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Paediatrica Indonesiana

VOLUME 52 NUMBER 1 January 2O12


Original Article
16 Paediatr Indones, Vol. 52, No. 1, January 2012
Calcium and vitamin D supplementation in children
with frequently relapsing and steroid-dependent
nephrotic syndrome
Ayi Dilla Septarini, Taralan Tambunan, Pustika Amalia
Abstract
Background Children with frequently relapsing and steroid-
dependent nephrotic svndrome (lRNS/SDNS) are at risk
for osteoporosis due to impaired metabolism of calcium and
vitamin D.
Objective 1o determine the effect of calcium and vitamin D
supplementation on bone mineral density, serum ionized calcium
levels and serum 25-hvdroxv-vitamin D levels in children with
lRNS and SDNS.
Methods A clinical trial with a before and after design was
performed. Subjects were SDNS or lRNS pediatric patients ~ 5
vears of a,e. Subjects received oOO m, elemental calcium and 1OO
lU vitamin D supplementation for o weeks. Serum ionized calcium,
serum 25-hvdroxv-vitamin D |25(H)D], and bone mineral densitv
(BMD) were determined before and after the supplementation.
Results f the 3O subjects, 2o completed the studv. However,
onlv 2O subjects underwent BMD determination before and after
supplementation. Of the 28 subjects, 22 had hypocalcemia and 26
had low vitamin D levels. steopenia was found in 11/2O subjects and
osteoporosis was in 2/2O subjects. After o weeks of supplementation,
mean serum ionized calcium increased from low |1.15 mmol/l (SD
O.O3)] to normal |1.1o mmol/l (SD O.O1)] (P<O.OO1) levels, but
mean serum 25(H)D onlv increased from vitamin D deficiencv
cate,orv |2O n,/ml (SD 7.7)] to vitamin D insufficiencv cate,orv
|25.5 n,/ml (7.7)] (P~O.O1O). Mean z-score BMD increased from
-1.1 (SD O.9) to -O.7 (SD O.2) after supplementation (P<O.OO1).
Conclusion Calcium vitamin D supplementation effectivelv in-
creased serum ionized calcium, serum 25(H)D, and BMD in subjects
with lRNS and SDNS. [Paediatr Indones. 2012;52:16-21].
Keywords: frequent relapse nephrotic syndrome,
steroid dependent, supplementation, calcium, vitamin
D, bone mineral density, osteoporosis
lrom the Department of Child Health, lacultv of Medicine, Universitv of
Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
Reprint requests to: Avi Dilla Septarini, Department of Child Health,
lacultv of Medicine, Universitv of lndonesia, Cipto Man,unkusumo
Hospital, Jl. Dipone,oro 71, Jakarta, 1el. 62o5711362319.
P
atients with nephrotic syndrome (NS), a
glomerular disease, usually respond to steroid
treatment, but may experience relapses. Of
those who achieve remission, 6O-7O' will
experience relapses and 5O' of those with relapses
will become frequent relapsers.
1,2
Steroid dependency
will occur in 5O' of frequent relapsers.
2
Treatment
of lRNS and SDNS is challen,in, because children
with these conditions must receive hi,h-dose and
long-term steroid therapy. Steroids are known to cause
osteoporosis and affect bone mineral densitv (BMD)
in NS patients.
3-6
Durin, relapse, the condition is
thou,ht to worsen, due to frequent loss of vitamin D
metabolites and calcium in the urine.
7,o
The disease
itself and the treatment medication affects skeletal
mineralization. Diminished bone mineralization
has been reported in children with NS tested by
densitometry methods.
5,9
Calcium and vitamin D plav an important role
in maintaining bone health.
1O,11
Studies on the role
of calcium and vitamin D supplementation in NS
Ayi Dilla Septarini et al: Calcium and vitamin D supplementation in nephrotic svndrome
Paediatr Indones, Vol. 52, No. 1, January 2012 17
patients are limited. However, lon,itudinal studies
bv Oulati et al.
12
showed that calcium and vitamin
D supplementation mav improve the BMD in NS
patients. Randomized, controlled clinical trials by
Bak et al.
13
concluded that calcium and vitamin D
supplementation can reduce the incidence of low
BMD in NS patients.
