Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD)
Authors: Trudzinski Franziska C. , Jörres Rudolf A. , Alter Peter , Watz Henrik , Vogelmeier Claus F. , Kauczor Hans-Ulrich , Thangamani Subasini , Debic Manuel , Welte Tobias , Behr Jürgen , Kahnert Kathrin , Bals Robert , Herr Christian , Heußel Claus Peter , Biederer Jürgen , von Stackelberg Oyunbileg , Fähndrich Sebastian , Wouters Emiel F. M. , Waschki Benjamin , Rabe Klaus F. , Herth Felix J. F. , Palm Viktoria ,   COSYCONET study group, Andreas Stefan , Kanerth Kathrin , Bahmer Thomas , Bewig Burkhard , Ewert Ralf , Stubbe Beate , Ficker Joachim H. , Grohé Christian , Held Matthias , Henke Markus , Kirsten Anne-Marie , Koczulla Rembert , Kronsbein Juliane , Kropf-Sanchen Cornelia , Herzmann Christian , Pfeifer Michael , Randerath Winfried J. , Seeger Werner , Studnicka Michael , Taube Christian , Timmermann Hartmut , Schmeck Bernd , Wirtz Hubert 
Published: July 2024

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.