent for the assessment of risk factors for vascular disease was obtained from each subject. The study protocol was approved by the ethics committee of the Department of Obstetrics and Gynecology in Hiroshima University.
Measurements of Bone Mineral Density
Assessment of Risk Factors for Vascular Disease Samples of venous blood were placed in polystyrene tubes containing sodium ethylenediamine tetraacetic acid (EDTA) (1 mg/mL). The EDTA-containing tubes were immediately chilled in an ice bath. The plasma was separated by centrifugation at 3100 rpm at 4°C for 10 min. Serum was separated at 1000 rpm at room temperature for 10 min. Samples were stored at -80°C until assayed. We used routine chemical methods to determine the serum concentrations of high-density lipoprotein cholesterol, triglycerides, and apolipoproteins A1, A2, and B. The serum concentration of low-density lipoprotein cholesterol was determined by Freidewald’s method (Friedewald et al., 1972). Plasma angiotensin-converting-enzyme activity, which may be one of the factors that protect against cardiovascular disease (Proudler et al., 1995), was measured with angiotensin-converting-enzyme color (Fujirebio Co., Ltd., Tokyo, Japan). Blood pressure and resting heart rate were also measured as possible risk factors for vascular disease. Five subjects had no apolipoprotein data. One subject had no data for angiotensin-converting-enzyme activity and resting heart rate.
Panoramic Radiographic Measurements Mandibular cortical shape on the panoramic radiographs was categorized into one of three groups according to a method described previously (Klemetti et al., 1994), as follows: "normal cortex", the endosteal margin of the cortex is even and sharp on both sides; "mildly to moderately eroded cortex", the endosteal margin shows semilunar defects or appears to form endosteal cortical residues; and "severely eroded cortex", the cortical layer forms heavy endosteal cortical residues and is clearly porous. Overall agreements for intra- and inter-examiner performances were 92% and 82%, respectively.
Measurement of mandibular cortical width was made bilaterally on panoramic radiographs at the site of the mental foramen, according to our previous study (Taguchi et al., 1995). A line parallel to the long axis of the mandible and tangential to the inferior border of the mandible was drawn. A line perpendicular to this tangent, intersecting the inferior border of the mental foramen, was constructed, along which mandibular cortical width was measured by calipers (Fig.
Statistical Analysis We used analysis of covariance (adjusted for age, years since menopause, and body mass index) to investigate relationships between skeletal bone mineral density and subclinical risk factors for vascular disease in cortical erosion category and cortical width quartiles (SPSS v8.0, SPSS Inc., Chicago, IL, USA). When investigating the relationships among panoramic radiographic measures and endothelium-dependent and -independent vasodilations, we also adjusted forearm blood flow at baseline in addition to age, years since menopause, and body mass index. Comparisons among means of individual groups were made if the overall F value was significant at 0.05. We used logistic regression analysis to estimate odds ratio for the treatment need in some subclinical variables if these were associated with cortical measures. P-values less than 0.05 were considered statistically significant.
Characteristics of 87 subjects are shown in Table 1  . There was significant correlation between the mandibular cortical erosion category and cortical width quartiles (Kendall’s tau = -0.50, P < 0.001). The mandibular cortical erosion category was significantly associated with skeletal bone mineral density and low-density lipoprotein cholesterol (Table 2). Subjects with any cortical erosion had significantly higher low-density lipoprotein cholesterol than those with normal cortex after adjustment for age, years since menopause, and body mass index (mean ± SEM, 161.7 ± 7.3 vs. 136.1 ± 5.6 mg/dL, P = 0.014). There were also significant differences in apolipoprotein B (102.1 ± 3.8 vs. 115.4 ± 4.8 mg/dL, P = 0.048) and resting heart rate (63.3 ± 1.0 vs. 67.5 ± 1.4 beat/min, P = 0.032) between subjects with normal cortex and those with any cortical erosion. Adjustment for history of hysterectomy and oophorectomy did not change these associations. Subjects with severe cortical erosion had significantly lower endothelium-dependent vasodilation—that is, endothelial dysfunction—than did the others after adjustment for confounding variables (26.0 ± 5.2 vs. 37.5 ± 1.5 mL/min/100 mL tissue, P = 0.039), although there was no significant difference in endothelium-independent vasodilation (P = 0.546).
Mandibular cortical width quartiles were significantly associated with skeletal bone mineral density, low-density lipoprotein cholesterol, and apolipoprotein A1 (Table 3 ). There were no significant differences in any other subclinical variables, including endothelium-dependent and -independent vasodilations, among mandibular cortical width quartiles.