Althou,h the deteriorative effect of steroid
treatment on childrens bones has been well known
for years, no recommendation has been suggested
for the prevention or treatment of diminished
BMD in children with NS. 1here have been few
lndonesian studies to date evaluatin, the role of
calcium and vitamin D supplementation in lNRS
and SDNS patients. 1his studv was conducted
to determine the role of calcium and vitamin D
supplementation on BMD, serum ionized calcium
levels, and serum 25(H)D levels in children with
lRNS and SDNS.
Methods
A clinical trial with a before and after design was
performed in the Nephrology Outpatient Care Unit,
Department of Child Health, Cipto Man,unkusumo
Hospital, Jakarta from November 2O1O until April
2O11. Subjects were SDNS or lRNS children with
normal renal function ~ 5 vears of a,e. lxclusion
criteria were osteo,enesis imperfecta, juvenile
osteoporosis, historv of calcium and vitamin D
supplementation for the preceding 6 months, and
previous bisphosphonate (anti-resorptive a,ent)
therapy.
We consecutivelv recruited 3O subjects who
fulfilled the study criteria, but only 28 completed
the study. These subjects consisted of 16 FRNS
patients and 12 SDNS patients. nlv 2O subjects
underwent BMD determination before and after
supplementation. NS was defined bv edema, massive
proteinuria (> 1O m,/m
2
/hr), hypoalbuminemia
(<2.5 g/dl), and hyperlipidemia. Frequent relapse
was defined as ~ 2 relapses within the first 6 months
after presentation or ~ 1 relapses within anv 12
month period. Steroid dependency was defined
as two consecutive relapses while under steroid
treatment or relapse at least 14 days after steroid
withdrawal.
History of illness was obtained from each
subject, including disease onset, duration of illness,
number of total relapses, steroid therapy duration, and
cumulative steroid dose. Urea and creatinine levels
were also tested. Subjects received oOO m, elemental
calcium and 1OO lU vitamin D supplementation
daily for 8 weeks. Serum ionized calcium, serum
25(H)D, and BMD were determined before and
after supplementation. Serum ionized calcium was
measured by Ciba-Corning Model 288 blood gas
analyzer

(normal ran,e 1.17-1.29 mmol/l) and


serum 25(H)D
3
bv llecsvs Vitamin D3 (25-H)
2O1O cobas e111

, using electrochemiluminescence
immunoassay (ECLIA).
BMD of the lumbar spine (l
1
-L
4
) was measured
bv dual ener,v x-rav absorptiometrv (DlXA) lunar
Ol Medical Svstems

, and the patients data were


expressed as z-scores (number of SDs from the mean
values of healthv Asian children matched for sex and
chronolo,ical a,e). A lumbar spine BMD z-score of
between -1.O and -2.O was classified as osteopenia,
while a z-score of less than -2.O was classified as
osteoporosis.
Data was analvzed usin, SPSS for windows
version 17.O pro,ram, with P<O.O5 considered as
si,nificant. Studv approval was obtained from the
lthics Committee, lacultv of Medicinem, Universitv
of Indonesia.
Results
We recruited 28 subjects for our study, consisting of
16 lRNS and 12 SDNS patients. 1here were 21 bovs
and 7 ,irls (3:1) a,ed 5-11.7 vears. Oender, a,e, a,e at
onset of illness, body weight, body height, nutritional
status based on body mass index (BMI), and blood
pressure between the two groups were comparable.
Subjects with SDNS had ,reater cumulative steroid
dose compared to that of FRNS subjects. All subjects
had normal renal function (Table 1).
verall, 22/2o subjects were hvpocalcemic
(serum ionized calcium level <1.17 mmol/l). 1wentv-
six subjects had low serum vitamin D levels, with
1O subjects classified to be in a state of insufficiencv
(serum 25(H)D at 2O - 3O n,/ml) and the other 16
subjects to be in a state of deficiency (serum 25(OH)
D at < 2O n,/ml). 1here were no differences in
Ayi Dilla Septarini et al: Calcium and vitamin D supplementation in nephrotic svndrome
18 Paediatr Indones, Vol. 52, No. 1, January 2012
calcium status or vitamin D status between the two
groups (Table 2).
f the 2O subjects who underwent bone
densitometrv, 11/2O had osteopenia (z-score BMD
between -1.O and -2.O) and 2/2O had osteoporosis
(z-score BMD < -2.O) (Table 3). Table 4 shows the
mean serum ionized calcium levels, mean serum
25(H)D levels and BMD before and after o weeks
of supplementation. Mean serum ionized calcium
increased from low |1.15 mmol/l (SD O.O3)] to
normal |1.1o mmol/l (SD O.O1)] (P <O.OO1).
