COPD: Bone Density (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

The purpose of this study was to determine if the loss of fat free mass (FFM) and bone mineral density (BMD) were associated and clinically inapparent in patients with chronic obstructive pulmonary disease (COPD) and that both were related to the severity of lung disease. A secondary purpose of the study was to determine if increased breakdown of cellular and bone protein would relate to FFM and BMD loss in COPD.

Inclusion Criteria:
  • Previous diagnosis of COPD
  • Respiratory outpatients before pulmonary rehabilitation
  • Clinically stable (no antibiotics or oral corticosteroids or any increase in respiratory symptoms in the month before recruitment)
Exclusion Criteria:
  • Neoplastic disease
  • Any disease with an inflammatory or metabolic component
  • Cardiac failure
  • Chronic oral corticosteroid treatment
  • Weight-lowering drugs
Description of Study Protocol:

Recruitment Subjects were recruited from primary care.  Recruitment of controls not described.

Design:  Case-Control Study.

Subjects with COPD were compared to healthy subjects. COPD patients were subdivided into those with FEV1 < 50% predicted and those with FEV1 >50% predicted. 

Blinding used (if applicable): Not applicable

Intervention (if applicable):  Not applicable 

Statistical Analysis

  • Analyses included the X2 test, independent t test, one-way analysis of variance with a post hoc Tukey test, Pearson correlation and multiple regression.
  • P<0.05 was considered significant.
Data Collection Summary:

Timing of Measurements:  one time measurements 

Dependent Variables

  • Height, Weight and BMI, Body Composition through DEXA 
  • Fat Free Mass index  (FFMI) and Fat Mass index (FMI) through DEXA
  • Bone Mineral Density (BMD) through DEXA 
  • Serum samples for measurement of Inflammatory markers

Independent Variables

  • COPD versus Healthy Subjects

Control Variables

 

Description of Actual Data Sample:

Initial N: 81 subjects (43 males) and 38 healthy controls (19 males)

Attrition (final N): as above

Age: Subjects median 65.8 years (range 39-82), control group 60.8 years (range 44-77)

Ethnicity: Not stated

Other relevant demographics:

Anthropometrics: There were signficant differences between the subjects and control groups in the following categories: age, FEV1 (liters and percent predicted), BMI (kg/m2), BMD total lumbar (g/cm2), BMD total hip (g/cm2), total FFM (kg/m2), total FFMI (kg/m2), total FMI (kg/m2), height of females (m).

Location:  United Kingdom   

 

Summary of Results:

 

Variables

COPD subjects

Healthy controls

P value

FEV1, % predicted; median (range)

44 (16-105)

104 (83-148)

<0.01

BMI, kg/m2, mean (95% CI)

23.95 (22.91, 25.0)

27.01 (25.69,28.36)

<0.01

BMD total lumbar, g/cm2, mean (95% CI)

0.9 (0.861,0.94)

1043 (0.974, 1.111)

<0.01

BMD, total hip, g/cm2, mean (95% CI) 0.797 (0.75, 0.84) 0.64 (0.9,1.03) <0.01
 Total FFM, kg, mean (95% CI) 43.97 (41.63, 46.3) 50.15 (46.42,53.87) <0.01
Total FFMI, kg/m2, mean (95% CI) 16.17 (15.53,  16.82) 17.8 (16.92,18.64) <0.01
Total FMI, kg/m2, mean (95% CI) 7.25 (6.60,7.91) 8.65 (7.85,9.46) <0.05

Other Findings:

The PSU/FFMI was greater in the subjects than the controls (mean, 95% CI) (1.963 (1786, 2.158) versus 1.622 (1.449, 1.82), P<0.05, and was greater in those with an FEV1 <50% predicated compared with an FEV1 >50% predicted (P= 0.02).  Among subjects, the PSU/FFMI was inversely related to the actual FEV1 (r= -0.403, P <0.01).

The NTx was greater in those with severe lung disease. Circulating concentrations of IL-6 and the tumor necrosis factors were significantly greater in the subjects compared to the controls.

Author Conclusion:
Loss of FFM and loss of BMD were related, occurred commonly, and could be subclinical in patients with COPD. Loss of both was greatest with severe lung disease. Increased excretion of cellular and bone collagen protein breakdown products in those with low FFM and BMD indicates a protein catabolic state in these patients.
Funding Source:
Reviewer Comments:

Limited info on healthy controls - ie exercise level, weight lifting, etc.  Controls not matched.

Authors note limitations of not exploring the possible contribution of physical inactivity and catabolic/anabolic hormone balance to FFM, as well as cumulative steroid usage.

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? ???
  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) N/A
  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? 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.) ???
  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.) 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? N/A
  6.6. Were extra or unplanned treatments described? Yes
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  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)? Yes
  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