Gao R, Zeng JK, Yang K, Wang P, Zhou S. Novel association between chronic obstructive pulmonary disease and osteoporosis: A prospective cross-sectional study. World J Orthop 2025; 16(2): 102101 [DOI: 10.5312/wjo.v16.i2.102101]
Corresponding Author of This Article
Sheng Zhou, MD, Professor, Department of Diagnostic Radiology, Gansu Provincial Hospital, No. 204 Donggang West Road, Lanzhou 730000, Gansu Province, China. lzzs@sina.com
Research Domain of This Article
Radiology, Nuclear Medicine & Medical Imaging
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Rong Gao, Jian-Kang Zeng, Kai Yang, Ping Wang, Sheng Zhou, First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
Rong Gao, Kai Yang, Ping Wang, Sheng Zhou, Department of Diagnostic Radiology, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
Author contributions: Gao R and Yang K contributed to writing and reviewing the manuscript; Gao R and Wang P contributed to designing the survey and executing the study; Gao R, Zhou S, and Wang P contributed to the statistics and reviewing the manuscript; All authors have reviewed and approved the final manuscript. Gao R and Zeng JK contributed equally to the conception and design of the study and are co-first authors.
Supported by National Natural Science Foundation of China (NSFC) of China, No. 82360358; Internal Medicine Research Project of Gansu Provincial People's Hospital, No. 22GSSYD-77; and Natural Science Foundation of Gansu Province, No. 22JR5RA659.
Institutional review board statement: Ethical approval for this study was obtained from Gansu Provincial People's Hospital, No. 2023-304.
Informed consent statement: Participants were informed about the study’s purpose, methods, and voluntary nature, with the option to withdraw at any time. By voluntarily participating, informed consent was implied. No identifiers were collected, and the anonymity and confidentiality of participants were strictly maintained.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
STROBE statement: The authors have read the STROBE Statement-a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: Raw data and materials are available upon reasonable request to the Corresponding Author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sheng Zhou, MD, Professor, Department of Diagnostic Radiology, Gansu Provincial Hospital, No. 204 Donggang West Road, Lanzhou 730000, Gansu Province, China. lzzs@sina.com
Received: October 8, 2024 Revised: December 18, 2024 Accepted: January 11, 2025 Published online: February 18, 2025 Processing time: 126 Days and 12.2 Hours
Abstract
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition often associated with a high incidence of osteoporosis. Studies indicate that patients with COPD present with a significant decrease in bone mineral density (BMD), potentially related to inflammation and corticosteroid use.
AIM
To investigate the relationship between BMD and lung function, mainly the forced expiratory volume in the forced expiratory volume in 1 second (FEV1)/ forced vital capacity percentage (FVC%), in patients with COPD using quantitative computed tomography (QCT).
METHODS
This prospective cross-sectional study included 85 patients with COPD treated at Gansu Provincial People's Hospital. Exposure variables included lung function parameter (FEV1/FVC%), age, sex, body mass index, smoking status, tea-drinking habits, and physical activity. BMD was measured using QCT. Linear regression and generalized additive models were employed to analyze the relationship between exposure variables and BMD.
RESULTS
Linear regression analysis revealed a significant positive relationship between BMD and FEV1/FVC% (β = 0.1, 95% confidence interval [CI]: 0.1-0.1; P < 0.0001). Non-linear analysis identified a unique BMD breakpoint of 128.08 mg/cm³. Before the breakpoint, BMD was significantly positively correlated with FEV1/FVC% (β = 0.245; P = 0.0019); while after the breakpoint, the relationship was negative and showed no statistical significance (β = -0.136; P = 0.0753). This finding underscores the critical role of BMD in COPD management and highlights the importance of individualized clinical interventions in improvement of lung function and overall health status in patients.
CONCLUSION
There is a complex non-linear relationship between BMD and lung function in patients with COPD, highlighting the importance of monitoring change in bone density during the management of COPD.
Core Tip: This study investigated the relationship between bone mineral density (BMD) and lung function, mainly the forced expiratory volume in 1 second (FEV1)/forced vital capacity percentage (FVC%), in patients with chronic obstructive pulmonary disease (COPD). A significant non-linear association was observed, and BMD ≤ 128.08 mg/cm³ was considered a critical threshold for lung function assessment. Higher BMD values correlated positively with higher FEV1/FVC%, suggesting that BMD may be a valuable biomarker for evaluating lung function changes in this population. These findings provide new insights into the interplay between bone health and respiratory function in patients with COPD.
