Osteoporosis and atherosclerosis frequently occur concomitantly, may share similar pathogenic mechanisms, and could be biologically linked [
Coronary artery calcification (CAC) score is a surrogate marker for total calcified plaque burden and may predict future coronary events [
The fracture risk assessment tool (FRAX), combining BMD and clinical risk factors to provide a comprehensive osteoporotic fracture risk assessment, may serve as a general guideline for the clinical management of osteoporosis [
The association of BMD or osteoporosis and other calcifications, such as coronary artery, carotid artery, and cardiac valve calcifications, has been reported, but with a paucity of clinical data. Further evaluation from the BMD value to the fracture risk is another issue. The purpose of this study was to explore the relationship of the 10-year probability of a hip fracture (HF) and a major osteoporotic fracture (MOF) as calculated with the FRAX and CAC scores.
We enrolled all clients who had received health examinations at the preventive medical center of a regional teaching hospital in Southern Taiwan between May 2014 and November 2015 to this study. A retrospective medical record review was performed. Those who were diagnosed with coronary arterial diseases; received coronary arterial catheter procedure, bypass surgery, and major heart operation; or followed with a history of bone fracture were all excluded. In addition, subjects need to receive both coronary CT scans and BMD tests during their health examination. This retrospective study was approved by the ethics committee of our institution, which approved waiver of informed consent from each patient. Medical records revealed personal information as follows: (1) comorbidities, such as hypertension, diabetes mellitus, and hyperlipidemia; (2) parent fractured hip history, current smoking, glucocorticoid usage, rheumatoid arthritis, secondary osteoporosis, and alcohol consumption; (3) anthropomorphic characteristics (age, sex, height, weight, and body mass index (BMI)); and (4) clinical laboratory findings including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose level, systolic blood pressure (SBP), and diastolic blood pressure (DBP).
CAC score was obtained from unenhanced axial images scanned prior to coronary CT angiography. The scans were performed using a multidetector CT system (LightSpeed VCT, GE Medical Systems). CAC was quantified with the Agatston scoring method, as previously described [
BMD was assessed by dual-energy X-ray absorptiometry (DXA) using a Discovery Wi DXA system (Hologic Inc.). Absolute BMD values and T-scores (number of standard deviations below the BMD of a young normal reference group, Asia database) were calculated for all patients. The measured areas included the lumbar spine and bilateral hips (total and (femoral) neck regions). The same densitometer was used for all patients in order to ensure accurate comparisons.
The 10-year probability (expressed as a percentage) of HF and MOF were calculated for all subjects. All fracture risk factors included in the FRAX (age, sex, weight, height, previous fracture history, parent fractured hip history, current smoking, glucocorticoid usage, rheumatoid arthritis, secondary causes of osteoporosis, and alcohol intake of 3 or more units/day) were assessed, as well as right and left hip femoral neck BMD data. The FRAX score was calculated on country-specific (Taiwan) data on the website (
Results were expressed as mean ± standard deviation, or number (percentage), as appropriate. Differences in means or frequencies were tested by chi-squared test or
Demographic and clinical characteristics of subjects are presented in Table
Demographic and clinical characteristics of study participants.
