The relationship between alkaline phosphatase and bone alkaline phosphatase activity and the growth hormone/insulin-like growth factor-1 axis and vitamin D status in children with growth hormone deficiency

• Authors: Ewelina Witkowska-Sędek , Anna Stelmaszczyk-Emmel , Anna Majcher , Urszula Demkow , Beata Pyrżak
• Languages of publication: EN

Abstracts

EN

The relationships between bone turnover, the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and vitamin D are complex, but still not fully explained. The GH/IGF-1 axis and vitamin D can mutually modulate each other's metabolism and influence the activation of cell proliferation, maturation, and mineralization as well as bone resorption. The aim of this study was to evaluate the reciprocal associations between bone formation markers [alkaline phosphatase (ALP), bone alkaline phosphatase (BALP)], the GH/IGF-1 axis and 25-hydroxyvitamin D [25(OH)D] in children with growth hormone deficiency at baseline and during recombinant human growth hormone (rhGH) therapy. ALP, BALP, 25(OH)D and IGF-1 levels were evaluated in 53 patients included in this prospective three-year study. ALP, BALP and IGF-1 increased during rhGH therapy. Baseline ALP activity correlated positively with baseline height velocity (HV). ALP and BALP activity at 12 months correlated positively with HV in the first year of therapy. We found positive correlations between ALP and IGF-1 at baseline and during the first year of therapy, between BALP activity at 12 months and rhGH dose in the first year of therapy, and between doses of cholecalciferol in the first year of rhGH therapy and early changes in BALP activity during rhGH therapy. Our results indicate that vitamin D supplementation enhances the effect of rhGH on bone formation process, which could improve the effects of rhGH therapy. ALP and BALP activity are useful in the early prediction of the effects of rhGH therapy, but their utility as long-term predictors seemed insufficient.

Keywords

EN

bone formation markers; vitamin D; recombinant human growth hormone treatment; children

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2018
• Volume: 65
• Issue: 2
• Pages: 269-275

Dates

published

2018

received

2017-12-04

revised

2018-01-29

accepted

2018-02-20

(unknown)

2018-04-13

Contributors

author

Ewelina Witkowska-Sędek

• Department of Paediatrics and Endocrinology, Medical University of Warsaw, Warszawa, Poland

author

Anna Stelmaszczyk-Emmel

• Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warszawa, Poland

author

Anna Majcher

• Department of Paediatrics and Endocrinology, Medical University of Warsaw, Warszawa, Poland

author

Urszula Demkow

• Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warszawa, Poland

author

Beata Pyrżak

• Department of Paediatrics and Endocrinology, Medical University of Warsaw, Warszawa, Poland

