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Short-term effects on linear growth and bone turnover in children randomized to receive prednisolone or dexamethasone
S F Ahmed1, P Tucker, T Mushtaq
1Department of Child Health, Royal Hospital for Sick Children, Yorkhill, Glasgow, UK. gcl328@clinmed.gla.ac.uk
Insights
Dexamethasone (Dex) significantly suppresses growth and increases weight gain more than prednisolone (Pred) in children with acute lymphoblastic leukemia (ALL). Dex is also more potent in reducing bone turnover markers compared to Pred.
Area of Science:
- Pediatric Endocrinology
- Oncology
- Pharmacology
Background:
- Glucocorticoids are essential in acute lymphoblastic leukemia (ALL) chemotherapy.
- Prednisolone (Pred) and dexamethasone (Dex) are commonly used, but their differential effects on growth and bone turnover require clarification.
Purpose of the Study:
- To compare the relative potency of Pred and Dex on short-term growth and bone turnover in children undergoing ALL induction chemotherapy.
Main Methods:
- A prospective study randomized 19 children with ALL to receive either Pred (40 mg/m2) or Dex (6.5 mg/m2) for 5 weeks.
- Measurements included lower leg length velocity (LLLV), weight, IGF-I, bone alkaline phosphatase (bALP), and deoxypyridinoline cross-links (DPD).
Main Results:
- Dexamethasone significantly reduced LLLV more than Pred (P < 0.05) and increased weight gain (up to 17.5% vs 8.7%, P < 0.05).
- Dex markedly suppressed IGF-I levels and bone turnover markers (bALP, DPD) more potently than Pred.
- On average, Dex suppressed LLLV three times lower, increased weight gain three times higher, lowered bALP 1.3 times, and lowered DPD 1.5 times compared to Pred.
Conclusions:
- Both Pred and Dex impact short-term growth and bone turnover in children with ALL.
- Dexamethasone demonstrates significantly higher potency than Pred in suppressing linear growth and bone turnover, and in stimulating weight gain.
- The differential effects highlight the variable impact of glucocorticoids on growth and bone metabolism, influenced by the specific steroid used.
Aim:
To compare the relative potency of prednisolone (Pred) and dexamethasone (Dex) on short-term growth and bone turnover.
Method:
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).
Measurements:
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).
Subjects:
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.
Conclusion:
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.