Seventeen subjects with both normal cortical shape and the uppermost quartile of cortical width had significantly lower low-density lipoprotein cholesterol than did 70 subjects with both any cortical erosion and the lower three quartiles of cortical width, after adjustment for confounding variables (116.5 ± 8.8 vs. 153.3 ± 4.3 mg/dL, P < 0.001). When the low-density lipoprotein cholesterol target for treatment was considered less than 140 mg/dL (Saito et al., 2002), logistic regression analysis revealed the odds of treatment need in 70 subjects with both any cortical erosion and lower three quartiles of cortical width to be 5.5 (95% confidence interval = 1.6 to 19.4).
The mandibular cortical erosion category was significantly associated with low-density lipoprotein cholesterol level and apolipoprotein B level, both of which contribute to an early stage of atherogenesis (Skalen et al., 2002). It is likely that these risk factors may have an influence on poor endothelium-dependent vasodilation in subjects with severe cortical erosion. These results suggest that the initial stage of vascular disease may be detected by mandibular cortical shape on panoramic radiographs. Younger post-menopausal women with any mandibular cortical erosion may already have an endothelial dysfunction or risk factors related to early stages of atherogenesis, resulting in clinical manifestation of atherosclerosis. Subjects with normal cortical shape had significantly higher skeletal bone mineral density and lower resting heart rate than those with any cortical erosion. This agrees with the recent study in which women 65 years or older with resting heart rates of 80 beats/min or more had an increased risk of several osteoporotic fractures and of mortality from coronary heart disease (Kado et al., 2002). Our results suggest that vascular disease risk related to resting heart rate may be detected on panoramic radiographs, even in younger post-menopausal women. Mandibular cortical width quartiles were significantly associated with skeletal bone mineral density, low-density lipoprotein cholesterol, and apolipoprotein A1, but not with endothelial dysfunction. Both cortical shape and width are considered as markers of skeletal bone mineral density in women. However, recent studies suggest that cortical shape may reflect bone turnover after menopause (Taguchi et al., 2003), but that cortical width may reflect peak bone mass at a younger age (Horner et al., 2002; Taguchi et al., 2003). This suggests that endothelial dysfunction may be associated not with skeletal bone mineral density, but with bone turnover after menopause. Since a higher apolipoprotein A-1 level was associated with a decreased likelihood for myocardial infarction (Walldius et al., 2001), lower low-density lipoprotein cholesterol and higher apolipoprotein A1 levels in subjects in the uppermost quartile of cortical width may indicate that women with significant cortical width have a lower risk for vascular disease. It is still unknown why subjects in the uppermost quartile of cortical width had lower low-density lipoprotein cholesterol. One possibility is that long exposure to endogenous estrogens due to early hormonal age might result in both higher skeletal bone mineral density and lower low-density lipoprotein cholesterol in these subjects. Another is that hyperlipidemia contributes not only to atherosclerotic plaque formation, but also to osteoporosis, following a similar biologic mechanism involving lipid oxidation (Parhami et al., 2000). When cortical width quartiles were combined with the cortical erosion category, subjects in both the uppermost quartile of cortical width and with normal cortical shape had a lower risk of treatment need for low-density lipoprotein cholesterol reduction compared with the others. These subjects do not need to undergo examinations for vascular disease risk. In contrast, five of seven subjects with both severe cortical erosion and in the lowest quartile of cortical width had low-density lipoprotein cholesterol more than 140 mg/dL, indicating that these women, with severe cortical erosion and thin cortical width, should consult medical professionals for further examination for vascular disease. This study had limitations. All subjects were not healthy volunteers, but were patients who visited our clinic for bone mineral density assessment. Our subjects therefore are not representative of normal Japanese post-menopausal women. The small sample size also limits the interpretation of our findings. Further investigations in a large population would be necessary to confirm our findings. In conclusion, panoramic radiographic measurements are associated with subclinical risk factors for vascular disease in post-menopausal women. Dentists making incidental findings can refer at-risk women to medical professionals.
This study was supported by grant-in-aid 14571786 for scientific research, from the Japan Society for the Promotion of Science. Received for publication January 13, 2003. Revision received May 14, 2003. Accepted for publication June 26, 2003.
Journal of Dental Research, Vol. 82, No. 10,
838-843 (2003) This article has been cited by other articles:
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