References

• Ameri P, Giusti A, Boschetti M, Bovio M, Teti C, Leoncini G, Ferone D, Murialdo G, Minuto F (2013) Vitamin D increases circulating IGF1 in adults: potential implication for the treatment of GH deficiency. Eur J Endocrinol 169: 767-772.doi: 10.1530/EJE-13-0510.
• Andersson B, Swolin-Eide D, Kriström B, Gelander L, Magnusson P, Albertsson-Wikland K (2015) Seasonal variations in vitamin D in relation to growth in short prepubertal children before and during first year growth hormone treatment. J Endocrinol Invest 38: 1309-1317.doi: 10.1007/s40618-015-0360-1.
• Anderson PH, Lam NN, Turner AG, Davey RA, Kogawa M, Atkins GJ, Morris HA (2013) The pleiotropic effects of vitamin D in bone. J Steroid Biochem Mol Biol 136: 190-194.doi: 10.1016/j.jsbmb.2012.08.008.
• Barnes MS, Robson PJ, Bonham MP, Strain JJ, Wallace JM (2006) Effect of vitamin D supplementation on vitamin D status and bone turnover markers in young adults. Eur J Clin Nutr 60: 727-733.doi: 10.1038/sj.ejcn.1602374.
• Bogazzi F, Rossi G, Lombardi M, Tomisti L, Sardella C, Manetti L, Curzio O, Marcocci C, Grasso L, Gasperi M, Martino E (2011) Vitamin D status may contribute to serum insulin-like growth factor I concentrations in healthy subjects. J Endocrinol Invest 34: e200-e203.doi: 10.3275/7228.
• Braegger C, Campoy C, Colomb V, Decsi T, Domellof M, Fewtrell M, Hojsak I, Mihatsch W, Molgaard C, Shamir R, Turck D, van Goudoever J, ESPGHAN Committee on Nutrition (2013) Vitamin D in the healthy European paediatric population. J Pediatr Gastroenterol Nutr 56: 692-701.doi: 10.1097/MPG.0b013e31828f3c05.
• Ciresi A, Cicciò F, Giordano C (2014) High prevalence of hypovitaminosis D in Sicilian children affected by growth hormone deficiency and its improvement after 12 months of replacement treatment. J Endocrinol Invest 37: 631-638.doi: 10.1007/s40618-014-0084-7.
• Ciresi A, Giordano C (2017) Vitamin D across growth hormone (GH) disorders: from GH deficiency to GH excess. Growth Horm IGF Res 33: 35-42.doi: 10.1016/j.ghir.2017.02.002.
• Devesa J, Almengló C, Devesa P (2016) Multiple effects of growth hormone in the body: is it really the hormone for growth? Clin Med Insights Endocrinol Diabetes 9: 47-71.doi: 10.4137/CMED.S38201.
• Eapen E, Grey V, Don-Wauchope A, Atkinson SA (2008) Bone health in childhood: usefulness of biochemical biomarkers. EJIFCC 19: 123-136.
• EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2016) Dietary reference values for vitamin D. EFSA J 14: 4547.doi: 10.2903/j.efsa.2016.4547
• Garnero P, Delmas PD (1993) Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease. J Clin Endocrinol Metab 77: 1046-1053.doi: 10.1210/jcem.77.4.8104954.
• Gómez JM, Maravall FJ, Gómez N, Navarro MA, Casamitjana R, Soler J (2004) Relationship between 25-(OH) D3, the IGF-I system, leptin, anthrophometric and body composition variables in a healthy, randomly, selected population. Horm Metab Res 36: 48-53.doi: 10.1055/s-2004-814103.
• Greulich WW, Pyle SI (1959) Radiographic atlas of skeletal development of the hand and wrist. 2nd edn. Stanford, CA: Stanford University Press.
• He J, Rosen CJ, Adams DJ, Kream BE (2006) Postnatal growth and bone mass in mice with IGF-I haploinsufficiency. Bone 38: 826-835.doi: 10.1016/j.bone.2005.11.021.
• Juul A, Pedersen SA, Sørensen S, Winkler K, Jørgensen JO, Christiansen JS, Skakkebaek NE (1994) Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset. Eur J Endocrinol 131: 41-49.