All | Male | Female |
| |
---|---|---|---|---|
Number | 81 | 51 | 30 | |
Age (range) (years) | 55.8 ± 9.9 (27–81) | 55.1 ± 10.6 (27–81) | 57.1 ± 8.6 (34–75) | 0.379 |
Height (cm) | 164.0 ± 8.2 | 168.3 ± 6.8 | 156.6 ± 4.2 | <0.001 |
Weight (kg) | 67.9 ± 12.3 | 73.1 ± 11.2 | 59.0 ± 8.5 | <0.001 |
BMI (kg/m2) | 25.1 ± 3.2 | 25.7 ± 3.0 | 24.1 ± 3.5 | 0.029 |
Smoking (%) | 6 (7.4) | 6 (11.8) | 0 (0.0) | 0.080 |
Drinking (%) | 4 (4.9) | 4 (7.8) | 0 (0.0) | 0.291 |
Hypertension (%) | 19 (23.5) | 10 (19.6) | 9 (30.0) | 0.286 |
Diabetes mellitus (%) | 9 (11.1) | 7 (13.7) | 2 (6.7) | 0.473 |
Hyperlipidemia (%) | 5 (6.2) | 3 (5.9) | 2 (6.7) | >0.999 |
Secondary osteoporosis (%) | 14 (17.3) | 8 (15.7) | 6 (20.0) | 0.620 |
TC (mg/dL) | 189.1 ± 32.7 | 183.1 ± 32.3 | 199.3 ± 31.3 | 0.031 |
LDL-C (mg/dL) | 121.6 ± 27.5 | 116.8 ± 30.1 | 129.7 ± 20.4 | 0.025 |
HDL-C (mg/dL) | 48.6 ± 15.0 | 43.7 ± 10.7 | 57.0 ± 17.5 | <0.001 |
Triglycerides (mg/dL) | 145.2 ± 95.5 | 166.0 ± 109.0 | 109.8 ± 51.1 | 0.002 |
Glucose (mg/dL) | 107.4 ± 20.8 | 110.1 ± 24.5 | 102.8 ± 11.0 | 0.073 |
SBP (mmHg) | 126.0 ± 22.9 | 127.2 ± 18.3 | 124.1 ± 29.4 | 0.606 |
DBP (mmHg) | 78.7 ± 15.4 | 81.7 ± 15.4 | 73.7 ± 14.1 | 0.022 |
Lumbar spine BMD (g/cm2) | 0.969 ± 0.139 | 1.011 ± 0.129 | 0.898 ± 0.129 | <0.001 |
Lumbar spine T-score | −0.63 ± 1.21 | −0.33 ± 1.16 | −1.12 ± 1.14 | 0.004 |
Right neck BMD (g/cm2) | 0.732 ± 0.118 | 0.769 ± 0.123 | 0.669 ± 0.075 | <0.001 |
Right neck T-score | −1.04 ± 0.95 | −0.81 ± 1.00 | −1.41 ± 0.74 | 0.006 |
Right total BMD (g/cm2) | 0.838 ± 0.141 | 0.874 ± 0.128 | 0.778 ± 0.144 | 0.003 |
Right total T-score | −0.42 ± 0.93 | −0.37 ± 0.84 | −0.51 ± 1.08 | 0.492 |
Left neck BMD (g/cm2) | 0.738 ± 0.122 | 0.772 ± 0.121 | 0.682 ± 0.105 | 0.001 |
Left neck T-score | −1.01 ± 0.99 | −0.78 ± 1.00 | −1.39 ± 0.87 | 0.007 |
Left total BMD (g/cm2) | 0.840 ± 0.139 | 0.882 ± 0.118 | 0.768 ± 0.143 | <0.001 |
Left total T-score | −0.41 ± 0.91 | −0.30 ± 0.83 | −0.59 ± 1.01 | 0.166 |
Right MOF (FRAX) (%) | 4.84 ± 2.87 | 4.03 ± 2.18 | 6.21 ± 3.37 | 0.003 |
Right HF (FRAX) (%) | 1.39 ± 1.62 | 1.27 ± 1.59 | 1.60 ± 1.68 | 0.379 |
Left MOF (FRAX) (%) | 4.88 ± 3.11 | 3.99 ± 2.35 | 6.39 ± 3.66 | 0.002 |
Left HF (FRAX) (%) | 1.41 ± 1.74 | 1.22 ± 1.69 | 1.73 ± 1.80 | 0.207 |
CAC score | 123.8 ± 294.2 | 137.1 ± 315.0 | 101.1 ± 258.7 | 0.598 |
BMI: body mass index; TC: total cholesterol; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; SBP: systolic blood pressure; DBP: diastolic blood pressure; BMD: bone mineral density; MOF: 10-year probability of a major osteoporotic fracture; HF: 10-year probability of a hip fracture; FRAX: fracture risk assessment tool; TBS: trabecular bone score; CAC score: coronary artery calcification score. Data are expressed as mean ± standard deviation, unless otherwise specified.
