The Indian Journal of Pediatrics (November 2019) 86(11):987–994

https://doi.org/10.1007/s12098-019-03019-x

ORIGINAL ARTICLE

Effects of Exercise Intervention Program on Bone Mineral Accretion

in Children and Adolescents with Cystic Fibrosis: A Randomized
Controlled Trial
Sumita Gupta 1 & Aparna Mukherjee 1 & Rakesh Lodha 1 & Madhulika Kabra 1 & Kishore K. Deepak 2 & Rajesh Khadgawat 3 &
Anjana Talwar 2 & Sushil Kumar Kabra 1

Received: 8 February 2019 / Accepted: 14 June 2019 / Published online: 8 July 2019
# Dr. K C Chaudhuri Foundation 2019

Abstract
Objective To evaluate effect of one year exercise intervention program on bone mineral accrual in children and adolescent with
cystic fibrosis (CF).
Methods Fifty-two CF children (mean age 149.79 mo) were randomized into experimental (15 boys and 10 girls) and control
groups (15 boys and 12 girls). Experimental group performed prescribed exercises three times/week, while control group
continued with routine physical activities for one year. Following were assessed at baseline and at one year: Bone mineral
density (BMD) of whole body and lumbar spine, pulmonary function, exercise capacity, quality of life and habitual activity.
Results Change in whole body and lumbar spine BMD over 12 mo in experimental group was lower by 0.006 g/cm2 (95% CI
-0.02 to 0.02) and higher by 0.001 g/cm2 (95% CI -0.04 to 0.03) than controls, respectively. However, difference between
groups was non-significant for both parameters. Experimental group had a significant improvement in their exercise capacity
(p = 0.006), quality of life, and serum vitamin D (p = 0.007) levels. Differences between groups for changes in pulmonary
function and habitual activity were non-significant.
Conclusions Exercise regime was not associated with significant improvement in BMD of CF patients, but it had a positive
impact on both physical and psychological health of these patients.

Keywords Bone mineral density . Cystic fibrosis . Exercise . Exercise capacity . Quality of life . Vitamin D

