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HEIGHT ATTAINMENT IN CHILDREN WITH STEROID-RESPONSIVE NEPHROTIC SYNDROME
917
HEIGHT ATTAINMENT IN CHILDREN WITH
STEROID-RESPONSIVE NEPHROTIC SYNDROME K. D. FOOTE
J. T. BROCKLEBANK S. R. MEADOW
Department of Paediatrics and Child Health, St James’s University Hospital, Leeds
heights of 80 patients with steroidresponsive nephrotic syndrome (SRNS) were measured 5-24 years after diagnosis. During childhood most patients had received repeated courses of highdose corticosteroids and prolonged maintenance therapy. Although at the time of taking corticosteroids growth was suppressed, those who had completed growth had a mean height standard deviation score (SDS) of - 0·22, equivalent The
Summary
to a
height
on
the 40th centile. Total corticosteroid dose
prescribed was correlated only weakly with height SDS; there was no correlation between total dose and height when the post-pubertal patients were studied separately, indicating that their ultimate height attainment was not affected significantly. Introduction
STUNTING of growth is a well-recognised complication of corticosteroid therapy; children who have to receive repeated courses of high-dose steroids or prolonged maintenance therapy are at greatest risk.1-3 The largest group of children treated in this way are those with steroid-responsive nephrotic syndrome (SRNS). We studied a group of nephrotic children to determine the height attained and to see whether treatment had resulted in short stature.
children who could be kept in remission only by such large doses of steroids that they had features of gross hypercortisolism. Of 73 patients for whom detailed information was available, 8 had no relapses, 28 had 1-5 relapses, 20 had 6-10 relapses, 13 had 11-15 relapses, and 4 had between 16 and 39 relapses. Mean number of relapses was 7. For 72 children it was possible to calculate the total steroid dose prescribed before completion of puberty (defined as 18 years in boys and 16 years in girls). Duration of therapy was obtained by calculating the number of days on which the patient was taking prednisolone or was on alternate-day therapy. The percentage of total treatment days on which the patient received alternate-day prednisolone was also calculated. Mean total prednisolone dose was 15 000 mg/m2, median duration of therapy 1 - 9 years, and percentage time spent on an alternate-day regimen 52%.
Methods
patients were visited at home where height was measured with anthropometer; the remaining 19 were seen in the outpatient clinic where a stadiometer was used. The heights of both parents of 37 children were measured. All measurements were made by the same investigator (K.D.F.). Heights of boys and girls at different ages were compared by calculating the height standard deviation score (SDS) according to the following equation: 61
an
SDS=—— where x is the height measured, x the mean height, and Sx the standard deviation. x and Sx for a given age and sex were taken from standard tables for British children.4
Results
80 patients (50 male, 30 female) referred to the regional paediatric nephrology unit between 1969 and 1979 and diagnosed as having SRNS were studied. In 42 the diagnosis of minimal change was confirmed histologically on renal biopsy. All patients had been treated with standard doses of prednisolone (60 mg/m2/24 h) which were continued (for an average of 6 weeks) until the urine was protein free for 2 days. The steroids were tapered and stopped during the next 2 weeks unless proteinuria recurred; in this case the dose was not reduced beyond the level required to maintain remission. A course of cyclophosphamide was given to those
Height SDSs of the 80 patients shown in fig 1 are normally distributed (probability 0.99, Kolmogorov-Smirnov test5). The mean height SDS of - 0’ 29 represents a height on the 37th centile or about 2 cm below average height. Height SDSs of the 74 parents measured were also normally distributed (probability 0 76, mean - 0 14). Since we were interested in the height attainment after completion of growth we examined the heights of the prepubertal and post-pubertal groups separately. The 52 prepubertal patients had a mean height SDS of -0’33, equivalent to a height on the 37th centile or about 2 cm below average height. Mean height SDS of the 28 post-pubertal patients was - 0 22, equivalent to a height on the 40th centile or 1 5 cm below average height, showing that corticosteroid treatment as used in this study does not affect ultimate height attainment.
