Highlights
- Mild to moderate COPD is independently associated with accelerated vertebral bone mineral density (BMD) loss over six years, but only in individuals with vitamin D deficiency.
- Nearly half of the study cohort exhibited vitamin D deficiency, underscoring its prevalence in the general population.
- This finding points to vitamin D status as a potential clinical target to mitigate osteoporosis risk in COPD.
Study Background and Disease Burden
Chronic obstructive pulmonary disease (COPD) and osteoporosis are both common, chronic conditions that significantly increase morbidity in aging populations. The link between severe COPD and osteoporosis is well established, with shared risk factors such as advanced age, smoking, systemic inflammation, glucocorticoid use, and physical inactivity contributing to bone loss. However, most population-level data have focused on patients with severe COPD, leaving a knowledge gap regarding bone health in those with mild to moderate disease, who represent the majority of COPD cases. This is clinically relevant, as even modest reductions in vertebral BMD are associated with future fracture risk and increased mortality. Identifying modifiable factors that influence bone loss in this group could inform prevention strategies and reduce the burden of osteoporotic fractures.
Study Design
This longitudinal cohort analysis utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA), a well-established, prospective epidemiological study. Eligible participants underwent chest computed tomography (CT) scans at two time points: Exam 5 (2010–2012) and Exam 6 (2016–2018). Mild to moderate COPD was defined as a forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio of <0.70 and FEV1 ≥50% predicted. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D <20 ng/mL. Bone health was assessed by a deep learning algorithm that performed automated, multilevel segmentation of thoracic vertebral bodies (T1–T10) from chest CTs to obtain three-dimensional volumetric BMD measurements. The primary endpoint was the rate of change in BMD over six years.
Key Findings
The study analyzed 1,226 participants, of whom 173 had mild to moderate COPD at baseline. After adjusting for confounders including age, sex, race/ethnicity, BMI, bisphosphonate use, alcohol consumption, smoking status, diabetes, physical activity, C-reactive protein, and vitamin D status, mild to moderate COPD was associated with a statistically significant faster rate of vertebral BMD decline (β = -0.38 mg/cm³/year; 95% CI: -0.74, -0.02).
A notable and statistically robust interaction was observed between COPD status and vitamin D deficiency (interaction p = 0.001). Stratified analyses revealed that among participants with vitamin D deficiency (47% of the cohort), those with mild to moderate COPD experienced a markedly faster rate of BMD loss (-0.64 mg/cm³/year; 95% CI: -1.17 to -0.12) compared to those without COPD. No significant association between COPD and BMD decline was found among participants with normal vitamin D levels, in both unadjusted and adjusted models.
The magnitude of BMD loss observed in vitamin D-deficient, mild to moderate COPD patients is clinically meaningful, given the established associations between vertebral BMD reduction and increased fracture risk. The use of advanced imaging and deep learning tools improves the accuracy and reproducibility of these findings, offering a new standard in epidemiological bone research.
Expert Commentary
These findings add a critical dimension to our understanding of bone health in COPD. While osteoporosis screening and prevention have traditionally focused on severe COPD or those with high glucocorticoid exposure, this study suggests that bone loss in mild to moderate COPD is far from negligible—especially in the context of vitamin D deficiency. Given that vitamin D deficiency is common and treatable, this interaction identifies a high-risk, modifiable subgroup.
The use of longitudinal chest CT data and automated vertebral segmentation represents a methodological advance, allowing researchers to track bone loss accurately over time in large, diverse populations. Nonetheless, the study is limited by the observational design, potential for residual confounding, and reliance on chest CT (rather than DXA) for BMD assessment. Also, the study does not address whether vitamin D supplementation would mitigate bone loss in this population, which remains a key research gap.
Conclusion
Mild to moderate COPD is associated with accelerated loss of vertebral bone mineral density over six years, but only among individuals with vitamin D deficiency. This finding underscores the importance of routine assessment and correction of vitamin D deficiency in patients with COPD, even in earlier disease stages. Future interventional studies are needed to determine whether targeted vitamin D supplementation can prevent bone loss and reduce fracture risk in this population.
References
1. Romme EA, et al. Bone attenuation on routine chest CT correlates with bone mineral density on DXA in patients with COPD. J Bone Miner Res. 2012;27(11):2338-2343.
2. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-281.
3. Miller J, et al. Vitamin D, bone mineral density, and osteoporosis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;185(12):1306-1313.
4. Multi-Ethnic Study of Atherosclerosis (MESA). https://www.mesa-nhlbi.org/.
