Vertebral fractures and abdominal aortic calcification in postmenopausal women. A cohort study

Bone 56 (2013) 213–219

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Vertebral fractures and abdominal aortic calcification in postmenopausal women. A cohort study A. El Maghraoui a,⁎, A. Rezqi a, A. Mounach a, L. Achemlal a, A. Bezza a, M. Dehhaoui b, I. Ghozlani a a b

Rheumatology Department, Military Hospital Mohammed V, Rabat, Morocco Statistics Department, Agronomic University Hassan II, Rabat, Morocco

a r t i c l e

i n f o

Article history: Received 11 December 2012 Revised 6 May 2013 Accepted 29 May 2013 Available online 10 June 2013 Edited by: Harry Genant Keywords: Vertebral fracture assessment (VFA) Dual-energy X-ray absorptiometry (DXA) Osteoporosis Women Vertebral fractures Abdominal aortic calcification

a b s t r a c t Introduction: Vertebral fracture assessment (VFA) imaging with a bone densitometer can simultaneously detect prevalent vertebral fractures (VFs) and abdominal aortic calcification (AAC). Objective: To study the relation between the prevalence of VFs using VFA in asymptomatic women and the prevalence and severity of AAC. Design: This is a cross-sectional study. Settings: Subjects were recruited in a third care center from asymptomatic women selected from the general population. Participants: We enrolled 908 post-menopausal women with a mean age of 60.9 years ± 7.7 (50 to 91) with no prior known diagnosis of osteoporosis or taking medication interfering with bone metabolism. Primary and secondary outcome measures: Lateral VFA images and scans of the lumbar spine and proximal femur were obtained using a GE Healthcare Lunar Prodigy densitometer. VFs were defined using a combination of Genant semiquantitative (SQ) approach and morphometry. VFA images were scored for AAC using a validated 24 point scale. Results: VFA images showed that 179 of the participants (19.7%) had at least one grade 2/3 VF, 81% did not have any detectable AAC whereas the prevalence of significant atherosclerotic burden, defined as AAC score of 5 or higher, was 12%. The group of women with 2/3 VFs had a statistically significant higher AAC score and higher proportion of subjects with extended AAC, and lower weight, height, and lumbar spine and hip BMD and T-scores than those without VFA-identified VFs. Multiple regression analysis showed that the presence of grade 2/3 VFs was significantly associated with age, BMI, history of peripheral fracture, AAC score ≥ 5 and densitometric osteoporosis. Conclusion: In post-menopausal women, extended AAC is independently associated with prevalent VFs regardless of age, BMI, history of fractures, and BMD. © 2013 Elsevier Inc. All rights reserved.

Introduction Vascular calcifications and osteoporotic fractures prevalence increase with age and both are commonly observed in the elderly [1]. Although multiple reports have suggested a link between atherosclerosis and osteoporosis, making an unequivocal connection between these two age-dependent conditions has been difficult [2]. Moreover, due to the great increase in life expectancy, a marked rise in the prevalence of both of these disorders is expected. Cardiovascular disease remains the leading cause of mortality among elderly women. Abdominal aortic calcification (AAC) is easily detected on routine lateral lumbar spine radiographs and has been shown to be significantly predictive of overall cardiovascular disease incidence and mortality, coronary heart disease, stroke, congestive ⁎ Corresponding author at: Rheumatology Department, Military Hospital Mohammed V, P.O. Box: 1018, Rabat, Morocco. Fax: +212 537716805. E-mail address: [email protected] (A. El Maghraoui). 8756-3282/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.bone.2013.05.022

heart failure, and peripheral vascular disease, independently of classic risk factors such as high blood pressure, high total and LDL cholesterol levels, smoking, obesity, and the presence of diabetes mellitus [3,4]. Bone densitometry is now widely recommended for all women age 65 and older [5]. Simultaneous lateral spine imaging also called vertebral fracture assessment (VFA) is now also recommended for a sizable subset of the elderly female population to detect prevalent vertebral fractures (VFs) and has been shown to be cost-effective for that subset [6,7]. It has been shown in many populations that this technique can simultaneously identify AAC (Fig. 1) and then improve the utility of this technology for this population even further [8,9]. Although the associations of age and bone mineral density (BMD) with AAC have been well examined [10–13], whether osteoporotic vertebral fractures (VFs) and AAC are related to each other or are independent, age-related processes remain uncertain. Identifying women at risk for both cardiovascular events and osteoporotic fracture may help reduce morbidity and mortality associated with these highly common conditions. The purpose of the present study was to test the hypotheses

