Syncope is a common problem that occurs in 5% to 26% of adults at one time in their life, accounts for 1% of hospital admissions and ap- proximately 3% of emergency room visits. The literature dealing with HUT, with or without isoproterenol for unexplained syncope, is very dif- ficult to interpret. The review by Kapoor et al summarizes much of this literature and provides us with several important conclusions. Nevertheless, their strong reco mmendation to avoid using isopro terenol does not appear warranted.

Hal Barron, MD Adam Fitzpatrick, MD, MRCP Nora Goldschlager, MD, FACC

University of California San Francisco

San Francisco, California

1. Kapoor WN, Smith MA, Miller NL. Upright tilt testing in evaluating syncope: a comprehensive literature review. Am J Med. 1994;97:78-88. 2. Strasberg B, Rechatia E, Sagie A, et al. The head up tilt table test in patients with syncope of unknown origin, Am Heart J. 1989;l l&923-927. 3. Fitzpatrick AP, Theodorakis G, Vardas P, Sutton R. Methodology of head-up tiit testing in patients with unexplained syncope. J Am Coil Cardiof. 1991; 17:125-130. 4. Brignole M, Menozzi C, Gianfranchi L, et al. Neurally mediated syncope detected by carotid sinus massage and head-up tilt test in sick sinus syndrome. Am J Cardiol. 1991;68:1032-1036. 5. Hackel A, Linzer M, Anderson N, Williams R. Cardiovascular and catecholamine responses to headup tilt in the diagnosis of recurrent unexplained syncope in elderly patients. J Am Geriatr Sot. 1991; 39:663&69. 6. LermanSagie T, Rechavia E, Strasberg B, et al. Headup tilt for the evaluation of syncope of unknown origin in children. J Pediatr. 1991;118: 676-679. 7. Raviele A, Gasparini G, Di PF, et al. Usefulness of headup tiit test in evaluating patients with syncope of unknown origin and negative electrophysiologic study. Am J Cardiol. 1990;65: 1322-1327. 8. Brignole M, Menozzi C, Gianfranchi L, et al. Carotid sinus massage, eyeball compression, and head-up tilt test in patients with syncope of uncertain origin and in healthy control subjects. Am Heart J. 1991;122:1644-1651. 9. Waxman MB, Yao L, Cameron DA, et al. Isopro terenol induction of vasodepressor-type reaction in vasodepressorprone persons. Am J Cardiol. 1989; 63:58-65. 10. Thilenius OG, Quinones JA, Husayni TS, Novak J. Tilt test for diagnosis of unexplained syncope in pediatric patients. Pediatrics. 1991;87:334-338.

Manuscript submitted November 29, 1994 and accepted February 20, 1995.

The Reply: Drs. Barron, Fitzpatrick, and

Goldschlager have outlined many of the issues with upright tilt test- ing. Their major point is that the yield from the passive portion of upright tilt testing with isopro terenol should be compared with the yield from the studies using pas sive tilt only. As shown in Table lII, the yield is higher in studies using passive tilt. They argue then that the additional testing using isopro- terenol increases positive re sponses. The major issue in this comparison, however, is the dura- tion of tilt testing. Studies with iso proterenol used shorter duration of passive tilt testing, but had a longer overall duration of tilt testing. Thus, the comparison of passive tilt stud- ies with passive portion of isopro terenol tilt studies is invalid be cause the duration of upright tilt testing is not taken into account. It is well recognized that the duration of upright tilt testing is a major pre dictor of positive responses. We felt that the only way to compare the two types of tilt testing is to com- pare the total yield of passive stud- ies with those using isoproterenol.

We agree with Dr. Barron et al, that studies of upright tilt testing are difficult to interpret. The stud- ies have had widely differing pro- tocols and used different doses of isoproterenol and different angles of testing. The duration of tilt test- ing of the passive phase as well as the isoproterenol phase has varied considerably as well. Since there is a large body of literature now avail- able on this modality, a summary is useful so that limitations of this methodology can be answered.

As noted in our paper, we recom- mend adopting standard methodol- ogies. Studies of standard methodol- ogies are then needed to determine sensitivity and speciticity of upright tilt testing. These studies should ide- ally be done in multiple different centers, using blinded assessment of positive results with speciEc deEni- tions of positive end points.

Wishwa Kapoor, MD, MPH University of Pittsburgh

Medical Center Pittsburgh, Pennsylvania

Manuscript submitted February 17, 1995 and accepted February 20, 1995.

OSTEOPENIA IN ADULTS WITH CYSTlc FIBROSIS

To the Editor: We read with interest the recent

paper by Bachrach et al’ “Osteo- penia in adults with cystic fibrosis,” and would like to add our obser- vations. We studied a group of 24 children and adults with cystic E- brosis; they ranged in age from 3 to 29 years, and only 1 was on system- ic corticosteroids. The bone min- eral density of the lumbar spine was assessed by quantitative com- puted tomography using a Siemens scanner. This technique preferen- tially measures high-turnover tra- becular bone and is not influenced by vertebral body size. In compar- ison with the reference data of Gilsanz et al,2 16 individuals had a bone mineral density below the mean, with 6 individuals having val- ues more than 2 standard devia- tions below the mean (Figure). Similiar to Bachrach et al, we found no correlation of bone den- sity with Schwachmann score, F’EY,, or the chest roentgenogram score. The only significant correla- tion was with delayed puberty in those individuals in the pubertal age range (r = .51, P = 0.03).