Introduction Many factors contribute to low bone mineral density

Cystic fibrosis (CF) was thought to be a disease of the
Caucasian population, but studies suggest that it is far more
prevalent in India than previously thought. Its estimated prev-
alence in Indian population is 1/43,321 to 1/100,323 [1].
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s12098-019-03019-x) contains supplementary
material, which is available to authorized users.
* Sushil Kumar Kabra
skkabra@hotmail.com
1
Department of Pediatrics, All India Institute of Medical Sciences,
New Delhi 110029, India
2
Department of Physiology, All India Institute of Medical Sciences,
New Delhi, India
3
Department of Endocrinology, All India Institute of Medical
Sciences, New Delhi, India
(BMD) in CF patients like malnutrition, chronic respiratory
inflammation, delayed puberty, reduced physical activity and
glucocorticoid usage [2].
Several pharmaceutical agents assist in managing bone
turnover in CF patients but these just add to number of drugs
already prescribed to them. “Weight bearing exercises” are
established as most effective non-pharmacological method to
optimise bone mass in healthy population [3].
In children with CF, exercise has recognised health benefits
such as improving lung function, exercise capacity, and qual-
ity of life [2]. Several correlation studies suggest that exercise
may have some positive impact on BMD in CF patients [4, 5].
Though, the main focus of these studies was not to investigate
relationship between exercise and bone health, they do pro-
vide some evidence that regular exercise may benefit bone
health of these patients. As no interventional trial has investi-
gated effects of exercise on bone health of CF patients, this
study aimed to evaluate the effect of one year exercise
988
intervention program on bone mineral accretion in children
and adolescents with CF, aged 6–18 y.
Material and Methods
Children with confirmed diagnosis of CF, attending the out-
patient department of a tertiary care hospital in northern India
were enrolled in this one year randomized controlled trial.
The study was approved by the Institutional Ethics
Committee (IESC/T-178/04.05.2012) and registered with
Clinical Trials Registry-India (Trial No: REF/2013/01/
004447).
CF children aged 6–18 y were invited to participate in
the study. Inclusion criteria were confirmed diagnosis of
CF, not having required intravenous antibiotics prior to 1
mo of enrolment and forced expiratory volume in 1 s
(FEV1) ≥ 20% predicted. Children with any prior diag-
nosed musculoskeletal disorder such as rheumatoid ar-
thritis, muscular dystrophy or chronic renal failure were
excluded. Eligible children were enrolled in the study
after obtaining informed consent from parents or the le-
gal guardians.
Anthropometric parameters were recorded at baseline
and at the end of one year. All participants’ body mass
was measured to nearest 0.1 kg using calibrated scales
(Seca 803; Seca, Hamburg, Germany), height was mea-
sured to nearest 0.1 cm using a standardized stadiometer
(Harpenden Stadiometer; Holtain Limited, Crymych, UK)
and body mass index (BMI) (in kg/m2) was calculated.
Z scores were calculated using WHO Anthroplus software
(Version 1.0.4 based on WHO Growth Reference 2007 for 5–
19 y). Pubertal development was determined by a self-
assessment questionnaire using drawings and written descrip-
tions of Tanners’ breast, genital and pubic hair classification
[6].
All enrolled subjects were managed as per the unit’s pro-
tocol. Measurements which included clinical assessment, pul-
monary function, bone mineral density, exercise testing, qual-
ity of life, daily physical activity, bone related biochemical
parameters and dietary intake were conducted at baseline
and at end of one year exercise intervention. All enrolled sub-
jects were followed up every 3 mo (+ 2 wks) for a period of 12
mo. The three monthly assessment included spirometric mea-
surements and assessment of compliance.
As there were no studies to document the effect of
physical exercise on BMD in CF children, dual energy
X-ray absorptiometry (DXA) scans of 26 patients with
CF, aged 7–16 y, were used to calculate the sample size.
Taking alpha as 0.05, power of 90%, mean [SD] whole
body BMD value of 0.81 [0.13] g/cm2, and assuming
15% improvement in experimental group and none in
Indian J Pediatr (November 2019) 86(11):987–994
control group, sample size was calculated as 25 subjects
in each group.
The primary outcome was whole body and lumbar spine
BMD measured by DXA scan (Hologic QDR 4500A,
Hologic Inc., Bedford, MA, USA). Measurements taken were
lumbar spine and whole body bone mineral density (in g/cm2),
lean body mass and fat mass (in grams).
Since there are substantial changes in bone dimensions
during childhood especially in early teens and DXA scan
does not take into account thickness of bone, bone min-
eral apparent density (BMAD) was calculated for lumbar
spine and whole body using the method suggested by
Katzman et al. [7]. BMAD minimizes the effect of bone
geometry and allows comparisons of mineral status
among bones of similar shape but different size.
Short term precision error for DXA scans was calculated by
triplicate measurement of 15 healthy subjects as per method
suggested by Glűer et al. [8]. Single trained technician per-
formed and analysed all scans to avoid inter personnel varia-
tions. Calculated coefficient of variation was 1.3% for whole
body BMD.
Secondary outcomes included pulmonary function, ex-
ercise capacity, daily physical activity and quality of life.
For pulmonary function, spirometric parameters were
measured every 3 mo for a period of one year with a
portable spirometer (Super Spiro Micromedics,
Rochester, UK), using standard method for test perfor-
mance [9]. For each child best of the three attempts was
recorded. Based on pulmonary function test, disease se-
verity was classified as [10]:
Normal: FEV1 ≥ 90% of predicted
Mild: FEV1 70–89% of predicted
Moderate: FEV1 40–69% of predicted
Severe: FEV1 < 40% of predicted
Maximal exercise testing was done on treadmill using
Modified Bruce protocol as per the American College of
Sports Medicine guidelines [11]. Heart rate was monitored
by continuous ECG and saturation with pulse oximeter.
Measurements included were maximum oxygen uptake, max-
imum minute ventilation, exercise duration, maximum heart
rate and minimum oxygen saturation. Effort was considered to
be at a maximal level when the participant showed clinical
signs of intense effort or saturation fell below 90% and when
at least one of the following criteria was met: heart rate at peak
exercise >180 beats·min−1 or a respiratory exchange ratio at
peak exercise >1.0 [11].
Habitual activity estimation scale (HAES) was used to as-
sess daily physical activity [12]. Subject was asked to recall
one usual weekday and one usual weekend day separately
from past 2 wk. Sum of somewhat active and active categories
was used for comparison.