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representativeness of the general population with a particular regard to the inclusion of a wide range of body sizes and activities. We did not exclude individuals using inhalation steroids or with certain lifestyle habits such as heavy smoking, being sedentary, being athletic, or having a high or low calcium intake, which are examples of voluntary factors that may have some impact on bone metabolism. BMD measurement Bone mineral density was determined by a Lunar Prodigy Vision DXA system (Lunar Corp., Madison, WI). The DXA scans were obtained by standard procedures supplied by the manufacturer for scanning and analysis. All BMD measurements were carried out by 2 experienced technicians. Daily quality control was carried out by measurement of a Lunar phantom. At the time of the study, phantom measurements showed stable results. The phantom precision expressed as the coefficient of variation was 0.08%. Moreover, reproducibility has been assessed in clinical practice and showed a smallest detectable difference of 0.04 g/cm [2] (spine) and 0.02 (hips) [15,16]. Patient BMD was measured at the lumbar spine (anteroposterior projection at L1–L4) and at the femurs (i.e., femoral neck, trochanter, and total hip). Using the Moroccan female normative data [17], the World Health Organization (WHO) classification system was applied, defining osteoporosis as T-score ≤ −2.5 and osteopenia as −2.5 b T-score b −1. Study participants were categorized by the lowest T-score of the L1–4 lumbar spine, femur neck, or total femur. Vertebral fracture assessment

Fig. 1. A VFA image showing multiple vertebral fractures (T12 grade 3, T9 and T8 grade 1) and abdominal aortic calcifications (arrows) scored 3.

that there is a significant age-independent relation between AAC and osteoporosis and VFs. Material and methods Subjects A total of 973 Caucasian postmenopausal women (age range: 50− 91 yr) living in the Rabat area participated in the present study. Inclusion and exclusion criteria were described elsewhere [14]. Briefly, women were recruited through advertisements and “word of mouth” from June 2010 to March 2012. Original inclusion criteria were age > 50, menopause >1 year and no previous osteoporotic fracture or known diagnosis of osteoporosis. Women with liver or renal disease, endocrine or metabolic abnormalities, and receiving medicine known to influence bone mineralization, such as corticosteroids, heparin, anticonvulsants, vitamin D, and bisphosphonates, were excluded. Our institutional review board (Faculty of Medicine of Rabat) approved this study. The procedures of the study were in accordance with the Declaration of Helsinki, and local ethics committee approval was obtained for the study. All the participants gave an informed and written consent. Medical histories, obtained by the DXA technologists prior to scanning, included current medication use, history of peripheral traumatic fractures, and current use of tobacco and alcohol. Height and weight were measured in light indoor clothes without shoes. Body mass index (BMI)] was calculated by dividing weight in kilograms by height in meters squared. Although this is not a population-based cohort, care was taken to ensure

VFs was classified using a combination of Genant [18] semiquantitative (SQ) approach and morphometry in the following manner: each VFA image was inspected visually by one trained clinician (IG) to decide whether it contained a fracture in any of the visualized vertebrae and assigned a grade based on Genant SQ scale, where grade 1 (mild) fracture is a reduction in vertebral height of 20–25%, grade 2 (moderate) a reduction of 26–40%, and grade 3 (severe) a reduction of over 40%. In case of doubt regarding fracture grade, the vertebrae in question was measured using built-in morphometry. Automatic vertebral recognition by the software was used. Positioning of the six morphometry points was modified by an experienced clinician (IG) only when the software failed to correctly recognize vertebral heights. The intra-rater reproducibility was evaluated using the kappa score to 0.90 (p b 0.0001). Subjects with no fractures were included in the non-fracture group, whereas those with grade 1 or higher fractures were included in the fracture group. However, as many studies rarely report mild deformities as “fractures”, and to realize comparisons with the literature, we performed a double analysis including and excluding grade 1 fractures from the fracture group. The spinal deformity index (SDI), as described by Kerkeni et al. [19], was then calculated by summing in each patient the grade of each vertebra from T4 to L4. In theory, the SDI value can vary between 0 (no fracture) and 39 (all the assessed vertebrae are grade 3). Assessment of aortic calcifications All VFA scans were studied on a separate occasion by the same reader (IG) to assess the presence of AAC. To score the AAC extension, we used the score described by Kauppila et al. [20]. The anterior and posterior aortic walls were divided into four segments, corresponding to the areas in front of the lumbar vertebrae L1–L4. Within each of these 8 segments, aortic calcification was recognized visually as either a diffuse white stippling of the aorta extending out to the anterior and/or posterior aortic walls, or as white linear calcification of the anterior and/or posterior walls. Aortic calcification scored as 0 if there was no calcification, as 1 if one-third or less of the length of the aortic wall in that segment was calcified, as 2 if more than one-third but