• Korpal-Szczyrska M, Balcerska A (2008) The effect of growth hormone treatment on serum bone alkaline phosphatase in growth hormone deficient children. Pediatr Endocrinol Diabetes Metab 14: 211-214.
• Koszowska AU, Nowak J, Dittfeld A, Brończyk-Puzoń A, Kulpok A, Zubelewicz-Szkodzińska B (2014) Obesity, adipose tissue function and the role of vitamin D. Cent Eur J Immunol 39: 260-264.doi: 10.5114/ceji.2014.43732.
• Kuchuk NO, Pluijm SM, van Schoor NM, Looman CW, Smit JH, Lips P (2009) Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum parathyroid hormone and markers of bone turnover in older persons. J Clin Endocrinol Metab 94: 1244-1250.doi: 10.1210/jc.2008-1832.
• Larijani B, Hossein-Nezhad A, Feizabad E, Maghbooli Z, Adibi H, Ramezani M, Taheri E (2016) Vitamin D deficiency, bone turnover markers and causative factors among adolescents: a cross-sectional study. J Diabetes Metab Disord 15: 46.doi: 10.1186/s40200-016-0266-2.
• Lee JY, So TY, Thackray J (2013) A review on vitamin D deficiency treatment in pediatric patients. J Pediatr Pharmacol Ther 18: 277-291.doi: 10.5863/1551-6776-18.4.277.
• Leeming DJ, Koizumi M, Byrjalsen I, Li B, Qvist P, Tankó LB (2006) The relative use of eight collagenous and noncollagenous markers for diagnosis of skeletal metastases in breast, prostate, or lung cancer patients. Cancer Epidemiol Biomarkers Prev 15: 32-38.doi: 10.1158/1055-9965.EPI-05-0492.
• Léger J, Mercat I, Alberti C, Chevenne D, Armoogum P, Tichet J, Czernichow P (2007) The relationship between the GH/IGF-I axis and serum markers of bone turnover metabolism in healthy children. Eur J Endocrinol 157: 685-692.doi: 10.1530/EJE-07-0402.
• Locatelli V, Bianchi VE (2014) Effect of GH/IGF-1 on bone metabolism and osteoporosis. Int J Endocrinol 2014: 235060.doi: 10.1155/2014/235060.
• Magnusson P, Larsson L, Magnusson M, Davie MW, Sharp CA (1999) Isoforms of bone alkaline phosphatase: characterisation and origin in human trabecular and cortical bone. J Bone Miner Res 14: 1926-1933.doi: 10.1359/jbmr.1999.14.11.1926.
• Millán JL, Whyte MP (2016) Alkaline phosphatase and hypophosphatasia. Calcif Tissue Int 98: 398-416.doi: 10.1007/s00223-015-0079-1.
• Niu T, Rosen CJ (2005) The insulin-like growth factor-I gene and osteoporosis: a critical appraisal. Gene 361: 38-56.doi: 10.1016/j.gene.2005.07.016.
• Ono T, Kanzaki S, Seino Y, Baylink DJ, Mohan S (1996) Growth hormone (GH) treatment of GH-deficient children increases serum levels of insulin-like growth factors (IGFs), IGF-binding protein-3 and -5, and bone alkaline phosphatase isoenzyme. J Clin Endocrinol Metab 81: 2111-2116.doi: 10.1210/jcem.81.6.8964836.
• Orimo H (2010) The mechanism of mineralization and the role of alkaline phosphatase in health and disease. J Nippon Med Sch 77: 4-12.doi: 10.1272/jnms.77.4.
• Paradowska A, Łącki JK (2007) Genetic aspects of osteoporosis. Centr Eur J Immunol 32: 172-180
• Pruessner HT (1998) Detecting celiac disease in your patients. Am Fam Physician 57: 1023-1034.
• Rao SR, Snaith AE, Marino D, Cheng X, Lwin ST, Orriss IR, Hamdy FC, Edwards CM (2017) Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer. Br J Cancer 116: 227-236.doi: 10.1038/bjc.2016.402.
• Rosen CJ (2004) Insulin-like growth factor I and bone mineral density: experience from animal models and human observational studies. Best Pract Res Clin Endocrinol Metab 18: 423-435.doi: 10.1016/j.beem.2004.02.007.
• Saraç F, Saygili F (2007) Causes of high bone alkaline phosphatase. Biotechnol Biotec EQ21: 194-197.doi: 10.1080/13102818.2007.10817444
