Changes in markers of bone metabolism during dexamethasone treatment for chronic lung disease in preterm infants

Abstract

Aim: To characterise the change in serum and urinary bone markers in the early postnatal period, and to assess the effect of systemic corticosteroid on bone metabolism in preterm infants.

Methods: Bone formation was quantified by measurement of serum concentrations of bone specific alkaline phosphatase (BALP) and osteocalcin. Bone resorption was measured by monitoring creatinine adjusted urinary deoxypyridinoline (Dpd) concentration. Blood and urinary samples were collected from corticosteroid treated infants (n = 19) immediately before the start (T(d-pre)), three weeks after the start (T(d-end)), and two (T(d-post2)) and four weeks (T(d-post4)) after the end of the dexamethasone course. Untreated patients (n = 30) had specimens taken at week 3 (T(wk-3)), 6 (T(wk-6)), 8 (T(wk-8)), and 10 (T(wk-10)) of postnatal age.

Results: Serum concentrations of BALP and osteocalcin at T(d-end) were significantly lower than pretreatment levels and the levels at the corresponding time point (T(wk-6)) of the non-treatment group. In contrast, urinary Dpd concentration at T(d-end) was not significantly decreased compared with the pretreatment level. However, it was significantly lower than the urinary Dpd concentration at T(wk-6) of the non-treatment group. The rate of increase in lower leg length was significantly higher in the non-treatment group between weeks 3 and 6 than in the corresponding period during dexamethasone treatment in the corticosteroid group.

Conclusion: Systemic corticosteroid causes appreciable suppression of serum BALP and osteocalcin and, to a lesser extent, urinary Dpd. The results suggest that corticosteroid inhibits bone growth mainly by decreasing bone formation.

Figure 1

Serum bone specific alkaline phosphatase (BALP) concentrations (U/l; square root) in very low birthweight infants receiving corticosteroid or not over the study period. The asterisks indicate significant increase or decrease in serum BALP concentration compared with the pretreatment (T_d-pre) or week 3 (T_wk-3) levels within the same group. The parentheses indicate a significant difference in serum BALP concentration between the two groups when the corresponding time periods are compared. Results are expressed as mean and SEM.

Figure 2

Serum osteocalcin concentrations (ng/l; log_e) in very low birthweight infants receiving corticosteroid or not over the study period. The asterisks indicate significant increase or decrease in serum osteocalcin concentration compared with the pretreatment (T_d-pre) or week 3 (T_wk-3) levels within the same group. The parentheses indicate a significant difference in serum osteocalcin concentration between the two groups when the corresponding time periods are compared. Results are expressed as mean and SEM.

Figure 3

Creatinine adjusted urinary deoxypyridinoline (Dpd) concentrations (nmol/mmol Cr) in very low birthweight infants receiving corticosteroid or not over the study period. The asterisks indicate a significant increase or decrease in creatinine adjusted urinary Dpd concentration compared with the pretreatment (T_d-pre) or week 3 (T_wk-3) levels within the same group. The parentheses indicate a significant difference between the two groups when the corresponding time periods are compared. Results are expressed as mean and SEM.

Figure 4

Rate of increase in the length of the lower leg (mm/week) in very low birthweight infants receiving corticosteroid or not over the study period. The asterisks indicate a significant increase or decrease in growth of the lower leg compared with the treatment period (T_d-pre–T_d-end) or week 3–6 of postnatal age (T_wk-3–T_wk-6) within the same group. The parentheses indicate a significant difference between the two groups when the corresponding time periods are compared. Results are expressed as mean and SEM.