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two-thirds or less of the aortic wall was calcified, or as 3 if more than two-thirds of the aortic wall was calcified. The scores were obtained separately for the anterior and posterior aortic wall, resulting in a range from 0 to 6 for each vertebral level and 0 to 24 for the total score. The reproducibility of the assessment was evaluated in another study in 30 patients (intra-class correlation 0.96; p b 0.0001).

Statistical analysis Results are presented as means (SD) and categorical variables are expressed as frequencies. To compare patients with and without vertebral fractures, chi-square test and analysis of variance ANOVA were used first. To compare patients with and without AAC, chi-square test and Student's t-test were used. Since a 24-point AAC scale score of ≥ 5 has been shown previously to be associated with a 2.4 fold increased risk of cardiovascular disease mortality [3,21], this cut-off was used to compare patients with and without extended AAC. Correlation between demographic characteristics, bone mineral density, abdominal aortic calcification score and spinal deformity index were assessed using the non parametric Spearman test. Potential risk factors for VFs were finally entered in a stepwise conditional binary logistic regression analysis and the resulting odds ratios with 95% confidence intervals were reported. The level for significance was taken as p ≤ 0.05. Excel 2007 and SPSS 15.0 were used for statistical analysis.

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Vertebral visualization and fracture identification on VFA In these 908 women, 88.7% of vertebrae from T4–L4 and 99% from T8–L4 were adequately visualized on VFA. The percentage of vertebrae not visualized at T4, T5, and T6 levels was 74.1%, 49.2, and 16.1% respectively. VFs were identified in 382 (42.1%): 203 (22.4%) had grade 1 and 179 (19.7%) had grade 2 or 3. Among the latter group, 108 (60.3%) women had multiple VFs. Fractures were most common in the mid-thoracic spine and at the thoracolumbar junction. The mean SDI was 1.02 ± 2.0 (0–12). In this study, VFA-identified fractures were observed in 145 (36.1%) women with osteopenia (63 (15.7%) had grade2/3) and in 174 (61.5%) women with osteoporosis (97 (34.3%) had grade 2/3) (p b 0.0001). Interestingly, a fracture was identified on VFA in 63 (28.3%) of women with normal BMD (8.5% had grade 2/3 VFs). AAC evaluation Histograms of the AAC scores on VFA images showed that 78.5% of the evaluable participants did not have any detectable AAC whereas the AAC score distribution ranged between 1 and 18 (Fig. 2). Conversely, the prevalence of significant atherosclerotic burden, defined as a radiographic 24-point AAC score of 5 or higher, was 11.9% and increased with increasing age (Fig. 3). Risk factors for VFs and AAC

Results Participants Among the recruited population, 908 (93.3%) of the VFA images visualized sufficient space anterior to the lumbar spine to contain the entire abdominal aorta. The mean age, body mass index, and BMD of participants with VFA images evaluable for AAC were equivalent to the 65 who did not have evaluable VFA images and who were then excluded from the analysis. In this series of 908 women, the mean ± SD (range) age, weight and BMI were 60.9 ± 7.7 (50 to 91) years, 73.2 ± 13.2 (35 to 150) Kg and 29.8 ± 5.3 (14.5 to 50.8) kg/m [2], respectively. According to the WHO classification, 283 had osteoporosis at any site (31.2%) and 402 had osteopenia (44.3%). Only 4 women (0.4%) were current smokers. One hundred and eighteen (12.9%) women reported a history of traumatic peripheral fracture before the age of 50.