1. Antoine B, Neveu T. Pathological urinary excretion of tissue macromolecules (histuria). J Lab Clin Med 1968; 71: 101-12. 2 Rosenmann E, Boss JH. Tissue antigens in normal and pathologic urine samples: a review Kidney Int 1979; 16: 337-44. 3 lesato K, Wakashin M, Warashin Y, Toyo S. Renal tubular dysfunction in Minamata disease. detection of renal tubular antigen and &bgr;2-microglobulin in the urine Ann Intern Med 1977; 86: 731-36. 4 Antoine B, Ward PD. Histuria and fibrinuria in cases of systemic lupus erythematosus. Clin Exp Immunol 1970; 6: 153-59 5 Antoine B, Neveu T, Leski M, Bach JF. Histuria during renal transplantation. Transplantation 1969; 8: 110-20. 6 Scherberich J, Mondorf W, Fassbmder W, Koch K. Tubular histuria and serum proteinuria following kidney allotransplantation. Kidney Int 1976, 10: 199 (abstr). 7 Krane SM, Munoz AJ, Harris ED Jr. Collagen-like fragments: excretion in urine of patients with Paget’s disease of bone Science 1967; 157: 713-16 8 Huttunen NP, Hallmann N, Rapola J. Glomerular basement antigens in congenital and acquired nephrotic syndrome in childhood. Nephron 1976; 16: 401-14. 9 Kneker WT, Sweeney NJ. Increased urinary basement membrane-like products (BMP) in infants with congenital nephrosis (CN) and their healthy relatives. Clin Res 1972; 20: 115 10. Edgington TS, Glassock RJ, Dixon FJ. Autologous immune complex nephritis induced with renal tubular antigen. JExp Med 1967, 127: 555-71 11 Douglas MFS, Rabideau DP, Schwartz MM, Lewis EJ. Evidence of autologous immune-complex nephritis. N EnglJ Med 1981, 305: 1326-29.
G, Milstein C. Continuous culture of fused cells secreting antibody of predefined specificity. Nature 1975; 256: 495-97 13. Coons AH, Kaplan MH Localisation of antigens in tissue cells. II. Improvements in a method for the detection of antigens by means of fluorescent antibody. J Exp Med 1950; 91: 1-13. 14. Towbin H, Straehelin T, Gordon J Electrophoretic transfer of proteins from polyacrylamide gels nitrocellulose. Proc Natl Acad Sci USA 1979; 76: 4350-54. 15 Lucertini S, Mutti A, Valcavi PP, Franchini I. Enzyme-linked immunosorbent assay of retinol-binding protein in serum and urine. Clin Chem 1984; 30: 149-51. 16. Valcavi PP, Lucertini S, Mutti A, Chezzi C Urinary albumin In: Bergmeyer HU, ed. Methods of enzymatic analysis. Vol IX Weineim Verlag Chemie (in press). 17 Bernard A, Lauwerys R. Retinol-binding protein in the urine: a more practical parameter than urinary &bgr;2-microglobulin for the routine screening of renal tubular function. Clin Chem 1981; 27: 1781-82. 18. Mutti A, Lucertini S, Fornari M, et al Urinary excretion ofa brush-border antigen revealed by monoclonal antibodies in subjects occupationally exposed to heavy metals Proceedings of the International Conference on heavy metals in the environment, vol 1, p 565-67 Edinburgh CEP Consultants, 1985. 19. MondorfAW, Scherberich JE, Stefanescu T, Mitrou PS, Schoeppe W. Elimination of brush border membrane protein in urine caused by toxic alterations of the tubular cell. Contr Nephrol 1981, 24: 99-108 20 Wilson CB. Nephritogenic antibody mechanisms involving antigens within the glomerulus Immunol Rev 1981; 55: 257-97. 21. Druet P, Bernard A, Hirsch F, et al. Immunologically mediated glomerulonephritis induced by heavy metals. Arch Toxicol 1982; 50: 187-94
Patients and Methods Patients
’
12. Köhler
918
To examine the ultimate height attainment of patients who had shown signs of severe steroid toxicity, the results of the 18 post-pubertal patients who were treated with cyclophosphamide were studied separately; mean height SDS was 0 -34, which is equivalent to a height on the 35th centile or about 2 - 3 cm below average height, and not significantly different from the group value. It was possible to examine the effects of total steroid dose, corrected for body size, on height SDS in 72 patients (fig 2). Patients who had received large total doses of corticosteroids tended to be smaller than those who had received lower doses (r=0-38, p=0-001). However, there was no effect of total steroid dose on ultimate height attainment in the 23 of the 28 post-pubertal patients who could be examined (r=0’06). Similarly, there was no correlation between height SDS and duration of treatment in the 72 patients (r=0’ 11). -
