Skeletal Abnormalities After Jejunoileal Bypass JOHN D. HALVERSON, M.D.,* STEVEN L. TEITELBAUM, M.D.,t4t JOHN G. HADDAD, M.D.,4 WILLIAM A. MURPHY, M.D.§
Jejunoileal bypass surgery is fraught with many longterm complications, among which is hypovitaminosis D. The relationship, if any, of hypovitaminosis D to the skeletal disease which may occur following this operation is, however, unknown. Consequently, we studied eight patients with low circulating levels of 25-hydroxyvitamin D who had undergone jejunoileal bypass at least two and one-half years previously. Despite the absence of skeletal symptoms, the bone biopsies of six of these patients were abnormal. The volume of trabecular bone was diminished in the group as a whole, and half the patients had an excess of unmineralized skeletal matrix. However, no noninvasive diagnostic technique identified those patients with skeletal disease. We therefore conclude that recognition of those jejunoileal bypass patients potentially at risk to develop clinically significant bone disease requires biopsy of the skeleton.
IN RECENT YEARS, jejunoileal bypass (JI bypass) has become a popular means of treating morbidly obese patients. Unfortunately, this procedure is accompanied by frequent, serious complications, among the less commonly recognized of which are those relating to mineral metabolism. For example, vitamin D homeostasis can be disrupted by small bowel bypass2I and some patients may develop histological abnormalities of the skeleton.3"5 Despite a theoretical relationship, a correlation between skeletal pathology and the low circulating levels of 25-hydroxycholecalciferol (25-OHD) which frequently occur after intestinal bypass surgery has not been demonstrated. Furthermore, it is unknown if patients with skeletal disease can be identified by methods other than bone biopsy. We herein report a study undertaken to determine the incidence and predictability of bone disease in JI bypass patients with persistently low blood levels of 25-OHD. We found * Department of Surgery, Barnes Hospital. t The Edward Mallinckrodt Institute of Radiology, Barnes
Hospital. t Department of Pathology, Jewish Hospital. § Division of Bone and Mineral Metabolism, Jewish Hospital. Supported in part by NIH Grants: RR 00036, AM 14570, and AM 11674. Reprint requests: John D. Halverson, M.D., Department of Surgery, 4960 Audubon Avenue, St. Louis, Missouri 63110. Submitted for publication: September 15, 1978.
From the Department of Surgery and The Edward Mallinckrodt Institute of Radiology (Barnes Hospital), Department of Pathology and the Division of Bone and Mineral Metabolism (Jewish Hospital), Washington University School of Medicine, St. Louis, Missouri
that, despite the absence of skeletal symptoms, the bone biopsies of most of these patients were abnormal. Furthermore, we identified no noninvasive test which was predictive of those individuals who develop histological abnormalities of the skeleton following surgery. Subjects Seven women and one man who had undergone JI bypass 37 + 6 (S.D.) months prior to admission and who had low circulating 25-OHD levels were admitted to the Clinical Research Center, Washington University School of Medicine. The mean age of these patients was 42 ± 9 (S.D.) years, and their average weight was 85 ± 26 (S.D.) kg representing a mean weight loss of 43%. Methods
At the time of admission, routine laboratory determinations were performed. Circulating levels of immunoreactive parathyroid hormone (iPTH) and 25OHD were also measured, as was urinary excretion of calcium and creatinine over a 24 hour period. Using a displacement assay8 25-OHD levels were measured. This assay uses a 1:4000 dilution of normal rat serum as the binding protein source. It does not distinguish between 25-hydroxycholecalciferol (25-OHD3) and 25hydroxyergocalciferol (25-OHD2). Therefore, the values obtained represent the sum of these moieties in serum as 25-hydroxycholciferol (25-OHD).9 Standard posteroanterior hand radiographs were obtained and the average combined cortical thickness calculated. Detailed radiographs of the fingers were evaluated for intracortical or subperiosteal resorption.'1 Bone density of the midradial cortex was measured
0003-4932/79/0600/0785 $00.80 © J. B. Lippincott Company
785
786
HALVERSON AND OTHERS
Ann. Surg. * June 1979
TABLE 1. Biochemical Measurements in Vitamin D Deficient Patients with Normal Osteoid (I) and Hyperosteoidosis (II)
Normals
Ca. 9-10.3 mg/dl
Po4 3.0-5.5 mg/dl
Mg. 1.5-2.4 meq/L
Albumin 3.5-5.0 g/dl
Alkaline Phosphatase 25-80 mu/ml
iPTH 2-10 ,ueq/ml
25-OHD 10-30 ng/ml
Urine Calcium per 24 Hours 50-400 mg/24 hrs
8.5 7.6 9.0 9.3
3.3 2.9 3.6 3.1
1.4 0.9 1.5 0.6
3.6 3.1 4.3 4.0
63 127 91 84
6 12 4
5.4 4.8 3.5 4.0
98 69 39 16
C.W. R. I* N. M.B. D.J.
