Title: Is There An Association Between Inhaled Corticosteroids And Bone Density In Postmenopausal Women
1Is There An Association Between Inhaled
Corticosteroids And Bone Density In
Postmenopausal Women?
- Thang Nguyen, M.D.
- Reviewer David Thom, MD, PhD
2Outline
- Elmstahl S, Ekstrom H, Galvard H, Johnell O,
Gerhardsson de Verdier M, Norjavaara E. Is there
an association between inhaled corticosteroids
and bone density in postmenopausal women?J
Allergy Clin Immunol. 2003 Jan111(1)91-6. - Jones A, Fay JK, Burr M, Stone M, Hood K, Roberts
G. Inhaled corticosteroid effects on bone
metabolism in asthma and mild chronic obstructive
pulmonary disease (Cochrane Review). In The
Cochrane Library, Issue 2, 2003. Oxford Update
Software. - Wong CA, Walsh LJ, Smith CJ, Wisniewski AF, Lewis
SA, Hubbard R, Cawte S, Green DJ, Pringle M,
Tattersfield AE. Inhaled corticosteroid use and
bone-mineral density in patients with
asthma.Lancet. 2000 Apr 22355(9213)1399-403.
3Background
- Osteoporosis
- bone resorption gt bone formation gt bone loss.
- Corticosteroids
- inhibit osteoblastic function
- reduce of osteoblast life span
- Systemic steroids at high doses
- vertebral fracture and hip fracture
4Background
- Inhaled corticosteroids
- main therapy for asthma
- adrenal suppression, skin thinning, increased
cataract formation, decreased linear growth in
children, metabolic changes and behavioral
abnormalities
5Elmstahl S, Ekstrom H, Galvard H, Johnell O,
Gerhardsson de Verdier M, Norjavaara E. Is there
an association between inhaled corticosteroids
and bone density in postmenopausal women?J
Allergy Clin Immunol. 2003 Jan111(1)91-6.
6Design
- Retrospective cohort study
- Postmenopausal women
- 155 subjects exposed to ICs
- 106 exposed to ICs only
- 49 exposed to ICs and OCs
- 674 non-exposed control subjects
- Demographics similar to underlying population
7Design
- Health questionnaire
- Medical history and medication use
- History of steroid use (type, route, dose,
duration) - Risk factors for BMD (e.g., smoking, physical
activity) - Steroid use was verified for all exposed subjects
via medical record review - Medical record review of random 5 controls
found 98 without steroid use - BMD measurements in wrist
8Analysis
- Students t-test used to assess differences in
BMD between groups - ANOVA and linear regression used to adjust for
age - Stratification by cumulative does, duration,
current daily dose - Not clear if used 1-tailed or 2-tailed p-values
9Results
- Mean duration of use was 8.2 years, range 1.5-26
years - Mean annual duration of inhalation 8.5-12 months
- Mean daily dose was 853 ug and 23 used doses gt
1000 ug/day - Budesonide most common
- 49 of 155 also used oral or intra-articular
steroids in addition to inhaled steroid (OC)
10Results
- Mean BMD values in IC group vs. controls
- No differences between exposed and control
- Same when adjusted for years of steroid use, age,
and annual duration of IC use
11Results
- Mean BMD values in OC vs. IC only
- BMD for OC lt IC (0.408 v. 0.434 p0.044)
- Difference only seen in 3 subgroups
- Cumulative dose lt4000mg
- Duration of exposure gt 6.3 years
- Current daily dose gt 1000 mg
12Results
- Same distribution of risk factors for exposed and
control subjects. - BMD higher in subjects with medium to heavy
physical activity vs. light activity. - Women on gt 1000 ug daily less physically active
than those on lt 1000 ug daily.
13Discusssion
- Confounding factors
- Selection bias unlikely
- Other studies support and contradict their
conclusions. - Need for prospective study
14Critique
- Selection bias study sample similar to
underlying population - Unexposed and exposed groups similar in all
important respects except for the exposure. - Information bias-outcomes identified in the same
way for both groups - Did not examine fracture rates
- Controlled for confounding
- External validity
15- Jones A, Fay JK, Burr M, Stone M, Hood K, Roberts
G. Inhaled corticosteroid effects on bone
metabolism in asthma and mild chronic obstructive
pulmonary disease (Cochrane Review). In The
Cochrane Library, Issue 2, 2003. Oxford Update
Software.
16Design
- Search
- Cochrane Airways Group trials register
- electronic reference databases
- UK National Research Register
- bibliographies of included studies
- contacted pharmaceutical companies
- Selection Criteria
- Quality and Validity Assessment
17Results
- Seven studies of IC and BMD
- Study subjects age less than 60 and
- The malefemale ratio was 21
- Mean duration of inhaled steroid use was 2-3
years - No differences in BMD and fracture rates
- Osteocalcin
- No differences at conventional doses of IC
- Decreased at experimental doses
18Wong CA, Walsh LJ, Smith CJ, Wisniewski AF, Lewis
SA, Hubbard R, Cawte S, Green DJ, Pringle M,
Tattersfield AE. Inhaled corticosteroid use and
bone-mineral density in patients with
asthma.Lancet. 2000 Apr 22355(9213)1399-403.
19Design
- 196 adults with asthma (119 women)
- Age 20-40 years
- Inhaled corticosteroid regularly for at least 6
months - Limited exposure to systemic steroids
- Questionnaires
- BMD measurements
20Results
- Median duration of inhaled corticosteroid
treatment 6 years (range 0.5-24) - Median cumulative dose was 876 mg (87-4380)
- Negative association between cumulative dose of
inhaled corticosteroid and bone-mineral density
at the - lumbar spine (L2-L4)
- femoral neck
- trochanter
- Before and after adjustments
21Conclusion
- Conflicting evidence
- No correlation mostly
- Higher doses more detrimental
- Consider preventive therapy