Session Information
Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Glucocorticoids have long been linked to
the development of osteonecrosis, mostly in heavily exposed patients from
specialty clinics. We tested the hypothesis that oral glucocorticoids were associated
with osteonecrosis in a dose-dependent relationship in people with chronic
inflammatory diseases and modified by age and inflammatory disease.
Methods: We performed a retrospective cohort study
using The Health Improvement Network, a population-representative medical
records database from the United Kingdom. The study population included people
at least 2 years old diagnosed with asthma; inflammatory bowel disease (IBD);
juvenile, psoriatic, or rheumatoid arthritis; psoriasis; or systemic lupus.
Those with prevalent glucocorticoid use, prior osteonecrosis, malignancy, or
other high-risk diseases were excluded. Prednisone-equivalent dose was
classified in tertiles by age. The association
between time-varying oral glucocorticoid exposure and incident osteonecrosis
was estimated using discrete time failure models and expressed as an adjusted
hazard ratio (aHR). Hypothesis testing was 1-sided,
since glucocorticoids were unlikely to decrease the rate of osteonecrosis.
Results: There were 428 cases of osteonecrosis
among 920,321 eligible subjects. After adjusting for age, sex, inflammatory
disease, history of fracture, and number of drugs prescribed, any
glucocorticoid exposure was most strongly associated with osteonecrosis among
adults ages 18-49 (aHR 2.0, 90% CI 1.4, 2.8,
P<0.001)(Table). A dose response with cumulative glucocorticoid exposure was
seen in adults (high vs. low dose, ages 18-49: aHR
3.2, 90% CI 1.6, 6.3, P=0.003; ages 50 and older: aHR
1.6, 90% CI 1.0, 2.6, P=0.048). Models examining maximum dose, dose intensity
(integrating dose and duration), and weight-based dosing were similar. No
significant association was seen for children in any model. Low-dose
glucocorticoid exposures, corresponding to average doses <7.5 mg daily
prednisone equivalents and maximum doses <30 mg daily in adults, were not
associated with osteonecrosis at any age. Arthritis, IBD, and systemic lupus
were independent risk factors (Table), but disease did not modify the effects
of glucocorticoid dose on osteonecrosis.
Conclusion: High dose glucocorticoids are associated
with osteonecrosis in adults, most strongly in those ages 18-49, but not in
children. Underlying disease is an important risk factor but does not magnify
the effect of glucocorticoid dose on osteonecrosis risk.
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Table. Primary multivariable analysis of oral glucocorticoid exposure and osteonecrosis, stratified by age
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Variables
|
Exposed Unexposed
|
Outcomes (N)
|
Unadj. hazard ratio
|
Adjusted hazard ratioa
|
CIb
|
P valuec
|
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Glucocorticoid exposure
|
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Ages 2-17 years
|
55,230 179,298 |
25 103 |
1.1 |
0.9 |
0.6, 1.4 |
0.384 |
|
Ages 18-49 years
|
109,388 338,829 |
43 80 |
2.3 |
2.0 |
1.4, 2.8 |
<0.001 |
|
Ages 50 years and older
|
98,419 144,157 |
76 101 |
1.6 |
1.2 |
0.9, 1.5 |
0.153 |
|
Chronic inflammatory disease d |
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Asthma (reference)
|
212,939 501,635 |
92 192 |
– |
– |
– |
– |
|
Psoriasis
|
15,681 85,051 |
7 33 |
0.9 |
1.2 |
0.9, 1.7 |
0.274 |
|
Juvenile, psoriatic, or rheumatoid arthritis
|
16,917 40,075 |
22 43 |
2.6 |
2.8 |
2.1, 3.8 |
<0.001 |
|
Inflammatory bowel disease
|
15,739 27,173 |
20 12 |
1.8 |
2.1 |
1.4, 3.1 |
<0.001 |
|
Systemic lupus erythematosus
|
1,761 3,350 |
3 4 |
3.2 |
3.7 |
1.7, 7.9 |
<0.001 |
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Other model variables |
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Prior fracture |
51,384 110,625 |
40 65 |
1.7 |
1.8 |
1.5, 2.3 |
<0.001 |
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Other autoimmune diseasee
|
9,846 9,308 |
12 13 |
3.2 |
2.0 |
1.3, 3.1 |
0.001 |
|
Number of drugs prescribed |
– |
– |
1.13 |
1.11 |
1.08, 1.15 |
<0.001 |
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a Models adjusted for all variables shown and the interaction between sex and age. b 90% confidence interval is shown for the association between oral glucocorticoid exposure and osteonecrosis. All other variables are shown with a 95% confidence interval. c One-sided P values are shown for the association between oral glucocorticoid exposure and osteonecrosis. All other P values are two-sided. d Individuals with two or more chronic inflammatory diseases of inclusion were categorized as having the latter disease as listed here. e Autoimmune diseases include connective tissue diseases other than systemic lupus (e.g., Sjšgren syndrome, systemic sclerosis), gout, and vasculitis. |
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To cite this abstract in AMA style:
Horton DB, Haynes K, Denburg MR, Thacker M, Rose CD, Putt ME, Leonard MB, Strom BL. Oral Glucocorticoid Use Is Associated with Osteonecrosis in Adults with Chronic Inflammatory Diseases but Not in Children: A Population-Based Cohort Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/oral-glucocorticoid-use-is-associated-with-osteonecrosis-in-adults-with-chronic-inflammatory-diseases-but-not-in-children-a-population-based-cohort-study/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/oral-glucocorticoid-use-is-associated-with-osteonecrosis-in-adults-with-chronic-inflammatory-diseases-but-not-in-children-a-population-based-cohort-study/