Skip to main content
Top
Published in: Respiratory Research 1/2020

Open Access 01-12-2020 | Chronic Obstructive Lung Disease | Research

Bone turnover biomarkers in COPD patients randomized to either a regular or shortened course of corticosteroids: a substudy of the randomized controlled CORTICO-COP trial

Authors: Pradeesh Sivapalan, Niklas R. Jørgensen, Alexander G. Mathioudakis, Josefin Eklöf, Therese Lapperre, Charlotte Suppli Ulrik, Helle F. Andreassen, Karin Armbruster, Praleene Sivapalan, Julie Janner, Nina Godtfredsen, Ulla M. Weinreich, Thyge L. Nielsen, Niels Seersholm, Torgny Wilcke, Philipp Schuetz, Tobias W. Klausen, Kristoffer Marså, Jørgen Vestbo, Jens-Ulrik Jensen

Published in: Respiratory Research | Issue 1/2020

Login to get access

Abstract

Background

Long-term treatment with corticosteroids causes loss of bone density, but the effects of using short-term high-dose systemic-corticosteroid therapy to treat acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to determine whether high-dose corticosteroid therapy affected bone turnover markers (BTMs) to a greater extent compared to low-dose corticosteroid therapy.

Methods

The CORTICO-COP trial (NCT02857842) showed that an eosinophil-guided corticosteroid intervention led to approximately 60% lower accumulated corticosteroid dose for hospitalized patients with AECOPD (low-dose group) compared with 5-day standard corticosteroid treatment (high-dose group). We compared the levels of BTMs C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) in 318 participants during AECOPD and at 1- and 3-month follow-up visits.

Results

CTX decreased and P1NP increased significantly over time in both treatment groups. There were no significant differences between the groups at 1- or 3-months follow-up for P1NP. A significant drop in CTX was seen at 3 months (down Δ24% from the baseline, p = 0.017) for the high dose group.

Conclusion

Short-term, high-dose systemic corticosteroid treatment caused a rapid suppression of biomarkers of bone resorption. Corticosteroids did not suppress biomarkers of bone formation, regardless of patients receiving low or high doses of corticosteroids. This therapy was, therefore, harmless in terms of bone safety, in our prospective series of COPD patients.