Fig 1-Height SDS at follow-up (all patients). To determine whether catch-up growth occurs once is stopped, 33 patients who had been off treatment for at least 5 years were reviewed. They had a mean height SDS of + 0 - 003, equivalent to a height on the 50th centile. This supports the view that catch-up growth occurs, but it is relevant that on average these patients had less severe disease, had received less treatment, and had fewer relapses than the treatment
group
as a
whole
(see accompanying table).
Fig 2-Height SDS vs
total corticosteroid dose.
Discussion
Patients included in this study represent most of those with SRNS referred to a regional paediatric nephrology unit between 1969 and 1979. They form a selected group whose
nephrotic syndrome was, on average, much more severe than would be encountered in a non-specialist unit. Thus most received large doses and long courses of prednisolone-many for more than 5 years. We felt justified in using Tanner standards for comparison of heights because, owing to regional variations, standards produced by Tanner 20 years ago for children living in SouthEast England are appropriate for children living in the Yorkshire region today. (Buckler JMH, unpublished). The height SDSs of the whole group conform so closely to a normal distribution that they are unlikely to conceal a subgroup who are more sensitive to the dwarfing effects of steroids. Mean height SDS of the 28 post-pubertal patients was not significantly less than that of the normal population. It is probable that some of the younger members of this group (5 were less than 19 years and 11 were less than 20 years) were still growing, because of variation in the age at which growth is completed and the delay in growth caused by the effect of steroids on bone maturation. This would mean that the figure of -0-22 for mean height SDS may underestimate the ultimate height attainment of the post-pubertal group. Although there was a tendency for the shorter patients to have received large doses of corticosteroids there was no
919
consistent relation between the total steroid dose and height SDS. In addition, there was no correlation between total dose and ultimate height attainment. Thus catch-up growth seems
attainment, despite the fact that many patients had received
pertinent that the natural history
We thank Dr J. M. H. Buckler for his advice on growth, Department of Mathematics, Leeds University, for assistance with statistics, and Miss J.
to occur.
In this context it is
ofSRNS is for relapses to become less frequent with age, and therefore for less corticosteroid to be needed between the ages of 10-15 years than, say, 5-10 years. In the patients with severe hypercortisolism (who were subsequently given cyclophosphamide), the steroid toxicity may have been due to the large doses that they had received or 6 to an increased sensitivity to the effects of corticosteroids. Even in this group ultimate height attainment was not significantly different from that of the normal population. There have been no reports of growth suppression due to treatment with cyclophosphamide alone, although cytotoxics used in conjunction with cranial irradiation can reduce growth hormone secretion.7, 8 There is no evidence from this study to suggest that cyclophosphamide treatment of nephrotic syndrome suppresses growth. We conclude that although large doses of steroids suppress growth in children at the time of administration, the regimens used in this study had little or no effect on ultimate height
Preliminary Communications
repeated courses of high-dose corticosteroids and prolonged therapy.
maintenance
Bland and Mrs A. M.
