Pediatrics International (2001) 43, 157–160

Original Article

Bone mineral density in children with cerebral palsy

HAYDAR ALI TASDEMIR,* MUSTAFA BUYUKAVCI, FATIH AKCAY, PINAR POLAT,

ALISAN YILDIRAN AND CAHIT KARAKELLEOGLU
Department of Pediatric Neurology, Atatürk University Faculty of Medicine, Erzurum, Turkey

Abstract Background: The purpose of the present study was to evaluate the severity of and factors related to
osteopenia in children with cerebral palsy (CP).
Methods: Bone mineral density (BMD), calcium (Ca), phosphate (P), alkaline phosphatase (ALP), creatinine,
parathyroid hormone (PTH) and 25-hydroxy vitamin D3 (25OHD3) concentrations were determined in
24 children with CP (15 ambulant, nine non-ambulant), aged between 10 months and 12 years (mean (~SD)
4.1~2.9 years). These vaules were compared with data obtained from a control group.
Results: Adjusted mean BMD values were lower in the patient group than in controls (P<0.05). However,
there was no difference between BMD values of ambulant and non-ambulant patients. The Ca and P levels of
the patient group were significantly higher than those of controls (P<0.05).
Conclusions: The present study showed that BMD was decreased in all children with CP, but to a greater
extent in non-ambulant children with CP, and immobilization is the major effective factor on bone
mineralization.

Key words bone mineral density, cerebral palsy.

Cerebral palsy (CP) is a complex of symptoms covering a Methods

group of non-progressive disorders that manifest as
abnormalities of motion and posture. These symptoms result
from central nervous system injury sustained in the early
period of brain development.1–3 Cerebral palsy is not a single
disease, but a group of specific difficulties with regard to the
parts of the body involved and associated disabilities.4 The
most common manifestations in CP are epileptic seizures,
cognitive impairments, sensory deficits, feeding problems,
communication disorders and behavior problems.2 In addition,
spontaneous fractures attributed to low bone mineral density
(BMD) can be found in children with CP.5 Low BMD
probably results from a combination of factors, including
immobility, poor nutritional status and anticonvulsant drug
use.6 In the present study, we aimed to detect the degree of
and factors related to osteopenia in children with CP.
Correspondence: Dr Alisan Yildiran, Ondokuz Mayis Universitesi
Tip Fakultesi, Pediatri ABD, Samsun, Turkey.
Email: ayildiran1@superonline.com.tr
*Present address: Pediatric Neurology, Ondokuz Maygs University
Faculty of Medicine, Samsun, Turkey.
Received 14 February 2000; revised 6 September 2000;
accepted 7 September 2000.
This study was performed in 24 children (16 boys, eight
girls) aged from 10 months to 12 years (mean (~SD) age
4.1~2.9 years) with CP who were admitted to the Depart-
ment of Pediatrics in the Faculty of Medicine of Atatürk
University between December 1994 and June 1996. Nineteen
age- and sex-matched children without any disease affecting
bone turnover were considered as the control group. The
Committee of Ethics permitted the study to proceed and
informed parental consent was obtained for both groups of
children.
Fasting blood samples were obtained for measurement of
calcium (Ca), phosphate (P), alkaline phosphatase (ALP),
creatinine, parathyroid hormone (PTH) and 25-hydroxy
vitamin D3 (25OHD3) concentrations. The Ca, P, ALP and
creatinine concentrations were measured using spectro-
photometric methods (Hitachi 717 autoanalyzer; Hitachi,
Tokyo, Japan). Parathyroid hormone and 25OHD3 were
measured by chemiluminescent enzyme immunoassay and
radioimmunoassay, respectively. Random urine samples
were obtained for the determination of hypercalciuria
according to the calcium/creatinine ratio.
The BMD of the three lumbar vertebrae (L1–L3) was
determined using quantitative computed tomography (QCT;
Toshiba TCT 600XT; Toshiba Corp., Medical Systems Co.,
Tokyo, Japan). Sections of approximately 10 mm were
158 HA Tasdemir et al.