*mean
+
S.D.
H. S. G.G. t V.P. M.H. t mean + S.D.
8.6
+
0.7
3.3
8.7 9.0 9.3 9.1
I
9.0
+
+
0.2
1.4
3.3 3.2 3.8 3.9 0.3
3.6
+
+
0.7
3.8
1.4
+
91
3.8 3.8 4.0 4.2
1.1 1.6 1.6 1.4
0.4
0.5
+
0.2
3.9
by photon absorptiometry using a Norland-Cameron Bone Mineral Analyzer®.19 A transiliac needle bone biopsy which included both cortices and intervening trabeculae was obtained from each patient following administration of time-spaced, fluorescent tetracycline skeletal markers. The nondecalcified specimen embedded in methylmethacrylate was cut longitudinally in 5.0 and 10.0 ,um histological sections on a Jung Model K Sledge Microtome.® The entire trabecular area of a 5.0 Am section taken from the midpoint of the specimen and stained by a modification of the Goldner technique was histologically quantitated using a Merz-Schenk Integrating Eyepiece®. The following histometric parameters were evaluated and were compared to those derived from autopsy specimens taken from a group of age and sex matched patients who died suddenly: a) Per cent total bone volume (per cent of marrow space composed of bone matrix) b) Per cent relative osteoid volume (per cent of trabecular bone matrix which is unmineralized, i.e. osteoid) c) Per cent osteoid surface (per cent of trabecular bone covered by osteoid) d) Per cent osteoblastic osteoid surface (per cent of trabecular surface covered by osteoid lined by characteristic osteoblasts) e) Per cent surface fibrosis (per cent of trabecular surface juxtaposed to marrow fibrosis) f) Number of osteoclasts/mm2 trabecular space g) Cellular rate of bone mineralization (a kinetic parameter derived by determining the mean distance between the midpoints of the two fluorescent tetracycline labels and dividing that distance by the days between the midpoints of administration of the two doses of the antibiotic. As no normal tetracycline-
+
+
27
108 90 81 80 0.2
90
+
7.3
+
4.2
+
0.8
56
+
35
9 9
2.8 3.0 6.6 3.2
100 120 50 46
6.5 ± 2.9
3.9 ± 1.8
80 ± 26
4 4
13
4.4
based data are available in our laboratory, the values obtained were compared to those present in the literature.12 Abnormality of a histometric parameter was defined as a value greater or less than 2 S.D. from the normal mean. Results The results of the variety of biochemical determinations performed on our patients were consistent with the post JI Bypass state (Table 1).1o Only one of the eight had mildly elevated circulating iPTH levels and, as selection for inclusion in the study was the presence of hypovitaminosis D, serum 25-OHD levels were less than 10 ng/ml in all patients. Six of the eight patients had abnormal bone biopsies as assessed by standard nonfluorescent microscopy (Table 2). As a group, the biopsies demonstrated osteopenia and contained an excess of osteoid (hyperosteoidosis). In three patients the percentage of total bone volume was decreased, and the relative osteoid volume was increased. Moreover, there was an inverse correlation between these two parameters within the group as a whole which failed to exist within the normal biopsies (Fig. 1). The biopsy of one of the five nonosteopenic bypass patients also contained an increased percentage of relative osteoid volume, and two patients had an increased percentage of total osteoid surface. The percentage of trabecular surface covered by osteoblasts was increased in four biopsies, being the only abnormality in one. Moreover, two bopsies contained an excess of osteoclasts and the mean number of these cells within the group was more than three times the normal mean. The biopsies of two patients failed to exhibit any
