Comparative Study

. 2024 Jul 13;25(1):274.

doi: 10.1186/s12931-024-02902-2.

Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD)

Franziska C Trudzinski¹, Rudolf A Jörres², Peter Alter³, Henrik Watz^{4

5}, Claus F Vogelmeier³, Hans-Ulrich Kauczor^{6

7}, Subasini Thangamani^{6

7}, Manuel Debic^{6

7}, Tobias Welte⁸, Jürgen Behr⁹, Kathrin Kahnert^{9

10}, Robert Bals¹¹, Christian Herr¹¹, Claus Peter Heußel^{7

12}, Jürgen Biederer^{6

7

13

14}, Oyunbileg von Stackelberg^{6

7}, Sebastian Fähndrich¹⁵, Emiel F M Wouters^{16

17

18}, Benjamin Waschki^{19

20}, Klaus F Rabe¹⁹, Felix J F Herth²¹, Viktoria Palm^{6

7}; COSYCONET study group

Collaborators, Affiliations

Affiliations

¹ Department of Pneumology and Critical Care Medicine), German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC-H), Thoraxklinik University of Heidelberg, Röntgenstrasse 1, 69126, Heidelberg, Germany. Franziska.trudzinski@med.uni-heidelberg.de.
² Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, German Center for Lung Research (DZL), LMU University Hospital, Ludwig-Maximilians-University (LMU), Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany.
³ Department of Medicine, Pulmonary and Critical Care Medicine, German Center for Lung Research (DZL), Philipps University of Marburg (UMR), Marburg, Germany.
⁴ Pulmonary Research Institute at LungenClinic Grosshansdorf, Grosshansdorf, Germany.
⁵ Airway Research Center North (ARCN), German Center for Lung Research (DZL), Woehrendamm 80, 22927, Grosshansdorf, Germany.
⁶ Department of Diagnostic & Interventional Radiology, University Hospital of Heidelberg, Heidelberg, Germany.
⁷ German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC-H), Heidelberg, Germany.
⁸ Department of Pneumology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
⁹ Department of Internal Medicine V, CPC Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), University Hospital, LMU Munich, Munich, Germany.
¹⁰ MediCenterGermering, Germering, Germany.
¹¹ Department of Internal Medicine V - Pulmonology, Allergology, Critical Care Care Medicine, Saarland University Hospital, Homburg, Germany.
¹² Department of Diagnostic and Interventional Radiology With Nuclear Medicine, Thoraxklinik, University Medical Center Heidelberg, Heidelberg, Germany.
¹³ Faculty of Medicine, University of Latvia, Riga, Latvia.
¹⁴ Faculty of Medicine, Christian-Albrechts-Universität Zu Kiel, Kiel, Germany.
¹⁵ Department of Pneumology, University Medical Centre Freiburg, Freiburg, Germany.
¹⁶ Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
¹⁷ Medical Faculty, Sigmund Freud University, Vienna, Austria.
¹⁸ Department of Internal Medicine, Sigmund Freud Private University, Vienna, Austria.
¹⁹ LungenClinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research, Pulmonary Research Institute, Woehrendamm 80, 22927, Grosshansdorf, Germany.
²⁰ Department of Pneumology, Itzehoe Hospital, Itzehoe, Germany.
²¹ Department of Pneumology and Critical Care Medicine), German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC-H), Thoraxklinik University of Heidelberg, Röntgenstrasse 1, 69126, Heidelberg, Germany.

PMID: 39003487
PMCID: PMC11245771
DOI: 10.1186/s12931-024-02902-2

Comparative Study

Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD)

Franziska C Trudzinski et al. Respir Res. 2024.

. 2024 Jul 13;25(1):274.

doi: 10.1186/s12931-024-02902-2.

