Osteoporosis and Its Clinical Burden in Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study

Osteoporosis is a common comorbidity in patients with chronic obstructive pulmonary disease (COPD). However, most previous studies have been conducted in European populations. This study aims to explore whether patients with COPD are at increased risk of osteoporosis and osteoporosis-related fractures compared to a propensity score-matched (PSM) cohort of non-COPD patients in the TriNetX US Collaborative Network de-identified electronic health record (EHR) database.

Adult patients aged 40-65 with a COPD diagnosis (ICD-10: J44.0-J44.9), confirmed by spirometry (FEV₁/FVC <70%), and a minimum follow-up of 10 years (3,650 days) were included. Both the ICD-10 code and spirometry criterion were required for COPD diagnosis. A 1:1 propensity score matching (PSM) was conducted to match non-COPD controls based on age, sex, BMI, smoking status, comorbidities, and medication use (including systemic corticosteroids, inhaled corticosteroids, and bone-active medications). The primary outcome was osteoporosis (ICD-10: M81.0). Secondary outcomes included osteoporosis with pathological fracture (M80) and pathological fractures (M84.4, M84.7). Cox proportional hazards models were used to estimate the hazard of osteoporosis after adjusting for confounding variables.

Following PSM, 2,682 COPD patients were compared with 2,682 non-COPD controls. COPD patients exhibited a significantly increased risk of osteoporosis [HR: 1.95 (1.37-2.77), p = 0.0002]. Underweight status (BMI <18.5 kg/m²) further elevated osteoporosis risk [HR: 3.95 (2.19-7.13), p<0.0001], while male sex was highly protective [HR: 0.15 (0.14-0.16), p<0.0001]. Age-stratified analysis showed progressively increasing risk across older age groups, peaking at ages 61-65 [HR: 20.01 (18.77-21.33), p < 0.0001].

COPD is independently associated with an increased risk of osteoporosis. These findings highlight the importance of systematic osteoporosis screening and monitoring as part of comprehensive COPD management, particularly in high-risk subgroups (older adults, females, and those with low BMI).