However, mean serum 25(H)D onlv increased
from the cate,orv of vitamin D deficiencv |2O n,/
ml (SD 7.7)] to insufficiencv |25.5 n,/ml (SD 7.7)]
(P~O.O1), possiblv indicatin, a suboptimal duration
of supplementation. Mean z-score BMD increased
from the cate,orv of osteopenia |-1.1 (SD O.9)]
to normal |-O.7 (SD O.2)] after supplementation
(P<O.OO1).
Discussion
Disorders of mineral metabolism mav occur in NS
patients with normal kidney function, including
hvpocalcemia and hvpovitaminosis D.
14
Hypocalcemia
in NS patients may be due to loss of calcium in the
urine, decreased calcium absorption in the intestine,
and steroidal side effects.
8,15
As a consequence, BMD
may decrease, leading to the risk of fracture.
14
Table 1. Subjects characteristics
Characteristic
FRNS
(n = 16)
SDNS
(n = 12)
Gender
Male, n
Female, n
Median age, years (range)
Median onset, years (range)
Median duration of illness months (range)
Mean total no. of relapses (SD)
Median steroid therapy duration, months (range)
Mean cumulative steroid dose, mg (SD)
Mean body weight, kg (SD)
Mean body height, cm ( SD)
Median BMI, kg/m2 (range)
Nutritional status (based on BMI)
Undernourished, n
Well-nourished, n
Overweight, n
Obese, n
Blood pressure
Mean systolic, mmHg (SD)
Mean diastolic, mmHg (SD)
Median urea, mg/dL (range)
Mean creatinine, mg/dL (SD)
11
5
8.3 (5.1-14.5)
3 (1.8-8.6)
64 (30-131)
12.2 (6)
34.5 (18-89)
14,943 (7,137)
30 (8.8)
125 (13.6)
19.8 (13.8-23.5)
0
9
1
6
104 (11)
72 (10)
17 (12-34)
0.43 (0.12)
10
2
6.8 (5-13.7)
2.6 (1-7.8)
35.5 (11-138)
11 (4.5)
25 (9-62)
20,780 (27,937)
23.8 (10.4)
115 (15.3)
17.1 (13.1-21.5)
1
8
2
1
107 (12)
72 (7)
16.5 (9-26)
0.37 (0.1)
SD: standard deviation
Table 2. Calcium and vitamin D status before supplemen-
tation
Criteria
FRNS
(n = 16)
SDNS
(n = 12)
P
Calcium status
Hypocalcemia
Normal
Vitamin D status
Normal
nsufciency
Deciency
13
3
2
5
9
9
3
0
5
7
0.159
)
0.719
<
)
Chi-square test
<
Kolmogorov-Smirnov test
Table 3. Bone mineral density in FRNS and SDNS patients
before supplementation
Criteria
FRNS
(n = 10)
SDNS
(n = 10)
P
Bone mineral density
Normal
Osteopenia
Osteoporosis
2
7
1
2
7
1
0.975
<
<
Kolmogorov-Smirnov test
Ayi Dilla Septarini et al: Calcium and vitamin D supplementation in nephrotic svndrome
Paediatr Indones, Vol. 52, No. 1, January 2012 19
Clinical manifestations of hvpocalcemia varv
from asvmptomatic to convulsions, dependin, on the
duration, severitv, and rapiditv of the hvpocalcemia.
Dia,nosis should not depend on the ionized calcium
level at one random examination.
16
Signs and symptoms
of hypocalcemia usually occur if the ionized calcium
level is < 1.1 mmol/l and rapid intravenous correction
is indicated if the level is < O.o mmol/l.
17
In our study, 22/28 subjects were hypocalcemic
(serum ionized calcium < 1.17 mmol/l), but no
subjects had < 1.1 mmol/L serum ionized calcium.
Furthermore, all subjects with hypocalcemia were
asymptomatic. Similar to our results, Nurmalia et al.
18
reported the proportion of hypocalcemia in FRNS
and SDNS subjects to be 16/22. We observed that
the pre-supplementation mean serum ionized calcium
was 1.15 mmol/l (SD O.O3), similar to the results of
Nurmalia et al.
18
|1.11 n,/ml (SD O.O1)].
Serum 25(H)Dtends to decrease in NS patients
due to the loss of vitamin D-bindin, protein in urine.