The group of women with moderate/severe vertebral fractures had a statistically significant higher AAC score and higher proportion of subjects with extended AAC, and lower weight, height, and lumbar spine and total hip BMD and T-scores than those without a VFAidentified vertebral fracture (Table 1). Table 2 shows that, compared to women without AAC, women with AAC are older, have a lower weight, height and BMD, higher number of pregnancies and time since menopause, and more prevalent VFs. Table 3 shows a significant positive correlation between the AAC score and age and the SDI, and a significant negative correlation between the AAC score and lumbar spine and total hip BMD. When all the variables significantly associated with high vertebral fracture prevalence in the univariate analysis were combined in a multiple stepwise conditional logistic regression analysis, it showed that the presence of grade 2/3 VFs was associated significantly to age, BMI, history of peripheral fracture, extended AAC score and densitometric osteoporosis (Table 4).

30

Percentage

25

20

15

10

5

0 1

2

3

4

5

6

7

8

9

11

12

13

14

15

AAC score Fig. 2. Frequency distributions of the abdominal aortic calcifications (AAC) 24-point score on VFA.

18

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a) 9 8 7 6 5 mean SDI

4

mean AAC score

3 2 1 0 50-54

55-59

60-64

65-69

70-74

75-79

>80

b) 9 8 7

AAC Score

6 5 Mean

4

Median

3

25th percentile 75th percentile

2 1 0 50-54

55-59

60-64

65-69

70-74

75-79

>80

(n=208)

(n=181)

(n=250)

(n=136)

(n=82)

(n=36)

(n=15)

Age categories Fig. 3. Mean abdominal aortic calcifications (AAC) score and mean spinal deformity index (SDI) distribution (a) and prevalence of extended AAC in our study population according to age categories (b).

Table 1 Comparison between patients with and without vertebral fractures.

Age (yrs): mean (SD) Weight (kg): mean (SD) Height (m): mean (SD) BMI (kg/m2): mean (SD) AAC score (0–24): mean (SD) Extended aortic calcifications (score ≥ 5): n (%) Lumbar spine BMD (g/cm2): mean (SD) Lumbar spine T-score: mean (SD) Total hip BMD (g/cm2): mean (SD) Total hip T-score: mean (SD) T ≤ −2.5 at any site: n (%)

Patients without vertebral fractures N = 526

Patients with grade 1 vertebral fractures N = 203

Patients with grade 2 or 3 vertebral fractures N = 179

p

59.1 74.4 1.57 30.0 0.39 16 0.998 −1.36 0.930 −0.78 109

60.7 74.5 1.55 30.7 1.16 30 0.945 −1.75 0.866 −1.22 77

66.5 (7.7) 68.5 (11.4) 1.55 (0.06) 28.4 (3.4) 2.37 (3.5) 62 (34.6) 0.873 (0.14) −2.40 (1.2) 0.815 (0.12) −1.63 (1.0) 98 (54.7)

b0.0001 b0.0001 b0.0001 b0.0001 b0.0001 b0.0001 b0.0001 b0.0001 b0.0001 b0.0001 b0.0001

(7.1) (13.0) (0.06) (4.0) (1.4) (3.0) (0.15) (1.2) (0.14) (1.0) (20.7)

(7.2) (14.3) (0.06) (4.1) (2.3) (14.8) (0.16) (1.3) (0.13) (1.1) (37.9)

Data as mean (SD) or number (percent). Statistical analysis used chi-square test and analysis of variance ANOVA. AAC: abdominal aortic calcification.

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Table 2 Comparison between patients with and without abdominal aortic calcification (AAC).

Age (yrs): mean (SD) Weight (kg): mean (SD) Height (m): mean (SD) BMI (kg/m2): mean (SD) Number of pregnancies: mean (SD) Time since menopause (yrs): mean (SD) History of peripheral fractures: n (%) Lumbar spine BMD (g/cm2): mean (SD) Lumbar spine T-score: mean (SD) Total hip BMD (g/cm2): mean (SD) Total hip T-score: mean (SD) T-score ≤ −2.5 at any site: n (%) Vertebral fractures grade 2/3: n (%) Spinal deformity index (SDI): mean (SD)

Patients without extended AAC N = 800

Patients with extended AAC N = 108

p

59.8 73.9 1.56 30.1 5.04 12.1 103 0.972 −1.57 0.903 −0.98 228 111 0.83

69.0 (7.3) 68.7 (11.6) 1.54 (0.06) 28.8 (4.9) 6.07 (2.9) 17.8 (10.1) 15 (13.8) 0.880 (0.16) −1.78 (1.7) 0.321 (0.9) −1.40 (1.1) 55 (50.9) 68 (40.5) 2.44 (2.5)

b0.0001 b0.0001 b0.0001 0.024 0.031 b0.0001 0.148 0.045 b0.0001 b0.0001 0.001 b0.0001 b0.0001 b0.0001

(7.1) (13.2) (0.06) (5.4) (2.5) (8.4) (12.8) (0.15) (1.2) (0.15) (1.0) (28.5) (15.0) (1.9)

Statistical analysis used chi-square test and Student's t-test.

