the axial and the appendicular skeleton. Differential ... Both appendicular and total body calcium measurements,

  • View
    0

  • Download
    0

Embed Size (px)

Text of the axial and the appendicular skeleton. Differential ... Both appendicular and total body calcium...

  • Differential effects of endocrine dysfunction on the axial and the appendicular skeleton.

    E Seeman, … , W J Johnson, B L Riggs

    J Clin Invest. 1982;69(6):1302-1309. https://doi.org/10.1172/JCI110570.

    In 100 patients with various types of endocrine dysfunction, we measured bone mineral density (BMD) at the midradius (greater than 95% cortical bone) and distal radius (75% cortical and 25% trabecular bone) by single photon absorptiometry and at the lumbar spine (greater than 66% trabecular bone) using the new technique of dual photon absorptiometry. BMD in each endocrine disorder deviated in at least one site from the sex-specific age regression of 187 normal subjects. For patients with primary hyperparathyroidism, hypercortisolism, and hyperthyroidism this deviation was negative (suggesting bone loss), whereas for patients with secondary hyperparathyroidism due to chronic renal failure, acromegaly, and postsurgical hypoparathyroidism it was positive (suggesting bone gain). When all six states of endocrine dysfunction were compared concomitantly by multivariate analysis of variance, the profile of the changes in BMD differed significantly (P less than 0.001), indicating a nonuniform response of bone to the various hormonal alterations. When values for BMD at each of the three scanning sites were compared the midradius and distal radius did not differ significantly; either of the radius measurements, however, differed significantly (P less than 0.001) from the lumbar spine. Thus, the BMD of the axial skeleton cannot be reliably predicted from measurements made in the appendicular skeleton. We conclude that the effects of endocrine dysfunction on bone density are complex and are […]

    Research Article

    Find the latest version:

    http://jci.me/110570/pdf

    http://www.jci.org http://www.jci.org/69/6?utm_campaign=cover-page&utm_medium=pdf&utm_source=content https://doi.org/10.1172/JCI110570 http://www.jci.org/tags/51?utm_campaign=cover-page&utm_medium=pdf&utm_source=content http://jci.me/110570/pdf http://jci.me/110570/pdf?utm_content=qrcode

  • Differential Effects of Endocrine Dysfunction on the Axial and the Appendicular Skeleton

    E. SEEMAN, H. W. WAHNER,K. P. OFFORD, R. KUMAR, W. J. JOHNSON,and B. L. RIGGS, Endocrinology Research Unit, Division of Endocrinologyl Metabolism and Internal Medicine, Section of Diagnostic Nuclear Medicine, Department of Medical Statistics and Epidemiology, Division of Nephrology and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905

    A B S T R A C T In 100 patients with various types of endocrine dysfunction, we measured bone mineral density (BMD) at the midradius (>95% cortical bone) and distal radius (75% cortical and 25% trabecular bone) by single photon absorptiometry and at the lum- bar spine (>66% trabecular bone) using the new tech- nique of dual photon absorptiometry. BMDin each endocrine disorder deviated in at least one site from the sex-specific age regression of 187 normal subjects. For patients with primary hyperparathyroidism, hy- percortisolism, and hyperthyroidism this deviation was negative (suggesting bone loss), whereas for patients with secondary hyperparathyroidism due to chronic renal failure, acromegaly, and postsurgical hypopara- thyroidism it was positive (suggesting bone gain). Whenall six states of endocrine dysfunction were com- pared concomitantly by multivariate analysis of vari- ance, the profile of the changes in BMDdiffered sig- nificantly (P < 0.001), indicating a nonuniform response of bone to the various hormonal alterations. When values for BMDat each of the three scanning sites were compared, the midradius and distal radius did not differ significantly; either of the radius measure- ments, however, differed significantly (P < 0.001) from the lumbar spine. Thus, the BMDof the axial skeleton cannot be reliably predicted from measure- ments made in the appendicular skeleton. We con- clude that the effects of endocrine dysfunction on bone density are complex and are both disease and site spe- cific.