Citation: Gao R, Zeng JK, Yang K, Wang P, Zhou S. Novel association between chronic obstructive pulmonary disease and osteoporosis: A prospective cross-sectional study. World J Orthop 2025; 16(2): 102101
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition characterized by persistent airway obstruction. It is primarily caused by an inflammatory response of the lungs to harmful particles, particularly cigarette smoke particles[1]. The pathogenesis of COPD is complex, involving various factors such as genetic susceptibility, environmental influences, and systemic inflammation[2,3]. As the global population is aging at a rapid pace, the prevalence of COPD is on the rise[4]. Epidemiological surveys have shown that the prevalence of COPD in China is 8.6%. Among them, 12% have never undergone a pulmonary function test (PFT) or received a timely diagnosis of COPD[5]. There are no obvious clinical symptoms in the early stages of COPD. Instead, patients will present with small airway damage, alveolar destruction, and decreased lung function[6].
Osteoporosis (OP) is a skeletal disorder characterized by reduced bone mass and an increased risk of fractures, and it has become a significant public health issue[7]. Epidemiological studies have indicated that the incidence of OP significantly increases among the elderly, especially postmenopausal women[8]. As the global population ages, the burden of OP-related complications, such as hip fractures, is expected to escalate, leading to higher morbidity rates and healthcare costs in this population[9]. The development of OP is multifactorial, associated with age, sex, genetic predisposition, nutritional status, and lifestyle choices[10]. In recent years, there has been a growing number of studies focusing on the potential link between COPD and OP. Evidence suggests that the prevalence of OP is significantly higher in patients with COPD than in the general population[11]. COPD is a risk factor for OP. Research shows that the severity of COPD in middle-aged and older men with OP is related to reduced bone formation. Additionally, patients with COPD may present with bone metabolism dynamics, indicating the occurrence of low bone turnover and osteoblastic dysfunction as COPD worsens[12]. Furthermore, the association between COPD and OP may be related to common risk factors such as age, severe emphysema, lack of regular exercise, systemic inflammation, vitamin D deficiency, and long-term use of corticosteroids[11]. Despite the abundant evidence linking COPD to OP, the mechanisms and strength of this relationship remain contentious.
Currently, PFTs remain the gold standard for diagnosing COPD, with characteristics of non-invasiveness, high reproducibility, and good feasibility. However, these tests primarily rely on patient symptoms and laboratory tests. As lung tissue has a strong compensatory ability, PFTs are unable to unravel the changes in lung anatomy. Consequently, PFTs have a very low sensitivity for diagnosis of early or mild disease and often lead to overdiagnosis in the elderly population due to age-related factors. Additionally, PFTs cannot assess the heterogeneous mechanisms underlying airflow limitation or disease progression[13]. Typically, pulmonary dysfunction only occurs when lung damage exceeds 30%[14]. Some patients with severe emphysema may be unable to complete PFTs, and communication barriers may reduce patient compliance. This method is time-consuming and labor-intensive in this population. Thus, relying solely on PFTs are inadequate to uncover the complexity of COPD. Routine chest computed tomography (CT) is part of the standard clinical examination for COPD. It not only enables early detection of COPD but also accurately reflects the location and extent of lesions. Quantitative chest CT (QCT) provides a new tool for clinical diagnosis of COPD. This method avoids additional radiation exposure and can also be used to analyze bone mineral density (BMD)[15].
There is a limited number of studies exploring the relationship between lung function and BMD in patients with COPD. This study addressed this question based on imaging data from routine chest CT combined with QCT. This study may provide new insights and effective practical evidence for the clinical management of COPD, hoping to improve the overall health of the patients.
MATERIALS AND METHODS
Study design and participants
This prospective cross-sectional study enrolled 85 patients with COPD who underwent chest CT at Gansu Provincial People's Hospital (Gansu province, China) from January to August 2024. Both patients newly diagnosed with COPD and patients previously diagnosed with COPD and underwent re-examination during this hospitalization were included. All participants provided written informed consent.
Inclusion criteria: (1) COPD diagnosed primarily based on the percentage of forced expiratory volume in 1 second (FEV1), symptoms, and history of acute exacerbations, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, with baseline post-bronchodilator FEV1/forced vital capacity (FVC) < 0.70[1,16]. COPD was classified into four categories: Group A (FEV1 ≥ 80% of predicted value), Group B (FEV1 = 50%-80% of predicted value), Group C (FEV1 = 30%-50% of predicted value), and Group D (FEV1 < 30% of predicted value, requiring hospitalization); (2) Age ≥ 18 years; (3) COPD diagnosed for at least 6 months; (4) Complete imaging and clinical data; and (5) OP diagnosed based on BMD measured by QCT: BMD > 120 kg/cm³ indicates normal, BMD of 80-120 kg/cm³ indicates low bone mass, and BMD < 80 kg/cm³ indicates OP[17].
