TY - JOUR
T1 - Oral glucocorticoid use and osteonecrosis in children and adults with chronic inflammatory diseases
T2 - A population-based cohort study
AU - Horton, Daniel B.
AU - Haynes, Kevin
AU - Denburg, Michelle R.
AU - Thacker, Mihir M.
AU - Rose, Carlos D.
AU - Putt, Mary E.
AU - Leonard, Mary B.
AU - Strom, Brian L.
N1 - Funding Information:
This project was supported by grants from the National Institutes of Health (grant number T32-GM075766 to BLS for DBH's training, F32-AR066461 and K23-AR070286 to DBH, K23-DK093556 to MRD, U54-HD086984 to MEP, K24-DK076808 to MBL) and The NephCure Foundation American Society of Nephrology Research Grant to MRD.
Publisher Copyright:
© 2017 Article author(s) (or their employer(s) unless otherwise stated in the text of the article). All rights reserved. No commercial use is permitted unless otherwise expressly granted.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Objectives We studied oral glucocorticoids and osteonecrosis, a rare but serious bone disease, in individuals with various chronic inflammatory diseases. We hypothesised that we would find stronger associations in adults versus children and in people with autoimmune diseases. Design Retrospective cohort study. Setting Population-representative data (1994-2013) from general practices in the UK. Participants Children and adults diagnosed with asthma; inflammatory bowel disease; juvenile, psoriatic or rheumatoid arthritis; psoriasis; or systemic lupus. Exposures Oral glucocorticoid patterns. Primary and secondary outcome measures Diagnosed osteonecrosis (primary) and osteonecrosis plus clinical features (eg, symptoms, pain medication, surgical repair) (secondary). Discrete time failure models estimated the adjusted hazard ratio (aHR) of incident osteonecrosis following oral glucocorticoid exposure. Hypothesis testing was one sided (with corresponding 90% CI) since glucocorticoids were unlikely protective. Results After adjusting for demographic, disease-related and health utilisation factors, glucocorticoid exposure was associated with osteonecrosis in adults (ages 18-49, aHR 2.1 (90% CI 1.5 to 2.9); ages ≥50, aHR 1.3 (90% CI 1.01 to 1.7)). However, low-dose glucocorticoids, corresponding to average doses <7.5 mg prednisolone daily and maximum doses <30 mg daily, were not associated with osteonecrosis in adults. Furthermore, even at high glucocorticoid doses, there was no evidence of increased osteonecrosis among glucocorticoid-exposed children (p=0.04 for interaction by age) (any glucocorticoid exposure, ages 2-9: aHR 1.1 (90% CI 0.7 to 1.7); ages 10-17: aHR 0.6 (90% CI 0.3 to 1.6)). Arthritis, inflammatory bowel disease and lupus were independently associated with osteonecrosis, but there was a similar dose relationship between glucocorticoids and osteonecrosis among adults with low-risk and high-risk diseases. Conclusions Glucocorticoid use was clearly associated with osteonecrosis in a dose-related fashion in adults, especially young adults, but this risk was not detectable in children. The absolute risk of glucocorticoid-associated osteonecrosis in the general paediatric population and in adults taking low glucocorticoid doses is at most extremely small.
AB - Objectives We studied oral glucocorticoids and osteonecrosis, a rare but serious bone disease, in individuals with various chronic inflammatory diseases. We hypothesised that we would find stronger associations in adults versus children and in people with autoimmune diseases. Design Retrospective cohort study. Setting Population-representative data (1994-2013) from general practices in the UK. Participants Children and adults diagnosed with asthma; inflammatory bowel disease; juvenile, psoriatic or rheumatoid arthritis; psoriasis; or systemic lupus. Exposures Oral glucocorticoid patterns. Primary and secondary outcome measures Diagnosed osteonecrosis (primary) and osteonecrosis plus clinical features (eg, symptoms, pain medication, surgical repair) (secondary). Discrete time failure models estimated the adjusted hazard ratio (aHR) of incident osteonecrosis following oral glucocorticoid exposure. Hypothesis testing was one sided (with corresponding 90% CI) since glucocorticoids were unlikely protective. Results After adjusting for demographic, disease-related and health utilisation factors, glucocorticoid exposure was associated with osteonecrosis in adults (ages 18-49, aHR 2.1 (90% CI 1.5 to 2.9); ages ≥50, aHR 1.3 (90% CI 1.01 to 1.7)). However, low-dose glucocorticoids, corresponding to average doses <7.5 mg prednisolone daily and maximum doses <30 mg daily, were not associated with osteonecrosis in adults. Furthermore, even at high glucocorticoid doses, there was no evidence of increased osteonecrosis among glucocorticoid-exposed children (p=0.04 for interaction by age) (any glucocorticoid exposure, ages 2-9: aHR 1.1 (90% CI 0.7 to 1.7); ages 10-17: aHR 0.6 (90% CI 0.3 to 1.6)). Arthritis, inflammatory bowel disease and lupus were independently associated with osteonecrosis, but there was a similar dose relationship between glucocorticoids and osteonecrosis among adults with low-risk and high-risk diseases. Conclusions Glucocorticoid use was clearly associated with osteonecrosis in a dose-related fashion in adults, especially young adults, but this risk was not detectable in children. The absolute risk of glucocorticoid-associated osteonecrosis in the general paediatric population and in adults taking low glucocorticoid doses is at most extremely small.
KW - gastroenterology
KW - glucocorticoids
KW - orthopaedic & trauma surgery
KW - paediatrics
KW - rheumatology
KW - thoracic medicine
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U2 - 10.1136/bmjopen-2017-016788
DO - 10.1136/bmjopen-2017-016788
M3 - Article
C2 - 28733303
AN - SCOPUS:85025641109
SN - 2044-6055
VL - 7
JO - BMJ Open
JF - BMJ Open
IS - 7
M1 - e016788
ER -