Hartup for preparation of the typescript. Correspondence should be addressed to K. D. F., Clarendon Wing, General Infirmary, Belmont Grove, Leeds LS2 9NS. REFERENCES 1 Friedman M, Strang LB Effect of long-term corticosteroids and corticotrophin on the growth of children Lancet 1966; ii. 568-72. 2. Lam CN, Arneil GC. Long-term dwarfing effects of corticosteroid treatment for childhood nephrosis Arch Dis Child 1968; 43: 589-94 3. Trompeter RS, Lloyd BW, Hicks J, White RHR, Cameron JS. Long-term outcome for children with minimal-change nephrotic syndrome. Lancet 1985, i: 368-70. 4. Tanner JM, Whitehouse RH, Takaishi M. Standards from birth to maturity for height, weight, height velocity and weight velocity: British Children, 1965. Part II. Arch Dis Child 1966; 41: 613-35 5. Siegel S. Non-parametric statistics for the behavioral sciences. New York: McGraw Hill, 1956 47-52. 6 Kennedy MCS, Thursby-Pelham DC. Corticosteroids, corticotrophin, and children’s growth. Lancet 1966, ii: 907 7. Shallet SM, Beardwell CG, Aarons BM, Pearson D, Morris-Jones PH Growth impairment in children treated for brain tumours Arch Dis Child 1978; 53: 491 -94. 8 Schiliro G, Russo A, Sciotto A, Distefano G, Vigo R Radiotherapy, chemotherapy, and growth-hormone deficiency. Lancet 1976, ii 1031.
with precursor cells to become virus infection in these cells in a particular multinucleated, bone might well persist indefinitely and spread by continuously infecting further recruited blood-borne preosteoclasts. Previous workers have concentrated mainly on human infections, such as measles and respiratory syncytial virus,4, 7, 9 but we think it is equally likely that Paget’s disease might be due to infection with a virus of animal origin, perhaps in domestic pets. Clinical and radiological evidence osteoclasts
fuse a
PAST PETS AND PAGET’S DISEASE
J. B. O’DRISCOLL
D. C. ANDERSON
Department of Medicine, University of Manchester, Hope Hospital, Eccles Old Road, Salford M6 8HD There is strong morphological evidence that Paget’s disease is caused by a chronic focal infection of osteoclasts, but the source of this paramyxovirus virus and the reason for the wide variation in the incidence of the disease are unknown. The infection may be a zoonosis, with a domestic animal as the usual host. Past exposure to pets was studied in 50 patients with Paget’s disease and 50 age and sex matched control subjects with diabetes mellitus. Dog ownership was significantly more common in the patients than in the control subjects (odds ratios at different ages varied between 4 and 8). 44 of the Paget’s patients and 30 of the control subjects had had dogs before diagnosis of Paget’s disease (or the equivalent age in the control subjects). Exposure to domestic cats was identical in both groups (26 each), and there was no significant difference in exposure to budgerigars. This suggests that a canine virus (possibly canine distemper) might be the primary infective agent, although other factors probably contribute to the particularly high incidence in the North West of England.
