Long-term effects of inhaled corticosteroids on bone mineral density in older women with asthma or COPD: a registry-based cohort study
We assessed the association between long-term inhaled corticosteroid (ICS) use and bone mineral density (BMD) in older women with chronic respiratory disease. Women with > 50% adherence to ICS use had very slightly accelerated BMD loss at the total hip compared with those with lower or ICS use.
This study evaluated the impact of long-term ICS therapy on bone loss in older women with asthma or chronic obstructive pulmonary disease (COPD).
We used a population-based bone densitometry registry linked with administrative health data covering the province of Manitoba, Canada (1999–2013), to identify women aged > 40 years who had diagnosed asthma or COPD. ICS exposure was defined as cumulative dispensed days and medication possession ratio (MPR). Associations were examined both cross-sectionally and longitudinally, and results were covariate adjusted.
Among 6561 women with asthma and/or COPD (mean age 65 years [SD = 11]), compared to no ICS treatment, those in the highest tertile of prior ICS use (≥ 720 days) had lower BMD at the femoral neck (− 0.09 T-score, 95% CI − 0.16, − 0.02) and total hip (− 0.14 T-score, 95% CI − 0.22, − 0.05), but not at the lumbar spine. Over a mean of 5 years of follow-up, the highest tertile of ICS exposure (MPR > 0.5) was associated with a − 0.02 SD/year (95% CI − 0.04, − 0.01) greater decline in total hip BMD relative to non-users, with no significant effect at the femoral neck or lumbar spine. Middle and lower tertiles of ICS use were not associated with baseline or longitudinal change in BMD.
The highest tertile of ICS use was associated with a slightly lower hip BMD at baseline and slightly greater reduction in total hip BMD over time in older women with asthma or COPD. No adverse effects on BMD were seen from low to moderate ICS exposure.
KeywordsWomen Bone mineral density Inhaled corticosteroids Asthma Chronic obstructive pulmonary disease Osteoporosis
The authors acknowledge the Manitoba Centre for Health Policy for use of data contained in the Manitoba Population Research Data Repository under HIPC Project Number 2011/2012-31). The results and conclusions are those of the authors and no official endorsement by the Manitoba Centre for Health Policy, Manitoba Health, or other data providers is intended or should be inferred. Data used in this study are from the Manitoba Population Research Data Repository housed at the Manitoba Centre for Health Policy, University of Manitoba and were derived from data provided by Manitoba Health. This article has been reviewed and approved by the members of the Manitoba Bone Density Program.
WDL, MS, and JMF formulated the study idea. WDL designed the study and performed all data analyses. JMF and MS contributed to the study design and interpretation of findings. WC and KJ wrote the first draft of the manuscript (they are co-first authors). All authors critically commented on the manuscript and approved the final version. WDL is the guarantor of the manuscript.
No funding was received for this research project. MS receives salary support from the Canadian Institutes of Health Research and Michael Smith Foundation for Health Research.
Compliance with ethical standards
Conflict of interest
JMF has served on advisory boards for Novartis, Pfizer, AstraZeneca, Boehringer-Ingelheim, and Merck. He has also been a member of speakers’ bureaus for AstraZeneca, Boehringer-Ingelheim, Novartis, and Merck. He has received research funding paid directly to the University of British Columbia from AstraZeneca, Glaxo-SmithKline, Boehringer-Ingelheim, Merck, Sanofi, and Novartis. Dr. FitzGerald is a member of the Global Initiative for Asthma (GINA) Executive and Science Committees. Dr. Sadatsafavi receives salary support from the Canadian Institutes of Health Research and Michael Smith Foundation for Health Research. WDL, MS, KJ, and WC have no conflicts to declare.