    INTRODUCTION

    Parathyroid hormone, cortisol, thyroxine, and growth hormone affect bone remodeling and, thereby, can

    Address reprint requests to Dr. Riggs. Received for publication 7 December 1981 and in revised

    form 16 February 1982.

    alter skeletal mass. Alterations in bone mineral density (BMD)' resulting from states of hormonal dysfunction have previously been studied only in the appendicular skeleton. In a few instances, total body calcium has been measured by neutron-activation analysis; these results, in general, have agreed with those of appen- dicular measurements. Both appendicular and total body calcium measurements, however, are relatively insensitive to changes in trabecular bone, especially when these changes occur in the axial skeleton. The appendicular skeleton is composed predominantly of cortical bone, whereas the axial skeleton contains large amounts of trabecular bone (1). Moreover, because the whole skeleton contains 85% cortical but only 15% tra- becular bone (2), changes in trabecular bone would have a relatively small effect on total body calcium measurements. If changes in density of cortical and trabecular bone and changes in circulating hormones occurred pari passu in all regions of the skeleton, BMD measurements of the appendicular skeleton would suf- fice. There are several reasons for believing, however, that BMDmeasurements of the axial skeleton will be required to characterize definitively the skeletal ef- fects of states of endocrine dysfunction. First, the metabolic activity of the two bone types differs con- siderably: cortical bone has a turnover rate of only 3%/ yr (3), whereas trabecular bone has a turnover rate of up to 30%/yr (4). Second, autopsy studies have shown good correlation for BMDamong sites containing large amounts of cortical bone but a poorer correlation be- tween BMDof these sites and that of the vertebrae (5). Third, in most metabolic bone diseases, fractures occur almost exclusively at skeletal sites that contain substantial amounts of trabecular bone.

    These considerations led us to examine the possi-

    I Abbreviations used in this paper: BMC, bone mineral content; BMD, bone mineral density; iPTH, immunoreactive parathyroid hormone.

    1302 J. Clin. Invest. © The American Society for Clinical Investigation, Inc. * 0021-9738/82/06/1302/08 $1.00 Volume 69 June 1982 1302-1309

  • bility that states of hormonal dysfunction have differ- ential effects on the appendicular and axial skeleton. Wetested this hypothesis by making concurrent mea- surements of BMDin both regions of the skeleton in patients with primary hyperparathyroidism, second- ary hyperparathyroidism due to chronic renal failure, hypercortisolism, hyperthyroidism, acromegaly, and postsurgical hypoparathyroidism.

    METHODS

    Patients. We studied 100 patients with endocrine dys- function. There were 29 patients (21 female and 8 male) with primary hyperparathyroidism. In 26 of them, the di- agnosis was confirmed by surgical removal of a parathyroid adenoma; in the remaining 3, the diagnosis was based on clinical and laboratory criteria, including hypercalcemia and an elevated level of serum immunoreactive parathyroid hor- mone (iPTH). 21 patients presented with asymptomatic hy- percalcemia, and 8 presented with nephrolithiasis; none presented because of bone disease. The mean serum calcium concentration was 11.6 mg/dl (range, 10.3-14.4) (normal range, 8.9-10.1). The mean serum iPTH level was 156 Aleq/ ml (range, 39-2,200) (normal range,

  • TABLE I

    Mean BMDfor Each Scanning Site, Expressed as Positive or Negative Standard Deviations from the Age- and Sex-specific Normal Mean

    Group No. Lumbar spine Midradius Distal radius

    Normal subjects 187 0.00 0.00 0.00 Primary hyperparathyroidism 29 -1.15* -0.45 -0.921 Secondary hyperparathyroidism

    (chronic renal failure) 14 0.11 1.15§ 0.02 Hypercortisolism 17 -1.94° 0.29 -0.33 Hyperthyroidism 13 -0.82° -0.70 -0.67 Acromegaly 7 0.681 0.83 0.41 Postsurgical hypoparathyroidism 20 1.50" 0.70t 0.68§

    *P. 0.001. t P < 0.01. § P < 0.05.

    bone), distal radius (75% cortical and 25% trabecular bone), and lumbar spine (>66% trabecular bone).

    Statistical methods. To investigate the changes of BMD at each scanning site and at two or three sites concomitantly, we used linear regression, two-sample univariate and mul- tivariate t tests, and paired t tests. These comparisons were made within and across states of endocrine dysfunction. All P values reported were two-tailed.

    In order to compare men and women of varying ages, individual BMDvalues were expressed as standard deviation from the predicted mean for normal subjects obtained from regression equations that predicted the bone density as a function of age. The SD corresponds to "standardized de- partures from normal," "standardized deviations," or z- scores. Separate regression equations were used for men and for women. The BMDdifference (observed minus predicted mean) divided by Sy., (the estimate of the variability about the fitted regression line) is the SD. By definition, the mean SD from the sex-specific age regression for normal subjects

    is zero. The methods described in the Statistical Analysis System (12) were used to carry out all statistical computa- tions.

    RESULTS

    Comparison of patients with endocrine dysfunc- tion and normal subjects. Table I gives mean values for SD at three scanning sites for each of the six states of endocrine dysfunction. Individual values are dis- played graphically in Fig. 1A and B. For patients with primary hyperparathyroidism, the mean SD was neg- ative at all three scanning sites a