Discussion In this series of postmenopausal women over 50, extended aortic calcifications are indicators of the increased risk for prevalent fracture regardless of age, BMI, history of traumatic fracture and BMD. As an indicator of the risk of fracture, AAC score ≥ 5 is both independent (significant after adjustment for other confounding variables including BMD) and robust (adjustment for other variables has a limited effect on the OR of AAC score): the unadjusted model OR for AAC score > 5 was 7.868 (5.124–12.082); OR for AAC score > 5 adjusted for age was 4.052 (2.539–6.466), OR for AAC score > 5 adjusted for age and osteoporosis was 4.036 (2.501–6.512), and finally OR for AAC score > 5 adjusted for all variables was 4.663 (2.417–8.997). Thus, our study suggests that the association between severe AAC and VFs implies that DXA exam may provide opportunity to identify women for prevention of future fracture and cardiovascular events. Our results agree with several studies that concluded that aortic calcification is strongly associated to low bone density and fragility fractures in men and women from various populations [12]. A longitudinal analysis of bone loss and vascular calcification over a 25-year period in the Framingham Heart Study showed that cortical bone loss measured at the metacarpal was associated with the progression of atherosclerotic aortic calcification in women [11]. A series of publications followed indicating that aortic calcification may represent a strong predictor of low bone density and an increased risk of fracture [12,22,23]. Schulz et al. [24] showed that aortic calcifications were a strong predictor not only of low bone density at lumbar spine but also of fragility fractures in women. However, the results of clinical studies of the relationship between bone fragility and vascular calcification have been inconsistent. Most studies found that arterial calcification and low bone mass are linked, while others failed to identify a link [13]. Overall, it appears that the

Table 3 Correlation between demographic characteristics, bone mineral density, abdominal aortic calcification score and spinal deformity index.

Age BMI AAC LS BMD TH BMD

BMI

AAC

LS BMD

TH BMD

SDI

−0.049 – –

0.36⁎ −0.09⁎ –

–

–

−0.32⁎ 0.27⁎ −0.16⁎ – –

−0.36⁎ 0.28⁎ −0.25⁎ 0.62⁎ –

0.36⁎ −0.09⁎ 0.23⁎ −0.30⁎ −0.30⁎

AAC: abdominal aortic calcification, BMD: bone mineral density, BMI: body mass index, LSBMD: lumbar spine BMD, THBMD: total hip BMD, SDI: spinal deformity index. Correlation was assessed using Spearman test. ⁎ Means correlation is significant at the 0.01 level (2-tailed).

choice of the parameters used to assess bone loss (DXA, quantitative ultrasound or bone markers) and vascular disorders (cardiovascular events, calcification scores) or the composition of the cohorts influenced the published results [25]. On the other hand, the NHANES III study, described that men with a history of myocardial infarction had a higher prevalence of low BMD [26] and more recently, cardiovascular disease in old white men has been inversely associated with BMD [27]. Cardiovascular disease and osteoporosis are major public health problems that frequently coexist and account for significant morbidity and mortality in the aging population. Coronary heart disease and stroke, respectively, are the first and third leading single causes of mortality among elderly women. Moreover, it has been shown that over 60% of women who die of coronary heart disease have no prior symptoms of the disease [28]. Thus, identification of those at risk of cardiovascular disease and for whom aggressive preventive measures should be directed has relied on clinical risk factors such as hypertension, smoking, dyslipidemia, obesity, family history, and diabetes mellitus. However, nearly 40% of the population is at intermediate risk when judged by these risk factors, and it is unclear just how aggressively their modifiable risk factors, such as LDL cholesterol, should be treated. A variety of imaging studies to detect subclinical cardiovascular disease, including lateral spine radiography, have been proposed to improve identification of those who would benefit from more aggressive treatment of risk factors such as LDL cholesterol and blood pressure. Many studies showed that AAC scored semi-quantitatively with a 24 point scale on lateral lumbar spine radiographs or DXA is predictive of cardiovascular disease incidence and mortality independent of other clinical risk factors [3,21,29]. Atherosclerosis is a long-term process characterized by endothelial dysfunction, vascular inflammation, and the build-up of lipids, cholesterol, calcium, and cellular debris within the intima of the vessel wall [30]. Atherosclerotic calcification is a regulated process with many cellular mechanisms similar to bone formation and resorption [2]. Although vascular smooth muscle cells have been shown to Table 4 Stepwise regression analysis for the presence of grade 2/3 vertebral fractures.