Indian J Pediatr (November 2019) 86(11):987–994
Quality of life was assessed using validated Cystic
fibrosis questionnaire – revised (CFQ-R) [13]. This ques-
tionnaire had three versions – child, parent and adoles-
cent. The questions had to be answered keeping in mind
physical and psychological health status over last 2 wk,
proceeding the day of administration of the question-
naire. Scores ranged from 0 to 100 with higher scores
indicating better health. Scores of all domains were
summed to generate a questionnaire score for
comparison.
In addition, fasting blood samples were taken to measure
calcium, phosphorus, alkaline phosphatase (Hitachi Modular
P 800 autoanalyser), 25-hydroxyvitamin D (DiaSorin
LIAISON, Minnesote, USA) and intact parathyroid hormone
(Roche COBAS e411, Japan). The reference range of serum
25[OH] D was taken as [14]:
Sufficient: 20–100 ng/ml
Insufficient: 15–19 ng/ml
Deficient: below 15 ng/ml
Dietary intake was assessed using validated 24-h food
recall and semi-quantitative food frequency questionnaire
for calcium rich sources. The data collected were entered
into an Indian Nutritional Software (Diet Soft, Invincible
Ideas, Delhi, India) which gave the calories, carbohy-
drates, proteins, fat, minerals and vitamins content of
consumed food.
Enrolled children were stratified into two strata based on
their pubertal stage as pre-pubertal and peri-/post-pubertal.
Children of both strata were further stratified into two
groups based on their pulmonary function, that is, children
with FEV1 (% predicted) ≥ 20% & ≤ 50% and children with
FEV1 (% predicted) > 50%. Children of the four strata were
then assigned to experimental or control group by block
randomization, using computer software by an individual
not involved in the study. Concealment of allocation was
achieved by enclosing assignments in sequentially num-
bered opaque, sealed envelopes for the four strata. There
was no blinding of the study subjects. However, the per-
sonnel performing the DXA and laboratory assays were
unaware of the assigned group.
In addition to routine management both groups were
given vitamin D and calcium supplements at twice the
recommended dietary allowance. Control group was asked
to continue with routine physical activity and experimental
group was prescribed a set of home based exercise pro-
gram to be done three times a week. The exercise pro-
gram incorporated resistance training and plyometric
jumping exercises. Exercise intensity was increased every
three monthly. Resistance training was performed using
sand-bag tied to waist or ankles and consisted of squats,
forward lunges, toe raise-heel drops, push-ups and
989
quadriceps strengthening. Intensity of exercise was in-
creased by increasing the weight and the number of rep-
etitions. Plyometric regime started with three types of
jumps each to be done 20 times/day. Intensity was in-
creased by adding new type of jumps.
Exercises were demonstrated and taught for 2 d during first
week. A CD of animated demonstration of exercise was given
to each subject in experimental group. Telephonic guidance
and assessment of compliance was done every 2 wk. Patients
were asked to record details of exercises performed in a dairy.
Compliance to exercise regime was calculated as: (Number of
exercise done in a year/Number of exercise prescribed in a
year) X 100.
Data were analysed using Stata 12.0 software
(StataCorp, College Station, TX, USA). Comparison of
data collected at baseline and at end of one year was
done. Both inter- and intra-group comparison of primary
and secondary outcome variables was carried out.
Student t-test was used for continuous variables. Mann-
Whitney test was used for analysis of non-parametric
data and Chi-square test for proportions. A p value of
<0.05 was considered as significant.
Results
The participants' disposition as per CONSORT guidelines
is shown in Fig. 1. Fifty-seven children with CF were
assessed for eligibility from May 2013 through
July 2014. Five children (8.8%) were not eligible; four
had recent pulmonary exacerbations and one had FEV1
(% predicted) less than 20%.
Fifty-two enrolled children were divided into four
groups according to their pubertal stage and pulmonary
status. Children of the four groups were then randomized
into experimental and control group. There were 25 chil-
dren in experimental (females = 10) and 27 (females = 12)
in control group. There was 100% follow-up every 3
monthly (total 4 follow-ups) with a maximum delay of
2 wk with no drop-out throughout the study from either
of the two groups (Fig. 1).
The mean [SD] age of enrolled children was (149.79
[37.84]) mo; range: 75–214 mo. Baseline characteristics of
two groups were similar. Table 1 presents baseline character-
istics of participants.
All children in experimental group did home exercise pro-
gram. Overall compliance to exercise program was 63%.
Eight (32%) children had adherence above 70% to exercise
whereas 5 (20%) had adherence below 50%.
The change in whole body BMD over 12 mo of study
period was lower by 0.006 g/cm2 (95% CI -0.04 to 0.03)
in experimental group as compared to controls. For lum-
bar spine BMD, the change in experimental group was
990
Fig. 1 Design and flow of participants through the trial
0.001 g/cm2 (95% CI -0.02 to 0.02) more than controls.
However, the effect size in both cases was non-signifi-
cant. Similarly, changes in whole body and lumbar spine
BMAD of the two groups over 12 mo remained compa-
rable (Table 2).
At the end of one year study period, changes in FEV1 (%
predicted) and forced vital capacity (FVC) (% predicted) of
the two groups showed no significant difference between the
groups (Table 3).
In terms of exercise testing variables, in experimental
group there was significant improvement in maximal ox-
ygen uptake and exercise duration whereas there were no
statistically significant difference in maximum minute
ventilation, heart rate and saturation. Change in experi-
mental group for maximal oxygen uptake was 4.15 ml/
kg/min (95% CI 1.22 to 7.08; p = 0.006) and for exercise
Indian J Pediatr (November 2019) 86(11):987–994
duration was 1.43 min (95% CI 0.32 to 2.55; p = 0.01)
more than the controls (Table 3).
The activity scores of HAES of the two groups did not
show any significant inter-group difference either for week-
days or for weekend (Table 3).
For CFQ-R, reports were available for 16 child-parent
pairs in each group. For adolescent version, reports were
retrieved from 9 and 11 subjects in experimental and
control group, respectively. The changes in experimental
group’s scores of child (mean difference 41.31; p = 0.02)
and adolescent versions (mean difference 86.6; p = 0.005)
over 12 mo were significantly higher than controls but
changes in score of parent version were similar in both
groups (Table 4).
In biochemical parameters, only vitamin D showed signif-
icantly more increase over 12 mo in experimental group in
Indian J Pediatr (November 2019) 86(11):987–994 991