Exclusion criteria: (1) Asthma or other respiratory diseases; (2) History of spinal fixation surgery within the past 6 months; (3) Other metabolic or endocrine disorders; and (4) Recent use of anti-OP medications. The study protocol was approved by the Ethics Committee of Gansu Provincial People's Hospital (Ethics Approval No. 2023-304).
Statistical analyses
Participants were divided into three groups based on their BMD values (n = 28-29 per group): Low BMD (≤ 80.5 mg/cm³), moderate BMD (80.6-115.7 mg/cm³), and high BMD (> 115.7 mg/cm³). The sample sizes in each group were well-balanced, which ensured balanced groups while maintaining clinically relevant differences among groups. Basic data included age, sex, height, weight, body mass index (BMI), FEV1/FVC%, FEV1, tea-drinking habits, physical activity, and smoking status. Variables are presented as the mean ± standard deviation, and P-values were calculated to identify statistical significance. Univariate linear regression models were used to assess the impact of exposure variables on BMD. Multivariate regression analysis was performed using non-adjusted model, adjusted model I, and adjusted model II. Adjusted model I and adjusted model II were used following adjustment for height, sex, age, weight, BMI, tea-drinking habits, physical activity, and smoking status. Variables analyzed in multivariate models were selected based on previous research and biological plausibility. Results are expressed as β values 95% confidence intervals (CIs) and P-values. A generalized additive model (GAM) was employed to analyze the effect of FEV1/FVC% on BMD at both the linear and non-linear levels. Threshold effect was analyzed using two models: Model I assessed linear effects, while model II identified inflection point (K-value = 128.08). All statistical analyses were performed using Empower Stats software (www.empowerstats.com), with statistical significance set at P < 0.05.
RESULTS
Characteristics of the participants
Participants were categorized into three subgroups by tertiles of baseline BMD values. Significant differences were observed across groups in terms of multiple demographic and clinical characteristics (Table 1). Age showed a significant inverse relationship with BMD value (P < 0.001). The mean age decreased from 71.0 ± 10.2 years in the lowest tertile group to 57.1 ± 11.1 years in the highest tertile group. Anthropometric measures, including height (P = 0.007), weight (P < 0.001), and BMI (P < 0.001) demonstrated positive associations with BMD value. Lung function parameters, including FEV1 and FEV1/FVC%, also showed significant differences across groups (both P < 0.001). Sex distribution varied significantly across BMD tertiles (P < 0.001). The proportion of males increased from 55.7% in the lowest tertile group to 77.8% in the highest tertile group. Smoking status also significantly differed across BMD tertiles (P < 0.001). The highest tertile group showed the largest proportion of former smokers (24.3%) and the lowest proportion of current smokers (21.4%). No statistically significant differences were observed across BMD tertiles with regard to tea-drinking habits (P > 0.05) or physical activity (P > 0.05). Taken together, BMD was associated with age, anthropometric measures, lung function, sex, and smoking status in this study population. However, whether there is a causal relationship cannot be inferred, requiring further research.
Table 1 Baseline characteristics of participants (n = 85), (mean ± standard deviation).
Characteristic
Low
Middle
High
P value
No. of participants
28
29
28
Age (years)
71.0 ± 10.2
65.1± 8.7
57.1 ± 11.1
< 0.001
Height (cm)
1.6 ± 0.1
1.7 ± 0.1
1.7 ± 0.1
0.007
Weight (kg)
60.6 ± 9.2
64.6 ± 11.0
67.4 ± 10.4
< 0.001
BMI (kg/m2)
22.3 ± 3.2
23.1 ± 3.5
24.0 ± 3.4
< 0.001
FEV1 (L)
1.8 ± 0.7
1.9 ± 0.9
2.4 ± 0.1
< 0.001
FEV1/FVC% (L)
62.2 ± 11.9
64.2 ± 16.3
71.2 ± 15.9
< 0.001
BMD (mg/cm3)
53.9 ± 17.1
98.2 ± 9.0
139.8 ± 24.7
< 0.001
Sex, n (%)
< 0.001
Male
55.7
75.5
77.8
Female
44.3
24.5
22.2
Smoke, n (%)
< 0.001
Yes
52.2
39.1
54.3
No
5.9
20.3
24.3
Yes, give up
41.9
33.8
33.0
Physical activity, n (%)
0.014
Univariate analysis revealed significant associations between FEV1/FVC% and multiple factors (Table 2). BMD was positively associated with FEV1/FVC% (β = 0.1, 95%CI: 0.1-0.1; P < 0.0001), and FEV1/FVC% increased with increasing BMD value (β = 9.0, 95%CI: 5.3-12.8; P < 0.0001). Age showed a negative relationship with FEV1/FVC% (β = -0.3, 95%CI: -0.4 to -0.1; P < 0.0001). Females tended to have a higher FEV1/FVC% than males (β = 3.4, 95%CI: 0.0-6.8; P = 0.0488). BMI was positively correlated with FEV1/FVC% (β = 0.8, 95%CI: 0.3-1.3; P = 0.0006). Smoking status was significantly associated with FEV1/FVC%, and current smokers had a markedly lower FEV1/FVC% than never-smokers (β = -10.7, 95%CI: -14.0 to -7.4; P < 0.0001). Tea consumption (β = 4.1, 95%CI: 0.9-7.4; P = 0.0135) and moderate-intensity physical activity (β = 5.9, 95%CI: 2.4-9.5; P = 0.0012) was correlated higher FEV1/FVC% values. FEV1 demonstrated a strong positive correlation with FEV1/FVC% (β = 10.9, 95%CI: 9.7-12.1; P < 0.0001). These findings provide important insights into the relationship among BMD, age, sex, BMI, smoking status, lifestyle factors, and lung function, laying the foundation for further research.
