Patient characteristics
Among the 89 patients who met all the inclusion and exclusion criteria, 67 patients responded to participate in this study. A comparison of the demographic characteristics of the osteoporotic and nonosteoporotic groups is summarized in Table 1. The mean age of the whole cohort was 69.6 years, and 52% of the patients were older than 70 years. The participants in the osteoporotic group were slightly older than those in the nonosteoporotic group, but the difference was not significant. Almost all patients (94%) had used inhaled corticosteroids in the past year. The duration and dose of inhaled corticosteroids did not significantly differ between the two groups. According to the GOLD classification system of airflow limitation severity, most of the patients in the two groups had stage II limitations. The median CAT score, number of exacerbations in the previous year, and number of oral corticosteroid users did not differ between the two groups. The mean BMI of all the participants was 21.27 ± 3.8 kg/m2, and the majority of the patients (73.1%) had a BMI ≥ 18.5 kg/m2. The mean FFMI of all participants was 17.35 ± 1.92 kg/m2, and 18 patients (26.9%) had a depleted FFMI (FFMI < 16 kg/m2). The mean BMI and FFMI values were significantly lower in the osteoporotic group than in the nonosteoporotic group. All calcaneus parameters other than BUA were significantly lower in the osteoporotic group. In both groups, the femoral T-score was lower than the lumbar spine T-score.
Table 1 Baseline characteristics of the study population
|
Osteoporosis
N = 48
|
Nonosteoporosis
N = 19
|
p-value
|
Age, years
Body mass index (kg/m2)
Tobacco use
Current smoker, no (%)
Ex-smoker, no (%)
Pack-years
Charlson comorbidity index
Duration of inhaled corticosteroid, year
Fluticasone equivalent dose, mcg/day
Oral corticosteroid uses in the past year, no (%)
GOLD COPD staging, no (%)
I: FEV1 ≥ 80% predicted
II: FEV1 50–80% predicted
III: FEV1 30–50% predicted
IV: FEV1 < 80% predicted
COPD Assessment Test (CATTM) score
Numbers of exacerbation in the previous year
FFMI (kg/m2)
Global Physical Activity Questionnaire total activity, metabolic equivalent intensity min/week
Serum 25(OH)D level, ng/ml
Calcaneus QUS
SOS, m/s
BUA, dB/MHz
OSI
T-score
Femoral neck T-score
Lumbar spine T-score
|
70.21 ± 8.97
20.35 ± 3.62
8 (16.7%)
39 (81.3%)
28.50 (10, 60)
3.73 ± 1.14
4.42 (1.25, 7.63)
500 (250, 500)
17 (35.4%)
7 (14.6%)
21 (43.8%)
12 (25%)
8 (16.7%)
12 (4, 18)
0 (0, 1)
16.94 ± 1.95
840 (380, 1920)
7.80 ± 0.37
1533.15 ± 17.97
53.38 ± 18.18
2.41 ± 0.30
-1.51 ± 0.88
-3.49 ± 1.04
-3.21 ± 1.33
|
68 ± 7.62
23.62 ± 3.26
5 (26.3%)
13 (68.4%)
30 (7.5, 40)
3.53 ± 1.12
2.75 (1, 7)
250 (250, 500)
6 (31.6%)
4 (21.1%)
10 (52.6%)
5 (26.3%)
0 (0%)
11 (1, 16)
0 (0, 1)
18.38 ± 1.42
840 (280, 2520)
7.86 ± 0.28
1553.47 ± 25.79
60.76 ± 18.22
2.76 ± 0.67
-0.48 ± 1.55
-1.37 ± 1.06
-0.63 ± 1.50
|
0.348
0.001*
0.496
0.513
0.587
0.744
0.766
0.289
0.411
0.514
0.002*
0.850
0.531
0.004*
0.140
0.040*
0.012*
<0.001*
<0.001*
|
Values are mean ± SD or median (range). Abbreviations: FEV1 = force expiratory volume in the first second, BMI = body mass index, FFMI = fat-free mass index, SABA = short-acting beta-agonists, SAMA =short acting muscarinic antagonists, LAMA = long-acting muscarinic antagonist, 25(OH)D = 25-hydroxyvitamin D, *p-value is significant.
Prevalence of osteoporosis determined by DXA and factors associated with osteoporosis
The mean T-score and prevalence of osteoporosis and osteopenia are presented in Table 2. The mean T-score of the femoral neck (-2.89 ± 1.42) was significantly lower than that of the lumbar spine (-2.48 ± 1.8, p = 0.002). The prevalence of osteoporosis and that of osteopenia at the femoral neck were 64.2% and 28.4%, respectively. The prevalence of osteoporosis and that of osteopenia at the lumbar spine were 50.7% and 34.3%, respectively. When the lowest T-score at either the lumbar spine or femoral neck was used for diagnosis, there were 48 patients (71.6%) with osteoporosis and 16 patients (23.9%) with osteopenia.