Vitamin D plavs an important role for maintenance
of calcium and phosphorus metabolism, involved
in controlling interactions between the intestine,
bone, and kidnev. 1he active form of vitamin D
(1,25(OH)
2
D) has several functions: stimulatin, the
absorption of calcium and phosphorus in the intestine,
calcium mobilization from bone, and stimulating
calcium reabsorption at the distal renal tubules
(parathormone-dependent).
19
Without vitamin D,
onlv 1O to 15' of dietarv calcium is absorbed.
2O
We found that 26/2o subjects had low levels
of vitamin D, with 1O subjects in a vitamin D
insufficiency state and 16 subjects in a deficiency state.
Nurmalia et al.
18
reported the proportion of vitamin
D insufficiencv to be 1O/22 and vitamin D deficiencv
to be 9/22. ur subjects had mean serum 25(H)D
level of 2O n,/ml (SD 7.7), while Nurmalia et al.
18
reported a similar mean serum 25(H)D of 21.32 n,/
ml (SD 6.65).
Two subjects had osteoporosis but none experien-
ced fractures. Children with NS, especially those
who are frequent relapsers or steroid-dependent, are
exposed to the risk of reduced BMD, and thus have
a greater risk of fracture or inadequate peak bone
mass attainment.
16
These conditions may occur due
to biochemical and metabolic disturbances caused
by loss of protein and minerals in urine during the
nephrotic stage.
7,o
ln addition to calcium and vitamin D levels,
side effects of steroid therapy are another important
factor affecting bone health. Steroids are the mainstay
of therapy for NS patients. It is uncertain when the
most rapid bone loss occurs, but it is thought that
the highest decrease occurs in the first 6-12 months
of steroid therapv. Several studies showed that the
extent of the decrease of bone mass correlated
with the dose and duration of therapy. The greater
dose and the longer duration of steroid therapy, the
greater the bone loss. Therefore, patients with NS,
particularlv lRNS and SDNS, have a hi,her risk of
Table 4. Serum ionized calcium, serum 25(OH)D and BMD before and after supplementation in FRNS
and SDNS groups
Parameter by group
Before
supplementation
After
supplementation
P
FRNS (n=16)
Mean ionized calcium, mmol/L (SD)
Mean 25(OH)D, ng/mL (SD)
SDNS (n=12)
Mean ionized calcium, mmol/L (SD)
Mean 25(OH)D, ng/mL (SD)
FRNS and SDNS (n=28)
Mean ionized calcium, mmol/L (SD)
Mean 25(OH)D, ng/mL (SD)
FRNS (n=10)
Mean z-score BMD L1-4 (SD)
SDNS (n=10)
Mean z-score BMD L1-4 (SD)
FRNS and SDNS (n=20)
Mean z-score BMD L1-4 (SD)
1.15 (0.02)
20.8 (8.5)
1.15 (0.03)
18.9 (6.7)
1.15 (0.03)
20 (7.7)
-1.2 (1)
-1 (0.7)
-1.1 (0.9)
1.19 (0.04)
27.4 (6.8)
1.18 (0.04)
22.8 (8.4)
1.18 (0.04)
25.5 (7.7)
-0.7 (1.3)
-0.8 (0.9)
-0.7 (0.2)
0.042*
0.021*
<0.001^
0.217*
<0.001*
0.010*
0.325*
0.018^
0.003^
*
Paired t-test; ^Wilcoxon test
Ayi Dilla Septarini et al: Calcium and vitamin D supplementation in nephrotic svndrome
20 Paediatr Indones, Vol. 52, No. 1, January 2012
impaired BMD.
15,21
Risk factors for reduced BMD are
cumulative steroid dose >5OO m,, steroid exposure
>12 months, prednisone dose >7.5 m,/dav, and ~1
courses of high-dose prednisone.
22
We found osteopenia in 11/2O subjects and
osteoporosis in 2/2O subjects. Nurmalia et al.
18
reported
osteopenia in 4/22 subjects and osteoporosis in 5/22
subjects. ln a studv on 1OO subjects with lRNS,
SDNS, infrequent NS (llNS), and steroid-resistant NS
(SRNS), Oulati et al.
12
found that 61' had osteopenia
and 22' had osteoporosis. ln contrast leonard et
al.
22
, Mishra et al.
23
, and Shouman et al.,
24
found that
children with NS had BMDs not si,nificantlv different
from healthv children. ur subjects had mean BMD
z-score of -1.1 (SD O.9), which was included in the
osteopenia category, similar to results of Nurmalia et
al.