We also measured serum 25-hy- droxyvitamin D by liquid chroma- tography and parathyroid hor- mone using an intact molecule assay (Nichols Institute, San Juan Capistrano, California). Only 4 in- dividuals had evidence of subopti- mal vitamin D status, and only 2 individuals had a marginal eleva- tion in parathyroid homone activ- ity. Thus there were no consistent abnormalities of vitamin D or parathyroid hormone status, and this was therefore not an etiologi-

690 December 1995 The American Journal of Medicinea Volume 99

CORRESPONDENCE

cal factor in the development of their osteopenia.

Thus, we would agree that os- teopenia is common in individuals with cystic fibrosis. Although de- layed puberty may be partly re- sponsible, it is clear that this is not the only factor as it was also pre- sent in prepubertal children. We have no bone biopsy evidence, but it is unlikely that the osteopenia is due to osteomalacia, as this would be expected to be associated with increased parathyroid hormone activity. It is more likely that this is a genuine reduction in bone mass, that is, osteoporosis.

As yet, there is no clear evidence of increased fractures occurring in adult patients with cystic fibrosis, but this may well become appar- ent with increasing munbers sur- viving into adulthood.

Nicholas Shaw, MRCP Christopher Bedford, MRCP

David Heaf, FRCP Helen Carty, FRCP

Royal Liverpool Children’s Hospital

Alder Hey, United Kingdom John Dutton, PhD

University Department of Cli,nical Chemistry

Liverpool, United Kingdom

1. Bachrach LK, Loutit CW, Moss RB, Marcus R. Osteoporosis in adults with cystic fibrosis, Am J Med. 1994;96:27-34. 2. Gilsanz V, Roe TF, Mora S, et al. Changes in vertebral bone density in black girls and white girls during childhood and puberty. NEJM. 1991;325: 1597-1600.

Manuscript submitted December 13, 1994 and accepted February 20, 1995.

The Reply: The observations of Shaw et al

confirm the findings of a growing number of investigators that bone mass is often reduced in children and adults with cystic fibrosis.1-6 An estimated 20% to 5% of the subjects studied have significant osteopenia (bone density >2 standard devia- tions below the expected). In addi- tion, several centers including our own have observed pathological

SDS 4

8 3

2 i

n

l- e

l I AGE (YEARS)

0 ,m I l 1 1 I 1 4 5 10 l 15 20 25 30

8

mm m

m m

m

l

m

figure. The bone mineral density of the lumbar spine in 24 individuals with cystic fibrosis aged 3 to 29 years expressed as a standard deviation score (SDS) compared with agematched controls.

fractures involving the spine, hip, forearm, or rib.is3p6 Although we can- not establish an exact relative risk for fracture due to relatively small numbers, atraumatic fractures ap pear to be a more frequent compli- cation in this patient population.

Despite the consensus that osteopenia exists, the etiology of these deficits remains uncertain. We would agree that vitamin D deficiency cannot account for this disorder, since many patients have adequate serum levels of %hydroxy- vitamin D and since these levels do not correlate with bone mineral status. 1~3~5~6 Gonadal dysfunction, including delayed puberty and hy- pogonadism in older patients, does appear to be a significant risk fac- tor.1,4z6 Malnutrition as reflected in low body mass is also a correlate of low bone mass.1*6 Glucocorti- coid therapy is an additional risk factor, but osteopenia is observed in many patients who have never received steroids. 1,2,4 The contribu- tion of reduced weight-bearing ac- tivity in this disorder warrants fur- ther study.

Osteopenia is a common and dis- abling complication of cystic fibro- sis that will continue to plague sur- vivors of this disorder until effective

therapy is devised to augment gain and diminish loss of bone mass. Attention to bone mineral must be considered a standard component of the comprehensive care of these patients. Efforts should be made to optimize overall nutrition, vitamin D and calcium intake, and weight- bearing activity, and to limit gluco corticoids to the mmimally effective dose. Bone mineral status should be monitored with densitometry. Pre Iiminary data suggest that bone turnover is increased in some cys tic fibrosis patienti; thus, bisphos- phonates or other antiresorptive agents may prove beneficial, but should be used as part of controlled trials to provide a detinitive mea- sure of efficacy. Cooperative multi- center studies are urgently needed to define effective therapy for OS teopenia in cystic fibrosis.

Laura K. Bachrach, MD Robert Marcus, MD

Stanford University Medical Center

Stanford, California

1. Bachrach LK, Loutit CW, Moss RB, Marcus R. Osteoporosis in adults with cystic fibrosis. Am J Med. 1994;96:27-34. 2. Gibbens DT, Gilsanz V, Boechat MI, et al. Osteo porosis in cystic fibrosis. J Pediatr. 1988;113: 295-300.

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