Summary
INTRODUCTION
CURRENT evidence favours a paramyxovirus infection of osteoclasts in the aetiology of Paget’s disease of the bone.1-9 The frequency of the disease varies greatly, and some towns in the North West of England have probably the highest incidence in the world.IO-13 Clustering of Paget’s disease in families has been reported but is thought to be caused by a common environmental factor rather than an inherited one.14 It has also been proposed that vitamin D deficiency might operate in conjunction with a virus.15 Since
Ownership for patients with Paget’s disease ( .and control subjects (0) by 10-year cumulative cohorts. Horizontal axis shows age in years (left) and years before diagnosis (nght), for all patients up to and including the age of 80. A and B show total cumulative years of dog ownership, C and D show total numbers who had a dog living in the home
at
any
time
HEIGHT ATTAINMENT IN CHILDREN WITH
STEROID-RESPONSIVE NEPHROTIC SYNDROME K. D. FOOTE
J. T. BROCKLEBANK S. R. MEADOW
Department of Paediatrics and Child Health, St James’s University Hospital, Leeds
heights of 80 patients with steroidresponsive nephrotic syndrome (SRNS) were measured 5-24 years after diagnosis. During childhood most patients had received repeated courses of highdose corticosteroids and prolonged maintenance therapy. Although at the time of taking corticosteroids growth was suppressed, those who had completed growth had a mean height standard deviation score (SDS) of - 0·22, equivalent The
Summary
to a
height
on
the 40th centile. Total corticosteroid dose
prescribed was correlated only weakly with height SDS; there was no correlation between total dose and height when the post-pubertal patients were studied separately, indicating that their ultimate height attainment was not affected significantly. Introduction
STUNTING of growth is a well-recognised complication of corticosteroid therapy; children who have to receive repeated courses of high-dose steroids or prolonged maintenance therapy are at greatest risk.1-3 The largest group of children treated in this way are those with steroid-responsive nephrotic syndrome (SRNS). We studied a group of nephrotic children to determine the height attained and to see whether treatment had resulted in short stature.
children who could be kept in remission only by such large doses of steroids that they had features of gross hypercortisolism. Of 73 patients for whom detailed information was available, 8 had no relapses, 28 had 1-5 relapses, 20 had 6-10 relapses, 13 had 11-15 relapses, and 4 had between 16 and 39 relapses. Mean number of relapses was 7. For 72 children it was possible to calculate the total steroid dose prescribed before completion of puberty (defined as 18 years in boys and 16 years in girls). Duration of therapy was obtained by calculating the number of days on which the patient was taking prednisolone or was on alternate-day therapy. The percentage of total treatment days on which the patient received alternate-day prednisolone was also calculated. Mean total prednisolone dose was 15 000 mg/m2, median duration of therapy 1 - 9 years, and percentage time spent on an alternate-day regimen 52%.
Methods
patients were visited at home where height was measured with anthropometer; the remaining 19 were seen in the outpatient clinic where a stadiometer was used. The heights of both parents of 37 children were measured. All measurements were made by the same investigator (K.D.F.). Heights of boys and girls at different ages were compared by calculating the height standard deviation score (SDS) according to the following equation: 61
an
SDS=—— where x is the height measured, x the mean height, and Sx the standard deviation. x and Sx for a given age and sex were taken from standard tables for British children.4
Results
80 patients (50 male, 30 female) referred to the regional paediatric nephrology unit between 1969 and 1979 and diagnosed as having SRNS were studied. In 42 the diagnosis of minimal change was confirmed histologically on renal biopsy. All patients had been treated with standard doses of prednisolone (60 mg/m2/24 h) which were continued (for an average of 6 weeks) until the urine was protein free for 2 days. The steroids were tapered and stopped during the next 2 weeks unless proteinuria recurred; in this case the dose was not reduced beyond the level required to maintain remission. A course of cyclophosphamide was given to those
Height SDSs of the 80 patients shown in fig 1 are normally distributed (probability 0.99, Kolmogorov-Smirnov test5). The mean height SDS of - 0’ 29 represents a height on the 37th centile or about 2 cm below average height. Height SDSs of the 74 parents measured were also normally distributed (probability 0 76, mean - 0 14). Since we were interested in the height attainment after completion of growth we examined the heights of the prepubertal and post-pubertal groups separately. The 52 prepubertal patients had a mean height SDS of -0’33, equivalent to a height on the 37th centile or about 2 cm below average height. Mean height SDS of the 28 post-pubertal patients was - 0 22, equivalent to a height on the 40th centile or 1 5 cm below average height, showing that corticosteroid treatment as used in this study does not affect ultimate height attainment.
