Short-term effects on linear growth and bone turnover in children randomized to receive prednisolone or dexamethasone.
OBJECTIVE
To compare the relative potency of prednisolone (Pred) and dexamethasone (Dex) on short-term growth and bone turnover.


METHODS
Prospective study over 16 weeks of children randomized to receive Pred (40 mg/m2) or Dex (6.5 mg/m2) for the first 5 weeks as part of the MRC-ALL97/99 induction chemotherapy for acute lymphoblastic leukaemia (ALL).


METHODS
Lower leg length velocity (LLLV) and weight, serum IGF-I, serum bone alkaline phosphatase (bALP) levels and creatinine-adjusted, urinary excretion of deoxypyridinoline cross-links (DPD).


METHODS
Nineteen children (eight boys, 11 girls) with a median age of 5.9 years (range 2.6-13) and with a diagnosis of ALL.


RESULTS
At week 2 of therapy, median LLLV in the Dex group was -1.5 mm/week (range 0.7 to -2.1) and significantly lower than the LLLV in the Pred group which was -0.1 mm/week (range 0.20 to -0.28; P < 0.05). In the Dex group, LLLV remained lower at week 8 (med LLLV, -0.3 mm/week, range 0 to -1.3) compared to LLLV in the Pred group at 0.3 mm/week (range 0.2-1.0; P < 0.05). Body weight showed an increase after week 2 and reached a peak in both groups of children at week 6. The change in weight from baseline was greater in the Dex group than the Pred group reaching a maximum change by week 5 of 17.5% (range 5-25) and 8.7% (range -3 to 18), respectively (P < 0.05). At presentation, median IGF-I level for the whole group was 83.5 micro g/l (range 31.8-293). IGF-I levels fell markedly during Dex therapy and continued to remain lower than baseline. At weeks 4, 6 and 8, median change in IGF-I from baseline was lower in the Dex group than the Pred group. From week 1 to week 3, median change in bALP was 72% (range -8 to 304) in the Pred group, whereas in the Dex group change in bALP was -1% (range 23 to -28; P < 0.005). By week 3, median bALP was higher in the Pred group at 65 U/l (range 36-187) than in the Dex group at 39 U/l (range 26-60; P < 0.05) but by week 6 median bALP in the Pred group had fallen to a similar level to the Dex group. At presentation, median DPD was 22 nmol/l (range 17-38) and 20 nmol/l (range 12-26) in the Pred and Dex groups, respectively (ns), reaching a nadir between weeks 3 and 6. The median percentage change in DPD in the Pred and Dex group from week 1 to week 3 was -34% (range -7 to 14) and -53% (range -6 to -69), respectively (ns). By week 8, DPD excretion had started to rise more dramatically in the Pred group such that the median DPD was 35 nmol/l (range 10-53) in the Pred group and 22 (range 9-30) in the Dex group (P < 0.05). On average, between weeks 2 and 8, LLLV was three times lower, percentage gain in weight was three times higher, bALP was 1.3 times lower and DPD was 1.5 times lower in the Dex group than the Pred group.


CONCLUSIONS
Pred and Dex both affect short-term growth and bone turnover. The mechanism of the effect on bone formation may be different between the two drugs. Dex may be about 18 times more potent than Pred at suppressing short-term linear growth and stimulating weight gain, and about nine times more potent at suppressing bone turnover. Glucocorticoids have a variable effect on different parameters of growth and bone turnover and the intensity may depend on the steroid used.
Ahmed
S F
SF
Department of Child Health, Royal Hospital for Sick Children, Yorkhill, Glasgow, UK. gcl328@clinmed.gla.ac.uk
Tucker
P
P
Mushtaq
T
T
Wallace
A M
AM
Williams
D M
DM
Hughes
I A
IA
D000293:Adolescent; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000201:enzymology; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006128:Growth / Q000187:drug effects*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D011239:Prednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies
D000596:Amino Acids; D015415:Biomarkers; D005938:Glucocorticoids; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; C036020:deoxypyridinoline; D011239:Prednisolone; D000469:Alkaline Phosphatase