Authors

Affiliations

¹ Department of Pneumology and Critical Care Medicine), German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC-H), Thoraxklinik University of Heidelberg, Röntgenstrasse 1, 69126, Heidelberg, Germany. Franziska.trudzinski@med.uni-heidelberg.de.
² Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, German Center for Lung Research (DZL), LMU University Hospital, Ludwig-Maximilians-University (LMU), Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany.
³ Department of Medicine, Pulmonary and Critical Care Medicine, German Center for Lung Research (DZL), Philipps University of Marburg (UMR), Marburg, Germany.
⁴ Pulmonary Research Institute at LungenClinic Grosshansdorf, Grosshansdorf, Germany.
⁵ Airway Research Center North (ARCN), German Center for Lung Research (DZL), Woehrendamm 80, 22927, Grosshansdorf, Germany.
⁶ Department of Diagnostic & Interventional Radiology, University Hospital of Heidelberg, Heidelberg, Germany.
⁷ German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC-H), Heidelberg, Germany.
⁸ Department of Pneumology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
⁹ Department of Internal Medicine V, CPC Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), University Hospital, LMU Munich, Munich, Germany.
¹⁰ MediCenterGermering, Germering, Germany.
¹¹ Department of Internal Medicine V - Pulmonology, Allergology, Critical Care Care Medicine, Saarland University Hospital, Homburg, Germany.
¹² Department of Diagnostic and Interventional Radiology With Nuclear Medicine, Thoraxklinik, University Medical Center Heidelberg, Heidelberg, Germany.
¹³ Faculty of Medicine, University of Latvia, Riga, Latvia.
¹⁴ Faculty of Medicine, Christian-Albrechts-Universität Zu Kiel, Kiel, Germany.
¹⁵ Department of Pneumology, University Medical Centre Freiburg, Freiburg, Germany.
¹⁶ Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
¹⁷ Medical Faculty, Sigmund Freud University, Vienna, Austria.
¹⁸ Department of Internal Medicine, Sigmund Freud Private University, Vienna, Austria.
¹⁹ LungenClinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research, Pulmonary Research Institute, Woehrendamm 80, 22927, Grosshansdorf, Germany.
²⁰ Department of Pneumology, Itzehoe Hospital, Itzehoe, Germany.
²¹ Department of Pneumology and Critical Care Medicine), German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC-H), Thoraxklinik University of Heidelberg, Röntgenstrasse 1, 69126, Heidelberg, Germany.

PMID: 39003487
PMCID: PMC11245771
DOI: 10.1186/s12931-024-02902-2

Abstract

Background: Patients with COPD are often affected by loss of bone mineral density (BMD) and osteoporotic fractures. Natriuretic peptides (NP) are known as cardiac markers, but have also been linked to fragility-associated fractures in the elderly. As their functions include regulation of fluid and mineral balance, they also might affect bone metabolism, particularly in systemic disorders such as COPD.

Research question: We investigated the association between NP serum levels, vertebral fractures and BMD assessed by chest computed tomography (CT) in patients with COPD.

Methods: Participants of the COSYCONET cohort with CT scans were included. Mean vertebral bone density on CT (BMD-CT) as a risk factor for osteoporosis was assessed at the level of TH12 (AI-Rad Companion), and vertebral compression fractures were visually quantified by two readers. Their relationship with N-terminal pro-B-type natriuretic peptide (NT-proBNP), Mid-regional pro-atrial natriuretic peptide (MRproANP) and Midregional pro-adrenomedullin (MRproADM) was determined using group comparisons and multivariable analyses.

Results: Among 418 participants (58% male, median age 64 years, FEV₁ 59.6% predicted), vertebral fractures in TH12 were found in 76 patients (18.1%). Compared to patients without fractures, these had elevated serum levels (p ≤ 0.005) of MRproANP and MRproADM. Using optimal cut-off values in multiple logistic regression analyses, MRproANP levels ≥ 65 nmol/l (OR 2.34; p = 0.011) and age (p = 0.009) were the only significant predictors of fractures after adjustment for sex, BMI, smoking status, FEV₁% predicted, SGRQ Activity score, daily physical activity, oral corticosteroids, the diagnosis of cardiac disease, and renal impairment. Correspondingly, MRproANP (p < 0.001), age (p = 0.055), SGRQ Activity score (p = 0.061) and active smoking (p = 0.025) were associated with TH12 vertebral density.

Interpretation: MRproANP was a marker for osteoporotic vertebral fractures in our COPD patients from the COSYCONET cohort. Its association with reduced vertebral BMD on CT and its known modulating effects on fluid and ion balance are suggestive of direct effects on bone mineralization.

Trial registration: ClinicalTrials.gov NCT01245933, Date of registration: 18 November 2010.

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Conflict of interest statement