Table 2 Univariate analysis of forced expiratory volume in 1 second/forced vital capacity percentage, n (%).
Multivariate analysis was conducted to further analyze the relationship between BMD and FEV1/FVC% (Table 3). The non-adjusted model showed a significant positive correlation between BMD and FEV1/FVC% (β = 0.1, 95%CI: 0.1-0.1; P < 0.0001). Comparatively, adjusted model I demonstrated a weakened relationship between BMD and FEV1/FVC%, which remained significant (β = 0.0, 95%CI: -0.0 to -0.1; P = 0.0387). However, the relationship between BMD and FEV1/FVC% was found with no statistical significance after adjustment for key variables (β = -0.0, 95%CI: -0.0 to -0.0; P = 0.896). These findings suggest that the relationship between BMD and FEV1/FVC% may be influenced by multiple factors, and various variables should be considered when interpreting this association.
Table 3 Relationship between bone mineral density and forced expiratory volume in 1 second/forced vital capacity percentage.
GAM was employed to investigate the relationship between FEV1/FVC% and BMD in participants aged 60 years or younger (n = 85), and a significant non-linear association was observed (edf = 4.0045, F = 5.0685; P = 0.0003). The adjusted R-squared for the non-linear model was 0.1458, with 17.04% of deviance explained. The intercept of the model was 69.2021 (95%CI: 66.6175-71.7868; P < 0.001). The smooth term for BMD was statistically significant, indicating a complex non-linear relationship (Figure 1).
Figure 1 Association between bone mineral density and forced expiratory volume in 1 second/forced vital capacity percentage.
Figure 1 demonstrates a significant positive correlation between bone mineral density (BMD) and forced expiratory volume in 1 second (FEV1)/forced vital capacity percentage (FVC%), especially pronounced when the BMD was below 128.08 mg/cm³. This suggests that an increase in bone density may be related to better lung function. Additionally, the data revealed a non-linear relationship, indicating that beyond a certain threshold, the effect of increasing BMD on improving lung function is diminished.
Following adjustment for confounding factors such as sex, BMI, age, and smoking status, the linear model showed a positive but not significant relationship between BMD and FEV1/FVC% (β = 0.052, 95%CI: -0.031 to 0.135; P = 0.2228). However, the non-linear model revealed a significant positive relationship between FEV1/FVC% and BMD before BMD breakpoint of 128.08 mg/cm³ (β = 0.245, 95%CI: 0.094 to 0.396; P = 0.0019), but a negative relationship after the breakpoint (β = -0.136, 95%CI: -0.284 to 0.013; P = 0.0753). The difference between the two slopes was statistically significant (β difference = -0.381, 95%CI: -0.633 to -0.128; P = 0.0037). The log-likelihood ratio test (P = 0.003) supported the use of the non-linear model. Collectively, there was a complex non-linear relationship between BMD and lung function, and the association was more pronounced at lower BMD levels (Table 4). Our findings indicate a complex nonlinear relationship between BMD and FEV1/FVC%, and BMD ≤ 128.08 mg/cm³ may be used as a reliable biomarker for assessing changes in lung function. Additionally, FEV1/FVC% increased by 0.245 L per 1 mg/cm³ increase in BMD, providing a new biological basis for lung function assessment in patients with COPD.
Table 4 Threshold effect analysis of bone mineral density and forced expiratory volume in 1 second/forced vital capacity percentage using piece-wise linear regression.