- 1.Global Initiative for Asthma (GINA) (2017) Global strategy for asthma management and prevention. Available from: https://ginasthma.org/download/832/. Accessed 25 Oct 2018Google Scholar
- 2.Vestbo J, Hurd SS, Agustí AG et al (2013) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 187(4):347–365Google Scholar
- 3.Watz H, Tetzlaff K, Wouters EFM, Kirsten A, Magnussen H, Rodriguez-Roisin R, Vogelmeier C, Fabbri LM, Chanez P, Dahl R, Disse B, Finnigan H, Calverley PMA (2016) Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: a post-hoc analysis of the WISDOM trial. Lancet Respir Med 4:390–398. https://doi.org/10.1016/S2213-2600(16)00100-4 CrossRefPubMedGoogle Scholar
- 5.Loke YK, Gilbert D, Thavarajah M, Blanco P, Wilson AM (2015) Bone mineral density and fracture risk with long-term use of inhaled corticosteroids in patients with asthma: systematic review and meta-analysis. BMJ Open 5:e008554. https://doi.org/10.1136/bmjopen-2015-008554 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Richy F, Bousquet J, Ehrlich GE, Meunier PJ, Israel E, Morii H, Devogelaer JP, Peel N, Haim M, Bruyere O, Reginster JY (2003) Inhaled corticosteroids effects on bone in asthmatic and COPD patients: a quantitative systematic review. Osteoporos Int 14:179–190. https://doi.org/10.1007/s00198-003-1398-z CrossRefPubMedGoogle Scholar
- 9.Jones A, Fay JK, Burr M et al (2002) Inhaled corticosteroid effects on bone metabolism in asthma and mild chronic obstructive pulmonary disease. Cochrane Database Syst Rev:CD003537. https://doi.org/10.1002/14651858.CD003537
- 10.Yang IA, Clarke MS, Sim EHA, Fong KM (2012) Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev:CD002991. https://doi.org/10.1002/14651858.CD002991.pub3
- 11.Leib ES, Saag KG, Adachi JD, Geusens PP, Binkley N, McCloskey EV, Hans DB (2011) Official positions for FRAX(®) clinical regarding glucocorticoids: the impact of the use of glucocorticoids on the estimate by FRAX(®) of the 10 year risk of fracture from joint official positions development conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(®). J Clin Densitom 14:212–219. https://doi.org/10.1016/j.jocd.2011.05.014 CrossRefPubMedGoogle Scholar
- 14.Fujita K, Kasayama S, Hashimoto J, Nagasaka Y, Nakano N, Morimoto Y, Barnes PJ, Miyatake A (2001) Inhaled corticosteroids reduce bone mineral density in early postmenopausal but not premenopausal asthmatic women. J Bone Miner Res 16:782–787. https://doi.org/10.1359/jbmr.2001.16.4.782 CrossRefPubMedGoogle Scholar
- 15.Government of Canada SC (2014) Population by sex and age group, by province and territory (Number, both sexes). http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/demo31a-eng.htm. Accessed 6 Feb 2015
- 26.Lix LM, Azimaee M, Osman BA, Caetano P, Morin S, Metge C, Goltzman D, Kreiger N, Prior J, Leslie WD (2012) Osteoporosis-related fracture case definitions for population-based administrative data. BMC Public Health 12:301. https://doi.org/10.1186/1471-2458-12-301 CrossRefPubMedPubMedCentralGoogle Scholar
- 27.O’Donnell S, Canadian Chronic Disease Surveillance System (CCDSS) Osteoporosis Working Group (2013) Use of administrative data for national surveillance of osteoporosis and related fractures in Canada: results from a feasibility study. Arch Osteoporos 8:143. https://doi.org/10.1007/s11657-013-0143-2 CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Lam WY, Fresco P (2015) Medication adherence measures: an overview. Biomed Res Int. https://doi.org/10.1155/2015/217047
- 30.Langhammer A, Norjavaara E, de Verdier MG, Johnsen R, Bjermer L (2004) Use of inhaled corticosteroids and bone mineral density in a population based study: the Nord-Trøndelag health study (the HUNT study). Pharmacoepidemiol Drug Saf 13:569–579. https://doi.org/10.1002/pds.941 CrossRefPubMedGoogle Scholar
- 32.Van Staa TP, Abenhaim L, Cooper C et al (2000) The use of a large pharmacoepidemiological database to study exposure to oral corticosteroids and risk of fractures: validation of study population and results. Pharmacoepidemiol Drug Saf 9:359–366. https://doi.org/10.1002/1099-1557(200009/10)9:5<359::AID-PDS507>3.0.CO;2-E CrossRefPubMedGoogle Scholar