Inhaled corticosteroids, bone formation, and osteocalcin

Inhaled corticosteroids, bone formation, and osteocalcin

1340 substantially higher after PBV in 3 patients in group 1 and 3 in 2, and the grade of right axis deviation (RAD) increased transiently in all 8 p...

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1340

substantially higher after PBV in 3 patients in group 1 and 3 in 2, and the grade of right axis deviation (RAD) increased transiently in all 8 patients after PBV (figure). These changes in QRS amplitude and QRS axis improved within seven days of PBV. Before PBV, QRS duration was within 0-08 s in all cases, but after the procedure it was substantially prolonged in 3 patients in group 1, and remained within 0 08 s throughout the clinical course in all patients in group 2 (figure). The prolonged QRS duration in group 1 improved slightly and this persisted for more than six months after PBV. QRS wave patterns in right precordial leads developed from notched R to a right bundle branch block pattern in 3 patients in group 1 and in 3 in group 2. This pattern persisted for more than six months after PBV in 5 of these 6 patients. None showed prolonged QTc after PBV.3 These changes on standard ECGs were not detected in patients with mild or moderate pulmonary valve stenosis or in school-aged children. During PBV, right ventricular pressure was strikingly increased during inflation of the balloon. Furthermore, the right ventricular

workers should provide details about their assay and express their results on an absolute scale. Moreover, they referred to the use of statistical tests but did not provide any data or p values, ranges, or standard deviation; nor did they indicate Bonferroni correction. Finally, in the figure, we do not understand why the osteocalcin concentrations obtained at day 0 are different for the two curves. We agree with Teelucksingh et al that the clinical relevance of the most recent findings should be established by long-term prospective studies in asthmatic patients with biochemical bone remodelling indices in parallel with bone densitometry

group

measurements.

Departments of Rheumatology and Nuclear Medicine, Free University of Brussels, ANNE PERETZ Hôpital Saint Pierre, PIERRE P. BOURDOUX B-100 Brussels, Belgium A, Praet JP, Bosson D, Rozenberg S, Bourdoux P. Serum osteocalcin m the of corticosteroid-induced osteoporosis. Effect of long and short term corticosteroid treatment. J Rheumatol 1989; 16: 363-67 2. Hodsman AB, Toogood JH, Jennings B, Fraher LJ, Baskerville JC. Differential effects of inhaled budesonide and oral prednisolone on serum osteocalcin. J Clin Endocrinol Metab 1991; 72: 530-40. 3. Jennings B, Andersson KE, Johansson SA. Assessment of systemic effects of inhaled glucocorticosteroids: comparison of the effects of inhaled budesonide and oral 1. Peretz

assessment

outflow tract was stenotic in breastfed infants and young children with severe pulmonary valve stenosis. Therefore the changes in QRS duration and QRS wave pattern reported here may indicate that the transient but striking increase of right ventricular pressure or physical stimulation of the inflated balloon further damage the right ventricular myocardium, especially the right ventricular conduction system and outflow tract, which have already been damaged by pressure overload due to pulmonary valve stenosis. Division of Paediatrics, Children’s Research Hospital, Kyoto Prefectural University of Medicine,

Kyoto 602, Japan 1. Kveselis

prednisolone on adrenal function and markers of bone turnover Eur J Clin Pharmacol 1991; 40: 77-82. 4. Pouw EM, Prummel MF, Oosting H, Roos CM, Endert E. Beclomethasone inhalation decreases serum osteocalcin concentrations. Br Med J 1991; 302: 627-28. 5. Ali NJ, Morrison D, Capewell S, Ward MJ Beclomethasone and osteocalcin. Br Med J 1991; 302: 1080. 6. Delmas PD, Christiansen C, Mann KG, Price PA. Bone gla protein (osteocalcin) assay strandardization report. J Bone Miner Res 1990; 5: 5-11.

KENJI HAMAOKA KOHICHI SAKATA ZENSHIRO ONOUCHI

Epi demic pneumocystis pneumonia in

DA, Rocchini AP, Snider AR, et al. Results of balloon valvuloplasty in the of congenital valvular pulmonary stenosis in children. Am J Cardiol

children before the AIDS

treatment

1985; 56: 527-32. 2. Tynan M, Baker EJ, Rohmer J,

et al. Percutanous balloon pulmonary valvuloplasty. J 1985, 53: 520-24. Stanger P. Transient prolongation of the QTc interval after balloon valvuloplasty and angioplasty in children. Am J Cardiol 1986; 58: 1233-35.