Inflection point of BMD (mg/cm3)
Effect size (β)
95%CI
P value
≤ 128.08
0.245
0.094, 0.396
0.0019
> 128.08
-0.136
-0.284, 0.013
0.0753
DISCUSSION
This study investigated the relationship between lung function (FEV1/FVC%) and BMD in patients with COPD. A prospective cohort study was designed, and 85 eligible patients with COPD who provided written informed consent were included. The prospective design and comprehensive assessment strategy ensured the reliability and validity of the study data. Study results demonstrated a significant positive correlation between BMD and FEV1/FVC% (β = 0.1, 95%CI: 0.1-0.1; P < 0.0001), indicating that increased BMD may be associated with improvements in lung function. In addition, age and smoking status also showed a significant relationship with lung function, suggesting that these factors may play an important role in the relationship between BMD and lung function. Collectively, monitoring for change in BMD is important in the management of COPD, particularly during the assessment for change in lung function. Routine CT scans can help clinicians obtain crucial information about bone density without increasing radiation risk to patients. This treatment strategy may facilitate the development of more effective personalized treatment plans, and it also provides new insights into the management of bone health in patients with COPD. Thus, the combined use of CT scans has significant clinical application value.
This study revealed a positive relationship between BMD and FEV1/FVC% in patients with COPD, consistent with previous research. It has been reported that there is a notable positive correlation between the BMD of the L2 vertebra and PFT results in patients with COPD, highlighting a significant reduction in the BMD of the hip and lumbar regions in these patients[18]. Another study found that FEV1/FVC% was negatively correlated with indices including emphysema index, gas retention, and mean lung density at expiration in patients with COPD[19]. However, the relationship between BMD and lung function in patients with COPD, particularly in patients with mild disease, may not be significant[20]. Research also showed that BMD is closely related to airflow limitation, the severity of imaging findings, and quality of life in patients with COPD, and patients in GOLD class D group had the lowest BMD[21]. This finding suggests that proactive interventions are required in GOLD class D patients to help prevent and manage OP. Conversely, BMD also showed a certain negative relationship with lung function and a weak positive correlation with mortality in patients with COPD[22]. A prospective cohort study by Campos-Obando et al[23] demonstrated a significant association between BMD and mortality related to chronic lung disease, emphasizing a link between decreased BMD and worsened lung function. OP and fractures are prevalent in patients with COPD, significantly affecting the morbidity and mortality[24]. A large multicenter study found that patients with COPD were at increased risk of fractures and OP, and administration of high-dose corticosteroids further elevated the risk[25]. Current national guidelines for COPD management mainly focus on the bone health of patients, but how should we implement this is not specified. During COPD management, it is of vital importance to perform assessment for fracture risk. In this context, a systematic and comprehensive approach to address bone health issues is required. Future research should pay more attention to the incidence of OP in patients with COPD and the related mortality. In addition, assessment for OP risk should be considered during COPD management to enable early prevention and treatment.
Prolonged duration of COPD has been shown to cause an increased risk of OP and muscle wasting (known as sarcopenia)[26], suggesting that disease duration may affect bone health. This finding highlights the necessity of collecting related data in future studies. Research by Schulze-Hagen et al[27] reported that low BMD predicted poor outcomes in patients with severe disease, and BMD below 122 HU at admission led to a significant reduction in overall survival rate. BMD may serve as a prognostic tool for patients admitted to the intensive care unit, and it may be particularly useful in the assessment of survival risk in these patients. Moreover, both BMD and lung function were found to decrease in people within industrial areas than in reference areas. Study results revealed that a 0.1 g/cm² decrease in BMD corresponded with a 53.0 mL decline in FVC and a 33.5 mL decline in FEV1, indicating that BMD was positively correlated with FVC and FEV1, and reduced BMD was associated with decreased lung function in the general population[28]. Environmental factors, such as air pollution, also play an important role in the relationship between BMD and lung function.
Collectively, BMD serves as a crucial biomarker in the clinical assessment of both critically ill patients and those with COPD. Future research directions should focus on the potential mechanisms linking BMD with lung function and survival outcomes in patients with COPD. Additionally, the impact of environmental factors on the incidence of OP in patients with COPD should be considered. Different from previous research, this study not only examined the relationship between BMD and lung function in patients with COPD but also identified a breakpoint for BMD (128.08 mg/cm³). This study confirmed that when BMD ≤ 128.08 mg/cm³, a 1 mg/cm³ increase in BMD corresponded to a 0.245 L increase in FEV1/FVC% in patients with COPD. This finding makes BMD an important biomarker for clinical management of COPD and offers insights for future research into the potential mechanisms linking BMD with lung function and survival outcomes in this population.
