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Biochemical Markers of Bone Metabolism in Infants and Children Under Intravenous Corticosteroid Therapy

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Abstract

The short-term effects of corticosteroids (CS) administered intravenously (IV) on biochemical parameters of bone metabolism were followed in infants and children. Forty-nine patients from 2 months to 10 years of age, admitted to Pediatrics Department for bronchiolitis, viral-associated wheezing and croup, were treated with IV hydrocortisone or methylprednisolone (10 or 2 mg/Kg/day, respectively) for 3 days. Blood and fasting urine were collected on admission (day 1), 2 days later (day 3) and 12 days after the end of therapy (day 15). Fifty-one children of similar age and gender without respiratory problems or bone diseases were used as controls. On day 3, suppression of the bone formation markers osteocalcin (OC) (P < 0.001) and total alkaline phosphatase (ALP) (P < 0.05) was observed, but not of the bone resorption markers of hydroxyproline, pyridinoline and calcium excretion (UHyp/UCr, UPYD/UCr and UDPD/UCr, UCa/UCr). Significant decreases were indicated in serum phosphate (Pi) and the maximum renal tubular Pi reabsorption (TmP/GFR) compared to basal (P < 0.001). No significant changes were noticed in the circulating levels of calcium (Ca), parathyroid hormone (iPTH), 25OHD, 24,25(OH)2D, 1,25(OH)2D, the insulin-like growth factor-I (IGF-I) and its binding protein-3 (IGFBP-3). Two weeks after therapy, the increase of OC to higher than basal (P < 0.01) indicated a probable activation of the osteoblasts. Serum Pi and the TmP/GFR index values that had significantly decreased by day 3 returned to pretreatment levels by day 15. When assessing the effects of the CS in relation to age, no changes were detected in the levels of OC and total ALP in the <12-month-old children, but a fall of OC was observed in the >1-year-old group (P < 0.001). In contrast to the OC, the effects on serum and renal tubular reabsorption of phosphate were similar for both groups. In conclusion, short-term IV administered CS led to significant but reversible inhibition of bone formation markers, especially detectable in the >1-year-old children, without affecting the bone resorption ones. The adverse effects on phosphate metabolism were also significant, but temporal and irrespective of age.

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References

  1. BWD Badley BM Ansell (1960) ArticleTitleFractures in Still’s disease. Ann Rheum Dis 19 135–141 Occurrence Handle1:STN:280:CC%2BC3MngtlQ%3D

    CAS  Google Scholar 

  2. TP Klassen (1997) ArticleTitleRecent advances in the treatment of bronchiolitis and laryngitis. Pediatr Clin North Am 44 249–261 Occurrence Handle1:STN:280:ByiB3M%2Fnt10%3D Occurrence Handle9057793

    CAS  PubMed  Google Scholar 

  3. InstitutionalAuthorNameAnonymous (1997) ArticleTitleThe British Guidelines on Asthma Management. Asthma in children under five years of age. Thorax 52 IssueIDsuppl 1 S9–S10

    Google Scholar 

  4. BP Lukert LG Raisz (1994) ArticleTitleGlucocorticoid-induced osteoporosis. Osteoporosis 20 629–650 Occurrence Handle1:STN:280:ByqD2sngtlQ%3D

    CAS  Google Scholar 

  5. IJM Doull NJ Freezer ST Holgate (1995) ArticleTitleGrowth of prepubertal children with mild asthma treated with inhaled beclamethasone dipropionate. Am J Respir Crit Care Med 151 1715–1719 Occurrence Handle1:STN:280:ByqB1crgtF0%3D Occurrence Handle7767512

    CAS  PubMed  Google Scholar 

  6. I Doull NJ Freezer ST Holgate (1996) ArticleTitleOsteocalcin, growth and inhaled corticosteroids: a prospective study. Arch Dis Child 74 497–501 Occurrence Handle1:STN:280:BymA3MfmvFc%3D Occurrence Handle8758124

    CAS  PubMed  Google Scholar 

  7. S Crowley P Trivedi L Risteli J Risteli PC Hindmarsh CJ Brook (1998) ArticleTitleCollagen metabolism and growth in prepubertal children with asthma treated with inhaled steroids. J Pediatr 132 409–413 Occurrence Handle1:CAS:528:DyaK1cXislSlsL4%3D Occurrence Handle9544892

    CAS  PubMed  Google Scholar 

  8. RS Bockman SA Weinerman (1990) ArticleTitleSteroid-induced osteoporosis. Orthop Clin N Am 21 (1) 97–107

    Google Scholar 

  9. V LoCascio E Bonucci B Imbimbo P Ballanti S Adami S Milani D Tartarotti C Della Rocca (1990) ArticleTitleBone loss in response to long-term glucocorticoid therapy. Bone Miner 8 39–51 Occurrence Handle1:STN:280:By%2BC28jjtlE%3D Occurrence Handle2306553