Trial registration

ClinicalTrials.​gov Identifier: NCT02857842. Submitted August 2nd, 2016.
Appendix
Available only for authorised users
Literature
1.
go back to reference Wang Q, Bourbeau J. Outcomes and health-related quality of life following hospitalization for an acute exacerbation of COPD. Respirology. 2005;10(3):334–40.CrossRef Wang Q, Bourbeau J. Outcomes and health-related quality of life following hospitalization for an acute exacerbation of COPD. Respirology. 2005;10(3):334–40.CrossRef
2.
go back to reference Walters JA, Tan DJ, White CJ, Gibson PG, Wood-Baker R, Walters EH. Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;9:CD001288. Walters JA, Tan DJ, White CJ, Gibson PG, Wood-Baker R, Walters EH. Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;9:CD001288.
3.
go back to reference Chen YW, Ramsook AH, Coxson HO, Bon J, Reid WD. Prevalence and risk factors for osteoporosis in individuals with COPD: a systematic review and meta-analysis. Chest. 2019;156(6):1092–110.CrossRef Chen YW, Ramsook AH, Coxson HO, Bon J, Reid WD. Prevalence and risk factors for osteoporosis in individuals with COPD: a systematic review and meta-analysis. Chest. 2019;156(6):1092–110.CrossRef
4.
go back to reference Manolagas SC, Weinstein RS. New developments in the pathogenesis and treatment of steroid-induced osteoporosis. J Bone Miner Res. 1999;14(7):1061–6.CrossRef Manolagas SC, Weinstein RS. New developments in the pathogenesis and treatment of steroid-induced osteoporosis. J Bone Miner Res. 1999;14(7):1061–6.CrossRef
5.
go back to reference Waljee AK, Rogers MA, Lin P, Singal AG, Stein JD, Marks RM, et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. Bmj. 2017;357:j1415.CrossRef Waljee AK, Rogers MA, Lin P, Singal AG, Stein JD, Marks RM, et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. Bmj. 2017;357:j1415.CrossRef
6.
go back to reference McEvoy CE, Ensrud KE, Bender E, Genant HK, Yu W, Griffith JM, et al. Association between corticosteroid use and vertebral fractures in older men with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157(3 Pt 1):704–9.CrossRef McEvoy CE, Ensrud KE, Bender E, Genant HK, Yu W, Griffith JM, et al. Association between corticosteroid use and vertebral fractures in older men with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157(3 Pt 1):704–9.CrossRef
7.
go back to reference Wang L, Heckmann BL, Yang X, Long H. Osteoblast autophagy in glucocorticoid-induced osteoporosis. J Cell Physiol. 2019;234(4):3207–15.CrossRef Wang L, Heckmann BL, Yang X, Long H. Osteoblast autophagy in glucocorticoid-induced osteoporosis. J Cell Physiol. 2019;234(4):3207–15.CrossRef
8.
go back to reference Canalis E, Bilezikian JP, Angeli A, Giustina A. Perspectives on glucocorticoid-induced osteoporosis. Bone. 2004;34(4):593–8.CrossRef Canalis E, Bilezikian JP, Angeli A, Giustina A. Perspectives on glucocorticoid-induced osteoporosis. Bone. 2004;34(4):593–8.CrossRef
9.
go back to reference Kim HJ, Zhao H, Kitaura H, Bhattacharyya S, Brewer JA, Muglia LJ, et al. Glucocorticoids suppress bone formation via the osteoclast. J Clin Invest. 2006;116(8):2152–60.CrossRef Kim HJ, Zhao H, Kitaura H, Bhattacharyya S, Brewer JA, Muglia LJ, et al. Glucocorticoids suppress bone formation via the osteoclast. J Clin Invest. 2006;116(8):2152–60.CrossRef
10.
go back to reference Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, et al. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med. 2011;49(8):1271–4.CrossRef Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, et al. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med. 2011;49(8):1271–4.CrossRef
11.
go back to reference Bowden SA, Akusoba CI, Hayes JR, Mahan JD. Biochemical markers of bone turnover in children with clinical bone fragility. J Pediatr Endocrinol Metab. 2016;29(6):715–22.CrossRef Bowden SA, Akusoba CI, Hayes JR, Mahan JD. Biochemical markers of bone turnover in children with clinical bone fragility. J Pediatr Endocrinol Metab. 2016;29(6):715–22.CrossRef
12.
go back to reference Angeli A, Guglielmi G, Dovio A, Capelli G, de Feo D, Giannini S, et al. High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study. Bone. 2006;39(2):253–9.CrossRef Angeli A, Guglielmi G, Dovio A, Capelli G, de Feo D, Giannini S, et al. High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study. Bone. 2006;39(2):253–9.CrossRef
13.
go back to reference Laan RF, van Riel PL, van de Putte LB, van Erning LJ, van't Hof MA, Lemmens JA. Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis. A randomized, controlled study. Ann Intern Med. 1993;119(10):963–8.CrossRef Laan RF, van Riel PL, van de Putte LB, van Erning LJ, van't Hof MA, Lemmens JA. Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis. A randomized, controlled study. Ann Intern Med. 1993;119(10):963–8.CrossRef
14.
16.
go back to reference Sivapalan P, Moberg M, Eklof J, Janner J, Vestbo J, Laub RR, et al. A multi-center randomized, controlled, open-label trial evaluating the effects of eosinophil-guided corticosteroid-sparing therapy in hospitalised patients with COPD exacerbations - the CORTICO steroid reduction in COPD (CORTICOCOP) study protocol. BMC Pulm Med. 2017;17(1):114. https://doi.org/10.1186/s12890-017-0458-7. Sivapalan P, Moberg M, Eklof J, Janner J, Vestbo J, Laub RR, et al. A multi-center randomized, controlled, open-label trial evaluating the effects of eosinophil-guided corticosteroid-sparing therapy in hospitalised patients with COPD exacerbations - the CORTICO steroid reduction in COPD (CORTICOCOP) study protocol. BMC Pulm Med. 2017;17(1):114. https://​doi.​org/​10.​1186/​s12890-017-0458-7.
17.