Table 1 Concentrations of 25-hydroxy vitamin D3, parathyroid hormone, calcium, phosphate, alkaline phosphatase and the urine
calcium/creatinine ratio of patients and control groups

25OHD3 PTH Calcium Phosphate ALP Urine Ca/Cr

(ng/mL) (pg/mL) (mg/dL) (mg/dL) (U/L) ratio

All CP patients (n=24) 27.2~6.2 18.1~2.7 10.0~0.2* 5.8~0.3* 102.3~7.8 0.14~0.002

Ambulant patients (n=9) 23.2~4.1 22.1~4.0 9.9~0.4 5.5~0.3 94.8~12.6 0.10~0.003
Non-ambulant patients (n=15) 25.5~3.11 15.5~3.6 10.0~0.3* 6.0~0.5* 106.8~10.2 0.17~0.003
Control subjects (n=19) 34.9~5.5 22.6~2.4 9.1~0.2 4.4~0.4 95.0~11.0 0.23~0.007

Data are the mean~SD. *P<0.05 compared with control.

25OHD3, 25-hydroxy vitamin D3; PTH, parathyroid hormone; ALP, alkaline phosphatase; Ca/Cr, calcium/creatinine; CP, cerebral palsy.

Table 2 Bone mineral density values of the patient and control Results
groups
There were 16 (67%) males (mean (±SD) age 3.8~3 years)
Adjusted mean BMD values(mg/cm3)
Patients Controls P and eight (33%) females (mean age 4.7~3 years) in the
(n) (n=19) patient group. In the control group, there were 14 (73%)
males (mean age 4.7~3.8 years) and five (27%) females
All CP patients 223 (24) 244 0.04 (mean age 3.5~2.4 years).
Ambulant 225 (9) 238 0.35 Fifteen (62%) patients were non-ambulant. Four of nine
Non-ambulant 221 (15) 248 0.01 ambulant patients were able to walk alone, while another five
Receiving
ambulant patients could only crawl. Twelve (50%) patients
anticonvulsants 222 (5) 243 0.14
Malnourished 216 (12) 240 0.06 had malnutrition (30% severe and 20% moderate).
Five patients were taking anticonvulsant drugs. Three
The mean bone mineral density (BMD) values are adjusted children had been taking phenobarbital (5 mg/kg per day)
according to the covariate age. CP, cerebral palsy. for 1 year, one child had been taking phenytoin (5 mg/kg per
day) for 2 years and another child had been taking phenytoin
and phenobarbital (both drugs at 5 mg/kg per day) for 10
months. Findings related to rickets were not determined on
obtained through the midpoint of vertebral bodies using physical examination or wrist roentgenogram. There were
the single energy technique (80 kV, 70 mA). Quantitative no statistical differences in serum Ca, P, ALP and 25OHD3
computed tomography was used because dual-energy X-ray concentrations between patients receiving anticonvulsants
absorptiometry (DXA) was unavailable in our center. and those not receiving these drugs (P>0.05).
Malnourished patients were determined as weight by age Differences in serum 25OHD3, PTH and ALP concentra-
below the 3rd percentile using percentile standards for Turkish tions between the patient and control groups were not
children.7 Patients who had 75th and 89th percentage of statistically significant (P>0.05). However, Ca and P levels
bodyweight according to weight by age were accepted as of children with CP were significantly higher than those of
mild malnutrition, 60th to 74th as moderate malnutrition and controls (P<0.05; Table 1).
cases below the 60th percentage as severe malnutrition.8 Adjusted mean BMD values were lower in the patient
Ambulant patients were those moving themselves by group than in the controls (P<0.05). The BMD values of
walking or crawling, while non-ambulants were those not patients with malnutrition and who were receiving anti-
being able to move in any way. convulsants were similar to the control group. There was no
Statistical analyses were performed by means of a Mini- significant difference between the BMD of ambulant and
tab statistical package program (http://www.minitab.com). non-ambulant patients (the adjusted means were 236 and
Covariance analyses were used to compare BMD values of 219 mg/cm3, respectively; P=0.6). There was also no
both groups and correlation analyses were used to detect the difference between BMD values of ambulant patients and
degree of correlation of BMD and age and weight para- the control group. However, the BMD values of both non-
meters of the groups. Age was accepted as a covariate ambulant and all patients as a group were significantly
because bone mineralization increases with age. different from the control group (Table 2).