Vol. 189 . No. 6
SKELETAL ABNORMALITIES AFTER BYPASS
787
TABLE 2. Histological Data from Vitamin D Deficient Patients
Patient
C.W. N.R. M.B. D.J. H.S. G.G. V.P. M.H. Mean ± S.D. Normal mean ± S.D. *
Per Cent Total Bone Volume
Per Cent Relative Osteoid Volume
Per Cent Total Osteoid Surface
Per Cent Osteoblastic Osteoid Surface
Per Cent Surface Fibrosis
Osteoclasts/ mm2
Cellular Rate of Bone Mineralization (um/Day)
26.1 15.9 21.9 19.2 16.4 9.3* 7.8 5.7* 15.3 ± 7.It
0.2 0.4 1.6 2.0 4.2* 4.4* 7.1* 8.2* 3.5 ± 5.1
1.1 4.2 9.1 16.6 24.5 21.1 26.6* 25.1* 16.0 ± 9.6t
0 0.5 4.0* 2.7 16.3* 1.3 18.0* 8.6* 6.4 ± 7.1
0 0 0 0 0 0 0 0 0
0.231 0.347 0.248 1.029* 0 0.452* 0.318 0 0.33 ± 0.31
0* 0* 1.15* 0.89 0.83 0.73 0.66 0.73 0.62 ± 0.42
24.8 ± 5.1
1.1 ± 1.4
7.6 ± 8.7
1.0 ± 1.4
0
0.10 ± 0.14
0.70 ± 0.16
+2 s.d. from normal mean. tDifference from normal mean
(p < 0.01).
tetracycline fluorescence, and in one, the cellular rate of bone mineralization was increased. All eight patients had metacarpal cortical thickness measurements within two standard deviations of the age-sex norm. Densitometric osteopenia (below 95% confidence limits) was documented in two patients with hyperosteoidosis and in two patients with normal histomorphology (Table 3). Early intracortical resorption was found only in two patients with excess osteoid, only one of whom had densitometric osteopenia. Regression analysis was performed between all morphometric and clinical and biochemical parameters,
and no significant relationships were demonstrated. Furthermore, when the patients were divided into I) those with normal quantities of osteoid and II) those with excess osteoid, there were no clinical (Table 4) or biochemical (Table 1) differences between the groups. In short, no biochemical or radiographic measurements made in this group of vitamin D deficient patients were of value in predicting bone histology.
Discussion JI bypass has become widely accepted as a means of treating morbidly obese patients who are intractable
10r 9 w 0 0
81 7
a
FIG. 1. Relationship of percentage of relative osteoid volume and percentage total C,) bone volume in bone biop- 0 sies of eight postjejunoileal w bypass patients with low circulating 25-OHD (R = .88, p= .~~~~
-T'h.
FIGS. 2a and b. (a, top) Bone biopsy 07M
markedly shortened small intestinal segment in our patients therefore represents a continuing threat to their vitamin D economy, in spite of the previously reported adaptive response.21 Furthermore, there is evidence that, aside from its effect on intestinal calcium transport, vitamin D is necessary for normal bone mineralization to occur.5'21'22 Whether 25-OHD is a/the metabolite responsible for this event remains to be determined. However, post-JI bypass patients have low serum 25-OHD concentrations and ineffectively absorb a challenge oral dose of 25-OHD.20'21 Consequently, the threat of continuing vitamin D depletion and clinically significant bone
9,.