OP is much more prevalent in patients with COPD than in healthy people. Physical inactivity has been shown to be a significant risk factor for OP in patients with COPD. COPD assessment test (CAT) is a new tool for evaluating the health status and daily activities in patients with COPD. Research revealed decreased daily physical activity (DPA) and higher CAT scores in patients with COPD with OP than those without OP. In addition, DPA positively correlated with the BMD of the lumbar spine, total hip, and femoral neck, whereas CAT scores negatively correlated with the BMD of the total hip and femoral neck. Moreover, lower femoral neck BMD in patients with COPD was associated with higher CAT scores. These results suggest that pulmonologists should pay attention to the low DPA and high CAT scores in patients with COPD with OP[29]. Moderate physical activity, along with adequate vitamin D and calcium intake, are recommended in patients with COPD, which may help enhance BMD and then improve bone health in these patients. Regular CAT and monitoring for change in BMD are also advised to help promptly adjust treatment plans. These strategies are expected to reduce the risk of OP in patients with COPD and enhance their overall health.
Chronic inflammation in patients with COPD may affect bone metabolism and lead to decreased BMD, and the increase in inflammatory factors is a significant pathological process of COPD-related OP. Research has reported that with increasing COPD severity (from GOLD 1 to GOLD 4), the levels of inflammatory markers, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), were significantly increased (P < 0.01), whereas the levels of repair-related markers, such as matrix metalloproteinase-9 and vascular endothelial growth factor, were reversely significantly decreased. This finding indicates that inflammatory responses play a critical role in the progression of COPD[30]. The significant correlations among IL-6, IL-8, and TNF-α suggest that they may jointly contribute to the inflammatory response in COPD. Elevated levels of IL-6 and TNF-α may promote the production of IL-8, thereby exacerbating airway inflammation. In addition, changes in IL-6, IL-8, and TNF-α are closely related to the survival and clinical outcomes of patients with COPD, indicating that these markers are potential biomarkers for assessing COPD severity and prognosis. The relationship between atherosclerosis and OP in patients with COPD may be mediated by common inflammatory mechanisms. It has been reported that there is a positive correlation between pro-inflammatory factors and bone metabolism-related proteins (e.g., IL-1β, IL-6, IL-17A, and TNF) in the bones and aortas of deceased donors[31]. In all, chronic inflammation in patients with COPD may negatively impact bone metabolism by increasing the levels of IL-6, IL-8, and TNF-α, thereby leading to OP. Acute exacerbation of COPD (AECOPD) may intensify the inflammatory response in patients, while intake of vitamin D may assist in accelerating inflammation resolution. However, the precise role of vitamin D in inflammation resolution during AECOPD warrants further research[32]. A previous study focused on various bone metabolism biomarkers and reported a close correlation between COPD severity and BMD. Study results have indicated that the severity of COPD, measured by FEV1%, is only associated with serum alkaline phosphatase, pro-collagen type 1 N-terminal propeptide, and tartrate-resistant acid phosphatase 5b[12]. However, the effects of inflammatory factors, bone metabolism markers, and medication changes on BMD in patients with COPD was not covered in this study. In future research, how these inflammatory factors impact bone metabolism should be clarified to provide a better understanding of the pathophysiological mechanisms linking COPD with OP.
Other research has shown that Hawthorn Five Flavors Powder (SWP) improves lung function and suppresses the inflammatory response in COPD rats by altering the gut microbiota, increasing short-chain fatty acid production, enhancing gut barrier function, and reducing levels of pulmonary inflammatory factors such as TNF-α, IL-6, and IL-8[33]. Additionally, treatment targeting Dachshund homolog 1 may alleviate smoking-induced airway inflammation by activating the nuclear factor erythroid 2-related factor 2 signaling pathway, providing a new therapeutic direction for patients with COPD[34].
Limitations
This study has several limitations that affect the generalizability and external validity of the findings. First, this was a single-center study, which limits the generalizability of the results. Analyses with larger samples in multicenter studies are needed to validate our findings. Second, the study population primarily consisted of Chinese individuals; thus, caution is advised in applying these results to other ethnic groups. Significant differences in genetics, environment, and lifestyle may exist across different populations and potentially influence the relationship between COPD and BMD. Third, this observational study primarily focused on the association between COPD and BMD but did not investigate their causal relationship. Thus, the results of the study should be interpreted carefully. Fourth, clinical laboratory indicators, such as inflammatory factors, were not covered in this study, which limits our understanding of the influence of inflammatory markers on the relationship between COPD and OP. Lastly, although multiple measurable confounding factors were used for analysis in this study, we could not account for other potential unmeasurable confounders. These unmeasured factors may exert a potential influence on the results, thereby affecting the conclusions. Future research should address these limitations to further validate and expand upon the findings of this study.
