Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality in adults and is the fourth leading cause of death in the world [1]. COPD is now considered as a multi-component disorder associated with systemic inflammation and extra pulmonary manifestations [2]. Though osteoporosis has been found to be one of the systemic effects of COPD, the precise mechanisms are still unclear [3]. The prevalence of osteoporosis is estimated to be 2 to 5 times higher in COPD patients as compared to healthy subjects [4,5]. COPD has been identified as a disease associated with osteoporosis and has been included in the fracture risk assessment in a few guidelines on osteoporosis and fracture prevention [6]. However, Indian data is scarce on the association between COPD and BMD and hence, we aimed to assess the relationship between these two common entities. The aim of the study was to estimate the prevalence of osteopenia and osteoporosis in patients with COPD.
The primary objective of the study was to evaluate BMD in COPD patients using qualitative ultrasonic bone densitometer. The secondary objective was to determine the correlation between BMD and COPD severity, smoking status.
Materials and Methods
This prospective cross-sectional study of 60 patients was conducted in the Department of Respiratory Medicine at a tertiary care hospital in Southern India from 1st September 2012 to 31st August 2013. Consecutive patients with COPD confirmed by clinical examination and subsequent spirometry as per GOLD guidelines were included in the study [2]. Patients with: 1) Spirometry proven bronchial asthma; 2) Patients on long term oral steroids; 3) Patients with coexisting lung diseases such as pulmonary tuberculosis and bronchiectasis; 4) Patients with chronic co-morbidities including congestive heart failure, chronic liver disease and 5) Patients with recent acute coronary syndrome, unstable angina were excluded. Informed consent was obtained from all patients. The study protocol was approved by the institutional ethics committee board.
All included patients underwent a detailed clinical evaluation including collection of details such as age, sex, residence, smoking history and disease severity followed by thorough examination. Subsequently, they underwent spirometry using ‘KOKO legend’ desktop spirometer, model no. 314000 that satisfied the American Thoracic Society performance criteria [7].
Spirometry was performed again after 20 minutes following the administration of Salbutamol (5mg) nebulisation for assessing reversibility. The following parameters were noted: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), FEV1/FVC ratio, Forced Expiratory Flow 25%-75% (FEF) and Peak Expiratory Flow Rate (PEFR). The procedure was repeated thrice and the average values were taken.
Bone mineral density was assessed in the left heel bone (calcaneus) using ACHILLES quantitative ultrasound bone densitometer produced by GE HEALTH CARE. According to WHO criteria [8], patients with T score more than -1.0 were considered to possess normal bone density; those with T score between -1.0 and -2.5 were considered to be osteopenic and those less than -2.5 were considered to be osteoporotic.
Stastistical Analysis
Descriptive statistics including mean and standard deviation were used to summarize the baseline characteristics of the patients. For analysis of factors affecting BMD, we used the Pearson’s Chi Square test to estimate the difference in BMD score according to disease severity and smoking status. Pearson’s correlation coefficient was used to measure the correlation between BMD score and increasing age, number of pack years and FEV1%.
Results
Baseline characteristics are shown in [Table/Fig-1]. Most of the patients were males (85%) and aged 61 years and above (47%) while 37% were between 50 and 60 years. A large number of patients 46 (77%) were smokers (current 38, reformed 8) comp-rising only of male patients. None of the female patients were smokers. Based on FEV1, 43 (72%) patients had moderate obstruction, 16 (26.7%) had severe obstruction while only 1 (1.7%) had very severe obstruction. There were no patients with mild obstruction. Overall, 40 (67%) patients had an abnormal BMD of which 21 had osteoporosis and 19 patients had osteopenia. Among the osteoporotic patients, 13 (62%) patients had severe obstruction while 8 (38%) had moderate obstruction (p<0.001). Out of the 20 patients with normal BMD scores, 19 (95%) had moderate obstruction while only 1 (5%) had severe obstruction. Out of 16 patients with severe obstruction, 13 (81%) had osteoporosis (p<0.001).
Baseline characteristics of the study population (n=60).
Characteristics | Males, n (%)* | Females, n (%) | Total, n (%) |
---|
Total | 51 (85) | 9 (15) | 60(100) |
Mean age | 61.2±10.2 | 57.6±7.1 | |
Age groups |
40-50 | 8(16) | 2 (22) | 10 (17) |
50-60 | 18(35) | 4 (44) | 22(37) |
>61 | 25(49) | 3 (33) | 28 (47) |
Smokers | 46 (90) | 0 | 46 (77) |
Current | 38 (75) |
Reformed | 8 (15) |
Mean NPY𠈂 | 17.9±12.9 |
Mean FEV1 %‡ | 53.59+10.6 | 60.33±7.7 | |
Mean FEV1/FVC§ | 63.04±9.1 | 67.67+8.2 | |
Mean BMD|| | -1.63±1.2 | -0.8±1.26 | |
*n (%) = number (percentage) of given characteristics, 𠈂 = No.of pack years, ‡ = Forced Expiratory Volume at 1 second, §=Forced Vital Capacity, || = Bone Mineral Density
Among the patients who smoked, 34 (74%) had abnormal BMD scores while 6 (37%) non-smokers had abnormal BMD. The mean number of pack years was inversely related to BMD scores. Only one female patient had osteoporosis while three females had osteopenia [Table/Fig-2]. We found a significant correlation between age, FEV1%, Number of Pack Years (NPY) and BMD scores [Table/Fig-2].