go back to reference Sivapalan P, Lapperre TS, Janner J, Laub RR, Moberg M, Bech CS, et al. Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): a multicentre, randomised, controlled, open-label, non-inferiority trial. Lancet Respir Med. 2019;7(8):699–709. https://doi.org/10.1016/S2213-2600(19)30176-6. Sivapalan P, Lapperre TS, Janner J, Laub RR, Moberg M, Bech CS, et al. Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): a multicentre, randomised, controlled, open-label, non-inferiority trial. Lancet Respir Med. 2019;7(8):699–709. https://​doi.​org/​10.​1016/​S2213-2600(19)30176-6.
18.
go back to reference Matthew J, Gurka LJE, Nylander-French L. Testing transformations for the linear mixed model. Comput Statist Data Anal. 2007;51(9):4297–307. Matthew J, Gurka LJE, Nylander-French L. Testing transformations for the linear mixed model. Comput Statist Data Anal. 2007;51(9):4297–307.
19.
go back to reference Lu K. On efficiency of constrained longitudinal data analysis versus longitudinal analysis of covariance. Biometrics. 2010;66(3):891–6.CrossRef Lu K. On efficiency of constrained longitudinal data analysis versus longitudinal analysis of covariance. Biometrics. 2010;66(3):891–6.CrossRef
20.
go back to reference Korczowska I, Lacki JK. Changes in certain biochemical markers of bone turnover in rheumatoid arthritis patients treated with short-term low dose glucocorticosteroids. Przegl Lek. 2005;62(12):1384–6.PubMed Korczowska I, Lacki JK. Changes in certain biochemical markers of bone turnover in rheumatoid arthritis patients treated with short-term low dose glucocorticosteroids. Przegl Lek. 2005;62(12):1384–6.PubMed
21.
go back to reference Wislowska M, Jakubicz D, Stepien K, Cicha M. Serum concentrations of formation (PINP) and resorption (Ctx) bone turnover markers in rheumatoid arthritis. Rheumatol Int. 2009;29(12):1403–9.CrossRef Wislowska M, Jakubicz D, Stepien K, Cicha M. Serum concentrations of formation (PINP) and resorption (Ctx) bone turnover markers in rheumatoid arthritis. Rheumatol Int. 2009;29(12):1403–9.CrossRef
22.
go back to reference Censi S, Manso J, Pandolfo G, Franceschet G, Cavedon E, Zhu YH, et al. Bone turnover markers, BMD and TBS after short-term, high-dose glucocorticoid therapy in patients with Graves' orbitopathy: a small prospective pilot study. J Endocrinol Investig. 2019;42(7):859–65.CrossRef Censi S, Manso J, Pandolfo G, Franceschet G, Cavedon E, Zhu YH, et al. Bone turnover markers, BMD and TBS after short-term, high-dose glucocorticoid therapy in patients with Graves' orbitopathy: a small prospective pilot study. J Endocrinol Investig. 2019;42(7):859–65.CrossRef
23.
go back to reference Bornefalk E, Dahlen I, Michaelsson K, Ljunggren Ö, Ljunghall S. Age-dependent effect of oral glucocorticoids on markers of bone resorption in patients with acute asthma. Calcif Tissue Int. 1998;63(1):9–13.CrossRef Bornefalk E, Dahlen I, Michaelsson K, Ljunggren Ö, Ljunghall S. Age-dependent effect of oral glucocorticoids on markers of bone resorption in patients with acute asthma. Calcif Tissue Int. 1998;63(1):9–13.CrossRef
24.
go back to reference Naylor KE, Jacques RM, Paggiosi M, Gossiel F, Peel NF, McCloskey EV, et al. Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study. Osteoporos Int. 2016;27(1):21–31.CrossRef Naylor KE, Jacques RM, Paggiosi M, Gossiel F, Peel NF, McCloskey EV, et al. Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study. Osteoporos Int. 2016;27(1):21–31.CrossRef
25.
go back to reference Miller PD, Pannacciulli N, Malouf-Sierra J, Singer A, Czerwinski E, Bone HG, et al. Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates. Osteoporos Int. 2020;31(1):181–91.CrossRef Miller PD, Pannacciulli N, Malouf-Sierra J, Singer A, Czerwinski E, Bone HG, et al. Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates. Osteoporos Int. 2020;31(1):181–91.CrossRef
26.
go back to reference Christgau S, Bitsch-Jensen O, Hanover Bjarnason N, Gamwell Henriksen E, Qvist P, Alexandersen P, et al. Serum CrossLaps for monitoring the response in individuals undergoing antiresorptive therapy. Bone. 2000;26(5):505–11.CrossRef Christgau S, Bitsch-Jensen O, Hanover Bjarnason N, Gamwell Henriksen E, Qvist P, Alexandersen P, et al. Serum CrossLaps for monitoring the response in individuals undergoing antiresorptive therapy. Bone. 2000;26(5):505–11.CrossRef
27.
go back to reference Hygum K, Starup-Linde J, Harslof T, Jorgensen NR, Hartmann B, Holst JJ, et al. The diurnal variation of bone formation is attenuated in adult patients with type 2 diabetes. Eur J Endocrinol. 2019;181(3):221–31.CrossRef Hygum K, Starup-Linde J, Harslof T, Jorgensen NR, Hartmann B, Holst JJ, et al. The diurnal variation of bone formation is attenuated in adult patients with type 2 diabetes. Eur J Endocrinol. 2019;181(3):221–31.CrossRef
28.
go back to reference Qvist P, Christgau S, Pedersen BJ, Schlemmer A, Christiansen C. Circadian variation in the serum concentration of C-terminal telopeptide of type I collagen (serum CTx): effects of gender, age, menopausal status, posture, daylight, serum cortisol, and fasting. Bone. 2002;31(1):57–61.CrossRef Qvist P, Christgau S, Pedersen BJ, Schlemmer A, Christiansen C. Circadian variation in the serum concentration of C-terminal telopeptide of type I collagen (serum CTx): effects of gender, age, menopausal status, posture, daylight, serum cortisol, and fasting. Bone. 2002;31(1):57–61.CrossRef
Metadata
Title
Bone turnover biomarkers in COPD patients randomized to either a regular or shortened course of corticosteroids: a substudy of the randomized controlled CORTICO-COP trial
Authors
Pradeesh Sivapalan
Niklas R. Jørgensen
Alexander G. Mathioudakis
Josefin Eklöf
Therese Lapperre
Charlotte Suppli Ulrik
Helle F. Andreassen
Karin Armbruster
Praleene Sivapalan
Julie Janner
Nina Godtfredsen
Ulla M. Weinreich
Thyge L. Nielsen
Niels Seersholm
Torgny Wilcke
Philipp Schuetz
Tobias W. Klausen
Kristoffer Marså
Jørgen Vestbo
Jens-Ulrik Jensen
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-01531-9

Other articles of this Issue 1/2020

Respiratory Research 1/2020 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.