Table 3 Correlations between bone mineral density and age and
weight in the patient group
No. r P
patients
Age/BMD
For all patients 24 –0.373 <0.05
For non-ambulant patients 15 –0.559 <0.05
Weight/BMD for all patients 24 –0.292 >0.05
BMD, bone mineral density.
There was a significant negative correlation between
BMD and age. This correlation was more prominent in
non-ambulant patients. The correlation between BMD and
weight was not significant (Table 3).
Discussion
Problems that may evolve in patients with CP that are
dependent on the disease itself or are secondary factors
should be well known and carefully followed up. One of
these problems is spontaneous fractures. There are many
factors to be mentioned leading to osteopenia, the main
reason for these fractures.5,6,9
In the present study, ALP, Ca and P levels of patients
with CP were within the normal range and 25OHD3, PTH
and ALP levels of patients with CP were similar to levels in
the control group. These findings suggest osteopenia was
not related to a deficiency of vitamin D. Shaw et al. and
Root et al. have also reported similar results.6,10
It is known that long-term immobilization leads to
transient mild hypercalcemia and resulting hypercalciuria.11
Although the cause of hypercalcemia is not known exactly,
it may be due to increased bone resorption.12,13 Serum Ca
and P levels of our patients were within normal limits but
were significantly higher than those of the control group
(P<0.05). However, hypercalciuria was not detected in
patients with CP. Nevertheless, a significant elevation of Ca
and P levels in the patient group may suggest relatively
increased bone resorption.
The average BMD value of all patients was lower than
that of the control group. Hayashi et al. have argued that a
lack of movement has a more prominent negative effect on
bone mineralization when compared with the use of anti-
convulsants.14 In addition, they have detected an increase of
bone mineralization with vitamin D3 therapy. Shaw et al.
selected their patients from non-ambulant children with CP
and found lower BMD values than normal.6 Our findings
also showed that decreases in BMD values in non-ambulant
CP patients was more significant.
Bone density and cerebral palsy 159
In the present study, the mean (~SD) BMD values of
ambulant patients with CP were higher than those of non-
ambulant patients, but the difference was not significant. In
the studies of Root et al. and Wilmshurst et al., ambulant
patients had significantly higher BMD values than non-
ambulant patients.10,15 Their results were similar to the
findings of the present study. There are many speculations
about this. Abnormal muscle stresses, a direct neuropathic
effect of CP and some chemical factors released (or not
released) from spastic muscles may also play a negative role
in bone mineralization.9,16 In the present study, BMD was
found to be significantly decreased in all patients with CP. In
patients with decreased bone density, immobilization seems
to be responsible for decreasing bone mineral content. Thus,
we have determined that the bone densities of patients who
are malnourished and patients who are receiving anti-
convulsant therapy were similar to those of the control
group. The fact that 25OHD3 levels (one of the main
circulating vitamin D metabolites) of patients were within
the normal range suggests that anticonvulsant therapy has no
effect on the BMD of patients. Clinical and roentgeno-
graphic findings of rickets were not determined. Never-
theless, anticonvulsant therapy over a longer period of time
may negatively impact on BMD and further studies using a
larger patient population are needed. Similar results have
been found in two other studies.6,10 Henderson et al. also
reported that ambulatory status is the best-correlated factor
with BMD and that nutritional status is the second
significant variable in children with spastic CP.17 Shaw et al.
argued that decreases in BMD may be due to insufficient
nutrition, anticonvulsant drugs and immobilization.6
Bone mineralization of children increases with age and
bodyweight.18 This is much more evident in children
participating in weight-bearing activities, such as football or
basketball.19 Lin and Henderson have reported that children
with hemiplegia have a lower bone density on the affected
side.9,17 Nishimura et al. have revealed that immobilization
leads to a decrease the bone density of healthy young
adults.20 We detected a negative correlation between BMD
and the age of patients, which was more prominent in non-
ambulant cases. We think that long-term immobilization may
lead to a decrease in bone density.
A weight-bearing physical activity program may be
useful, at least in part, in children with CP.21
In conclusion, the findings of the present study show that
BMD decreases in children with CP and that immobili-
zation or a reduction in daily activity is the major factor
that affects bone mineralization, as found in previous
studies. Furthermore, nutritional status and anticonvulsant
therapy may not be correlated with BMD and increases
demineralization with age, particularly in non-ambulant
patients. A weight-bearing physical activity may be useful
in these patients.
160 HA Tasdemir et al.
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