The Effects Of Inhaled Glucocorticoids On Bone Density,Bone Metabolism, And Adrenal Function In Children With Asthma

Objective.Our study was designed to establish the safety on bone metabolism, bone density and adrenal function for the asthmatic children who have inhaled glucocorticoids(GCS) for 1.5 years..Methods.Object of Study and Dividing Groups60 children were chosen from our pediatrical clinic and ward, aged 3-12 years, including 36 boys and 24 girls. All the cases accord with the criterion of asthma and none of them who had inhaled glucocorticoids before. The children are divided to two groups at random (treatment group and control group). The children of treatment group begun to inhale bedesonide (BUD) at beginning of the study. According to the scheme of the global initial for asthma (GINA) : mild 200 micrograms/d , qd; moderate 400 micrograms/d , bid; severe 600 micrograms/d tid. Inhaled β 2-agonist if it is necessary. The children of control group received the same treatments as the treatment group except inhaled BUD. The treatment of the treatment group can be stepped down or stepped up according to GINA scheme. If the symptoms has released and maintained at least for 1-3 months, the dose can be decreased. The whole treatment needs 18 months. If the wheezing symptoms get worse, the control group should inhale BUD immediately.All the cases received the measurement of bone metabolism, bone density and adrenal function.Study MethodBone MetabolismSerum calcium, phosphorus, and alkaline phosphate levels, urine calcium / creatinine ratio were measured prior to starting inhaled glucocorticoids (ICS) therapy and18 months later. All the assays were performed twice by a technician double-blinded.Bone DensityThe bone density of the lumbar spine(L2-L4) were obtained prior to starting ICS therapy and 18 months later, using Dual-energy X-ray absorptiometry (DXA).Adrenal FunctionThe urinary free cortisol of 24 hours was examined prior to starting ICS therapy and 18 months later, which reflects the adrenal function. It was measured twice by radioimmunoassay with the reagent box.StatisticsThe study adopt t-test to analyze the results. P > 0.05 indicated statistical significance.ResultsNo child in the treatment group gives up the therapy. Six children in control group inhaled BUD in succession, because of frequent asthma attack.Bone MetabolismBefore therapy: 82/90 children's serum calcium, phosphorus, and alkaline phosphate levels were in normal scope, 5 children's serum calcium were at the normal edge, and 3 children's serum phosphorus were below the normal. The abnormality related to season, often happening in winter, has no difference between the treatment and control groups. These indexes didn't change obviously when the study ends.Table 1: Serum calcium, phosphorus, and alkaline phosphate levels, urine calcium / creatinine ratio before and after study.? 2+, , ? . c r.3+/ i n s serum alkaline phosphate urine calcium /creatinine serum Ca* (mmol/L) Serum P3 (mmol/L)_<sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub>(U/p ratio (Ca/Cr)group cases Before After Before After Before After Before After _<sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub>treatment treatment treatment treatment treatment treatment treatment treatmenttreatment 3Q 2.26±0.13 2.25 + 0.12 0.94 + 0.10 0.93±0.11 67.72 + 7.65 66.67 + 8.10 0.09+0.06 0.09+0.07 groupcontrol group 24 2.28 + 0.14 2.26 + 0.15 0.96 + 0.07 0.97 + 0.08 65.34 + 8.88 65.46 + 9.02 0.08 + 0.08 0.09 + 0.05 nOrmgar1oCu°pntro1 30 2.24+0.15 0.92+0.10 67.68+9.12 0.09 + 0.06The results had no obvious difference among the groups.Bone DensityThe bone density had no obvious difference before and after the study.Table 2: the bone density before and after the studygroup cases Before treatment (g/cm2) After treatment (g/cm")treatment group 30 0.64 + 0.06 0.63 + 0.06control group 24 0.63 + 0.08 0.63 + 0.07normal control 3Q 0.62 + 0.09group_<sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub><sub>The results had no obvious difference among the groups.Adrenal FunctionThe urinary free cortisol of 24 hours reflects the adrenal functionTable 3: the urinary free cortisol of 24 hours before and after the studygroup cases Before treatment(ug/24h) After treatment(ug/24h)threatment group 30 22.8+ 8.5 23.2+ 8.7control group 24 22.6 + 8.9 22.4± 8.5 30The results had no obvious difference among the groups.In a word, the study proved that inhaled glucocorticoids have little influence on bone metabolism, bone density and adrenal function. However, it still need a long time to observe and study the further function and side-effects on the infants who has inhaled the glucocorticoids for a long time.