18
Compliance in our study was good in both groups
(o2.2 ' and oO.1').
1wo previous studies examined the role of calcium
and vitamin D supplementation in NS patients. ln a
studv bv Oulati et al.,
12
oo subjects with lRNS, SDNS,
llNS, and SRNS received fixed doses (5OO m, calcium
carbonate equivalent to 2OO m, elemental calcium
and 2OO lU vitamin D) per dav for 6-12 months.
1hev reported that the mean spinal BMD values were
si,nificantlv better on follow-up (O.6O7O.O13 ,/
cm2) as compared to baseline values (O.561O.O1O ,/
cm2) (P<O.OOO1).
12
Bak et al.
13
examined the role of
calcium and vitamin D supplementation in llNS and
new NS patients. 1hev were ,iven 1OOO m, elemental
calcium and 1OO lU vitamin D for o weeks. BMD was
significantly decreased in both the treatment and non-
treatment ,roups, but the percenta,e of BMD decrease
was found to be significantly lower in the treatment
,roup than in the non-treatment ,roup (1.62.1' vs.
13.O1.O', respectivelv, P<O.OO1).
Side effects due to the use of calcium and vitamin
D supplementation have been rarelv reported. 1he
maximum safe dose of vitamin D is 2OOO lU/dav,
25
while that of elemental calcium is 25OO m,/dav.
26
Vitamin D intoxication is defined as the occurrence
of hvpercalcemia (>2.65 mmol/l) and increased
level of 25(H)D (>15O n,/ml).
27
Hypercalcemia
causes svmptoms such as anorexia, nausea, vomitin,,
polyuria, weakness, constipation, abdominal pain,
headache, arrhythmia, and bradycardia.
28
No side
effects were reported by our subjects after 8 weeks of
calcium and vitamin D supplementation.
A limitation of this study was the design
used (before and after treatment) because we
had no control subjects who did not receive
supplementation. Another limitation was the lack
of analvsis of dietarv intake of calcium and vitamin
D. Compliance rate was also obtained bv historv-
taking only and thus may result in inaccurate
information.
ln conclusion, we observed that supplementation
with oOO m, elemental calcium and 1OO lU vitamin
D dailv for o weeks, effectivelv increased serum
ionized calcium levels, serum 25(H)D levels, and
BMD in NS patients. Since 25(H)D levels were not
adequately increased, further randomized, controlled
trials with longer treatment duration and more
subjects are needed. No side effects were associated
with the supplementation.
References
1. Alatas H, 1ambunan 1, 1rihono PP, Pardede S. Konsensus
tata laksana sindrom nefrotik primer pada anak. Jakarta: Unit
Kerja Koordinasi Nefrolo,i lkatan Dokter Anak lndonesia,
2OO5. p. 1-1o.
2. Vo,t BA, Avner lD. Nephrotic svndrome. ln: Behrman
RE, Kliegman RM, Jenson HB, editors. Nelsons textbook of
pediatrics. 17th ed. Philadelphia: Saunders, 2OO1. p. 1753-7.
3. Kano K, Hoshi M, Nishikura K, Yamada Y, Arisaka .
Skeletal effects of short-term prednisolone therapy in
children with steroid-responsive nephrotic svndrome. Clin
lxp Nephrol. 2OO1,5:1O-3.
4. Fujita T, Satomura A, Hidaka M, Ohsawa I, Endo M, Ohi
H. Acute alteration in bone mineral density and biochemical
markers for bone metabolism in nephrotic patients receivin,
high-dose glucocorticoid and one-cycle etidronate therapy.
Calcif 1issue lnt. 2OOO,66:195-9.
5. Basiratnia M, lallahzadeh MH, Derakhshan A, Hosseini-Al-
Hashemi O. Bone mineral densitv in children with relapsin,
nephrotic svndrome. lran J Med Sci. 2OO6,31:o2-6.
6. l,aard K, Storm 1, Van Wovern N. Olucorticoid induced
osteoporosis in lumbar spine, forearm and mandible of
nephrotic patients: a double blind study on high dose long-
term effects of prednisolone versus deflazocort. Calcif 1issue
lnt. 1992,5O:16O-7.
7. Mittal SK, Dash SC, 1iwari SC, A,arwal SK, Saxena S,
Fishbane S. Bone histology in patients with nephrotic syndrome
and normal renal function. Kidnev lnt. 1999,55:1912-9.
