EAL

COPD: Bone Density (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To estimate the long-term risk of all fractures through retrospective analysis in a cohort of patients that were first diagnosed with asthma at age 35 years or more (to rule out increased fracture risk associated with growth delay with early onset asthma).

Inclusion Criteria:

Diagnosis of asthma based on three defined criteria
35 years or older when first diagnosed with asthma
Rochester area resident
Signed permission for project access to medical records

Exclusion Criteria:

No authorization for access to records
Not Rochester resident

Description of Study Protocol:

Recruitment

From medical records linkage system (The Rochester Epidemiology Project).

Design: Retrospective Cohort Study

Blinding used (if applicable): not applicable

Intervention (if applicable): not applicable

Statistical Analysis

All statistical analysis was conducted with SAS.
Standardized incidence ratios (SIR) derived by applying age and specific incidence of fracture rates from local population and comparing them to those of the cohort
Product-limit life table methods were used to project the cumulative incidence of new fractures up to 30 years following initial diagnosis of asthma, and the resultant curves compared with the log-rank statistic
Cox proportional hazards models for impact analysis of covariates were used to analyze retrospective data.

Data Collection Summary:

Timing of Measurements: not applicable

Dependent Variables

Fracture occurrence determined through assessment of subject and community medical records and radiographic reports

Independent Variables

Diagnosis of asthma

Control Variables

Description of Actual Data Sample:

Initial N: 233 subjects with adult-onset asthma

Attrition (final N): 226

Age: 35 to 95 years old

Ethnicity: All but two subjects were white

Other relevant demographics:

Anthropometrics:

Location: Rochester, Minnesota

Summary of Results:

Variable	Observed Asthma Cohort	Expected	Statistical Significance of Group Difference
% with at least one new fracture	63	59	p=0.004
Number of fractures due to severe trauma	37	33.2	NS
Vertebral fractures due to moderate trauma (fall from standing height or less)	49	17.2	p<0.001 SIR = 2.9 (2.1-3.8)
Rib fractures due to moderate trauma	19	9.26	p<0.05 SIR = 2.0 (1.2-3.2)
Femur fractures due to moderate trauma	17	9.73	p<0.05 SIR = 1.8 (1.02-2.8)
Overall risk of fracture with moderate trauma	87	52.2	p<0.05 SIR = 1.7 (1.3-2.1)

Other Findings

The above reported sites with increases in risk fracture were observed for both men and women.

No significant increase in fracture risk of the skull/face, hands/fingers, distal forearm, other arm, clavicle/scapula/sternum, pelvis, other leg, and feet/toes was observed between the adult-onset asthma cohort and the general population.

Significant independent predictors of fracture due to moderate trauma were:

corticosteroid use greater than the median cumulative dose of 1,775 mg, but not with inhaled steroids after adjustment for age in the multivariate analysis
age
history of COPD
cigarette smoking

With stratification by COPD comorbidity with asthma, the overall increase in moderate trauma fracture risk was specific to COPD subgroup and not significant in asthma only subgroup.

Author Conclusion:

The authors concluded:

The risk of fracture of the vertebra, ribs, and hip (proximal femur) was 2-fold, 3-fold, and 2 fold respectively in the adult-onset asthma cohort compared to others.
Long-term or high dose corticosteroid therapy (above cumulative median dose) increased the risk of fracture in this cohort, although, more specifically, inhaled corticosteroid did not result in a significant increase in risk.
Elevated risk of fracture was especially prominent when asthma was comorbid with COPD.

Funding Source:

Reviewer Comments:

Population limited to Rochester, MN residents.

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?		???
	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?	???
3.	Were study groups comparable?		N/A
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	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?	N/A
	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.)	N/A
	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%.)	N/A
	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?		???
	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.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	???
	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?		???
	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?	Yes
	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?	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?	???
	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?	N/A
	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?	???
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