1. Antoine B, Neveu T. Pathological urinary excretion of tissue macromolecules (histuria). J Lab Clin Med 1968; 71: 101-12. 2 Rosenmann E, Boss JH. Tissue antigens in normal and pathologic urine samples: a review Kidney Int 1979; 16: 337-44. 3 lesato K, Wakashin M, Warashin Y, Toyo S. Renal tubular dysfunction in Minamata disease. detection of renal tubular antigen and &bgr;2-microglobulin in the urine Ann Intern Med 1977; 86: 731-36. 4 Antoine B, Ward PD. Histuria and fibrinuria in cases of systemic lupus erythematosus. Clin Exp Immunol 1970; 6: 153-59 5 Antoine B, Neveu T, Leski M, Bach JF. Histuria during renal transplantation. Transplantation 1969; 8: 110-20. 6 Scherberich J, Mondorf W, Fassbmder W, Koch K. Tubular histuria and serum proteinuria following kidney allotransplantation. Kidney Int 1976, 10: 199 (abstr). 7 Krane SM, Munoz AJ, Harris ED Jr. Collagen-like fragments: excretion in urine of patients with Paget’s disease of bone Science 1967; 157: 713-16 8 Huttunen NP, Hallmann N, Rapola J. Glomerular basement antigens in congenital and acquired nephrotic syndrome in childhood. Nephron 1976; 16: 401-14. 9 Kneker WT, Sweeney NJ. Increased urinary basement membrane-like products (BMP) in infants with congenital nephrosis (CN) and their healthy relatives. Clin Res 1972; 20: 115 10. Edgington TS, Glassock RJ, Dixon FJ. Autologous immune complex nephritis induced with renal tubular antigen. JExp Med 1967, 127: 555-71 11 Douglas MFS, Rabideau DP, Schwartz MM, Lewis EJ. Evidence of autologous immune-complex nephritis. N EnglJ Med 1981, 305: 1326-29.
G, Milstein C. Continuous culture of fused cells secreting antibody of predefined specificity. Nature 1975; 256: 495-97 13. Coons AH, Kaplan MH Localisation of antigens in tissue cells. II. Improvements in a method for the detection of antigens by means of fluorescent antibody. J Exp Med 1950; 91: 1-13. 14. Towbin H, Straehelin T, Gordon J Electrophoretic transfer of proteins from polyacrylamide gels nitrocellulose. Proc Natl Acad Sci USA 1979; 76: 4350-54. 15 Lucertini S, Mutti A, Valcavi PP, Franchini I. Enzyme-linked immunosorbent assay of retinol-binding protein in serum and urine. Clin Chem 1984; 30: 149-51. 16. Valcavi PP, Lucertini S, Mutti A, Chezzi C Urinary albumin In: Bergmeyer HU, ed. Methods of enzymatic analysis. Vol IX Weineim Verlag Chemie (in press). 17 Bernard A, Lauwerys R. Retinol-binding protein in the urine: a more practical parameter than urinary &bgr;2-microglobulin for the routine screening of renal tubular function. Clin Chem 1981; 27: 1781-82. 18. Mutti A, Lucertini S, Fornari M, et al Urinary excretion ofa brush-border antigen revealed by monoclonal antibodies in subjects occupationally exposed to heavy metals Proceedings of the International Conference on heavy metals in the environment, vol 1, p 565-67 Edinburgh CEP Consultants, 1985. 19. MondorfAW, Scherberich JE, Stefanescu T, Mitrou PS, Schoeppe W. Elimination of brush border membrane protein in urine caused by toxic alterations of the tubular cell. Contr Nephrol 1981, 24: 99-108 20 Wilson CB. Nephritogenic antibody mechanisms involving antigens within the glomerulus Immunol Rev 1981; 55: 257-97. 21. Druet P, Bernard A, Hirsch F, et al. Immunologically mediated glomerulonephritis induced by heavy metals. Arch Toxicol 1982; 50: 187-94
Patients and Methods Patients
’
12. Köhler
918
To examine the ultimate height attainment of patients who had shown signs of severe steroid toxicity, the results of the 18 post-pubertal patients who were treated with cyclophosphamide were studied separately; mean height SDS was 0 -34, which is equivalent to a height on the 35th centile or about 2 - 3 cm below average height, and not significantly different from the group value. It was possible to examine the effects of total steroid dose, corrected for body size, on height SDS in 72 patients (fig 2). Patients who had received large total doses of corticosteroids tended to be smaller than those who had received lower doses (r=0-38, p=0-001). However, there was no effect of total steroid dose on ultimate height attainment in the 23 of the 28 post-pubertal patients who could be examined (r=0’06). Similarly, there was no correlation between height SDS and duration of treatment in the 72 patients (r=0’ 11). -