Factors affecting BMD score among the study population.
| BMD Score |
---|
Factors | Normal (n=20)(> -1.0) | Osteopenia (n=19)(-1.0 to -2.5) | Osteoporosis (n=21)(< -2.5) | p-value |
---|
FEV1 % | | | | |
Mild (>80%) | - | - | - | |
Moderate (50-79%) | 19 (44.2%) | 16 (37.2%) | 8 (18.6%) | <0.001 |
Severe (30-49%) | 1(6.3%) | 2 (12.5%) | 13 (81.3%) | |
Very severe(<30%) | 0 | 1 | 0 | |
Non smokers | 8 (57.1%) | 5 (35.7%) | 1(7.1%) | 0.02 |
Smokers | 12 (26.1%) | 14 (30.4%) | 20(43.5%) | |
Mean NPY | 16 | 22 | 28 | |
Females | 5(56%) | 3(33%) | 1(11%) | |
| Correlation coefficient(r) BMD score | |
Age | -0.253 | 0.05 |
FEV1% | 0.497 | 0.0001 |
NPY (Number of Pack Years) | -0.591 | 0.0001 |
Discussion
Osteoporosis is a disease with features of microarchitectural destruction of bone tissue leading to a low bone density, increased bone fragility and thus increased fracture risk [9]. Osteopenia is the preclinical stage of osteoporosis. Multiple mechanisms have been postulated to explain the high prevalence such as smoking, inflammatory cytokine production, vitamin D deficiency, physical inactivity and use of steroids.
We used the ultrasound bone densitometer to assess BMD in our patients. Similar studies using the same mechanism have been done by Parthasarathi et al., [3] and Vrieze et al., [10] to estimate the prevalence of osteopenia and osteoporosis in COPD patients.
We found a 67% prevalence of osteopenia and osteoporosis among COPD patients in our study. The prevalence of osteopenia and osteoporosis in the general population varies between 35% and 56% in Indian studies [11], much lower than the prevalence we found in our study. There is very little data on the prevalence of these abnormalities in COPD patients especially in Southern India. A recent study by Hattiholi et al., demonstrated the prevalence to be as high as 86% among their patients [12].
Importantly, we found a large difference in the prevalence of osteoporosis between patients with moderate and severe obstruction (18.6 % vs. 81.2%, p<0.001) which indicates a significant negative correlation between BMD and COPD severity. Moreover, we also found a positive correlation between FEV1% values and BMD scores (p=0.0001). Patients with mild obstruction were not encountered in our study as this was a hospital based study and they may have been asymptomatic or had mild symptoms not requiring access to health care. In a study done by Sin et al., in 2003, patients with severe airflow obstruction were at an increased risk for osteoporosis (Odds Ratio 2.4, 95% CI: 1.3 to 4.4) [13]. However, patients with mild obstruction had no increased risk of osteoporosis.
Age is an established risk factor for osteoporosis and in our study 47% were > 60 years of age and 37% were between 50 and 60 years of age. We found a significant negative correlation between increasing age and lower BMD values (p=0.05). Graat-Verboom et al., found patients between 55 and 65 years and over 65 years had a 6-fold and 11 increased risk respectively for developing osteoporosis [14].
In our study, 77% were smokers out of which 30% were osteopenic and 45% were osteoporotic. Patients with osteoporosis had a higher NPY (28) when compared to those with osteopenia (16) and normal BMD (22). We found a significant negative correlation between NPY and BMD (p=0.0001) indicating that smoking is a major risk factor for low bone mineral density. It is pertinent to note that a meta-analysis by Ward and Klesges concluded that tobacco smoking was an independent risk factor for low BMD and also had a cumulative, dose-dependent effect [15].
We compared our results with data from other recent Indian studies and found similar results (correlation between COPD severity, smoking and lower BMD) have been reported by Hattiholi et al., [Table/Fig-3] [12].
Comparison between various Indian studies.
Studies done in India | Total No. | Mean AgeTotal | Mean BMD in Osteoporotic Patients | Correlation between COPD Severity and Lower BMD | Correlation between Smoking and Lower BMD | Osteoporosisn (%)* |
---|
Present study | 60 | 60.7±9.9 | -2.72±0.15 | Yes | Yes | 21(35) |
Hattiiholi et al., [12] | 102 | M𠈂-66.6±7.8F‡-64.4±11.5 | 0.74±0.12 | Yes | Yes | 68(66.7) |
Bhattacharya et al., [3] | 37 | | -2.84±0.23 | No | Not done | 8(22) |
*n (%) = number (percentage) of given characteristics𠈂=M – male ‡ = F – female
Female gender is a well-known independent risk factor for osteoporosis and consequent fractures [16]. In our study, there were only nine females and only one patient had osteoporosis while three had osteopenia. This could be due to the small number of female patients included in our study.
Limitation
This study included a relatively small number of patients. We used the ACHILLES clinical bone sonometer to assess skeletal status although dual energy X-ray absorptiometry is the preferred quantitative technique.
Conclusion
Our study has demonstrated a high prevalence of BMD abnormalities among COPD patients which increases with disease severity, smoking and age. Large studies are required on an emergent basis to identify the extent of the problem and consider whether routine BMD screening is necessary for this high risk group of patients especially in low income countries.
*n (%) = number (percentage) of given characteristics, 𠈂 = No.of pack years, ‡ = Forced Expiratory Volume at 1 second, §=Forced Vital Capacity, || = Bone Mineral Density*n (%) = number (percentage) of given characteristics𠈂=M – male ‡ = F – female