Online data supplement:
Current status of research on osteoporosis in COPD: a systematic review
Lidwien Graat-Verboom, MD*,#; Emiel F.M. Wouters, Prof, PhD, MD#,¶; Frank W.J.M.
Smeenk, PhD, MD*; Ben E.E.M. van den Borne, PhD, MD*; Ragnar Lunde, MD+;
Martijn A. Spruit, PhD¶
*Department of Respiratory Medicine; Catharina Hospital Eindhoven, the Netherlands
#Department
of Respiratory Medicine; Maastricht University Medical Centre, the Netherlands
¶Department
of Research, Development & Education; Centre for Integrated Rehabilitation of Organ
failure (CIRO) Horn, the Netherlands
+Department
of Respiratory Medicine; St Jans Gasthuis Weert, the Netherlands
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METHODS
Prevalence of osteoporosis in COPD
To determine the overall prevalence of osteoporosis of the thirteen studies we found
we combined variables of these studies into a database including the number of
patients, gender, mean age, mean FEV1, mean BMI, mean FFMI and number of
patients with osteoporosis. We determined the overall mean, standard deviation and
variance of the FEV1, BMI and FFMI for all the studies. In addition, the absolute
number and percentage male and female patients were assessed. Finally, the overall
prevalence of osteoporosis was determined. To investigate differences between the
patients with- and without osteoporosis discrete variables were compared with the
Chi-square test and presented as percentages and continuous variables were
compared with student’s T-test and presented as means ± standard deviation (SD).
A p-value <0.05 was used to indicate statistical significance. To see the influence of
the variables on osteoporosis we used univariate binary logistic regression analysis
with osteoporosis versus no osteoporosis as the dependent variable and age,
gender, FEV1, BMI and FFMI respectively as independent variables. Odds ratio (OR)
with 95% confidence intervals (CI) are reported.
In the 4 studies including a control group of healthy subjects (HS) we determined the
prevalence of osteoporosis in the COPD patients and the HS and compared these
prevalence’s with the chi-square test. All statistical analyses were performed using
Statistical Package for Social Sciences (SPSS) version 16.0.
RESULTS
Prevalence of osteoporosis in COPD
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There were 2 papers by Bolton and colleagues, one published in 2004 and the other
one in 2008. For the prevalence of osteoporosis we excluded the paper of 2008
because a sub-group of 58 patients of the cohort of the 81 patients in the 2004 paper
was analyzed.
Univariate binary logistic regression analysis was performed on the 13 found studies
combined. The results are shown in table 1.
Table E1 (online supplement): Univariate binary logistic regression analysis with
osteoporosis (and no osteoporosis) as the dependent variable.
p-value
B
OR
95%-CI
Age
0.17
1.017
0.988-1.047
0.259
0.568
1.764
1.195-2.606
0.004
-0.028
0.973
0.959-0.987
<0.001
BMI
-0.300
0.741
0.687-0.798
<0.001
FFMI
-0.733
0.480
0.362-0.638
<0.001
Gender:
Female
Male*
FEV1
*Reference category
Treatment of osteoporosis in COPD
No trials in only COPD patients were found. However, to get some insight in the
effects of treatment of osteoporosis we additionally reviewed the studies where mixed
groups of asthma and COPD patients were included. Outcome had to be the effect of
lifestyle interventions and/or the medication under study on BMD and/or prevalence
of osteoporosis. To assess the methodological quality of the identified trials the
Delphi list was used(16). The Delphi list is a comprehensive criteria list for quality
assessment of RCTs for conducting systematic reviews. It consists of 9 items all
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having a ‘yes’, ’no’ or ’don’t know’ answer. If bias was unlikely, the criterion was rated
positive (‘yes’). In cases where information was lacking or insufficient and/or if bias
was likely, the criterion was rated negative (‘no’ or ‘don’t know’, respectively). All ‘yes’
scores (1 point per ‘yes’) were summed to produce an overall quality score.
RESULTS
Treatment of osteoporosis in COPD
We found 3 studies investigating pharmacological therapy of osteoporosis in patients
with asthma or COPD. Points assigned to these 3 studies based on the Delphi
scoring list vary from 2 to 8 (table E2).
Table E2 (online supplement): Delphi scoring list for 3 trials
Question
Smith 2004[30]
Mirzai 2003[31]
Alen/Pla 54/71
Rocal/Co 30/7
Method of randomization
Yes
Yes
performed?
Treatment allocation concealed?
Yes
No
Groups similar at baseline
Yes
No
regarding most important
prognostic indicators?
Eligibility criteria specified?
Yes
Yes
Outcome assessor blinded?
Don’t know
No
Care provider blinded?
Yes
No
Patient blinded?
Yes
No
Point estimates and measures of Yes
variability presented?
Intention-to-treat analysis
Yes
No
included?
Total score
8
2
Lau 2001[32]
Alen/Pla 38/40
Yes
Don’t know
Yes
Yes
Don’t know
Don’t know
Don’t know
Yes
No
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Abbreviations: Alen = alendronate, Pla = placebo, Rocal = rocaltrol
In a randomized control trial of alendronate compared to placebo in patients with
airway disease (asthma and COPD) there was improvement in BMD at the lumbar
spine, but not at the hip after one year of treatment[30]. In asthma and COPD
patients treated with inhaled corticosteroids alendronate prevented accelerated bone
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loss as measured by BMD after 6 and 12 months[32]. In another group of patients
with asthma or COPD treated with oral corticosteroids, a slight increase in BMD was
seen in the rocaltrol treated group, whereas in the control group BMD decreased
after 12 months[31].
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