COPD: Bone Density (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To evaluate the impact of long-term inhaled corticosteroid use on bone mineral density.
Inclusion Criteria:
  • Use of 1 or more inhaled corticosteroid
  • Provided defined inclusion/exclusion criteria for study participants
  • Defined the number of patients in each study arm
  • Included only adults or presented adult and pediatric data separately
  • At least 1 year of follow-up
  • Defined the treatment protocol (i.e. medications used)
  • Defined the inhaled corticosteroid dose for each treatment group
  • Presented primary results
  • In English, French, Spanish, Italian, German, Russian or Polish
  • Results included 1 or more of the following outcome measures:  BMD, parathyroid hormone levels, osteocalcin levels, and/or rate of fractures
Exclusion Criteria:
  • Review articles and meta-analyses
  • Excluded if not included above
Description of Study Protocol:

Recruitment

Published and unpublished literature were identified by searches of MEDLINE and EMBASE databases and consultation with experts from 1966 - 2002.  Studies reporting BMD among adults asthma and COPD patients using inhaled corticosteroids and controls were identified.  Search terms included inhaled corticosteroid, bone mineral density, serum osteocalcin, parathyroid hormone, fracture, and break.

Design:  Meta-Analysis 

Blinding used (if applicable):  not applicable 

Intervention (if applicable):

Two independent reviewers evaluated studies; data from those meeting specified inclusion criteria were abstracted for inclusion in the meta-analysis.

Statistical Analysis

Meta-analyses performed using random-effects model.  Analyses were conducted on endpoints presented in 4 or more studies.  Subgroup analyses were also performed if data were available from 4 or more studies.  Heterogeneity of studies included in meta-analyses were ealuated using the Q statistic.

Data Collection Summary:

Timing of Measurements:  not applicable 

Dependent Variables

  • Bone mineral density
  • Parathyroid hormone levels
  • Osteocalcin levels
  • Rate of fractures

Independent Variables

  • Use of inhaled corticosteroids for at least 1 year

Control Variables

 

Description of Actual Data Sample:

Initial N: 266 studies were reviewed

Attrition (final N):  14 studies met inclusion criteria, 252 rejected

Age: not mentioned

Ethnicity:  not mentioned

Other relevant demographics:

Anthropometrics:

Location:  Worldwide studies

 

Summary of Results:

Primary Analyses:  Change in Endpoint over 12 months or longer

Variables

Lumbar BMD (L1-L4)

Lumbar BMD (L2-L4) Lumbar BMD (Any) Femoral Neck

Trochanter Major

Mean

-0.81% -0.67% -0.23% -0.17% 1.46%

95% Confidence Interval

-3.41% to 1.80%

-5.50% to 4.15%

-1.84% to 1.38% -1.88% to 1.54%

-3.26% to 6.19%

Other Findings

None of the studies indicated significant heterogeneity.

Sufficient data were available to perform meta-analysis on 3 measures for inhaled corticosteroid-using patients (lumbar, femoral neck, and major trochanter BMD) and 1 measure (lumbar BMD) for non-using controls.

Using current National Asthma Education and Prevention Program definitions, the majority of studies (12 of 14) included patients receiving moderate to high doses of inhaled corticosteroids.

Among inhaled corticosteroid users, annual changes from baseline in lumbar (-0.23%), femoral neck (-0.17%) and major trochanter BMD (+1.46%) were not statistically significant.

Mean changes in lumbar BMD were also not significantly different from controls (-0.02%).

Annual changes in lumbar BMD were not statistically significant for subgroups of patients with asthma or COPD. 

Author Conclusion:
This meta-analysis, indicating no significant decrease in BMD among patients receiving long-term inhaled corticosteroid therapy, provides further evidence of the safety for this important treatment option for asthma and COPD.  Given the substantial evidence for the effectiveness of inhaled corticosteroids and their safety profile when used appropriately, it can be concluded that inhaled corticosteroids have a favorable risk/benefit profile when used at the lowest effective dose.  Future work should focus on both patient and provider education regarding the safety of inhaled corticosteroids and the need to adhere with their use as prescribed and recommended in appropriate treatment guidelines.
Funding Source:
Reviewer Comments:
Authors note limitations of only 14 studies meeting inclusion criteria.
Quality Criteria Checklist: Review Articles
Relevance Questions
  1. Will the answer if true, have a direct bearing on the health of patients? Yes
  2. Is the outcome or topic something that patients/clients/population groups would care about? Yes
  3. Is the problem addressed in the review one that is relevant to dietetics practice? Yes
  4. Will the information, if true, require a change in practice? Yes
 
Validity Questions
  1. Was the question for the review clearly focused and appropriate? Yes
  2. Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? Yes
  3. Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? Yes
  4. Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? Yes
  5. Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? Yes
  6. Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? Yes
  7. Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? Yes
  8. Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? Yes
  9. Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? Yes
  10. Was bias due to the review's funding or sponsorship unlikely? Yes