EAL

COPD: Bone Density (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the association between corticosteroid use and vertebral fracture prevalence in older men with COPD.

Inclusion Criteria:

Male patients greater than 50 years old
Primary diagnosis of COPD
FEV1/FVC ratio less than 70
20 pack year or more smoking history
Minimum of six refills of beta-agonist inhaler within last year

Exclusion Criteria:

1) History of:

Chronic renal failure with Creatinine greater than 2.5
Cirrhosis
Hyperthyroidism
Hypogonadism
Metabolic bone disease
Malabosorption syndrome
Cushing's syndrome
Thalassemia
Lymphoma\leukemia
Myeloma
Rheumatoid arthritis
Paget's disease
Hyperparathyroidism

2) Use of:

Phenytoin
Heparin
Androgens
Fluoride

3) Immobility or inability to ambulate without assistance

Description of Study Protocol:

Recruitment

Subjects were identified through computer-generated Minneapolis, MN Veteran's Administration Medical Center Pharmacy records by their inhaled beta-agonist, inhaled corticosteroid, and oral prednisone use during the past 2 years, prescreened for qualification through telephone interviews.

Design

Cross sectional with random sample of 3 COPD groups: Never Steroid Users, Inhaled Steroid Users, and Systemic Steroid Users. Nonresponder rates were calculated and reported.

Blinding used (if applicable)

Skeletal radiologists that evaluated radiographs were blind to the subjects corticosteroid use.

Intervention (if applicable)

Not applicable.

Statistical Analysis

Chi-square, Bonferroni for multiple comparisons, and multiple logistic regression techniques for age- and multi-variate adjusted analyses were performed. Statistical methods were also employed to address attrition and power.

Data Collection Summary:

Timing of Measurements

Single measurements.

Dependent Variables

Vertebral fracture measured by lateral lumbar and thoracic radiographs that were evaluated by two independent skeletal radiologists for deformities with Grades 0 (normal) through 3 (severe).

Independent Variables

Independent predictors of verterbral fracture included:

Age
Weight
Age of smoking initiation

Control Variables

A priori determined potential confounding variables included:

FEV1% of predicted (measured by automated MG System 1070/1085),
Pack years of tobacco use
Current smoking status
Activity Limitation Score (ALS)
General Health Status Score (GHSS)
Baseline Dyspnea Index (BDI)

Description of Actual Data Sample:

Initial N: 411 men were evaluated initially and 312 of these were eligible and enrolled

Attrition (final N): 312

Age: 50 years of age or older

Ethnicity: White

Other relevant demographics:

Anthropometrics:

Location: Minneapolis, Minnesota Veterans Affairs Medical Center

Summary of Results:

Variable	Never Used Steroids	Inhaled Steroid User	Systemic Steroid User
At least one vertebral fracture (%)	48.7	57.1	63.3
Multiple (>2) fractures (%)	23.0	17.1	35.8
Severe fractures (%)	7.0	3.5	22.1
Six or more fractures (number of subjects)	0	0	10

For systemic steroid users, lifetime duration of prednisone use in weeks (mean = 163) and lifetime dose of prednisone in grams (mean = 10.5) was associated with adjusted odds ratios for verterbral fractures of 1.41 and 1.35, respectively.

Other Findings

Significant independent predictors of one or more vertebral fractures were:

increasing age (p<0.02)
earlier age of smoking initiation (p<0.03)
greater weight (p<0.02)

Author Conclusion:

Authors conclude that:

Vertebral fractures are prevalent in white men with COPD independent of steroid use
Systemic corticosteroids users are twice as likely to have vertebral fractures and are more likely to have multiple and severe vertebral fractures than inhaled steroid users and those who have never used steroids.
Larger prospective studies with disease matched controls are needed to determine if intermittent versus continuous use may minimize the damaging effects of corticosteroids on bone and improve outcomes of COPD management.

Funding Source:

Reviewer Comments:

Conclusions suggested that white men were exclusively studied, but there was no specific section of the methods that addressed racial/ethnic distribution. Authors note that study lacked power to rule out type II error, as well as ability to control for all confounders.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	N/A
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	N/A

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		No
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	No
3.	Were study groups comparable?		???
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	No
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	???
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	Yes
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	???
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	???
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	Yes
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		N/A
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	N/A
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	???
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes