ORYGINAL ARTICLES / Prace oryginalne

Pediatric Endocrinology, Diabetes and Metabolism 2011, 17, 1, 35-40 ISSN 2081-237X

The clinical eficacy of vitamin D in children with primary low bone mass
Skuteczno kliniczna witaminy D u dzieci z nisk mas kostn
Jolanta Karalus, Danuta Chlebna-Sok
Department of Paediatric Propedeutics and Bone Metabolic Diseases, Medical University of Lodz, Poland

Klinika Propedeutyki Pediatrii i Chorb Metabolicznych Koci I Katedry Pediatrii Uniwersytetu Medycznego w odzi

Abstract Introduction: Vitamin D suplementation in prevention and treatment of osteoporosis is a widely accepted standard, but the latest studies show the necessity of increasing the intake of this vitamin to keep its concetration on higher levels above 30 ng/ml. The best index describing the body vitamin D supply is hepatic metabolite of vitamin D (25OHD) concentration in the serum. There are few data on efficacy of this vitamin intake in children with low bone mass. Aim of the study was to find out if vitamin D supplementation causes a significant increase in the hepatic metabolite concentrations and how it affects the clinical course of the disease and the results of densitometric tests in children with primary low bone mass. Material and methods: Seventy six children aged 6 to 18.5 years (35 girls and 41 boys) with primary osteoporosis or low bone mass diagnosed based on clinical and densitometric signs were included in the study. In all children, the concentrations of 25OD and PTH were measured and densitometric evaluations were taken twice, before and after 1 year of vitamin D intake. According to literature data, 30 ng/ml was adopted as the lower limit of normal 25OHD levels in children with osteoporosis and low bone mass. Results: Vitamin D supplementation for 12 months of osteoporosis and low bone mass therapy in children caused a statistically significant increase in concentrations of the hepatic metabolite of vitamin D and a significant reduction in serum PTH levels. The changes in 25OHD levels depended on the vitamin D dose used (658 IU/day), and only this amount allowed to achieve an improvement in the densitometric parameters, in particular the increase in bone mineral density (BMD) in the lumbar spine. Conclusions: 1. Based on the performed study in children with idiopathic reduction of bone mineral density the normalisation of the calcitropic hormones and improvement in the densitometric parameters assessing bone mineral density is necessary. 2. A detailed statistical analysis has shown that the increase in both vitamin D metabolites and bone mineral density is caused by vitamin D supplementation at a dose of 685 IU/day; this is an important practical aspect of this study. KEY WORDS: vitamin D, low bone mass, children Streszczenie Wprowadzenie: Stosowanie witaminy D w profilaktyce i leczeniu osteoporozy jest powszechnie zaakceptowanym standardem, jednak najnowsze dane wskazuj na konieczno dawkowania tej witaminy tak, aby utrzyma jej stenie w granicach wartoci wyszych ni dotychczas zalecano, Address for correspondence: tj powyej 30 ng/ml. Najlepszym wskanikiem sucym do oceny zaopatrzenia organizmu w t Jolanta Karalus MD, PhD witamin jest stenie metabolitu wtrobowego witaminy D (25OHD). Niewiele jest jednak danych Klinika Propedeutyki Pediatrii na temat skutecznoci stosowania tej witaminy u dzieci z samoistn nisk mas kostn. i Chorb Metabolicznych Koci, Celem pracy byo uzyskanie odpowiedzi na pytanie, czy suplementacja witamin D u dzieci z samoI Katedra Pediatrii Uniwersytetu istn nisk mas kostn powoduje istotny wzrost stenia metabolitu wtrobowego witaminy D Medycznego i w jaki sposb wpywa to na przebieg kliniczny choroby oraz na wyniki bada densytometrycznych. ul. Sporna 36/50 Materia i metody: Do badania wczono 76 dzieci w wieku 6-18,5 roku (35 dziewczt i 41 chop91-738 d cw) z samoistn nisk mas kostn (w tym z osteoporoz samoistn) rozpoznan na podstawie Poland phone: (+48 42) 617 77 18 objaww klinicznych i bada densytometrycznych. U wszystkich dzieci dwukrotnie, przed suplefax: (+48 42) 617 77 15 mentacj i po roku suplementacji witamin D oceniane byo stenie 25OHD oraz PTH, a take e-mail: wykonane zostao badanie DXA. Za wartoci prawidowe dla witaminy D dla dzieci z nisk mas propedeutyka@usk4.umed.lodz.pl kostn przyjto warto 25OHD w surowicy powyej 30 ng/ml.

35

Karalus J., Chlebna-Sok D. The clinical eficacy of vitamin D in children with primary low bone mass

Pediatric Endocrinology, Diabetes and Metabolism 2011, 17, 1

Wyniki: Poda witaminy D u dzieci z osteoporoz i nisk mas kostn spowodowaa istotny statystycznie wzrost stenia metabolitu wtrobowego witaminy D oraz istotne obnienie si stenia parathormonu. Zmiany stenia 25OHD byy zalene od dawki stosowanej witaminy (685 j.m./ dob). W wyniku leczenia uzyskano wzrost wskanikw densytometrycznych, a zwaszcza wzrost gstoci mineralnej koci w odcinku ldwiowym krgosupa (BMD Spine). Wnioski: 1. W oparciu o przeprowadzone badania u dzieci z idiopatyczn redukcj gstoci mineralnej koci konieczna jest normalizacja kalcytropowych hormonw i poprawa parametrw w badaniu densytometrycznym. 2. Szczegowa analiza statystyczna wykazaa, e wzrost metabolitw witaminy D i gstoci mineralnej koci jest spowodowany suplementacj witaminy D w dawce 685 IU/dziennie SOWA KLUCZOWE: witamina D, niska masa kostna, dzieci

Introduction
From the biochemical perspective, vitamin D is a hormone, so it is difficult to precisely determine its optimum dose, protecting from the negative effect of its deficit on the body. One of the best methods is to evaluate the serum concentrations of the hepatic metabolite, 25-hydrocholecalciferol, as the most precise functional index of the bodys supply of vitamin D Recent reports indicate that the previously used concentration 10 ng/ml (25 nmol/l) does not provide protection against vitamin D deficit and hyperparathyroidism, adversely affecting bone metabolism [1]. The considerations regarding the optimum recommended intake of vitamin D should be based on achieving the concentrations of 25OHD that protect against an increase in PTH levels, cause optimum calcium absorption and allow to maintain the best bone mineral density, reduce bone mass depletion and decrease the risk of bone and vertebral fractures [2, 3]. Currently, the concentrations above 20 ng/ml in children and above 30 ng/ml in adults are considered protecting, which is in contrast with the laboratory standards proposed by the manufacturers of reagents. It is emphasised that these values are recommended as optimum for healthy children, whereas children with chronic diseases of the skeletal system or other systems and organs need higher serum 25OHD concentrations to compensate for the impaired metabolic transformations of vitamin D. In the situation of impaired bone metabolism, 25OHD concentrations above 30 ng/ml are considered the most efficient [4, 5].

Aim of the study

Therefore, studies have been started with an objective to answer the question whether vitamin D supplementation causes a significant (adequate to the dose used) increase in the hepatic metabolite concentrations in the group of children with an idiopathic reduction of bone mineral density occurring in osteoporosis and low bone mass and how it affects the clinical picture of the disease.

Material and methods

Seventy six children aged 6 to 18.5 years (35 girls and 41 boys) with osteoporosis or low bone mass diagnosed based on clinical and densitometric signs (after exclusion of secondary causes) were included in the study. According to literature data, 30 ng/ml was adopted as the lower limit of normal 25OHD levels in children with osteoporosis and low bone mass, and all children involved in the study were divided into two subgroups: subgroup 1 children with 25OHD concentrations below 30 ng/ml (n=35) and subgroup 2 children with 25OHD values equal to or above 30 ng/ml (n=41). All children underwent a comprehensive medical examination with precise anthropometric measurements, assessment of the possible bone deformations and incorrect body posture. The clinical characteristics of the study group are shown in table I. The diagnosis of osteoporosis (clinical symptoms, Z-score spine and/or total body below -2,00) and low bone mass (clinical symptoms, Z-score spine and/or total body from -1,00 to -2,00) was determined based on comprehen-

Table I: Clinical characteristics of study patients results given as mean and standard deviation Tabela I: Charakterystyka kliniczna badanych pacjentw- wyniki podano jako rednia i odchylenie standardowe

Study variable Badana zmienna

Children with osteoprosis / Dzieci z osteoporoz n= 26 girls / dziewczynki boys / chopcy 14.45 [7.5-17.5] 46.7212.37 1.620.15 17.301.93

Children with low bone mass / Dzieci z nisk mas kostn n=50 girls / dziewczynki 12.30 [6-17.5] 44.513.38 1.420.16 18.04.65 boys / chopcy 12.33 [6-18] 44.414.7 1.540.17 18.12.88

Age [years] / Wiek [lata] Body mass / Masa ciaa [kg] Height / Wzrost [cm]

14.56 [10-18.5] 45.4610.36 1.570.11 18.192.59

36

BMI [kg/m2]

Karalus J., Chlebna-Sok D. Skuteczno kliniczna witaminy D u dzieci z nisk mas kostn

sive tests performed during hospitalisation at the Department of Paediatric Propedeutics and Bone Metabolic Diseases, Medical University of Lodz, including the assessment of clinical signs, radiological signs, densitometric and biochemical indices. In the entire study group twice before treatment commencement and after 12 months serum concentrations of the hepatic metabolite, 25-hydroxycholecalciferol (25OHD) and parathormone (PTH) were determined. 25-hydroxycholecalciferol concentrations were determined using a RIA assay with a Lencomm kit and PTH concentrations were determined using a chemiluminescence assay with an Immulite kit. All children underwent bone densitometry using the Dual Energy X-ray Absoprtiometry (DXA) method with a Lunar (USA) DPX device in a paediatric program for children with body weight up to 30 kg and in a standard program for adults for children with body weight above 30 kg. The parameters used in this study were: bone mineral density (BMD) of the whole body and of the lumbar spine, expressed in g/cm2. The BMD values were also analysed as Z-score index, calculated as the number of standard deviations from the mean for age and sex. The other analysed parameters included: total bone mineral content (BMC) in grams. To perform statistical analysis of the collected data, various statistical methods were used, and the minimum significance level of p=0.05 was adopted for all statistical tests used. Statistical analysis was performed using the SPSS PC and Statistica software.

revealed in table II. All results were within reference limits both in children with osteoporosis and low bone mass.

Changes in vitamin D metabolite concentrations after treatment

Vitamin D supplementation caused an increase (statistically significant) in concentrations of the hepatic metabolite (p<0.0001) with simultaneous reduction in serum parathormone concentrations in children with osteoporosis and low bone mass (tab. III). Individual assessment of 25OHD values showed after treatment, 76.3% study population (58 children) showed an increased concentration of 25OHD whereas in 23.7% (18 patients) there was no improvement. The mean daily dose of cholecalciferol used in the entire study group was 581 IU of vitamin D, corresponding to mean increase in 25OHD concentrations of 8.8 ng/ml. In children with osteoporosis, it was 807 IU of vitamin D with an increase in 25OHD concentrations of 15 ng/ml, and in those with low bone mass 463 IU/day and an increase of 5.6 ng/ml. The increase in serum 25OHD concentrations was accompanied by a reduction in PTH concentrations which turned out to be statistically insignificant for the entire study group, but in children from subgroup 1 a statistically significant reduction in PTH levels was seen (PTH (pg/ml) from mean 39.0 to 32.9; p=0.021), contrary to the group of children with normal body supply of vitamin D subgroup 2 (PTH (pg/ml) from mean 29.06 to 29.06.

Results
Vitamin D metabolite and PTH concentrations before treatment
Mean values of the hepatic metabolite of vitamin D and PTH in children with osteoprosis and low bone mass were

Evaluation of clinical symptoms after treatment

In the course of treatment in 26 children (53.06%) the skeletal system pains reduction was observed, including 10 childen with a reduction of vertebrae pains and 16 in upper and/or lower limbs.The improvement in pain reduction was statistically significant p<0.0001 (2 test). During the treatment no vertebrae fractures were noticed, while in 2 children during the therapy, the fractures of upper limb were revealed due to the low energy fall (tab. IV).

Table II: Mean 25OHD and parathormone concentrations in study patients Tabela II: rednie wartoci ste 25OHD i PTH u badanych pacjentw

Study variable Badana zmienna

Children with low bone mass / Dzieci z nisk mas kostn mean / rednia SD 16.9 13.5

Children with osteoprosis Dzieci z oseoporoz mean / rednia 31.4 40.0 SD 18.6 19.4

Changes in skeletal densitometric parameters after the treatment

After 12 months of treatment, follow-up DXA densitometry scan was performed in all children. The use of vitamin D caused an increase in mean values of the selected densitometry parameters indicating absolute bone mineral density. After vitamin D and calcium supplementation, a statistically significant increase in the Z-score Spine index values and bone mineral density was seen, both in the lumbar

25OHD [ng/ml] PTH [pg/ml]

35.5 30.3

Table III: Mean concentration values of vitamin D metabolites and parathormone, mean value of difference between concentrations of 25OHD and PTH, and difference significance level in all children participating in the study before and after treatment Tabela III: rednie stenia metabolite witaminy D I parathormonu i istotno statystyczna rnic u dzieci uczestniczcych w badaniu przed i po leczeniu

Study variable Badana zmienna 25OHD PTH

Before treatment Przed leczeniem 34.08 33.64

After treatment Po leczeniu 42.94 30.83

Mean difference rednia rnica 8.862 -3.138

SD

p (Student t-test)

p (Wilcoxon test)

19.191 17.130

<0.001 0.117

<0.001 0.119

37

Karalus J., Chlebna-Sok D. The clinical eficacy of vitamin D in children with primary low bone mass

Pediatric Endocrinology, Diabetes and Metabolism 2011, 17, 1

spine and in the entire skeleton; the total amount of the fatty tissue and bone mineral content in the lumbar spine (L2-L4 BMC) also increased. The obtained results of tests are shown in table V.

Assessment of the dose-response effect during treatment with vitamin D products

An attempt was made at determining whether any specific vitamin D doses are responsible for the improvement in vitamin D metabolites. The ROC curve analysis was used in the search for the optimum therapeutic dose of vitamin D.

Table IV: Clinical symptoms before and after treatment with vitamin D Tabela IV: Objawy kliniczne przed i po leczeniu witamin D

Study variable / Badana zmienna Bone pains / Ble kostne Vertebre / ebra Lower and upper limbs / Dolne i grne koczyny Bone fractures / Zamania koci Vetebrae fractures / Zamania eber

Before treatment / Przed leczeniem

After treatment / Po leczeniu

19/76 30/76 49/76 3/76

9/76 14/76 2/76 not observed / nie zaobserwowano

Mean value of the difference between the absolute values of densitometric parameters (pre- and post-treatment assessment), and statistical significance of these differences Tabela V: rednie wartoci rni midzy wskanikami densytometrycznymi przed i po leczeniu oraz istotno statystyczna tych rnic

Table V:

Mean difference rednia rnica

SD

95% confidence interval for the difference of means 95% przedzia ufnoci dla rnic rednich

p (Student t- test)

p (Wilcoxon test)

Bone density parameters / Parametry gstoci koci DXA Z-score spine / Z-score krgosup Z-score total body / Z-score cae ciao BMD spine / kregosup BMD total body / cae ciao Fat body mass / tkana tuszczowa L 2-L 4 BMC 0.174 0.101 0.066 0.045 624.3 5.208 0.595 0.491 0.094 0.045 2352.8 5.277 0.036 -0.022 0.045 0.034 -108.8 3.931 0.312 0.224 0.088 0.056 1357.5 6.485 0.014 0.105 <0.001 <0.001 0.093 <0.001 0.002 0.236 <0.001 <0.001 0.011 <0.001

ROC curve / Krzywa ROC A 1.0 0.8

Fig. 1. A. The ROC curve for the vitamin D dose responsible for 25OHD concentrations increase after treatment. B. The ROC curve for the vitamin D dose causing 25OHD concentrations increase to the value above the upper quartile (58 ng/ml) Ryc. 1. A. Krzywa ROC dla dawki witaminy D odpowiedzialnej za wzrost steenia 25OHD w surowicy po leczeniu. B. Krzywa ROC dla dawki witaminy D powodujcej wzrost stenia 25OHD powyej grnego kwartyla (58 ng/ml)

ROC curve / Krzywa ROC B 1.0 0.8 0.6 Sensitivity / Czuo 0.4 0.2 0.0
1,0

0,8

Sensitivity / Czuo

0.4 0.2 0.0 0.0 0.2 0.4 0.6 0.8 1.0 1-specificity / swoisto

Czuo

0.6

0,6

0,4

0,2

0,0

0.0 0,0

0.2 0.4 0.6 0.8 0,2 0,4 0,6 0,8 1 Swoisto 1-specificity / swoisto

1,0

1.0

referenceline / linia odniesienia vitamin D dose / vitamina D, dawka

38

Karalus J., Chlebna-Sok D. Skuteczno kliniczna witaminy D u dzieci z nisk mas kostn

Curves were constructed for the following variables: 1. 25OHD concentrations increase after treatment (fig. 1A); 2. 25OHD concentrations increase above the upper quartile after treatment (fig. 1B). The area under curve for vitamin D was compared to the area under the reference line which was the reference point showing the lack of the dose-response effects. Due to the fact that the area under curve for the vitamin D dose is not larger than the reference area (the area under the reference line), the vitamin D dose which causes a significant dose-response effect cannot be determined on this basis (fig. 1A). However, the area under the ROC curve for the vitamin D dose causing an increase in 25OHD concentration above the upper quartile has shown a significant difference (p=0.016) between the areas under this curve and the area under the reference curve (fig. 1B). Based on the coordinates of this curve, it can be determined that the vitamin D dose causing a significant increase in 25OHD is 685 IU/day. To recapitulate, it has been shown that only a significant increase in serum 25OHD concentrations (>58 ng/ml the upper quartile of the post-treatment 25OHD change) depends on the vitamin D dose used. In the group of the study subjects, the optimum dose of this vitamin was 685 IU; above this level, a further (>58 ng/ml) significant increase in 25OHD levels after the treatment is unlikely.

Discussion
The changes in vitamin D metabolism play an important role in the pathogenesis of osteoprosis, so treatment with this vitamin is widely accepted in the therapy of bone metabolism disturbances in adults, children and adolescents [6-8]. While the literature review regarding this subject, particularly regarding the developmental age, did not show wheather it is an effective procedure and what is a safe and effective dose of this vitamin. In the presented study the attempt to answer this questions was made. The use of cholecalciferol in the treatment of osteoporosis and low bone mass in children is therefore an effective and safe method, not only to compensate the deficits but also to saturate the body with vitamin D and because of its pleiotropic role/effect.The results of this study are consistent with the literature data showing that vitamin D administration via the oral route causes an increase in serum 25OHD concentrations [9]. In our studies, 12-month vitamin D supplementation in children caused a significant increase in the serum hepatic metabolite concentrations (p <0.001). This increase was also accompanied by a reduction in PTH levels, the trends in the two latter changes were best seen in children with osteoporosis. The results of the study presented in this article partially overlap with the reports of Al-Houhala M. et al. and Guillemant et al., who found that vitamin D supplementation in healthy children caused an increase in serum 25OHD concentrations compared to placebo [10, 11]. The study of Viljakainen et al. evaluating the effect of 1-year supplementation of vitamin D on bone mass in adolescent girls deserves special attention; this study not only showed an

increase in 25OHD concentrations compared to placebo (with unchanged PTH levels) but also an improvement in bone densitometry parameters in the study subjects [9]. The conclusions from the authors own studies also correspond with the interesting findings of the group of ElHajj Fuleihan et al., who studied adolescent girls; these authors have seen increases in 25OHD concentrations but only in girls who received high doses of vitamin D, whereas no such changes occurred in the group of girls receiving 200 IU of vitamin D daily or in the placebo group [12]. The effect of vitamin D and calcium supplementation on bone mineralisation in children with osteoporosis and low bone mass turned out to be of great value both in patients with reduced baseline concentrations of this vitamin (25OHD), and in children with 25OHD levels above 3 ng/ml. The improvement in bone mineral density indices was seen in the parameters assessing the lumbar spine and those for the total body, and these changes were statistically significant. As a consequence of the therapy, bone mineral density has increased: BMD and vertebral BMC both absolute values and the standardised Z-score Spine index, whereas the Z-score Total body index has not reached the significance level. The lack of a significant increase in the Z-score Total body index probably results from too short follow-up because lesions in the vertebrae are seen earlier; this can probably be explained by a higher metabolic activity of the trabecular bone, and the Z-score Total body index assesses the entire skeleton, so achieving a significant improvement requires longer treatment duration compared to the Z-score Spine index. As a confirmation of our results, the study by DawsonHudges et al. also revealed that after 3 years of vitamin D and calcium suplementation the densitometric indices of bone mineral density increased in all examined localisations: femoral neck, lumbar spine and in total body projection. It is notable that this effect for BMD Total body revealed after one year of treatment but it lasted in the 2nd and 3rd year of the study, which, according to the study authors, may show the longterm influence of vitamin D and calcium on bone mineralization [1]. Various doses of vitamin D and calcium have been used in the therapy of children with osteoporosis and low bone mass with consideration for the patients condition, including the underlying disease (higher doses in children with osteoporosis), the childs age (the soluble products or those in the form of drops intended for younger children); therefore, the dose range used in the entire population was wide, from 250 IU to 1500 IU daily. Based on estimation from the ROC curve, an attempt was made at determining which vitamin D dose was effective and necessary to cause an increase in serum 25OHD concentrations. However, it was not possible to determine the effective dose based on the ROC curve obtained with reference to each result of post-treatment increase in 25OHD concentration. On the contrary, it was possible to show a relationship with the dose used with high increase in serum vitamin D concentration (>58 ng/ml the upper quartile for post-treatment 25OHD change). In the study population, the optimum

39

Karalus J., Chlebna-Sok D. The clinical eficacy of vitamin D in children with primary low bone mass

Pediatric Endocrinology, Diabetes and Metabolism 2011, 17, 1

dose of vitamin D3 was 685 IU/day; this dose is similar to the values reported in the literature [1, 5]. For example, Dawson Hudges et al. have shown in the studies involving adults with osteoporosis that the effective dose which has a good effect on the DXA results is the supplementation of 700 IU of vitamin D daily with calcium (500 mg) [1]. Similar doses were used by Chapuy et al. who found that the use of vitamin D at a dose of 800 IU reduces the risk of iliac bone fracture by 43% and the total risk of fracture by 32% [13]. At the same time, a relationship was seen between the administered dose of vitamin D, the increase in 25OHD concentrations and the increase in the Z-score Spine index, which suggests that only a significant increase in 25OHD concentrations allows to improve the parameters of bone mineral density. This conclusion can be confirmed by the results of the studies of Viljakinen et al. who have shown that a statistically significant increase in BMC of the lumbar spine depends on the dose of vitamin D [14]. To recapitulate the obtained results of the study, it should be emphasised that vitamin D supplementation for 12 months of osteoporosis and low bone mass therapy in children caused a statistically significant increase in concentrations of the hepatic metabolite of vitamin D and a significant reduction in serum PTH levels, which should be considered a very good phenomenon. The changes in 25OHD levels depended on the vitamin D dose used (658 IU/day), and this amount allowed to achieve an improvement in the densitometric parameters. The presented results of the study may contribute to the confirmation of efficacy and to active promotion of treatment of bone metabolism disorders with vitamin D in children with bone diseases, because it has been shown that this disease not only allows to change the concentrations of vitamin D metabolites but also clear improvement in the bone mineral density indices. This issue requires further detailed studies; however, the present state of knowledge already suggests the need to thoroughly assess vitamin D metabolites in children with reduced bone mineral density and to supplement this vitamin not only in case of deficit but also to strive to achieve the concentrations of vitamin D metabolites which ensure that its effects are optimal in all sensitive tissues, and in particular in the bones.

malisation of the calcitropic hormones and improvement in the densitometric parameters assessing bone mineral density is necessary. 2. A detailed statistical analysis has shown that the increase in both vitamin D metabolites and bone mineral density is caused by vitamin D supplementation at a dose of 685 IU/day; this is an important practical aspect of this study.
The study was partly financed by the Department of Science and High Education grant nr N40706332/2713.

References
1. Dawson-Hughes B., Harris S.S., Krall E.A., Dallal G.E.: Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N. Engl. J. Med., 1997, 337, 670-676. 2. Bolanowski J., Bolanowski M.: Znaczenie wapnia i witaminy D w profilaktyce i leczeniu osteoporozy. Adv. Clin. Exp. Med., 2005, 14, 1057-1062. 3. Brannon P.M., Yetley E.A., Bailey R.L., Picciano M.F.: Summary of roundtable discussion on vitamin D research needs. Am. J. Clin. Nutr., 2008, 88, 587-592. 4. Holick MF.: Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am. J. Clin. Nutr., 2004, 79, 362-371. 5. Holick M.F.: High prevalence of vitamin D inadequacy and implications for health. Mayo Clin. Proc., 2006, 81, 353-373. 6. Bianchi M.L.: How to manage osteoporosis in children. Best Pract. Res. Clin. Rheumatol., 2005, 19, 991-1005. 7. Weaver C.M.: Vitamin D and calcium metabolism in adolescents. International Congress Series, 2007, 1297, 32-38. 8. Brumsen C., Hamdy N.A., Papapoulos S.E.: Long-term effects of bisphosphonates on the growing skeleton. Studies of young patients with severe osteoporosis. Medicine. 1997, 76, 266-283. 9. Viljakainen H.T., Natri A.M., Krkkinen M. et al.: A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a doubleblinded randomized placebo-controlled 1-year intervention. J. Bone Miner. Res., 2006, 21, 836-844. 10. Ala-Houhala M., Koskinen T., Koskinen M., Visakorpi J.K.: Double blind study on the need for vitamin D supplementation in prepubertal children. Acta Paediatr. Scand., 1988, 77, 89-93. 11. Guillemant J., Cabrol S., Allemandou A. et al.: Vitamin D-dependent seasonal variation of PTH in growing male adolescents. Bone, 1995, 17, 513-516. 12. El-Hajj Fuleihan G., Nabulsi M., Tamim H. et al.: Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial. J. Clin. Endocrinol. Metab., 2006, 91, 405-412. 13. Chapuy M.C., Chapuy P., Meunier P.J.: Calcium and vitamin D supplements: effects on calcium metabolism in elderly people. Am. J. Clin. Nutr., 1987, 46, 324-328. 14. Viljakainen H.T., Natri A.M., Krkkinen M. et al.: A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a doubleblinded randomized placebo-controlled 1-year intervention. J. Bone Miner. Res., 2006, 21, 836-844.
Received: 2011-01-21. Accepted: 2011-03-01. Conflict of interest: non declared

Conclusions
1. Based on the performed study in children with idiopathic reduction of bone mineral density the nor-

40