• Schwetz V, Trummer C, Pandis M, Grübler MR, Verheyen N, Gaksch M, Zittermann A, März W, Aberer F, Lang A, Treiber G, Friedl C, Obermayer-Pietsch B, Pieber TR, Tomaschitz A, Pilz S (2017) Effects of vitamin D supplementation on bone turnover markers: a randomized controlled trial. Nutrients 9: E432.doi: 10.3390/nu9050432.
• Seamans KM, Hill TR, Wallace JM, Horigan G, Lucey AJ, Barnes MS, Taylor N, Bonham MP, Muldowney S, Duffy EM, Strain JJ, Kiely M, Cashman KD (2010) Cholecalciferol supplementation throughout winter does not affect markers of bone turnover in healthy young and elderly adults. J Nutr 140: 454-460.doi: 10.3945/jn.109.113480.
• Sharma U, Pal D, Prasad R (2014) Alkaline phosphatase: an overview. Indian J Clin Biochem 29: 269-278.doi: 10.1007/s12291-013-0408-y.
• Soliman AT, Al Khalaf F, Alhemaidi N, Al Ali M, Al Zyoud M, Yakoot K (2008) Linear growth in relation to the circulating concentrations of insulin-like growth factor I, parathyroid hormone, and 25-hydroxy vitamin D in children with nutritional rickets before and after treatment: endocrine adaptation to vitamin D deficiency. Metabolism 57: 95-102.doi: 10.1016/j.metabol.2007.08.011.
• Thiering E, Brüske I, Kratzsch J, Hofbauer LC, Berdel D, von Berg A, Lehmann I, Hoffmann B, Bauer CP, Koletzko S, Heinrich J (2015) Associations between serum 25-hydroxyvitamin D and bone turnover markers in a population based sample of German children. Sci Rep 5: 18138.doi: 10.1038/srep18138.
• Tobiume H, Kanzaki S, Hida S, Ono T, Moriwake T, Yamauchi S, Tanaka H, Seino Y (1997) Serum bone alkaline phosphatase isoenzyme levels in normal children and children with growth hormone (GH) deficiency: a potential marker for bone formation and response to GH therapy. J Clin Endocrinol Metab 82: 2056-2061.doi: 10.1210/jcem.82.7.4081.
• Trummer C, Schwetz V, Pandis M, Grübler MR, Verheyen N, Gaksch M, Zittermann A, März M, Aberer F, Lang A, Friedl C, Tomaschitz A, Obermayer-Pietsch B, Pieber TR, Pilz S, Treiber G (2017) Effects of vitamin D supplementation on IGF-1 and calcitriol: a randomized-controlled trial. Nutrients 9: E623.doi: 10.3390/nu9060623.
• Turan S, Topcu B, Gökçe I, Güran T, Atay Z, Omar A, Akçay T, Bereket A (2011) Serum alkaline phosphatase levels in healthy children and evaluation of alkaline phosphatase z-scores in different types of rickets. J Clin Res Pediatr Endocrinol 3: 7-11.doi: 10.4274/jcrpe.v3i1.02.
• Wamberg L, Pedersen SB, Richelsen B, Rejnmark L (2013) The effect of high-dose vitamin D supplementation on calciotropic hormones and bone mineral density in obese subjects with low levels of circulating 25-hydroxyvitamin d: results from a randomized controlled study. Calcif Tissue Int 93: 69-77.doi: 10.1007/s00223-013-9729-3.
• Witkowska-Sędek E, Kucharska A, Pyrżak B (2014) ALP, b-ALP, PICP and ICTP in children with growth hormone deficiency during the first year of growth hormone treatment. Post N Med 10: 693-697
• Witkowska-Sędek E, Kucharska A, Rumińska M, Pyrżak B (2016) Relationship between 25(OH)D and IGF-I in children and adolescents with growth hormone deficiency. Adv Exp Med Biol 912: 43-49.doi: 10.1007/5584_2016_212.
• Witkowska-Sędek E, Stelmaszczyk-Emmel A, Kucharska A, Demkow U, Pyrżak B (2017) Association between vitamin D and carboxy-terminal cross-linked telopeptide of type I collagen in children during growth hormone replacement therapy. Adv Exp Med Biol 1047: 53-60.doi: 10.1007/5584_2017_109.

Identifiers

DOI

10.18388/abp.2017_2541