Br Heart 3. Martin GR,

Inhaled corticosteroids, bone formation, and osteocalcin SIR,--On the basis of changes in serum osteocalcin concentrations, Dr Teelucksingh and colleagues (July 6, p 60) claim that inhaled beclomethasone, even at low doses (400 Ilg per day), reduces bone formation in adults. Nowadays, osteocalcin is usually regarded as a good marker of bone formation, being especially sensitive to the inhibitory effects of corticosteroids.l The effects of inhaled corticosteroids (budesonide or beclomethasone) on bone metabolism have received much attention. Most workers have reported no change in osteocalcin concentrations for doses of budesonide lower than 800 ag per day, contrasting with the inhibitory effects (decrease in osteocalcin concentrations) at doses higher than 800 and up to 3200 Ilg per day.2,3 For beclomethasone, an inhibitory effect has been reported by Pouw et al4 and Ali et als at doses of 2000 ug per day. We investigated in a placebo-controlled trial the effects of beclomethasone 1000 ug daily (the usual inhaled dose) given twice a day for one week. Ten healthy volunteers took part. In contrast with Teelucksingh and colleagues’ results, neither serum osteocalcin (Incstar radioimmunoassay; reference range 2 2-6-2 jjg/1; interassay coefficient of variability 9’ 1 %) nor other indices of bone metabolism (serum alkaline phosphatase and immunoreactive parathyroid hormone, calciuria, hydroxyprolinuria) showed substantial changes during the study period. Teelucksingh and colleagues’ results are questionable. Osteocalcin was measured by an in-house radioimmunoassay without indication of the antibody used in the assay or of their reference range; they used plasma but did not mention sampling conditions. It has recently been emphasised that such information is essential for correct interpretation of published reports.’ Teelucksingh et al showed a maximum decrease of about 3 ug/1 in osteocalcin concentrations. In our hands, with the Incstar assay, this would lead to osteocalcin concentrations similar to those achieved by the daily administration of 60 mg of prednisolone.’ These

SIF

era

reports of clusters of Pneumocystis carinii in pneumoiiid (PCP) HIV-seronegative adults without prediposing disease!,2 are unusual in the clinical setting of the past 30 years. Before the AIDS epidemic, PCP in adults was almost exclusively restricted to the immunocompromised. Epidemic PCP in children in former years seems to have been overlooked even though these outbreaks happened within the memory of some physicians still in "wo

recent

practice. Epidemic "interstitial cell pneumonia" in children occurred in Europe in the late 1930s and during the 1940s and 1950s. It was first noted in German speaking countries. Ammich described 11cases among premature babies coming to necropsy in Berlin in 1938,3and in 1942 a report from the same hospital showed that the interstitial pneumonia frequently followed blood transfusions and noted that 4 .4 of the Icases described by Amrnich had received transfusions." These outbreaks are often attributed to prematurity and malnutrition in war-torn zones. This seems unlikely, however. Gormsen, reviewing 350 cases reported by 1950,5 noted that these outbreaks of pneumonia occurred in waves, often in the same clinics and rooms, suggesting that the disease was contagious or that it was a

reaction of premature infants

to some treatment

used in central

Europe where German was a common language in higher education. Especially striking are the large number of cases reported from German-speaking Switzerland (707 between 1941 and 1949) but not one from the French-speaking part.6 This may simply reflect lack of awareness: the French-speaking doctors may not have been familiar with the reports published in German. Most cases reported in the early 1950s-from Hamburg and Cologne, for example, and the Czech city of Olomouc. In 1957 Ahvenainen’ estimated that more than 2000 cases had been published and felt that the disease might have become so commonplace in some areas that cases were no longer reported. He suggested that the disease first arose in a fairly small area of central Europe and then slowly spread from country to country. P carinii was first described as the agent causing interstitial plasma cell pneumonia by the Czech investigator J. Vanek in 1951. were

He noted that the organisms can be seen in photomicrographs in Ammich’s paper of 1938. In the United States, where this disease was unknown, Vanek’s report was treated with scepticism until 1957, when an extensive review was published by GajdusekIn this