CONCLUSION
BMD ≤ 128.08 mg/cm³ is one of the reliable biological parameters for assessing change in lung function in patients with COPD. For every 1 mg/cm³ increase in BMD, FEV1/FVC% increases by 0.245 L. Chest QCT technology is a simple and feasible method for in vivo detection of BMD. It provides a useful screening tool for OP and changes in lung function in patients with COPD, and it can be employed to assess the likelihood of OP in primary care settings and community hospitals. This study has several clinically relevant implications. First, it provides new insights into the relationship between BMD and lung function in patients with COPD, helping clinicians perform more effective evaluation for the risk of OP associated with COPD. Second, regular BMD assessment is recommended in clinical practice. If needed, early intervention measures, such as supplementation with vitamin D and calcium, are required to reduce the risk of OP.
ACKNOWLEDGEMENTS
The authors sincerely thank all of the patients with COPD who participated in this research survey for their valuable time and insights.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.Am J Respir Crit Care Med. 2013;187:347-365.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 3156][Cited by in RCA: 3662][Article Influence: 305.2][Reference Citation Analysis (0)]
Penedones A, Mendes D, Alves C, Filipe A, Oliveira T, Batel-Marques F. Relationship Between Chronic Obstructive Pulmonary Disease and Osteoporosis: A Scoping Review.COPD. 2024;21:2356510.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
Wang C, Xu J, Yang L, Xu Y, Zhang X, Bai C, Kang J, Ran P, Shen H, Wen F, Huang K, Yao W, Sun T, Shan G, Yang T, Lin Y, Wu S, Zhu J, Wang R, Shi Z, Zhao J, Ye X, Song Y, Wang Q, Zhou Y, Ding L, Yang T, Chen Y, Guo Y, Xiao F, Lu Y, Peng X, Zhang B, Xiao D, Chen CS, Wang Z, Zhang H, Bu X, Zhang X, An L, Zhang S, Cao Z, Zhan Q, Yang Y, Cao B, Dai H, Liang L, He J; China Pulmonary Health Study Group. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study.Lancet. 2018;391:1706-1717.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 646][Cited by in RCA: 922][Article Influence: 131.7][Reference Citation Analysis (0)]
Woodruff PG, Barr RG, Bleecker E, Christenson SA, Couper D, Curtis JL, Gouskova NA, Hansel NN, Hoffman EA, Kanner RE, Kleerup E, Lazarus SC, Martinez FJ, Paine R 3rd, Rennard S, Tashkin DP, Han MK; SPIROMICS Research Group. Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function.N Engl J Med. 2016;374:1811-1821.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 463][Cited by in RCA: 497][Article Influence: 55.2][Reference Citation Analysis (0)]
Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY; Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women.Osteoporos Int. 2013;24:23-57.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 954][Cited by in RCA: 907][Article Influence: 75.6][Reference Citation Analysis (0)]
Looker AC, Borrud LG, Dawson-Hughes B, Shepherd JA, Wright NC. Osteoporosis or low bone mass at the femur neck or lumbar spine in older adults: United States, 2005-2008.NCHS Data Brief. 2012;1-8.
[PubMed] [DOI][Cited in This Article: ]
Kameyama N, Chubachi S, Sasaki M, Tsutsumi A, Irie H, Sakurai K, Sayama K, Nakamura H, Asano K, Betsuyaku T, Fukunaga K. Predictive and modifying factors of bone mineral density decline in patients with COPD.Respir Med. 2019;148:13-23.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 3][Cited by in RCA: 7][Article Influence: 1.2][Reference Citation Analysis (0)]
Tsukamoto M, Mori T, Nakamura E, Okada Y, Fukuda H, Yamanaka Y, Sabanai K, Wang KY, Hanagiri T, Kuboi S, Yatera K, Sakai A. Chronic obstructive pulmonary disease severity in middle-aged and older men with osteoporosis associates with decreased bone formation.Osteoporos Sarcopenia. 2020;6:179-184.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 3][Cited by in RCA: 5][Article Influence: 1.0][Reference Citation Analysis (0)]
Oniszczuk A, Kaczmarek A, Kaczmarek M, Ciałowicz M, Arslan E, Silva AF, Clemente FM, Murawska-Ciałowicz E. Sclerostin as a biomarker of physical exercise in osteoporosis: A narrative review.Front Endocrinol (Lausanne). 2022;13:954895.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 1][Reference Citation Analysis (0)]
Lv R, Xie M, Jin H, Shu P, Ouyang M, Wang Y, Yao D, Yang L, Huang X, Wang Y. A Preliminary Study on the Relationship Between High-Resolution Computed Tomography and Pulmonary Function in People at Risk of Developing Chronic Obstructive Pulmonary Disease.Front Med (Lausanne). 2022;9:855640.