    CAS  PubMed  Google Scholar 

  10. AD Adinoff JR Hollister (1983) ArticleTitleSteroid-induced fractures and bone loss in patients with asthma. N Engl J Med 309 265–268 Occurrence Handle1:STN:280:BiyB2cvovVI%3D Occurrence Handle6866051

    CAS  PubMed  Google Scholar 

  11. DJ Baylink (1983) ArticleTitleGlucocorticoid-induced osteoporosis. N Engl J Med 309 306–308 Occurrence Handle1:CAS:528:DyaL3sXltFKitb8%3D Occurrence Handle6866054

    CAS  PubMed  Google Scholar 

  12. DM Reid NSJ Kennedy M Smith P Tothill G Nuki (1982) ArticleTitleTotal body calcium in rheumatoid arthritis: effects of disease activity and corticosteroid treatment. Br Med J 285 330–332 Occurrence Handle1:CAS:528:DyaL38XmtVyksrg%3D

    CAS  Google Scholar 

  13. SA Abrams (1998) ArticleTitleInsights into bone metabolism from calcium kinetic studies in children. Adv Exp Med Biol 445 283–291 Occurrence Handle1:CAS:528:DyaK1cXmvFKnu7w%3D Occurrence Handle9781396

    CAS  PubMed  Google Scholar 

  14. R Sorva M Turpeinen K Juntunen-Backman SL Karonen A Sorva (1992) ArticleTitleEffects of inhaled budesonide on serum markers of bone metabolism in children with asthma. J Allergy Clin Immunol 90 808–815 Occurrence Handle1:STN:280:ByyD2Mngt1A%3D Occurrence Handle1430706

    CAS  PubMed  Google Scholar 

  15. P König L Hillman C Cervantes C Levine C Maloney B Douglass L Johnson S Allen (1993) ArticleTitleBone metabolism in children with asthma treated with inhaled beclomethasone dipropionate. J Pediatr 122 219–226 Occurrence Handle8429434

    PubMed  Google Scholar 

  16. OD Wolthers PJ Rilis S Pedersen (1993) ArticleTitleBone turnover in asthmatic children treated with oral prednisolone or inhaled budesonide. Pediatr Pulmonol 16 341–346 Occurrence Handle1:STN:280:ByuC1c7jtVw%3D Occurrence Handle8134155

    CAS  PubMed  Google Scholar 

  17. OD Wolthers A Juul M Nansen J Müller S Pedersen (1994) ArticleTitleThe insulin-like growth factor axis and collagen turnover during prednisolone treatment. Arch Dis Child 71 409–413 Occurrence Handle1:STN:280:ByqC38nms1w%3D Occurrence Handle7529981

    CAS  PubMed  Google Scholar 

  18. CK Niu SC Huang CB Huang (1998) ArticleTitleEffect of short-course budesonide on the bone turnover of asthmatic children. Pediatr Pulmonol 26 290–294 Occurrence Handle10.1002/(SICI)1099-0496(199810)26:4<290::AID-PPUL10>3.3.CO;2-H Occurrence Handle1:STN:280:DyaK1M%2FislajtA%3D%3D Occurrence Handle9811081

    Article  CAS  PubMed  Google Scholar 

  19. G Hedlin J Svedmyr AC Ryden (1999) ArticleTitleSystemic effects of a short course of betamethasone compared with high-dose inhaled budesonide in early childhood asthma. Acta Paediatr 88 48–51 Occurrence Handle10.1080/08035259950170592 Occurrence Handle1:STN:280:DyaK1M7ovV2mtA%3D%3D Occurrence Handle10090547

    Article  CAS  PubMed  Google Scholar 

  20. OD Wolthers A Juul M Hansen J Müller S Pedersen (1995) ArticleTitleThe insulin-like growth factor axis and collagen turnover in asthmatic children treated with inhaled budesonide. Acta Paediatr 84 393–397 Occurrence Handle1:STN:280:ByqA3MrmslM%3D Occurrence Handle7540898

    CAS  PubMed  Google Scholar 

  21. JS Hyams RE Moore AM Leichtner DE Carey BD Goldberg (1988) ArticleTitleRelationship of type I procollagen to corticosteroid therapy in children with inflammatory bowel disease. J Pediatr 112 893–898 Occurrence Handle1:STN:280:BieB3s%2FhtFc%3D Occurrence Handle3373393

    CAS  PubMed  Google Scholar 

  22. D Prockop D Udenfriend (1960) ArticleTitleA specified method for the analysis of hydroxyproline in tissues and urine. Ann Biochem 1 228–234 Occurrence Handle1:CAS:528:DyaF3MXns1GhtA%3D%3D