Table 1 Baseline characteristics

of participants Characteristics Experimental group Control group
(n = 25) (n = 27)

Age (months) 147.16 (33.96) 152.22 (40.02)

Gender, n males (%) 15 (60) 15 (55.6)
Height (cm) 138.44 (14.75) 137.67 (15.66)
Height for age Z score * −1.68 (−2.36, −1.15) −1.96 (−2.92, −1.15)
Weight (kg) 28.08 (10.13) 29.79 (11.69)
BMI (Kg/m2) 14.23 (3.16) 15.03 (2.97)
BMI for age Z score * −2.46 (−3.79, −1.48) −1.93 (−3.59, −0.91)
Vitamin D (ng/mL) 11.2 (5.85) 10.19 (5.79)
Calcium (mg/dL) 9.35 (0.47) 9.05 (0.57)
Phosphorus (mg/dL) 4.82 (0.63) 4.66 (0.7)
Parathyroid hormone (pg/mL) * 46.33 (37.09, 76.74) 48.15 (38.8, 70.89)
Alkaline phosphatase (I.U./L) 521.36 (193.92) 591.52 (332.53)
Shwachman-Kulczycki score 79.33 (13.63) 78.39 (16.87)
Number of Creon tablets (10,000 U lipase) taken daily * 15 (7, 20) 12 (7, 15)

Values as Mean (SD); *Values expressed as Median (IQR); BMI Body mass index

comparison to controls; effect size being 8.88 ng/ml (95% CI
2.57 to 15.18; p = 0.007) (Table 3). The between group com-
parison of all dietary variables had comparable values.
Twenty-seven (52%) of the total 52 enrolled children
were colonised with Pseudomonas. Experimental group
had a significantly higher number of children colonized
with Pseudomonas (17 [68%] vs. 10 [37.04%]; p = 0.03).
Forty-six (88.5%) of them were taking inhaled glucocor-
ticoids, 5 (9.6%) were on long term oral glucocorticoids
and 5 (9.6%) had taken oral corticosteroids for short
durations during the study period. Number of children
taking inhaled steroids was similar in both groups (p =
0.92).
There was no difference in the two groups with re-
gard to whole body bone mineral parameters and lum-
bar spine bone mineral parameters in relation to puber-
tal stage and pulmonary function tests (Supplementary
material).
Discussion
In view of paucity of data available on immediate association
between exercise and bone mass of CF patients, the present
study attempted to evaluate influence of exercise program on
bone accretion in children and adolescents with CF. There