FCT reported payments or honoraria for lectures and presentations from Boehringer Ingelheim Chiesi, GlaxoSmithKline, GrifolsNovartis, CSL Behring, Streamed up, RG Gesellschaft für Information and Organisation mbH, PA reports grants from German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET), grants from AstraZeneca GmbH, grants and non-financial support from Bayer Schering Pharma AG, grants, personal fees and non-financial support from Boehringer Ingelheim Pharma GmbH & Co. KG, grants and non-financial support from Chiesi GmbH, grants from GlaxoSmithKline, grants from Grifols Deutschland GmbH, grants from MSD Sharp & Dohme GmbH, grants and personal fees from Mundipharma GmbH, grants, personal fees and non-financial support from Novartis Deutschland GmbH, grants from Pfizer Pharma GmbH, grants from Takeda Pharma Vertrieb GmbH & Co. KG, outside the submitted work. CFV reports grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Chiesi, grants and personal fees from GlaxoSmithKline, grants and personal fees from Grifols, grants and personal fees from Novartis, personal fees from Berlin Chemie/Menarini, personal fees from CSL Behring, grants from German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET), personal fees from Nuvaira, personal fees from MedUpdate, outside the submitted work. HUK reports grants from Siemens, non-financial support from Bayer, during the conduct of the study; grants from Siemens, grants and personal fees from Philips, personal fees from Boehringer Ingelheim, personal fees from Merck Sharp Dohme, personal fees from Astra Zeneca, outside the submitted work. R.B. reports grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from GlaxoSmithKline, personal fees from Grifols, grants and personal fees from Novartis, personal fees from CSL Behring, grants from German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET), grants from Sander Stiftung, grants from Schwiete Stiftung, grants from Krebshilfe, grants from Mukoviszidose eV, outside the submitted work. He is Editor in Chief of Respiratory Research. FJF received personal money for adboard activities and lecture fees from Pulmonx, BTG, Olympus and Uptake. RJ, HW, ST, MD, TW, JB, KK, RB, CH, CPC, JB, OvS, SF, EFMW, BW, KFR, VP.

Figures

**Fig. 1**
Flow chart of the patients included in the analysis. Of the 2,741 COSYCONET participants included at visit V1, n = 1,427 completed the third follow-up visit (V4). A subgroup of 602 patients underwent prospective CT scans at separate study visits at the time of V4. For the present study, the imaging data of 418 patients were analyzed for bone density and the presence of vertebral fractures (see Fig. 1). The functional and clinical data and biomarker measurements of the patients included in the current study were collected at visit 1 (V1)

**Fig. 2**
Examples of osteoporotic vertebral fractures in chest CT. A Sagittal view of the thoracic spine with minor degenerations, no vertebral body fractures (B) Osteoporotic vertebral body compression fractures in TH5 (Genant 1) and TH8 (Genant 3) (arrows). C Sintered and beginning wedge-shaped vertebra TH7 (arrow) with compression fracture Genant 2

**Fig. 3**
Results of the binary logistic regression analysis with the presence of vertebral fractures as outcome variable. The plot shows the odds ratios with their corresponding 95% confidence intervals on a logarithmic scale corresponding to the numerical values given in Table 3. BMI = body mass index, FEV₁ = forced expiratory volume in 1 s, IPAQ = International Physical Activity Questionnaire, SGRQ = St George’s Respiratory Questionnaire, Cardiac disease = either coronary artery disease or heart failure, eGFR = estimated glomerular filtration rate, MRproANP = midregional pro-atrial natriuretic peptide, MRproADM = midregional pro-adrenomedullin. Please note that all predictors refer to Visit V1, as the values of MRproANP and MRproADM were assessed in blood samples obtained at this visit, while the outcome of fractures refers to Visit V4 about 3 years after Visit V1. Please note that some of the predictors were re-scaled in order to obtain odds ratios that were easier to interpret and distinguish from the reference value

See this image and copyright information in PMC

References

1. Lehouck A, Boonen S, Decramer M, Janssens W. COPD, bone metabolism, and osteoporosis. Chest. 2011;139(3):648–657. doi: 10.1378/chest.10-1427. - DOI - PubMed
1. Romme EA, Smeenk FW, Rutten EP, Wouters EF. Osteoporosis in chronic obstructive pulmonary disease. Expert Rev Respir Med. 2013;7(4):397–410. doi: 10.1586/17476348.2013.814402. - DOI - PubMed
1. Chen SJ, Liao WC, Huang KH, et al. Chronic obstructive pulmonary disease and allied conditions is a strong independent risk factor for osteoporosis and pathologic fractures: a population-based cohort study. QJM. 2015;108(8):633–640. doi: 10.1093/qjmed/hcv012. - DOI - PubMed
1. Palm V, Norajitra T, von Stackelberg O, et al. AI-supported comprehensive detection and quantification of biomarkers of subclinical widespread diseases at chest CT for preventive medicine. Healthcare (Basel). 2022;10(11):2166. doi: 10.3390/healthcare10112166. - DOI - PMC - PubMed
1. Anam AK, Insogna K. Update on osteoporosis screening and management. Med Clin North Am. 2021;105(6):1117–1134. doi: 10.1016/j.mcna.2021.05.016. - DOI - PubMed

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Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD)

Collaborators

Affiliations

Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD)

Authors

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Abstract

Conflict of interest statement

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