AAC score ≥ 5 History of peripheral traumatic fracture Osteoporosis any site Age BMI

OR [95% CI]

p

4.397 2.601 2.122 1.109 0.940

b0.0001 b0.0001 0.004 b0.0001 0.007

[2.268–8.524] [1.593–4.249] [1.366–3.298] [1.073–1.147] [0.899–0.984]

AAC: abdominal aortic calcification, BMI: body mass index. Potential risk factors for VFs were entered in a stepwise conditional binary logistic regression analysis and the resulting odds ratios (OR) with 95% confidence intervals are reported.

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express soluble factors known to regulate the osteoclastic differentiation process (such as RANKL or osteoprotegerin), the regulatory mechanisms governing this process in the vasculature are not yet clearly identified [2,31]. Many of the established atherogenic factors such as estrogen deficiency, dyslipidemia, oxidative stress, decreased nitric oxide availability, inflammatory cytokines, and sedentary lifestyle negatively affect osteogenesis and mineralization [1]. Human, animal, and in vitro studies reveal that some of these factors may also modulate atherosclerosis/vascular calcification [2,32–34]. Another putative link between aortic calcifications and bone fragility is homocysteine (Hcy). Higher Hcy level has been found to be a predictor of low BMD [35] and fracture [36] as well as a strong indicator of cardiovascular morbidity and mortality [37] and has been correlated with the extent of aortic calcifications. However, a recent study did not find any relationship between homocysteine levels and VF prevalence in postmenopausal women [38] and the role of Hcy as a link between fracture risk and cardiovascular pathology remains purely speculative. Bone densitometry is now widely recommended for all women age 65 and older. Simultaneous lateral spine imaging is now also recommended for a sizable subset of the elderly female population to detect prevalent vertebral fracture and has been shown to be cost-effective for that subset [5]. We believe, therefore, that it is reasonable for those who provide bone densitometry services with VFA to instruct their technicians to attempt to visualize adequate space anterior to the lumbar spine such that AAC can be assessed. Moreover, all these arguments suggest that VFA should be widely recommended in elderly women taking into account the high prevalence of VFs even in asymptomatic subjects and even in subjects without densitometric osteoporosis, added to the possibility to detect AAC, a marker of CV risk, it is certainly worth performing this low cost and noninvasive exam in patients needing a BMD assessment. Our study has strengths and limitations. The assessment of BMD and fractures was carefully conducted using standard procedures of acquisition, and standard reading of all VFA scans. All the morphometric assessments and AAC scoring were made by an experienced investigator after training sessions and after a previous global visualization. The prevalence of AAC was lower than expected in our study, which may reflect the young age of women in our series (mean 60 yrs). The main limitation lies in the procedures used to select subjects, who were all volunteers and ambulatory. The Rabat population may not be adequately representative of the whole Moroccan population. However, since the population living in the area of Rabat is a balanced mixture of the various regions constitutive of the country, we believe the impact on prevalence of VFs or AAC estimate is limited. In summary, in postmenopausal women, extended aortic calcifications are independently associated with prevalent VFA-identified VFs regardless of age, BMI, history of fractures and BMD. VFA imaging with a bone densitometer permits detection of prevalent VFs and AAC, an important cardiovascular disease risk factor. Clinicians should be aware of the association between AAC and incident cardiovascular disease. If significant AAC is noted, an assessment of the patient's cardiovascular disease risk should be indicated. Disclosure statement All the authors state that there is no conflict of interest related to this manuscript. Acknowledgments We thank Saliha and Rachid who performed all the DXA exams. References [1] Baldini V, Mastropasqua M, Francucci CM, D'Erasmo E. Cardiovascular disease and osteoporosis. J Endocrinol Invest 2005;28:69–72.

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