[PubMed] [DOI][Cited in This Article: ][Cited by in RCA: 3][Reference Citation Analysis (0)]
Sakurai-Iesato Y, Kawata N, Tada Y, Iesato K, Matsuura Y, Yahaba M, Suzuki T, Ikari J, Yanagawa N, Kasahara Y, West J, Tatsumi K. The Relationship of Bone Mineral Density in Men with Chronic Obstructive Pulmonary Disease Classified According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Combined Chronic Obstructive Pulmonary Disease (COPD) Assessment System.Intern Med. 2017;56:1781-1790.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 6][Cited by in RCA: 7][Article Influence: 0.9][Reference Citation Analysis (0)]
Campos-Obando N, Castano-Betancourt MC, Oei L, Franco OH, Stricker BH, Brusselle GG, Lahousse L, Hofman A, Tiemeier H, Rivadeneira F, Uitterlinden AG, Zillikens MC. Bone mineral density and chronic lung disease mortality: the rotterdam study.J Clin Endocrinol Metab. 2014;99:1834-1842.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 21][Cited by in RCA: 22][Article Influence: 2.0][Reference Citation Analysis (0)]
Gupta A, Jayes LR, Holmes S, Sahota O, Canavan M, Elkin SL, Lim K, Murphy AC, Singh S, Towlson EA, Ward H, Scullion J, McKeever TM, Bolton CE. Management of Fracture Risk in Patients with Chronic Obstructive Pulmonary Disease (COPD): Building a UK Consensus Through Healthcare Professional and Patient Engagement.Int J Chron Obstruct Pulmon Dis. 2020;15:1377-1390.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 1][Cited by in RCA: 2][Article Influence: 0.4][Reference Citation Analysis (0)]
Janson C, Lisspers K, Ställberg B, Johansson G, Gutzwiller FS, Mezzi K, Mindeholm L, Bjerregaard BK, Jorgensen L, Larsson K. Osteoporosis and fracture risk associated with inhaled corticosteroid use among Swedish COPD patients: the ARCTIC study.Eur Respir J. 2021;57.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 7][Cited by in RCA: 21][Article Influence: 5.3][Reference Citation Analysis (0)]
Schulze-Hagen MF, Roderburg C, Wirtz TH, Jördens MS, Bündgens L, Abu Jhaisha S, Hohlstein P, Brozat JF, Bruners P, Loberg C, Kuhl C, Trautwein C, Tacke F, Luedde T, Loosen SH, Koch A. Decreased Bone Mineral Density Is a Predictor of Poor Survival in Critically Ill Patients.J Clin Med. 2021;10.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 3][Cited by in RCA: 3][Article Influence: 0.8][Reference Citation Analysis (0)]
Pinto-Plata V, Casanova C, Müllerova H, de Torres JP, Corado H, Varo N, Cordoba E, Zeineldine S, Paz H, Baz R, Divo M, Cortopassi F, Celli BR. Inflammatory and repair serum biomarker pattern: association to clinical outcomes in COPD.Respir Res. 2012;13:71.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 48][Cited by in RCA: 57][Article Influence: 4.4][Reference Citation Analysis (0)]
Carmona-Fernandes D, Barreira SC, Leonardo N, Casimiro RI, Castro AM, Santos PO, Fernandes AN, Cortes-Figueiredo F, Gonçalves CA, Cruz R, Fernandes ML, Ivo M, Pedro LM, Canhão H, Fonseca JE, Santos MJ. Atherosclerosis and Bone Loss in Humans-Results From Deceased Donors and From Patients Submitted to Carotid Endarterectomy.Front Med (Lausanne). 2021;8:672496.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 2][Cited by in RCA: 3][Article Influence: 0.8][Reference Citation Analysis (0)]
Dastan F, Salamzadeh J, Pourrashid MH, Edalatifard M, Eslaminejad A. Effects of High-Dose Vitamin D Replacement on the Serum Levels of Systemic Inflammatory Biomarkers in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.COPD. 2019;16:278-283.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 5][Cited by in RCA: 4][Article Influence: 0.7][Reference Citation Analysis (0)]
Wang J, Ren C, Jin L, Batu W. Seabuckthorn Wuwei Pulvis attenuates chronic obstructive pulmonary disease in rat through gut microbiota-short chain fatty acids axis.J Ethnopharmacol. 2023;314:116591.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
Huang Q, Gu Y, Wu J, Zhan Y, Deng Z, Chen S, Peng M, Yang R, Chen J, Xie J. DACH1 Attenuates Airway Inflammation in Chronic Obstructive Pulmonary Disease by Activating NRF2 Signaling.Am J Respir Cell Mol Biol. 2024;71:121-132.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