    CAS  Google Scholar 

  23. A Challa A Bevington CM Angier AJ Asbury CJ Preston RGG Russell (1985) ArticleTitleA technique for the measurement of orthophosphate in human erythrocytes and some studies of its determinants. Clin Sci 69 429–434 Occurrence Handle1:CAS:528:DyaL2MXltlOquro%3D Occurrence Handle4042544

    CAS  PubMed  Google Scholar 

  24. A Moulas A Challa D Lapatsanis (1996) ArticleTitleMethod of quantitative determination of the main metabolites of vitamin D [25OHD, 24,25(OH)2D and 1,25(OH)2D] in the same sample of serum or plasma. Ostoun (Athens) 7 17–24

    Google Scholar 

  25. RM Shepard RL Horst AJ Hamstra HF De Luca (1979) ArticleTitleDetermination of vitamin D and its metabolites in plasma from normal and anephric man. J Biochem 182 55–69 Occurrence Handle1:CAS:528:DyaL3cXhvVWkuw%3D%3D

    CAS  Google Scholar 

  26. TM Reinhardt RL Horst JW Orf BW Hollis (1984) ArticleTitleMicroassay for 1,25-dihydroxyvitamin D not requiring high performance liquid chromatography: application to clinical studies. J Clin Endocrinol Metab 58 91–98 Occurrence Handle1:CAS:528:DyaL2cXmsVCitQ%3D%3D Occurrence Handle6605973

    CAS  PubMed  Google Scholar 

  27. E Ekenstam G Stalenheim R Hällgren (1988) ArticleTitleThe acute effect of high dose corticosteroid treatment on serum osteocalcin. Metabolism 37 141–144 Occurrence Handle1:CAS:528:DyaL1cXjt1ahsw%3D%3D Occurrence Handle3257542

    CAS  PubMed  Google Scholar 

  28. F Cosman J Nieves J Herbert V Shen R Linsday (1994) ArticleTitleHigh-dose glucocorticoids in multiple sclerosis patients exert direct effects on the kidney and skeleton. J Bone Miner Res 9 1097–1105 Occurrence Handle1:STN:280:ByqD38fmt1M%3D Occurrence Handle7942157

    CAS  PubMed  Google Scholar 

  29. P Chertok J Leroux F Blotman C Colette (1991) ArticleTitleHigh-dose intravenous methylprednisolone treatment and bone Gla-protein. Arthritis Rheum 34 1487 Occurrence Handle1:STN:280:By2D283itlA%3D

    CAS  Google Scholar 

  30. WF Lems JWG Jacobs HR Van Den Brink HJM Van Rijn JWJ Bijlsma (1993) ArticleTitleTransient decrease in osteocalcin and markers of type I collagen turnover during high-dose corticosteroid pulse therapy in rheumatoid arthritis. Br J Rheumatol 32 787–789 Occurrence Handle1:STN:280:ByyA2sbnvVI%3D Occurrence Handle8369888

    CAS  PubMed  Google Scholar 

  31. JWJ Bijlsma SA Duursma R Bosch JA Reymakers O Huber-Bruning (1988) ArticleTitleAcute changes in calcium and bone metabolism during methylprednisolone pulse therapy in rheumatoid arthritis. Br Med J 27 215–219 Occurrence Handle1:STN:280:BieB2c7itFY%3D

    CAS  Google Scholar 

  32. S Posen HS Grunstein (1982) ArticleTitleTurnover rate of skeletal alkaline phosphatase in humans. Clin Chem 28 153–154 Occurrence Handle1:CAS:528:DyaL38XotlamtQ%3D%3D Occurrence Handle7055900

    CAS  PubMed  Google Scholar 

  33. K Kruse U Kracht (1986) ArticleTitleEvaluation of serum osteocalcins, an index of altered bone metabolism. Eur J Pediatr 145 27–33 Occurrence Handle1:STN:280:BimB2svotl0%3D Occurrence Handle3015628

    CAS  PubMed  Google Scholar 

  34. J Griffiths A Vernocchi E Simoni (1995) ArticleTitleTransient hyperphosphatasemia of infancy and childhood. A study of serum alkaline phosphatase by electrofocusing techniques. Arch Pathol Lab Med 119 784–789 Occurrence Handle1:CAS:528:DyaK2MXoslarsLY%3D Occurrence Handle7668935

    CAS  PubMed  Google Scholar 

  35. G Lockitch MR Pudek AC Halstead (1984) ArticleTitleIsolated elevation of alkaline phosphatase. J Pediatr 105 773–775 Occurrence Handle1:STN:280:BiqD2MjktVQ%3D Occurrence Handle6502308