Table 2: Bone mineral density and prevalence of osteoporosis and osteopenia
Measurement
|
Mean T-score (SD)
|
Osteoporosis
n (%)
|
Osteopenia
n (%)
|
Normal
n (%)
|
DXA
Femoral neck
Lumbar spine
Calcaneus QUS
|
-2.89 (1.42)
-2.48 (1.80)
-1.22 (1.19)
|
43 (64.2)
34 (50.7)
6 (9.0)
|
19 (28.4)
23 (34.3)
39 (58.2)
|
5 (7.5)
10 (14.9)
22 (32.8)
|
Osteopenia: T-score between -1.0 SD and -2.5 SD, Osteoporosis: T-score <−2.5 SD
The significant risk factors associated with osteoporosis were BMI and FFMI, as shown in Table 3. The COPD patients with a low BMI (BMI < 18.5 kg/m2) had an almost 9-fold increased risk of osteoporosis than did the patients with a normal BMI. The patients who had an FFMI < 17 kg/m2 had a five times higher risk of osteoporosis than did those with an FFMI greater than 17 kg/m2.
Table 3: Factors associated with osteoporosis
Variable
|
OR
|
95%CI
|
p-value
|
Age (years)
50–59a
60–69
70–79
≥80
BMI (kg/m2)
<18.5
18.5-24.9a
≥25
Pack-years
Charlson comorbidity index
Inhaled corticosteroid uses in the past year
Oral corticosteroid uses in the past year
GOLD COPD staging
Stage Ia
Stage II
Stage III
Stage IV
COPD Assessment Test (CATTM) score
Numbers of exacerbation in previous year
FFMI (kg/m2)
<17
≥17a
|
reference
1.43
1.14
5.71
0.77
8.84
reference
0.62
1.01
1.18
0.83
1.19
reference
1.20
1.37
1.00
1.02
1.00
0.63
4.91
reference
|
(0.30, 6.74)
(0.26, 5.09)
(0.52, 62.66)
(0.64, 0.91)
(1.06, 74.03)
(0.16, 2.44)
(0.99, 1.03)
(0.73, 1.91)
(0.08, 8.55)
(0.38, 3.69)
(0.28, 5.07)
(0.27, 6.87)
(0, 1.00)
(0.96, 1.09)
(0.86, 1.17)
(0.44, 0.89)
(1.26, 19.06)
|
0.652
0.861
0.154
0.003*
0.044*
0.498
0.359
0.507
0.878
0.766
0.804
0.701
0.999
0.469
0.952
0.009*
0.022*
|
a reference category
*p-value is significant.
OR = odd ratio, CI = confidence interval
Ability of calcaneus QUS to detect osteoporosis
The mean T-score determined using calcaneus QUS was -1.22 ± 1.19, which was significantly higher than the T-score determined using DXA at both the femoral neck and lumbar spine (p < 0.001) (Table 2). The calcaneus QUS T-score was significantly correlated with the DXA T-score at the femoral neck (r = 0.62, p < 0.001) and lumbar spine (r = 0.53, p < 0.001). Each QUS parameter was analyzed using ROC analysis to determine which QUS parameter was able to identify the participants with osteoporosis at the femoral neck, the lumbar spine, and either site (either the femoral neck or the lumbar spine). All four QUS parameters could discriminate osteoporosis at both sites, with an AUC ranging from 0.64 to 0.83 and p < 0.05, indicating statistical significance (see Figure 1). The AUC reflects the accuracy of the test. In general, an AUC closer to 1.0 indicates a more accurate test, while an AUC of 0.5 suggests the test has no discriminative ability. The accuracy of the QUS T-score was in an acceptable range to detect osteoporosis at either site (AUC 0.7-0.79).
Among all four QUS parameters, the T-score is commonly used in clinical practice by most physicians. In this study, we interpreted the result of the QUS T-score on the basis of the DXA T-score criteria. Using a DXA T-score ≤ -2.5 as a reference for diagnosing osteoporosis, the prevalence of osteoporosis detected by calcaneus QUS was only 9%, which was significantly lower than that detected by DXA at both the femoral neck and lumbar spine (p < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of the different QUS T-score cutoff values are presented in Table 4. When a QUS T-score ≤ -2.5 was used as the cutoff, the sensitivity was less than 15%, while the specificity was approximately 95%. The positive predictive value was 83.3%, and the negative predictive value was approximately 29.5%–52.4%. Therefore, subjects with a QUS T-score ≤ -2.5 had a high likelihood of osteoporosis. However, with this cutoff level, calcaneus QUS missed diagnosing approximately 90% of the patients who were diagnosed with osteoporosis by DXA. When the QUS T-score cutoff value was increased, the sensitivity increased, while the specificity decreased. When the sensitivity exceeded 80%, the specificity was less than 70% (Table 4).
Table 4 The ability of QUS T-score at the different cutoff to predict DXA-determined osteoporosis
Site
|
QUS
T-score*
|
Sensitivity
(%)
|
Specificity
(%)
|
PPV
(%)
|
NPV
(%)
|
Any site
Femoral neck
Lumbar spine
|
-2.50
-1.25
-0.80
-0.09
-2.50
-1.25
-0.80
-0.09
-2.50
-1.25
-0.88
-0.09
|
10.42
70.83
83.33
91.66
11.62
72.09
83.72
93.02
14.70
85.29
91.18
97.06
|
94.73
73.68
47.37
31.57
95.83
66.67
41.67
29.17
96.97
69.70
45.45
27.27
|
83.33
87.18
80.00
77.19
83.33
79.49
72.00
70.18
83.33
74.36
63.27
57.89
|
29.50
50.00
52.94
60.00
37.70
57.14
58.82
70.00
52.46
82.14
83.33
90.00
|
*The threshold value of QUS T-score below this point, osteoporosis is diagnosed by calcaneus QUS.
PPV = positive predictive value, NPV = negative predictive value