EAL

COPD: Bone Density (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To compare bone mineral density outcomes of patients who had received continuous oral systemic glucocorticoids with bone mineral density outcomes of patients who had received multiple glucocorticoid courses, oral or IV.

Inclusion Criteria:

Every new patient with COPD and all those with a previous diagnosis of COPD
Documented COPD for at least 5 years

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

Selected from the outpatient clinic for pulmonary diseases of the Reinier de Graaf Groep in Delft and Voorburg, the Netherlands. Patients included in the study consulted one lung physician consecutively. The recruitment period lasted exactly 12 months.

Design: Cross-Sectional Study

Blinding used (if applicable): not applicable

Intervention (if applicable): not applicable

Statistical Analysis

Osteopenia and osteoporosis were studied with reference to a database of white male subjects. Demographics, pulmonary function tests and bone mineral density results were compared between groups using ANOVA and the post hoc least-squares difference procedure. Correlations between BMI and pulmonary function tests with bone mineral density were analyzed and expressed using Pearson correlation coefficients. Relations between these variables were further analyzed using stepwise regression analysis.

Data Collection Summary:

Timing of Measurements

Data analysis from medical records, bone densitometry, and pulmonary function tests of consecutive selected patients.

Dependent Variables

Bone mineral density measured through DEXA scanning of the lumbar spine, total hip and femoral neck region
Pulmonary function tests data included total lung capacity, residual volume, and FEV1

Independent Variables

Group 1: received oral prednisolone daily
Group 2: received multiple systemic prednisolone courses, up to a period of 2 weeks per course, with a cumulative dose of >1000 mg
Group 3: received multiple systemic prednisolone courses, but with a cumulative dose < 1000 mg
Group 4: never treated with systemic prednisolone and partly with inhaled corticosteroids

Control Variables

BMI
Lung function

Description of Actual Data Sample:

Initial N: 86 white men

Attrition (final N): 86 men

Age:

Group 1: mean age 63.6 ± 12.2 years
Group 2: mean age 69.5 ± 10.9 years
Group 3: mean age 64.8 ± 13.5 years
Group 4: mean age 63.2 ± 13.0 years

Ethnicity: all white

Other relevant demographics:

10 patients received oral prednisolone daily (group 1)
11 patients were treated for several exacerbations with multiple systemic prednisolone courses, up to a period of 2 weeks per course, with a cumulative dose of >1000 mg (group 2)
28 patients were treated with multiple systemic prednisolone courses, but with a cumulative dose < 1000 mg (group 3)
37 patients were never treated with systemic prednisolone and partly with inhaled corticosteroids (group 4)

Anthropometrics: All groups balanced for age and pack years of smoking

Location: the Netherlands

Summary of Results:

Bone Mineral Density in 86 Male COPD Patients

Variables	BMD (g/cm²)	P Value
Lumbar Spine - Group 1	1.168 ± 0.156	NS
Lumbar Spine - Group 2	0.759 ± 0.238	<0.001
Lumbar Spine - Group 3	1.121 ± 0.207	NS
Lumbar Spine - Group 4	1.118 ± 0.190	NS
Total Hip - Group 1	0.991 ± 0.175	NS
Total Hip - Group 2	0.683 ± 0.115	<0.0001
Total Hip - Group 3	0.928 ± 0.176	NS
Total Hip - Group 4	0.939 ± 0.145	NS
Femoral Neck - Group 1	0.922 ± 0.149	NS
Femoral Neck - Group 2	0.686 ± 0.125	<0.0001
Femoral Neck - Group 3	0.881 ± 0.167	NS
Femoral Neck - Group 4	0.882 ± 0.126	NS

Other Findings

In Group 2, BMI and FEV1 were lowest and hyperinflation was highest.

The cumulative systemic prednisolone dose was highest in Group 1, irrespective of the additional inhaled corticosteroid treatments.

DEXA scanning of the lumbar spine, total hip and femoral neck region revealed a T score <2.5 SD in 27 patients (31%), 31 patients (36%) and 34 patients (40%), respectively.

Bone mineral density outcomes at any site were lower in patients receiving multiple systemic prednisolone courses > 1000 mg, cumulatively (Group 2), compared to the other groups (P < 0.0001).

Multivariate regression analysis revealed a correlation between the cumulative dose of prednisolone in Group 2 and bone mineral density of the lumbar spine (adjusted r = 0.48; p < 0.01).

At the total hip and femoral neck regions, only a correlation between BMI and bone mineral density was observed (adjusted r = 0.65 and 0.58, respectively; p < 0.0001 for both sites).

Author Conclusion:

Despite a far lower cumulative glucocorticoid dose in comparison with patients treated with systemic corticosteroids continuously, after adjusting for BMI and lung function, osteoporosis of the lumbar spine was most frequent in patients receiving > 1000 mg of prednisolone cumulatively, administered in multiple courses for the treatment of exacerbations for COPD.

Funding Source:

Reviewer Comments:

Authors note limitations of:

pulmonary function test results were lower in groups 2 and 3
all pulmonary function tests measured in patients with stable disease and not during exacerbations
measurements of production of proinflammatory cytokines not available in medical records
Patients numbers in groups were small

Other factors affecting bone mineral density were not measured.

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?		Yes
	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?	Yes
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.)	No
	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?	No
	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.)	No
	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?	N/A
	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.)	Yes
	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?		???
	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?	Yes
	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?	N/A
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