Table 2 Bone mineral outcomes at baseline and one year after intervention for experimental (n = 25) and control (n = 27) groups

Measurement Month 0 Month 12 Within-group effect Between-group effect Between-group effect

Mean (SD) Mean (SD) Median (IQR) Mean (95% CI) p value

Whole body BMD (g/cm2)

• Experimental group 0.78 (0.12) 0.87 (0.13) 0.061 (0.04, 0.15) −0.006 (−0.04 to 0.03) 0.74
• Control group 0.79 (0.16) 0.87 (0.16) 0.064 (0.05, 0.17)
Whole body BMAD (g/cm3)
• Experimental group 0.08 (0.01) 0.09 (0.01) 0.005 (0.004, 0.011) −0.0003 (−0.004 to 0.004) 0.87
• Control group 0.08 (0.01) 0.09 (0.01) 0.005 (0.002, 0.013)
Lumbar spine BMD (g/cm2)
• Experimental group 0.59 (0.15) 0.62 (0.17) 0.019 (−0.01, 0.04) 0.001 (−0.02 to 0.02) 0.91
• Control group 0.61 (0.17) 0.64 (0.17) 0.016 (−0.02, 0.05)
Lumbar spine BMAD (g/cm3)
• Experimental group 0.12 (0.02) 0.12 (0.03) 0.001 (−0.007, 0.009) −0.001 (−0.006 to 0.003) 0.58
• Control group 0.12 (0.02) 0.12 (0.02) 0.002 (−0.004, 0.007)

BMAD Bone mineral apparent density; BMD Bone mineral density

992 Indian J Pediatr (November 2019) 86(11):987–994

Table 3 Spirometric parameters, exercise testing variables and biochemical parameters at baseline and after intervention of experimental (n = 25) and
control (n = 27) groups

Outcomes Month 0 Month 12 Within-group effect Between-group effect

EG CG EG CG EG CG EG minus CG p value
Mean (SD) Mean (SD) Mean (SD) Mean (SD) Median (IQR) Median (IQR) Mean (95% CI)

FEV1 (% predicted) 61.44 (24.72) 60.93 (24.87) 57.56 (24.06) 59.89 (22.16) −3 (−12, 3) −4 (−9, 3) −2.84 (−9.85 to 4.16) 0.42
FVC (% predicted) 68.8 (19.99) 65.89 (20.55) 71.04 (23.46) 68 (9.21) −1 (−8, 8) 0 (−7, 12) 0.13 (−7.65 to 7.91) 0.97
Maximal O2 uptake 29.91 (6.65) 27.15 (7.03) 32.51 (8.05) 25.59 (6.09) 2.71 (−0.81, 5.34) −1.27 (−5.31, 2.36) 4.15 (1.22 to 7.08) 0.006
(ml/kg/min)
Maximum minute 27.15 (9.73) 23.55 (8.72) 27.37 (10.29) 22.55 (8.3) 0.81 (−3.83, 3.43) −0.59 (−4.29, 2.91) 1.21 (−1.42 to 3.85) 0.36
ventilation (L/min)
Maximum heart 167.08 (9.39) 162.22 (13.27) 165.8 (9.48) 160.07 (15.24) 0 (−2, 2) 0 (−2, 2) 0.51 (−2.35 to 3.37) 0.7
rate (beats/min)
Exercise duration (min) 12.16 (2.1) 11.95 (3.32) 12.93 (3.09) 11.29 (3.54) 1.14 (−0.43, 2.26) −0.22 (−0.86, 0.62) 1.43 (0.32 to 2.55) 0.01
Minimum saturation (%) 96.16 (1.59) 95.63 (2.57) 95 (2.55) 95 (2.87) −1 (−2, 0) −1 (−1, 0) −0.53 (−1.23 to 0.17) 0.14
HAES weekend (hours) 6.49 (1.39) 6.28 (1.47) 6.83 (1.37) 6.26 (1.38) 0.18 (−0.28, 1.04) −0.18 (−0.61, 0.72) 0.36 (−0.14 to 0.87) 0.15
HAES weekdays (hours) 6.07 (1.59) 5.97 (1.83) 6.27 (1.67) 5.93 (1.73) −0.02 (−0.34, 0.65) 0.13 (−1.3, 1.03) 0.23 (−0.45 to 0.91) 0.49
Vitamin D (ng/ml) 11.2 (5.85) 10.19 (5.79) 27.6 (14.96) 17.7 (10.54) 14 (8, 22) 5 (1, 12) 8.88 (2.57 to 15.18) 0.007
Calcium (mg/dl) 9.35 (0.47) 9.05 (0.57) 9.77 (0.52) 9.2 (0.59) 0.59 (0.1, 0.79) −0.1 (−0.29, 0.59) 0.27 (−0.07 to 0.62) 0.12

