Evaluation of risk factors causing osteoporosis in chronic obstructive pulmonary disease (COPD) Patients

Methods: This prospective cross sectional study was done in pulmonology department Nishtar Hospital Multan. Total 369 patients of chronic obstructive pulmonary disease, diagnosed according to Global Initiative for Chronic Obstructive Lung Diseases (GOLD) criteria were enrolled by non-probability consecutive sampling. The study was conducted from January 2016 to November 2016. Ethical approval was taken from committee of the hospital. Written permission was signed by each patient included in study. Quantitative variables like age, body mass index, FEV1, pack years smoking and vitamin D were statistically measured in mean and standard deviation. Qualitative variables like gender and area of living were statistically analyzed in percentage and frequency. ANNOVA was applied to test the significance. P value <0.05 was taken as significant.


Introduction
Chronic obstructive pulmonary disease (COPD) is very common respiratory problem. It is a chronic inflammatory disease of lung {1}. Systemic chronic inflammation is caused by TNF-alpha, IL-6, CRP and IL-8 {2}. It greatly affects the quality of life {3}. Chronic obstructive pulmonary disease is characterized by persistent and irreversible air flow limitation {4}. Chronic obstructive pulmonary disease is treatable and progressive disease. Chronic obstructive disease occurs in adults and older age patients. Patients of chronic obstructive disease clinically present with symptoms of cough, chest pain, dyspnea and sputum mostly. It is cause of great burden on health care system. Chronic obstructive disease is one of the leading cause of mortality. It is expected to be the third most common cause of mortality in 2020 {5}. Many complications occur in chronic obstructive pulmonary disease patients like anemia, muscle wasting, cachexia and weight loss. Most cases of chronic obstructive pulmonary disease occur due to smoking {6}. Other factors such as bio mass fuel exposure {7}, environmental pollution, toxic agents on work place can cause chronic obstructive pulmonary disease. Inflammation to these hazardous agents in airways result in bronchospasm and mucous glands hyperplasia. Chronic obstructive pulmonary disease patients usually have many comorbidities like diabetes, hypertension and cardiovascular disease. Erectile dysfunction is also common problem in chronic obstructive pulmonary disease patients {8}. Acute exacerbation of chronic obstructive pulmonary disease is crucial event in the course of disease. It is main reason of hospitalization in chronic obstructive pulmonary disease patients. It is estimated that 50-70% cost associated with chronic obstructive pulmonary disease is due to its exacerbation.
Osteoporosis is bone disorder which is caused by change in micro architectural of the skeleton due to low bone mineral density (BMD) {9}. Bone strength and quality mainly depends on the three dimensional micro architectural of bone and also properties of material constituents. Type 1 collagen and hydroxyapatite crystals are the main constituents of bone {10}. Osteoporosis increase the chances of fracture by compromising the bone strength. There is no clinical tool to evaluate the quality of bone. However, bone mineral density is measured by dual-energy X-ray absorptiometry (DXA). According to WHO criteria osteoporosis is diagnosed when bone mineral density is 2.5 standard deviation or more to young adult mean. Bone mineral density reflects nearly 70% strength of bone.
It has been investigated that there is a strong association of osteoporosis in COPD patients. The development of osteoporosis in chronic obstructive pulmonary disease patients is caused by many risk factors. Age, smoking, low body mass index, use of steroid, low levels of vitamin D, decrease physical activity and chronic inflammation are the common factors that result in osteoporosis in chronic obstructive pulmonary disease patients. Osteoporosis has its complications in chronic obstructive pulmonary disease patients. It increases the chances of osteoporotic fractures and affects the quality of life {11}.
Rationale of the study was that osteoporosis is common and hidden comorbidity in chronic obstructive pulmonary disease patients. It is extremely under investigated and undertreated condition in chronic obstructive pulmonary disease. Currently, very limited research had been conducted on prevalence and risk factors of osteoporosis in chronic obstructive pulmonary disease in Pakistan. So this study will help to establish the facts and also provide base for further investigation. Study done by Chun-Wei lin et al. in Taiwan was taken as reference study {12}.

Materials and methods
This prospective cross sectional study was done in pulmonology department Nishtar Hospital Multan. Total 369 patients of chronic obstructive pulmonary disease, diagnosed according to Global Initiative for Chronic Obstructive Lung Diseases (GOLD) criteria were enrolled by non-probability consecutive sampling. The study was conducted from January 2016 to November 2016. Ethical approval was taken from committee of the hospital. Written permission was signed by each patient included in study. All patients having clinically stable chronic obstructive pulmonary disease disease and can perform mild physical activity were included in study. Exclusion criteria of study were: 1) patients who were using systemic corticosteroids, 2) patients having history of any malignancy, 3) any history of acute exacerbation of chronic obstructive pulmonary disease in last one year, 4) patients having history of other systemic diseases like endocrine, renal, gastrointestinal, cardiovascular and rheumatology which can effect bone mineralization and patients having other than chronic obstructive pulmonary disease respiratory disorder were excluded from the study. Sample size was collected from a reference study done by Chun Wei Lin et al. for which confidence interval was taken as 95%, study strength 80, 40% of chronic obstructive pulmonary disease patients having osteoporosis {12}.
All patients were recruited from outpatient department. A detailed history of disease, smoking habits, history of pain and physical activity were taken. Complete physical examination was done in every patient to assess the severity of disease, its complications and any clue of other systemic disorder. Personal information of each patient like age, gender, body mass index, area of living and smoking status was recorded by filling the Performa. On the investigation day pulmonary function tests, bone mineral density and fasting blood glucose were recorded.
Spirometry was done to check the pulmonary functions. It was done by same technician in each patient and in sitting position. Three technically correct values of FEV1, FVC and FEC1/FVC were recorded and highest of three value was taken in study.
Bone mineral density was checked by using dual energy X ray absorptiometry (DEXA). Left hip joint, anterior posterior lumbar spine (L1 to L4) and total bone mineral density were measured individually in absolute values in grams of minerals per unit area scanned (g/cm) and relative T-scores. According to WHO criteria osteoporosis is diagnosed when bone mineral density is 2.5 standard deviation or more to young adult mean In all patient's venous sample was drawn between 6 a.m. to 9 a.m. Complete blood analysis and fasting blood sugar levels were measured Quantitative variables like age, body mass index, FEV1, pack years smoking and vitamin D were statistically measured in mean and standard deviation. Qualitative variables like gender and area of living were statistically analyzed in percentage and frequency. ANNOVA was applied to check the significance. P value <0.05 was taken as significant.

Conclusion
Study concluded that osteoporosis is hidden and common comorbidity in COPD patients. Its prevalence was high among the patients. Significant number of COPD patients had osteoporosis. Pulmonologists should consider and properly investigate osteoporosis in COPD patients.