Mean lumbar spine T-scores on DXA were −0.33 ± 1.16 for men, −1.12 ± 1.14 for women, and −0.63 ± 1.21 for all patients. There were significant differences between male and female in the BMD values of the lumbar spine, femoral neck, and total regions of the bilateral hips. Spine and hip T-scores were significantly different between male and female, except the T-score of the total region of the bilateral hips (Table
The mean CAC score of all subjects was 123.8 ± 294.2 (range, 0–1771). Simple linear regression analysis showed that CAC score correlated positively with hypertension (
Simple linear regression analysis of coronary artery calcification.
|
Coefficient | 95% CI |
|
Std | |
---|---|---|---|---|---|
Age (years) | 0.045 | 6.27 | −0.23–12.76 | 0.058 | 0.21 |
Sex ( |
0.004 | 35.97 | −99.38–171.33 | 0.598 | 0.06 |
Height (cm) | 0.005 | −2.52 | −10.52–5.48 | 0.532 | −0.07 |
Weight (kg) | 0.001 | 0.64 | −4.71–6.00 | 0.812 | −0.03 |
BMI (kg/m2) | 0.008 | 8.35 | −11.87–28.56 | 0.414 | 0.09 |
Smoking | 0.002 | −45.09 | −294.91–204.73 | 0.720 | −0.04 |
Drinking | 0.007 | −110.98 | −412.17–190.21 | 0.465 | −0.08 |
Hypertension | 0.340 | 402.36 | 276.82–527.90 | <0.001 | 0.58 |
Diabetes mellitus | 0.011 | 99.57 | −107.59–306.73 | 0.342 | 0.11 |
Hyperlipidemia | 0.175 | 508.01 | 260.85–755.17 | <0.001 | 0.42 |
Secondary osteoporosis | 0.018 | 104.56 | −67.03–276.15 | 0.229 | 0.14 |
TCH (mg/dL) | 0.019 | 1.24 | −0.75–3.24 | 0.219 | 0.14 |
LDL (mg/dL) | 0.013 | −1.20 | −3.58–1.18 | 0.320 | −0.11 |
HDL (mg/dL) | <0.001 | 0.01 | −4.40–4.41 | 0.998 | <0.001 |
Triglycerides (mg/dL) | 0.136 | 1.14 | 0.50–1.78 | 0.001 | 0.37 |
Glucose (mg/dL) | <0.001 | 0.16 | −3.01–3.33 | 0.921 | 0.01 |
SBP (mmHg) | 0.049 | 2.83 | 0.02–5.63 | 0.048 | 0.22 |
DBP (mmHg) | 0.023 | 2.92 | −1.32–7.16 | 0.175 | 0.15 |
Lumbar spine BMD (g/cm2) | <0.001 | 2.21 | −470.38–474.80 | 0.993 | 0.001 |
Lumbar spine T-score | 0.002 | −10.21 | −64.60–44.18 | 0.710 | −0.04 |
Right neck BMD (g/cm2) | 0.044 | −524.47 | −1072.08–23.13 | 0.060 | −0.21 |
Right neck T-score | 0.060 | −75.63 | −142.53–8.74 | 0.027 | −0.25 |
Right total BMD (g/cm2) | 0.002 | −102.99 | −569.25–363.27 | 0.661 | −0.05 |
Right total T-score | 0.032 | −56.90 | −126.44–12.64 | 0.107 | −0.18 |
Left neck BMD (g/cm2) | 0.035 | −451.74 | −980.29–76.81 | 0.093 | −0.19 |
Left neck T-score | 0.046 | −63.47 | −128.25–1.31 | 0.055 | −0.21 |
Left total BMD (g/cm2) | 0.020 | −303.22 | −774.01–167.57 | 0.204 | −0.14 |
Left total T-score | 0.088 | −96.33 | −165.84–26.81 | 0.007 | −0.30 |
Right MOF (FRAX) (%) | 0.103 | 32.96 | 11.20–54.71 | 0.003 | 0.32 |
Right HF (FRAX) (%) | 0.096 | 56.27 | 17.56–94.97 | 0.005 | 0.31 |
Left MOF (FRAX) (%) | 0.066 | 24.34 | 3.85–44.84 | 0.021 | 0.26 |
Left HF (FRAX) (%) | 0.055 | 39.59 | 2.74–76.44 | 0.036 | 0.23 |
M: male; F: female; BMI: body mass index; TC: total cholesterol; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; SBP: systolic blood pressure; DBP: diastolic blood pressure; BMD: bone mineral density; MOF: 10-year probability of a major osteoporotic fracture; HF: 10-year probability of a hip fracture; FRAX: fracture risk assessment tool; TBS: trabecular bone score; CAC score: coronary artery calcification score.