Ayi Dilla Septarini et al: Calcium and vitamin D supplementation in nephrotic svndrome
Paediatr Indones, Vol. 52, No. 1, January 2012 21
o. lreundlich M, Bour,oi,nie J, zilleruelo O, Abitbol
C, Canteburv JM, Strauss J. Calcium and vitamin D
metabolism in children with nephrotic svndrome. J Pediatr.
19o6,1Oo:3o3-7.
9. Oulati S, Oodbole M, Sin,h U, Oulati K, Srivastava A. Are
children with idiopathic nephrotic syndrome at risk for
metabolic bone disease' Am J Kidnev Dis. 2OO3,11:1163-9.
1O. American Academv of Pediatrics. Calcium requirements
of infants, children, and adolescents. Pediatrics. 1999,1O1:
1152-7.
11. Wa,ner Cl, Oreer lR. Prevention of rickets and vitamin D
deficiencv in infants, children, and adolescents. Pediatrics.
2OOo,122:1112-52.
12. Oulati S, Sharma RK, Oulati K, Sin,h U, Srivastava A.
Longitudinal follow-up of bone mineral density in children
with nephrotic svndrome and the role of calcium and vitamin
D supplements. Nephrol Dial 1ransplant. 2OO5,2O:159o-
16O3.
13. Bak M, Serdaro,lu l, Ouclu R. Prophvlactic calcium and
vitamin D treatments in steroid-treated children with
nephrotic svndrome. Pediatr Nephrol. 2OO6,21:35O-1.
11. lreundlich M, Jofe M, Ooodman W, Saluskv lB. Bone
histology in steroid-treated children with non-azotemic
nephrotic svndrome. Pediatr Nephrol. 2OO1,19:1OO-7.
15. Canalis E. Mechanisms of glucocorticoid action in bone:
implications to glucocorticoid-induced osteoporosis.
lndocrinolo,v. 1996,o1:3111-7.
16. Shaw N. A practical approach to hypocalcaemia in
children. ln: Al,rove J, Shaw NJ, editors. Calcium and
bone disorders in children and adolescents. Basel: Karger;
2OO9. p. 73-92.
17. Sku,or M. Cleveland Clinic Center for Continuin,
lducation. Hvpocalcemia. |Cited 2O11 Mav 1]. Available
from: http://www.clevelandclinicmeded.com/medicalpubs/
diseasemanagement/endocrinology/hypocalcemia/#cesec6
1o. Nurmalia lD, 1ambunan 1, Amir l. Comparison of bone
mineral density in steroid dependent, frequent relapse, and
infrequent relaps nephrotic svndrome children. Paediatr
lndones. 2O1O,5O:193-o.
19. levine MA. Normal mineral homeostasis. ln: Hochber, z,
editor. Vitamin D and rickets. 2
nd
ed. Switzerland: Karger;
2OO3. pp. 11-33.
2O. Holick Ml. Vitamin D deficiencv. N ln,l J Med. 2OO7,
357:266-o1.
21. Hartman C, Hochber, z, Shamir R. steoporosis in
pediatrics. lMAJ. 2OO3,5:5O9-15.
22. leonard MB. Olucocorticoid-induced osteoporosis in
children: impact of the underlvin, disease. Pediatrics.
2OO7,119:166-71.
23. Mishra P, Meena SK, Sin,h SK, Prasad R, Mishra RN. Bone
mineral densitv in children with steroid-sensitive nephrotic
svndrome. lndian J Pediatr. 2OO9,76:1237-9.
21. Shouman MO, Na,wa Abdallah l, ll Me,uid A, Salama
lll, ll Ohorourv l, Abou lsmail lA, et al. Bone mineral
densitv markers in children with steroid sensitive idiopathic
nephrotic svndrome. lJAR. 2O1O,2:15O-6.
25. Vieth R. Vitamin D supplementation, 25-hvdroxvvitamin D
concentrations, and safetv. Am J Clin Nutr. 1999,69:o12-56.
26. Straub DA. Calcium supplementation in clinical practice:
a review of forms, doses, and indications. Nutr Clin Pract.
2OO7,22:2o6-96.
27. Vieth R. Vitamin D toxicitv, policv, and science. J Bone Miner
Res. 2OO7,22:61-o.
2o. Vieth R, Chan PR, Maclarlane OD. lfficacv and safetv of
vitamin D3 intake exceedin, the lowest observed adverse
effect level. Am J Clin Nutr. 2OO1,73:2oo-91.

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