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278 Osteoporosis in corticosteroid treated children
252
277
Abstracts
J ALLERGY CLIN IMMUNOL JANUARY 1996
Linear growth of asthmatic children on inhaled and systemic steroids. LC Kovalhuk MD. NA Rosario MD. L Lacerda. MD. J Gabardo PhD. A Schmidt MD. F Ferrari MD. Curitiba - Brazil.
279
Effects
280
Individual variations in e n d o g e n o u s cortisol. t o n u s in n o r m a l p o p u l a t i o n h a s no i n f l u e n c e on
Corficosteroids are the most potent antiinflammatory agents available. Growth retardation may be associated with the use of steroids. We studied linear growth of steroid dependent prepubertal asthmatic boys, mean age 7.2 + 1.5 ys., on oral qod prednisone (OS,n=20) or inhaled beclomethasone (IS;n=20).A group of mild/moderate asthmatics not requiring steroids served as control (C;n=20). Height was measured on a stadiometer at most visits and expressed as H-SDS (measured height - predicted height/height SD).Disease severity was estimated by a clinical score (0-3 scale). Patients were followed up from 8 to 21 months. Results are shown in the following table as mean :~ SD: G
ASTIIMA DOSES DURATION(y)
SCORE ENTRY
OS 6.2+ 1.8 4.1 ± 1.9# 6 , 7 ± 3 . 1 IS 5.2±2.4 394+ 1481 6.5±2.9 C 4.7 ± 2.6" --~ 3.3 ± I.l" * p<0.05,betweengroups;# rag/d;qmcg/d
II-SDS ENTRY -0.120± 0.9 +0.26 + 0.9 +0.18± 0.9
END .0.21+ 0.8 +0.12+0.9 +0.20~0.9
Scores at entry differed among groups on steroids and control. Scores decreased significantly in all 3 groups after treatment. There was no correlation between duration of disease and H-SDS. Irrespective of therapy mean H-SDS did not vary significantly throughout the study. Higher or lower H-SDS were not associated with any drug regimen (x2=1.6; NS).Low dose qod prednisone and low dose beclomethasone did not decrease growth velocity in these children with asthma.
278
Ostcoporosis in Corticosteroid Treated Children. P P a t e l . MD. SJ McC,e a d v . biD, Philadelphia, PA. Osteoporosis i s known t o c o m p l i c a t e s y s t e m i c corticosteroid (CS) t h e r a p y . Recently concern a b o u t i n h a l e d CS p r o d u c i n g a d v e r s e e f f e c t s on bone metabolism has been expressed also. Objective: to determine whether prolonged use o f o r a l a n d i n h a l e d CS i n a s t h m a i n c r e a s e s r i s k of osteoporosis in children. Method: lumbar bone mineral density-Zscore (~-Z) a t L 1 - L 4 w a s m e a s u r e d b y h o l o g i e QDR2000 d e x a s c a n i n 10 a s t h m a t i c s a g e 7 t o 17 years admitted to residential care. CS d o s e (inhaled and systemic) for last year was determined by chart review. Results: Average CS use Lumbar bone mineral density Mg/dAy Normal (S) Abnom~,l (3) Systemic 3.27 S,8S Inl~led 0.126 i.1O6 B o n e d e n s i t y (Z s c o r e ) was a b n o r m a l i n 50% o f asthmatic children studied. Those with d e c r e a s e d LBMD-Z r e c e i v e d h i g h e r s y s t e m i c a n d i n h a l e d CS c o m p a r e d t o t h o s e who h a d n o r m a l LBMD-Z. Conclusion: clinicians need to be aware of osteoporosis in asthmatic children and adolescents receiving high doses of inhaled and s y s t e m i c CS,
of prednisolone on bone turnover in patients with cortieosteroid resistant asthma •TH Lee MD..SJ Lane Phi). V Sashi *. R Swaminathan MD*. •Dept Allergy & Respiratory Medicine, and *Chemical Pathology, UMDS, Guy's Hospital, London UK We have tested the hypothesis that patients with corticosteroid resistant (CR) bronchial asthma are at similar risk of glucocorticoid (GC) side effects as corticosteroid sensitive (CS) asthmatics by examining the effects of C_rCson biochemical indices of bone turnover in 6 CR and in 6 CS subjects. Subjects received prednisoione 40mg orally at 09.00 daily for 5 days. At 08.30 on days 1/6 a fasting blood was taken for estimation of serum osteocalcin, tartrate resistant acid phosphatase (TRAP), total alkaline phospbatase (ALP) and the bone isoenzyrne of ALP and urine for estimation of free deoxy-pyridinoline crosslinks and hydroxyproline. TRAP, total and bone ALP were measured by a colorimea-ic method; osteocalcin and deoxy-pyridinoline crosslinks by ELISA and urinary hydroxyproline by a colorometric method after hydrolysis. Serum osteocalcin (nmol/L) decreased from 1.35:£-0.09 (rnean.-t:SEM) to 1.14i-0.07 (13=0.023) and from 1.19-k0.05 to 0.96+0.1 (p=0.037) in the CS and CR groups, respectively. There was no difference between baseline and post treatment levels in either group, Serum total ALP (units/L) decreased from 178+7 to 168+4 (p=O.02) and from 195+22 to 175:t:16 (p=0.04) in the CS and CR groups, respectively. There was no difference between baseline and post treatment levels in either group. There was no significant elevation of hydroxyproline, deoxy-pyridinoline crosslinks or TRAP and no suppression of bone ALP in either group. We conclude that CR asthmatics are equally at risk from the metabolic side effects of these drugs.