:.
disease appears strong enough to warrant judicious vitamin D prophylaxis. References 1. Arnaud, S., Goldsmith, R. S., Lambert, P. W., et al.: 25-OHD: Evidence of an Enterohepatic Circulation in Man. Proc. Soc. Exp. Biol. Med., 149:590, 1975. 2. Avioli, L. V., Lee, S. W., McDonald, J. E., et al.: Metabolism of Vitamin D3-3H in Human Subjects: Distribution in Blood, Bile, Feces and Urine. J. Clin. Invest., 49:983. 1967. 3. Compston, J. E., Laker, M. F., Woodhead, J. S.. et al.: Bone Disease after Jejunoileal Bypass for Obesity. Lancet. ii: 1. 1978. 4. DeWind, L. T. and Payne, J. H.: Intestinal Bypass Surgery for Morbid Obesity: Long-Term Results. JAMA. 236:2298. 1976.
790
HALVERSON AND OTHERS
5. Eastwood, J. B., Brodier, P. J., Clarkson, E. M., et al.: The Contrasting Effects on Bone Histology of Vitamin D and of Calcium Carbonate in the Osteomalacia of Chronic Renal Failure. Clin. Sci. Mol. Med., 47:23, 1974. 6. Frost, H. M.: Tetracycline-based Histological Analysis of Bone Remodeling. Calcif. Tissue Res., 3:211, 1969. 7. Gain, S. M., Poznanski, A. K. and Nagy, J. M.: Bone Measurement in the Differential Diagnosis of Osteopenia and Osteoporosis. Radiology, 100:509, 1971. 8. Haddad, J. G., and Chyu, K. J.: Competitive Protein-Binding Radioassay for 25-hydroxycholecalciferol. J. Clin. Endocrin. Metab., 33:992, 1971. 9. Haddad, J. G., Chyu, K. J., Hahn, T. J., et al.: Serum 25hydroxy-vitamin D in Sex-linked Hypophosphatemic Rickets. J. Lab. Clin. Med., 81:22, 1973. 10. Halverson, J. D., Wise, L., Wazna, M. F., et al.: Jejunoileal Bypass for Morbid Obesity: A Critical Appraisal. Am. J. Med., 64:461, 1978. 11. Meema, H. E., Oreopoulos, D. G. and Meema, S.: A Roentgenologic Study of Cortical Bone Resorption in Chronic Renal Failure. Radiology, 126:67, 1978. 12. Melson, F. and Moskilde, L.: Morphometric and Dynamic Studies of Bone Changes in Hyperparathyroidism. Acta Pathol. Microbiol. Scand. (A), 85:141, 1977. 13. Meuiner, P.: La Maladie Osseuse de Paget. Lyon Med., 233: 839, 1975. 14. Meuiner, P. J., Bianchi, G. G. S., Edouard, C. M., et al.: Bony Manifestations of Thyrotoxicosis. Orthop. Clin. North Am., 3:745, 1972.
Ann. Surg. * June 1979
15. Parfitt, A. M., Miller, M., Frame, B., et al.: Metabolic Bone Disease after Intestinal Bypass for Treatment of Obesity. Ann. Int. Med., 89:193, 1978. 16. Rao, D. S., Parfitt, M. J., Miller, D. L., et al.: Metabolic Bone Disease After Intestinal Bypass for Treatment of Obesity. (Abs) Proc. 3rd Internatl. Workshop on Calcified Tissues, Mar 5-9, 1978, Kiriat Anavim, Israel. 17. Scott, H. W., Jr., Dean, R., Shull, H. J., et al.: New Considerations in Use of Jejunoileal Bypass in Patients with Morbid Obesity. Ann. Surg., 177:723, 1973. 18. Sherrard, D. J., Baylink, D. J., Wergedal, J. E., et al.: Quantitative Histological Studies on the Pathogenesis of Uremic Bone Disease. J. Clin. Endocrinol. Metab. 39:119, 1974. 19. Sorenson, J. A. and Cameron, J. R.: A Reliable in vivo Measurement of Bone-Mineral Content. J. Bone Joint Surg., 49A: 481, 1967. 20. Stamp, T. C. B.: Intestinal Absorption of 25-Hydroxycholecalciferol. Lancet, ii:121, 1974. 21. Teitelbaum, S. L., Halverson, J. D., Bates, M., et al.: Abnormalities of Circulating 25-OH Vitamin D After Jejunoileal Bypass for Obesity: Evidence of an Adaptive Response. Ann. Int. Med., 86:289, 1977. 22. Teitelbaum, S. L., Hruska, K. A., Shieber, W. et al.: Tetracycline Fluorescence in Uremic and Primary Hyperparathyroid Bone. Kidney Int., 12:366, 1977. 23. Teitelbaum, S. L., Rosenberg, M. E., Bates, M. et al.: The Effects of Phosphate and Vitamin D Therapy on Osteopenic Hypophosphatemic Osteomalacia of Childhood. Clin. Orthop. 116:38, 1976.