CG Control group; EG Experimental group; FEV1 Forced expiratory volume during first second; FVC Forced vital capacity; HAES Habitual activity
estimation scale

was no increased bone accretion in experimental group with
exercise, but improvement in terms of exercise capacity,
quality of life, and changes in bone related biochemical pa-
rameter were indicative of better bone acquisition as com-
pared to controls.
More than one disease related factors like malnutrition
and pulmonary disease may have contributed for ob-
served results. The study cohort was malnourished, as
indicated by mean BMI (14.7 kg/m2) and BMI for age
Z score (−2.4) and no change in weight or energy intake
was observed over one year. Literature suggests that
sustained energy deprivation is associated with increased
bone resorption relative to bone formation [15]. It may
be possible that prolonged energy deprivation resulted in
negative systemic influences on bone metabolism which
may have overridden the positive effects of exercise of
experimental group.
Majority of subjects (63.5%) had moderate to severe
lung disease. Aerobic capacity of patients with severe
lung disease may be restricted due to decreased alveolar
ventilation and lung diffusion capacity. Decrease in FEV1
is associated with decrease in bone mass and increased
glucocorticoid usage is associated with decreased bone
mass [4, 5]. Also, there is increased osteoclastic activity
during episodes of exacerbations [16]. Patients with se-
vere disease might not have been able to perform

Table 4 Scores of child, parent and adolescent versions of cystic fibrosis questionnaire – revised at baseline and after intervention of experimental and
control groups

Measurement Month 0 Month 12 Within-group effect Between-group effect Between-group effect

Mean (SD) Mean (SD) Median (IQR) Mean (95%CI) p value

Score of child version

• EG (n = 16) 587.78 (92.51) 637.78 (104.44) 45.14 (26.29, 74.8) 41.31 (7.37 to 75.25) 0.02
• CG (n = 16) 559.59 (76.71) 568.28 (88.16) 0.88 (−9.62, 26.29)
Score of parent version
• EG (n = 16) 804.01 (77.49) 847.14 (137.93) 56.12 (1.39, 105.91) 17.99 (−47.67 to 83.66) 0.58
• CG (n = 16) 727.38 (146.39) 752.52 (141.82) 12.96 (−7.97, 51.3)
Score of adolescent version
• EG (n = 9) 834.54 (196.48) 924.74 (178.27) 66.67 (51.09, 80.55) 86.6 (30.01 to 143.19) 0.005
• CG (n = 11) 928.71 (199.59) 931.74 (217.34) 8.32 (−38.86, 34.44)