metabolism in subcutaneous a d i p o s e t i s s u e . IL KnuL~son MD. U EkstrSm MD. M Brtinne~rd PhD. U Un~erstedt PhD. S Werner PhD. P Stierna phi). C Marcus PhD. Stockholm, Sweden. The aim of this study was to define individual differences in endogenous cortisol production and corresponding pattern of the circadian rhythm, and whether these differences have an effect on glucose metabolism in subcutaneous adipose tissue. ~ : from 120 young healthy male volunteers screened with measurements of 24-bout U-conisol (x2), 12 individuals were chosen and allocated to one of two groups (6 high-cortisol respectively 6 low-conisol producers), and characterized concerning their circadian rhythm of cortisol (half-bout HOd samples during 24 hours). The glucose, glycerol and lactate metabolism of abdominal adipose tissue was continuously monitored in situ during the 24h trial with microdialysis probes. Results: good correlation was found between 24h U-cortisol measures and the mean value of 24h repeated S-cortisol sampling. The high eortisol producing group had a correspondingly high circadian rthythm profile while the inverse was true for the low cortisol producing group. However, no differences in glucose, glycerol and lactate concentrations were found between the two groups. ~ : large individual differences in endogenous cortisol production exists within the normal population under normal basal conditions without effecting glucose metabolism in subcutaneous adipose tissue This suggests that the variation in cortisol tonus is perhaps balanced by a corresponding variation in glucocorticoidsensitivity at/of the target cell, These results indicate the need for identifying tissue specific markets on the cellular and genetic level to predict individual responses towards glucocottlcoid therapy.
277
Abstracts
J ALLERGY CLIN IMMUNOL JANUARY 1996
Linear growth of asthmatic children on inhaled and systemic steroids. LC Kovalhuk MD. NA Rosario MD. L Lacerda. MD. J Gabardo PhD. A Schmidt MD. F Ferrari MD. Curitiba - Brazil.
279
Effects
280
Individual variations in e n d o g e n o u s cortisol. t o n u s in n o r m a l p o p u l a t i o n h a s no i n f l u e n c e on
Corficosteroids are the most potent antiinflammatory agents available. Growth retardation may be associated with the use of steroids. We studied linear growth of steroid dependent prepubertal asthmatic boys, mean age 7.2 + 1.5 ys., on oral qod prednisone (OS,n=20) or inhaled beclomethasone (IS;n=20).A group of mild/moderate asthmatics not requiring steroids served as control (C;n=20). Height was measured on a stadiometer at most visits and expressed as H-SDS (measured height - predicted height/height SD).Disease severity was estimated by a clinical score (0-3 scale). Patients were followed up from 8 to 21 months. Results are shown in the following table as mean :~ SD: G
ASTIIMA DOSES DURATION(y)
SCORE ENTRY
OS 6.2+ 1.8 4.1 ± 1.9# 6 , 7 ± 3 . 1 IS 5.2±2.4 394+ 1481 6.5±2.9 C 4.7 ± 2.6" --~ 3.3 ± I.l" * p<0.05,betweengroups;# rag/d;qmcg/d
II-SDS ENTRY -0.120± 0.9 +0.26 + 0.9 +0.18± 0.9
END .0.21+ 0.8 +0.12+0.9 +0.20~0.9
Scores at entry differed among groups on steroids and control. Scores decreased significantly in all 3 groups after treatment. There was no correlation between duration of disease and H-SDS. Irrespective of therapy mean H-SDS did not vary significantly throughout the study. Higher or lower H-SDS were not associated with any drug regimen (x2=1.6; NS).Low dose qod prednisone and low dose beclomethasone did not decrease growth velocity in these children with asthma.