Jejunoileal bypass surgery is fraught with many longterm complications, among which is hypovitaminosis D. The relationship, if any, of hypovitaminosis D to the skeletal disease which may occur following this operation is, however, unknown. Consequently, we studied eight patients with low circulating levels of 25-hydroxyvitamin D who had undergone jejunoileal bypass at least two and one-half years previously. Despite the absence of skeletal symptoms, the bone biopsies of six of these patients were abnormal. The volume of trabecular bone was diminished in the group as a whole, and half the patients had an excess of unmineralized skeletal matrix. However, no noninvasive diagnostic technique identified those patients with skeletal disease. We therefore conclude that recognition of those jejunoileal bypass patients potentially at risk to develop clinically significant bone disease requires biopsy of the skeleton.
IN RECENT YEARS, jejunoileal bypass (JI bypass) has become a popular means of treating morbidly obese patients. Unfortunately, this procedure is accompanied by frequent, serious complications, among the less commonly recognized of which are those relating to mineral metabolism. For example, vitamin D homeostasis can be disrupted by small bowel bypass2I and some patients may develop histological abnormalities of the skeleton.3"5 Despite a theoretical relationship, a correlation between skeletal pathology and the low circulating levels of 25-hydroxycholecalciferol (25-OHD) which frequently occur after intestinal bypass surgery has not been demonstrated. Furthermore, it is unknown if patients with skeletal disease can be identified by methods other than bone biopsy. We herein report a study undertaken to determine the incidence and predictability of bone disease in JI bypass patients with persistently low blood levels of 25-OHD. We found * Department of Surgery, Barnes Hospital. t The Edward Mallinckrodt Institute of Radiology, Barnes
Hospital. t Department of Pathology, Jewish Hospital. § Division of Bone and Mineral Metabolism, Jewish Hospital. Supported in part by NIH Grants: RR 00036, AM 14570, and AM 11674. Reprint requests: John D. Halverson, M.D., Department of Surgery, 4960 Audubon Avenue, St. Louis, Missouri 63110. Submitted for publication: September 15, 1978.
