Osteoporosis 2016 | Intermittent use of high-dose glucocorticoids and risk of fracture in Denmark: A population-based case-control study: Dr Andrea Burden #osteo2016
Dr Andrea Burden's presentation from Osteoporosis 2016: Intermittent use of high-dose glucocorticoids and risk of fracture in Denmark: A population-based case-control study.
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Similar to Osteoporosis 2016 | Intermittent use of high-dose glucocorticoids and risk of fracture in Denmark: A population-based case-control study: Dr Andrea Burden #osteo2016
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Osteoporosis 2016 | Intermittent use of high-dose glucocorticoids and risk of fracture in Denmark: A population-based case-control study: Dr Andrea Burden #osteo2016
1. Intermittent use of high-dose glucocorticoids and
risk of fracture in Denmark:
A population-based case-control study
Andrea M. Burden, PhD
Maastricht University
National Osteoporosis Society Conference 2016
7th November 2016
Birmingham, UK
2. Clinical Epidemiology
Glucocorticoids
β’ Oral GCs are primarily prescribed for inflammatory
disorders
β’ Chronic obstructive pulmonary disease (COPD), rheumatoid
arthritis, inflammatory bowel disease
β’ These indications often have frequent short-courses or
tapering regimens for symptom management
β’ Difficult to accurately examine exposure in databases
3. Clinical Epidemiology
Rationale and Objective
β’ Oral glucocorticoids (GCs) are associated with increased
fracture risk1
β’ Effect is dose dependent:
β’ High-dose (β₯15mg day) associated with high risk2
β’ Effect of the cumulative exposure to high doses is less
clear
β’ We aimed to examine the effect of intermittent and long-
term heavy use of GC on fracture risk
1 Amiche MA et al. Osteoporos Int. 2016; 27: 1709-18
2 van Staa TP et al. Rheumatology. 2000; 39: 1383-9
4. Clinical Epidemiology
Population and design
β’ Danish National Database
β’ Information is available for inpatient visits, hospitalizations, A&E
visits, prescriptions
β’ Case-control study
β’ Cases (Fracture Patients: Osteoporotic [Hip, Vertebral, Humerus, Radius])
β’ All patients β₯18 years
β’ Fracture during study period (1 JAN 1996 β 31 DEC 2011)
β’ Index Date = date of initial fracture
β’ Controls (No Fracture)
β’ Matched 1:1 on age (birth year) and sex
β’ Received same date as matched case
5. Clinical Epidemiology
GC Exposure
β’ Exposure to GCs was defined prior to index date as:
β’ Never User: no GC prescription before index (reference category)
β’ Current User: prescription in 91 days before index (primary exposure group)
β’ Also classified recent, past, and distant use
β’ Average daily dose: Total prednisone equivalent (mg)/time
β’ High daily dose defined as β₯15mg per day
β’ Cumulative exposure: Total amount of prednisone
equivalent (grams)
β’ Intermittent Exposure defined <1 gram cumulative exposure
β’ High Exposure defined as β₯1gram cumulative exposure
β’ Equivalent to 3 short-courses of a high dose
10. Clinical Epidemiology
Exposure Cases Controls Adjusted OR (95% CI)
Never GC Use 313,996 322,482 Reference
Current GC Use 14,751 9,789 1.41 (1.36 β 1.45)
Daily Dose β₯15 mg 2,504 1,259 1.83 (1.71 β 1.97)
Cumulative <1g 503 383 1.24 (1.07 β 1.43)
Cumulative β₯1g 2,001 876 2.10 (1.58 β 2.29)
*Adjusted for: COPD, history of fracture, rheumatoid arthritis, inflammatory bowel disease, secondary
osteoporosis, inhaled corticosteroids, inhaled bronchodilators, antipsychotics, antidepressants,
anxiolytics/hypnotics, anticonvulsants, and GC distant, past, recent use
Osteoporotic Fracture: daily and cumulative
11. Clinical Epidemiology
Exposure Cases Controls Adjusted OR (95% CI)
Never GC Use 64,736 67,579 Reference
Current GC Use 5,230 2,917 1.59 (1.50 β 1.67)
Daily Dose β₯15 mg 1,054 349 2.54 (2.23 β 2.90)
Cumulative <1g 154 100 1.41 (1.07 β 1.84)
Cumulative β₯1g 900 249 3.00 (2.58 β 3.50)
*Adjusted for: COPD, history of fracture, rheumatoid arthritis, inflammatory bowel disease, secondary
osteoporosis, inhaled corticosteroids, inhaled bronchodilators, antipsychotics, antidepressants,
anxiolytics/hypnotics, anticonvulsants, and GC distant, past, recent use
Hip Fracture: daily and cumulative
12. Clinical Epidemiology
Exposure Cases Controls Adjusted OR (95% CI)
Never GC Use 30,044 32,463 Reference
Current GC Use 2,163 790 2.54 (2.31 β 2.79)
Daily Dose β₯15 mg 430 104 4.01 (3.17 β 5.07)
Cumulative <1g 63 29 2.17 (1.33 β 3.55)
Cumulative β₯1g 367 75 4.69 (3.59 β 6.14)
*Adjusted for: COPD, history of fracture, rheumatoid arthritis, inflammatory bowel disease, secondary
osteoporosis, inhaled corticosteroids, inhaled bronchodilators, antipsychotics, antidepressants,
anxiolytics/hypnotics, anticonvulsants, and GC distant, past, recent use
Vertebral Fracture: daily and cumulative
13. Clinical Epidemiology
Interpretation
β’ High daily-dose (β₯15 mg) and high-exposure
(β₯1 gram) independently associated a increased
fracture risk
β’ Risk was only moderately increased in users with
intermittent use (<1gram)
β’ Most substantial increase in fracture risk is among
those with high-exposure to high-doses (β₯1 gram
at β₯15 mg per day)
β’ Clinicians should monitor these patients for fracture management
14. Clinical Epidemiology
Thank you for listening!
Thank you to collaborators:
Prof. Dr Peter Vestergaard
Dr. Frank de Vries
Annemariek Driessen, MSc
Also classified other exposure groups (distant use, past use, recent use)
Distant User: prescription >364 days before index
Past User: prescription between 183-364 days before index
Recent User: prescription between 92-182 days before index