278
Ostcoporosis in Corticosteroid Treated Children. P P a t e l . MD. SJ McC,e a d v . biD, Philadelphia, PA. Osteoporosis i s known t o c o m p l i c a t e s y s t e m i c corticosteroid (CS) t h e r a p y . Recently concern a b o u t i n h a l e d CS p r o d u c i n g a d v e r s e e f f e c t s on bone metabolism has been expressed also. Objective: to determine whether prolonged use o f o r a l a n d i n h a l e d CS i n a s t h m a i n c r e a s e s r i s k of osteoporosis in children. Method: lumbar bone mineral density-Zscore (~-Z) a t L 1 - L 4 w a s m e a s u r e d b y h o l o g i e QDR2000 d e x a s c a n i n 10 a s t h m a t i c s a g e 7 t o 17 years admitted to residential care. CS d o s e (inhaled and systemic) for last year was determined by chart review. Results: Average CS use Lumbar bone mineral density Mg/dAy Normal (S) Abnom~,l (3) Systemic 3.27 S,8S Inl~led 0.126 i.1O6 B o n e d e n s i t y (Z s c o r e ) was a b n o r m a l i n 50% o f asthmatic children studied. Those with d e c r e a s e d LBMD-Z r e c e i v e d h i g h e r s y s t e m i c a n d i n h a l e d CS c o m p a r e d t o t h o s e who h a d n o r m a l LBMD-Z. Conclusion: clinicians need to be aware of osteoporosis in asthmatic children and adolescents receiving high doses of inhaled and s y s t e m i c CS,
of prednisolone on bone turnover in patients with cortieosteroid resistant asthma •TH Lee MD..SJ Lane Phi). V Sashi *. R Swaminathan MD*. •Dept Allergy & Respiratory Medicine, and *Chemical Pathology, UMDS, Guy's Hospital, London UK We have tested the hypothesis that patients with corticosteroid resistant (CR) bronchial asthma are at similar risk of glucocorticoid (GC) side effects as corticosteroid sensitive (CS) asthmatics by examining the effects of C_rCson biochemical indices of bone turnover in 6 CR and in 6 CS subjects. Subjects received prednisoione 40mg orally at 09.00 daily for 5 days. At 08.30 on days 1/6 a fasting blood was taken for estimation of serum osteocalcin, tartrate resistant acid phosphatase (TRAP), total alkaline phospbatase (ALP) and the bone isoenzyrne of ALP and urine for estimation of free deoxy-pyridinoline crosslinks and hydroxyproline. TRAP, total and bone ALP were measured by a colorimea-ic method; osteocalcin and deoxy-pyridinoline crosslinks by ELISA and urinary hydroxyproline by a colorometric method after hydrolysis. Serum osteocalcin (nmol/L) decreased from 1.35:£-0.09 (rnean.-t:SEM) to 1.14i-0.07 (13=0.023) and from 1.19-k0.05 to 0.96+0.1 (p=0.037) in the CS and CR groups, respectively. There was no difference between baseline and post treatment levels in either group, Serum total ALP (units/L) decreased from 178+7 to 168+4 (p=O.02) and from 195+22 to 175:t:16 (p=0.04) in the CS and CR groups, respectively. There was no difference between baseline and post treatment levels in either group. There was no significant elevation of hydroxyproline, deoxy-pyridinoline crosslinks or TRAP and no suppression of bone ALP in either group. We conclude that CR asthmatics are equally at risk from the metabolic side effects of these drugs.
metabolism in subcutaneous a d i p o s e t i s s u e . IL KnuL~son MD. U EkstrSm MD. M Brtinne~rd PhD. U Un~erstedt PhD. S Werner PhD. P Stierna phi). C Marcus PhD. Stockholm, Sweden. The aim of this study was to define individual differences in endogenous cortisol production and corresponding pattern of the circadian rhythm, and whether these differences have an effect on glucose metabolism in subcutaneous adipose tissue. ~ : from 120 young healthy male volunteers screened with measurements of 24-bout U-conisol (x2), 12 individuals were chosen and allocated to one of two groups (6 high-cortisol respectively 6 low-conisol producers), and characterized concerning their circadian rhythm of cortisol (half-bout HOd samples during 24 hours). The glucose, glycerol and lactate metabolism of abdominal adipose tissue was continuously monitored in situ during the 24h trial with microdialysis probes. Results: good correlation was found between 24h U-cortisol measures and the mean value of 24h repeated S-cortisol sampling. The high eortisol producing group had a correspondingly high circadian rthythm profile while the inverse was true for the low cortisol producing group. However, no differences in glucose, glycerol and lactate concentrations were found between the two groups. ~ : large individual differences in endogenous cortisol production exists within the normal population under normal basal conditions without effecting glucose metabolism in subcutaneous adipose tissue This suggests that the variation in cortisol tonus is perhaps balanced by a corresponding variation in glucocorticoidsensitivity at/of the target cell, These results indicate the need for identifying tissue specific markets on the cellular and genetic level to predict individual responses towards glucocottlcoid therapy.