    CAS  PubMed  Google Scholar 

  36. R Oggero M Montert M Spinello A Iavarone J Buffa (1988) ArticleTitleTransient hyperphosphatasemia of infancy. Acta Paediatr Scand 77 257–259 Occurrence Handle1:STN:280:BieC1c%2FjtVI%3D Occurrence Handle3354337

    CAS  PubMed  Google Scholar 

  37. C Gennari B Imbimbo M Montagnani M Bernini P Nardi LV Avioli (1984) ArticleTitleEffects of prednisone and deflazacort on mineral metabolism and parathyroid activity in humans. Calcif Tissue Int 36 245–252 Occurrence Handle1:STN:280:BiuB1c3gs1Q%3D Occurrence Handle6432287

    CAS  PubMed  Google Scholar 

  38. D Morrison NJ Ali PA Routledge S Capewell (1992) ArticleTitleBone turnover during short course prednisolone treatment in patients with chronic obstructive airways disease. Thorax 47 418–420 Occurrence Handle1:STN:280:By2A2MfksFY%3D Occurrence Handle1496499

    CAS  PubMed  Google Scholar 

  39. RH Christenson (1997) ArticleTitleBiochemical markers of bone metabolism: an overview. Clin Biochem 30 573–593 Occurrence Handle10.1016/S0009-9120(97)00113-6 Occurrence Handle1:CAS:528:DyaK1cXmsFajtw%3D%3D Occurrence Handle9455610

    Article  CAS  PubMed  Google Scholar 

  40. PD Delmas (1992) ArticleTitleClinical use of biochemical markers of bone remodeling in osteoporosis. Bone 13 S17–S21

    Google Scholar 

  41. K Yosemura A Hishida M Kimura T Watanaber H Kumagai (1999) ArticleTitlePrednisolone induces increase in serum calcium concentration: possible involvement of the kidney, the bone and intestine. Calcif Tissue Int 65 567–571

    Google Scholar 

  42. BP Lukert JS Adams (1976) ArticleTitleCalcium and phosphorus homeostasis in man: effect of corticosteroids. Arch Intern Med 136 1249–1453 Occurrence Handle10.1001/archinte.136.11.1249 Occurrence Handle1:CAS:528:DyaE2sXls1Q%3D Occurrence Handle185973

    Article  CAS  PubMed  Google Scholar 

  43. JW Findling MD Adams J Lemann RW Gay CJ Thomas JB Tyrrell (1982) ArticleTitleVitamin D metabolites and parathyroid hormone in Cushing’s syndrome: relationship to calcium and phosphorus homeostasis. J Endocrinol Metab 54 1039–1044 Occurrence Handle1:STN:280:Bi2C2c3ptlY%3D

    CAS  Google Scholar 

  44. H Skjodt JA Gallagher JN Beresford M Couch JW Poser RGG Russsell (1985) ArticleTitleVitamin D metabolites regulate osteocalcin synthesis and proliferation of human bone cells in vitro. J Endocrinol 105 391–396 Occurrence Handle1:CAS:528:DyaL2MXktlKmsLo%3D Occurrence Handle3873510

    CAS  PubMed  Google Scholar 

  45. RG Klein SB Arnaud JC Gallagher HF DeLuca BL Riggs (1977) ArticleTitleIntestinal calcium absorption in exogenous hypercortisonism. Role of 25-hydroxyvitamin D and corticosteroid dose. J Clin Invest 60 253–259 Occurrence Handle1:CAS:528:DyaE2sXkvFKltL4%3D Occurrence Handle874087

    CAS  PubMed  Google Scholar 

  46. A Caniggia F Lore R Nuti A Vattimo (1984) ArticleTitleGlucocorticoids and intestinal absorption of calcium and phosphate. Adv Exp Med Biol 171 91–100 Occurrence Handle1:CAS:528:DyaL2cXktVSktb0%3D Occurrence Handle6372407

    CAS  PubMed  Google Scholar 

  47. PM Crofton SF Ahmed JC Wade MB Ranke WHB Wallace CJH Kelnar (1997) ArticleTitleGrowth markers during third intensification in children with acute lymphoblastic leukaemia. Horm Res 48 IssueIDsuppl 2 62 Occurrence Handle9251922

    PubMed  Google Scholar 

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Acknowledgements

The authors thank Aphrodite Papaghianni for her technical assistance and Hoffman La Roche for kindly providing the unlabeled vitamin D metabolites.

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Siomou, E., Challa, A., Tzoufi, M. et al. Biochemical Markers of Bone Metabolism in Infants and Children Under Intravenous Corticosteroid Therapy . Calcif Tissue Int 73, 319–325 (2003). https://doi.org/10.1007/s00223-002-2099-x

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