Fig 1-Height SDS at follow-up (all patients). To determine whether catch-up growth occurs once is stopped, 33 patients who had been off treatment for at least 5 years were reviewed. They had a mean height SDS of + 0 - 003, equivalent to a height on the 50th centile. This supports the view that catch-up growth occurs, but it is relevant that on average these patients had less severe disease, had received less treatment, and had fewer relapses than the treatment
group
as a
whole
(see accompanying table).
Fig 2-Height SDS vs
total corticosteroid dose.
Discussion
Patients included in this study represent most of those with SRNS referred to a regional paediatric nephrology unit between 1969 and 1979. They form a selected group whose
nephrotic syndrome was, on average, much more severe than would be encountered in a non-specialist unit. Thus most received large doses and long courses of prednisolone-many for more than 5 years. We felt justified in using Tanner standards for comparison of heights because, owing to regional variations, standards produced by Tanner 20 years ago for children living in SouthEast England are appropriate for children living in the Yorkshire region today. (Buckler JMH, unpublished). The height SDSs of the whole group conform so closely to a normal distribution that they are unlikely to conceal a subgroup who are more sensitive to the dwarfing effects of steroids. Mean height SDS of the 28 post-pubertal patients was not significantly less than that of the normal population. It is probable that some of the younger members of this group (5 were less than 19 years and 11 were less than 20 years) were still growing, because of variation in the age at which growth is completed and the delay in growth caused by the effect of steroids on bone maturation. This would mean that the figure of -0-22 for mean height SDS may underestimate the ultimate height attainment of the post-pubertal group. Although there was a tendency for the shorter patients to have received large doses of corticosteroids there was no
919
consistent relation between the total steroid dose and height SDS. In addition, there was no correlation between total dose and ultimate height attainment. Thus catch-up growth seems
attainment, despite the fact that many patients had received
pertinent that the natural history
We thank Dr J. M. H. Buckler for his advice on growth, Department of Mathematics, Leeds University, for assistance with statistics, and Miss J.
to occur.
In this context it is
ofSRNS is for relapses to become less frequent with age, and therefore for less corticosteroid to be needed between the ages of 10-15 years than, say, 5-10 years. In the patients with severe hypercortisolism (who were subsequently given cyclophosphamide), the steroid toxicity may have been due to the large doses that they had received or 6 to an increased sensitivity to the effects of corticosteroids. Even in this group ultimate height attainment was not significantly different from that of the normal population. There have been no reports of growth suppression due to treatment with cyclophosphamide alone, although cytotoxics used in conjunction with cranial irradiation can reduce growth hormone secretion.7, 8 There is no evidence from this study to suggest that cyclophosphamide treatment of nephrotic syndrome suppresses growth. We conclude that although large doses of steroids suppress growth in children at the time of administration, the regimens used in this study had little or no effect on ultimate height
Preliminary Communications
repeated courses of high-dose corticosteroids and prolonged therapy.
maintenance
Bland and Mrs A. M.