CG Control group; EG Experimental group

Indian J Pediatr (November 2019) 86(11):987–994
exercises to the required level of intensity to get the
desired results. The disease severity itself may have di-
minished the beneficial effects of exercise on bone
growth.
Studies investigating influence of exercise programs
on lung function, aerobic fitness, quality of life, etc in
CF patients have observed that results are dependent on
compliance and intensity of exercises [17–19]. Also re-
sults were better with supervised programs as compared
to unsupervised ones [20]. Current study was based on a
home-based, semi-supervised exercise program. Although
children were motivated, as indicated by 100% follow-
up, factors such as lack of time, particularly in school
going children, as well as, some other socio-cultural fac-
tors may not have allowed children and parents to give
due importance to the prescribed exercises.
Studies have shown that increase in maximal oxygen
uptake from training results primarily from increase in
cardiac output [21] indicating that experimental group
despite having pulmonary limitation had an improved
aerobic capacity via increased cardiac output. Evidence
also suggests that vitamin D has positive association with
cardiopulmonary fitness [22]. In this study, maximal ox-
ygen uptake was found to be related to vitamin D levels
[p = 0.001] and increase of experimental group was sig-
nificantly higher than controls. Therefore, both increase
in cardiac output and higher levels of vitamin D may
have contributed to improved aerobic capacity of exper-
imental group.
As per subject’s own assessment, experimental group
had a significant improvement in their quality of life.
This may have resulted from improvement in their aero-
bic capacity and from realization of their own physical
potential. However, respective parents’ responses did not
suggest that there was any significant change in their
children’s quality of life. This can probably be explained
by various factors such as variable involvement of par-
ents with their child’s way of life, parents having higher
expectations from the protocol, or due to fact that emo-
tions are expressed better personally than by an observer
such as parents.
Serum vitamin D levels of both groups increased sig-
nificantly, but experimental group had a significantly
higher increase over 12 mo as compared to controls.
Literature suggests that there is a relationship between
exercise and vitamin D levels, even when performed in-
doors [23, 24]. It is postulated that increased body heat
resulting from physical exercise facilitates increased for-
mation of vitamin D3 from previtamin D3, as this reac-
tion is temperature dependent [25]. Another theory is that
exercise stimulates osteoblastic bone formation for which
vitamin D endocrine system modifies to provide extra
calcium for the newly formed bone tissue [26].
993
The strengths of study include randomization and ex-
cellent follow-up with no drop-out. A comprehensive
investigation of bone mineral status and cardio-
pulmonary fitness of Indian CF patients was done for
the first time. This study not only helped in changing
the outlook of children and their parents regarding abil-
ity of these children to participate in vigorous physical
activities but also has shown a way for improving their
quality of life in a resource constrained environment.
Limitation of study was inclusion of children with
severe lung disease and malnutrition which may have
limited their ability to perform high impact exercise to
the prescribed levels. Also, the authors were unable to
provide individualized, supervised exercise protocol. The
authors followed the children once in 3 mo; a more fre-
quent follow-up may have improved the compliance with
the exercise program.
Conclusions
In this study, the experimental group did not show sig-
nificant improvement in BMD but had a significant im-
provement in terms of exercise capacity, quality of life
and changes in bone related biomedical parameters indic-
ative of improved bone acquisition in comparasion to the
control group. The findings of this study thus provide a
supportive evidence of using weight bearing exercises as
means of improving bone mineral accretion in a cost-
effective way in children and adolescents with CF.
Results of the study have stressed on implementation of
vigorous strategies to manage skeletal health of these
children from early childhood. In CF, several factors
concomitantly adversely affect bone mineral accretion.
Beneficial effects of improving any one of the above
factor on bone mass may be masked by other factors.
Therefore, a holistic approach, including nutritional sup-
port, weight bearing activity, sex steroid replacement etc.
may be helpful in improving bone accretion of these
patients. Further interventional studies are required to
determine the type, frequency and intensity of exercises
which may be most beneficial for skeletal health of these
patients.
Acknowledgements The authors would like to offer our humble thanks
to all the children and their parents for having faith in them, for partici-
pating in the study and for making it on all the scheduled visits, in-spite of
all odds.
Authors’ Contribution SG: Developed the protocol, collected the data
and wrote the manuscript; AM, RL, MK, KKD, RK, AT: Helped in
carrying out the study, review of data and manuscript writing; SKK:
Protocol development, monitoring of study and helped in manuscript
writing. SKK will act as guarantor for this paper.
994
Compliance with Ethical Standards
Ethical Approval All procedures performed in the study were in accor-
dance with the ethical standards of the institutional and/or national re-
search committee and with the 1964 Helsinki declaration and its later
amendments or comparable ethical standards.
Informed Consent Informed consent was obtained from parents or the
legal guardians of all individual participants included in the study.
Conflict of Interest None.
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