The FRAX scores for MOF risks of the bilateral hips showed a significant difference between male and female (Table
Multiple linear regression analysis of coronary artery calcification for FRAX.
|
Coefficient | 95% CI |
|
Std | |
---|---|---|---|---|---|
Right MOF (FRAX) (%) | 0.381 | 46.55 | 21.45–71.65 | <0.001 | 0.45 |
Right HF (FRAX) (%) | 0.369 | 68.31 | 28.91–107.70 | 0.001 | 0.38 |
Left MOF (FRAX) (%) | 0.316 | 29.22 | 4.44–53.99 | 0.021 | 0.31 |
Left HF (FRAX) (%) | 0.302 | 39.10 | 0.15–78.04 | 0.049 | 0.23 |
Each of the nine separate multiple linear regression models was adjusted for age, sex, TC, LDL-C, HDL-C, TG, SBP, and DBP.
Hip fractures are associated with higher risk of myocardial infarction [
A 2009 study which focused on the coronary artery found that the BMD of the femur and lumbar spine were negatively associated with the CAC score after adjusting for age and metabolic parameters in women, but not in men [
Our results indicated that the FRAX can help identify individuals who are at high risk of osteoporotic fractures and at higher risk of an increased CAC score, as well as cardiovascular events. In this study, adjusting for age, sex, TC, LDL-C, HDL-C, TG, SBP, and DBP did not attenuate the associations between MOF or HF risks and CAC severity. In our study, with consideration of a possible altered disease status and physiological condition after treatment, one model was adjusted with the lipid profile and BP, but not with the comorbidities. Thus, FRAX can be used to predict CAC severity and identify individuals in whom early treatment may prevent future fractures and cardiovascular events.
There were several limitations to this study. First, this was a retrospective and observational study with a relatively small sample size. We did not measure serum markers which may be possible mechanisms for the link between coronary CAC, osteoporosis, and bone fragility, such as bone resorption, estrogen, vitamin D, parathyroid hormone, calcium intake, thyroid-stimulating hormone, T3, free T4, or osteoprotegerin levels. We did not examine the results as compared to other fracture risk assessment tools, such as the osteoporosis self-assessment tool for Asians (OSTA), Garvan fracture risk calculator (GARVAN), osteoporosis risk assessment instrument (ORAI), osteoporosis index of risk (OSIRIS), and simple calculated osteoporosis risk estimation (SCORE).
Increased risks of MOF and HF as estimated by FRAX are significantly and independently associated with more severe CAC scores. DXA and FRAX can be used to predict fracture risk and CAC scores and identify patients who may benefit from early intervention.
Tzyy-Ling Chuang, Yi-Da Li, Fu-Tsung Hsiao, Mei-Hua Chuang, and Yuh-Feng Wang declare that they have no conflict of interest regarding the publication of this paper.
Author Tzyy-Ling Chuang and Yuh-Feng Wang designed the study and prepared the first draft of the paper. Yuh-Feng Wang is the guarantor. Yi-Da Li and Fu-Tsung Hsiao contributed to the experimental work. Tzyy-Ling Chuang and Mei-Hua Chuang were responsible for statistical analysis of the data. All authors revised the paper critically for intellectual content and approved the final version. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.