Hartup for preparation of the typescript. Correspondence should be addressed to K. D. F., Clarendon Wing, General Infirmary, Belmont Grove, Leeds LS2 9NS. REFERENCES 1 Friedman M, Strang LB Effect of long-term corticosteroids and corticotrophin on the growth of children Lancet 1966; ii. 568-72. 2. Lam CN, Arneil GC. Long-term dwarfing effects of corticosteroid treatment for childhood nephrosis Arch Dis Child 1968; 43: 589-94 3. Trompeter RS, Lloyd BW, Hicks J, White RHR, Cameron JS. Long-term outcome for children with minimal-change nephrotic syndrome. Lancet 1985, i: 368-70. 4. Tanner JM, Whitehouse RH, Takaishi M. Standards from birth to maturity for height, weight, height velocity and weight velocity: British Children, 1965. Part II. Arch Dis Child 1966; 41: 613-35 5. Siegel S. Non-parametric statistics for the behavioral sciences. New York: McGraw Hill, 1956 47-52. 6 Kennedy MCS, Thursby-Pelham DC. Corticosteroids, corticotrophin, and children’s growth. Lancet 1966, ii: 907 7. Shallet SM, Beardwell CG, Aarons BM, Pearson D, Morris-Jones PH Growth impairment in children treated for brain tumours Arch Dis Child 1978; 53: 491 -94. 8 Schiliro G, Russo A, Sciotto A, Distefano G, Vigo R Radiotherapy, chemotherapy, and growth-hormone deficiency. Lancet 1976, ii 1031.
with precursor cells to become virus infection in these cells in a particular multinucleated, bone might well persist indefinitely and spread by continuously infecting further recruited blood-borne preosteoclasts. Previous workers have concentrated mainly on human infections, such as measles and respiratory syncytial virus,4, 7, 9 but we think it is equally likely that Paget’s disease might be due to infection with a virus of animal origin, perhaps in domestic pets. Clinical and radiological evidence osteoclasts
fuse a
PAST PETS AND PAGET’S DISEASE
J. B. O’DRISCOLL
D. C. ANDERSON
Department of Medicine, University of Manchester, Hope Hospital, Eccles Old Road, Salford M6 8HD There is strong morphological evidence that Paget’s disease is caused by a chronic focal infection of osteoclasts, but the source of this paramyxovirus virus and the reason for the wide variation in the incidence of the disease are unknown. The infection may be a zoonosis, with a domestic animal as the usual host. Past exposure to pets was studied in 50 patients with Paget’s disease and 50 age and sex matched control subjects with diabetes mellitus. Dog ownership was significantly more common in the patients than in the control subjects (odds ratios at different ages varied between 4 and 8). 44 of the Paget’s patients and 30 of the control subjects had had dogs before diagnosis of Paget’s disease (or the equivalent age in the control subjects). Exposure to domestic cats was identical in both groups (26 each), and there was no significant difference in exposure to budgerigars. This suggests that a canine virus (possibly canine distemper) might be the primary infective agent, although other factors probably contribute to the particularly high incidence in the North West of England.
Summary
INTRODUCTION
CURRENT evidence favours a paramyxovirus infection of osteoclasts in the aetiology of Paget’s disease of the bone.1-9 The frequency of the disease varies greatly, and some towns in the North West of England have probably the highest incidence in the world.IO-13 Clustering of Paget’s disease in families has been reported but is thought to be caused by a common environmental factor rather than an inherited one.14 It has also been proposed that vitamin D deficiency might operate in conjunction with a virus.15 Since
Ownership for patients with Paget’s disease ( .and control subjects (0) by 10-year cumulative cohorts. Horizontal axis shows age in years (left) and years before diagnosis (nght), for all patients up to and including the age of 80. A and B show total cumulative years of dog ownership, C and D show total numbers who had a dog living in the home
at
any
time