EAL

COPD: Bone Density (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To quantify the impact of oral corticosteroids on BMD
To assess the risk of fracture associated with changes in BMD due to oral corticosteroids

Inclusion Criteria:

50 years or older
6 months or more of continuous or frequent intermittent (mean daily dose 5 mg) oral steroids
asthma, COPD, or fibrosing alveolitis

Exclusion Criteria:

Age less than 50 years
History of fracture for "other" reasons such as immobility, early menopause, drugs/supplements affecting bone mineral density

Description of Study Protocol:

Recruitment

From "general practices" in Nottingham, United Kingdom

Design: Cross-Sectional Analysis of a Cohort

Blinding used (if applicable)

Blinding mentioned for dose and duration of oral corticosteroid therapy without knowledge of bone mineral density

Intervention (if applicable): not applicable

Statistical Analysis

Multiple linear regression was used to determine relationship between cumulative oral corticosteroid dose and bone mineral density.

Data Collection Summary:

Timing of Measurements

One time measurement.

Dependent Variables

Bone mineral density at lumbar spine (L2-L4) and left proximal femur by dual energy x-ray absorptiometry
Lumbar spine morphometry by dual energy x-ray absorptionmetry
Vertebral fractures as defined by McCloskey et al.

Independent Variables

Potential confounding variable data collected by direct measurement, questionnaire at recruitment, practice records, or interview:

BMI
calcium intake
daily activity
current exercise
exercise history between 15-25 years of age
years since menopause (for female subjects)
smoking
inhaled corticosteroid use

Control Variables

Lifetime cumulative dose of oral and inhaled corticosteroid
Duration of therapy calculated from total time of continuous and/or intermittent therapy

Description of Actual Data Sample:

Initial N: 169 in original cohort fulfilled inclusion criteria

Attrition (final N): 117 (female = 56, male = 61) willing to participate

Age: 50 years or older

Ethnicity: Not specified

Other relevant demographics:

Anthropometrics:

Location: Nottingham, United Kingdom

Summary of Results:

Variable	1st quartile dose	2nd quartile dose	3rd quartile dose	4th quartile dose
Vertebral fracture by cumulative oral corticosteroid dose (%)	48	54	64	76
Vertebral fracture by cumulative inhaled corticosteroid dose (%)	57	61	61	64

Cumulative prednisolone dose was significantly related to BMD at the femoral neck and Ward's triangle. The first (lowest dose) and second predinisolone dose quartiles were not significantly different, but the 3rd and 4th (highest dose) were associated with a significant reduction in BMD. Trends were similar for trochanter and lumbar spine, but reductions were not statistically significant.

Vertebral fractures significantly increased with increasing quartiles of oral corticosteroid use with odds ratio of 4.4 between the highest and lowest quartiles. Inhaled corticosteroid used was not significantly related to vertebral fracture with odds ratio of 1.4 between the highest and lowest quartiles.

Prevalence of vertebral fracture in this cohort was five times higher than in the European Vertebral Osteoporosis Study, even though patients that were undergoing treatment for osteoporosis were excluded from the sample.

There was a non-linear relationship between prednisolone dose with reduced bone mineral density.

Author Conclusion:

The authors concluded:

First study of cumulative prednisolone dose, bone mineral density, and vertebral fracture.

Oral prednisolone use significantly increases the risk of vertebral fracture.

Reduction in bone mineral density with oral prednisolone use is not the (sole) cause of increased fracture risk. Other suggested possibilities accounting for increased fracture risk include corticosteroid-induced disruption of collagen matrix and bone architecture and proximal myopathy.

Non-linear loss of bone mineral density in relation to increasing dose quartiles may be due to more rapid bone loss early in treatment that tapers off later in treatment and that fractured vertebrae were excluded for estimation of bone mineral density.

Oral corticosteroid use should be considered a significant risk factor for vertebral fracture.

Funding Source:

Reviewer Comments:

Authors did not include specific odds ratio numbers (although one could estimate from graphs) for all quartiles. Authors note that the magnitude of effect of prednisolone was not statistically significant at the lumbar spine possibly due to the exclusion of fractured vertebrae from estimates of BMD.

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)	???
	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?		???
	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?	???
	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?	???
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?	???
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	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?	???
	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?	???
	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?		Yes
	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?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	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?	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?	Yes
	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?		???
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	???
	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