From the Department of Surgery and The Edward Mallinckrodt Institute of Radiology (Barnes Hospital), Department of Pathology and the Division of Bone and Mineral Metabolism (Jewish Hospital), Washington University School of Medicine, St. Louis, Missouri
that, despite the absence of skeletal symptoms, the bone biopsies of most of these patients were abnormal. Furthermore, we identified no noninvasive test which was predictive of those individuals who develop histological abnormalities of the skeleton following surgery. Subjects Seven women and one man who had undergone JI bypass 37 + 6 (S.D.) months prior to admission and who had low circulating 25-OHD levels were admitted to the Clinical Research Center, Washington University School of Medicine. The mean age of these patients was 42 ± 9 (S.D.) years, and their average weight was 85 ± 26 (S.D.) kg representing a mean weight loss of 43%. Methods
At the time of admission, routine laboratory determinations were performed. Circulating levels of immunoreactive parathyroid hormone (iPTH) and 25OHD were also measured, as was urinary excretion of calcium and creatinine over a 24 hour period. Using a displacement assay8 25-OHD levels were measured. This assay uses a 1:4000 dilution of normal rat serum as the binding protein source. It does not distinguish between 25-hydroxycholecalciferol (25-OHD3) and 25hydroxyergocalciferol (25-OHD2). Therefore, the values obtained represent the sum of these moieties in serum as 25-hydroxycholciferol (25-OHD).9 Standard posteroanterior hand radiographs were obtained and the average combined cortical thickness calculated. Detailed radiographs of the fingers were evaluated for intracortical or subperiosteal resorption.'1 Bone density of the midradial cortex was measured
0003-4932/79/0600/0785 $00.80 © J. B. Lippincott Company
785
786
HALVERSON AND OTHERS
Ann. Surg. * June 1979
TABLE 1. Biochemical Measurements in Vitamin D Deficient Patients with Normal Osteoid (I) and Hyperosteoidosis (II)
Normals
Ca. 9-10.3 mg/dl
Po4 3.0-5.5 mg/dl
Mg. 1.5-2.4 meq/L
Albumin 3.5-5.0 g/dl
Alkaline Phosphatase 25-80 mu/ml
iPTH 2-10 ,ueq/ml
25-OHD 10-30 ng/ml
Urine Calcium per 24 Hours 50-400 mg/24 hrs
8.5 7.6 9.0 9.3
3.3 2.9 3.6 3.1
1.4 0.9 1.5 0.6
3.6 3.1 4.3 4.0
63 127 91 84
6 12 4
5.4 4.8 3.5 4.0
98 69 39 16
C.W. R. I* N. M.B. D.J.
*mean
+
S.D.
H. S. G.G. t V.P. M.H. t mean + S.D.
8.6
+
0.7
3.3
8.7 9.0 9.3 9.1
I
9.0
+
+
0.2
1.4
3.3 3.2 3.8 3.9 0.3
3.6
+
+
0.7
3.8
1.4
+
91
3.8 3.8 4.0 4.2
1.1 1.6 1.6 1.4
0.4
0.5
+
0.2
3.9
by photon absorptiometry using a Norland-Cameron Bone Mineral Analyzer®.19 A transiliac needle bone biopsy which included both cortices and intervening trabeculae was obtained from each patient following administration of time-spaced, fluorescent tetracycline skeletal markers. The nondecalcified specimen embedded in methylmethacrylate was cut longitudinally in 5.0 and 10.0 ,um histological sections on a Jung Model K Sledge Microtome.® The entire trabecular area of a 5.0 Am section taken from the midpoint of the specimen and stained by a modification of the Goldner technique was histologically quantitated using a Merz-Schenk Integrating Eyepiece®. The following histometric parameters were evaluated and were compared to those derived from autopsy specimens taken from a group of age and sex matched patients who died suddenly: a) Per cent total bone volume (per cent of marrow space composed of bone matrix) b) Per cent relative osteoid volume (per cent of trabecular bone matrix which is unmineralized, i.e. osteoid) c) Per cent osteoid surface (per cent of trabecular bone covered by osteoid) d) Per cent osteoblastic osteoid surface (per cent of trabecular surface covered by osteoid lined by characteristic osteoblasts) e) Per cent surface fibrosis (per cent of trabecular surface juxtaposed to marrow fibrosis) f) Number of osteoclasts/mm2 trabecular space g) Cellular rate of bone mineralization (a kinetic parameter derived by determining the mean distance between the midpoints of the two fluorescent tetracycline labels and dividing that distance by the days between the midpoints of administration of the two doses of the antibiotic. As no normal tetracycline-
+
+
27
108 90 81 80 0.2
90
+
7.3
+
4.2
+
0.8
56
+
35
9 9
2.8 3.0 6.6 3.2
100 120 50 46
6.5 ± 2.9
3.9 ± 1.8
80 ± 26
4 4
13
4.4
based data are available in our laboratory, the values obtained were compared to those present in the literature.12 Abnormality of a histometric parameter was defined as a value greater or less than 2 S.D. from the normal mean. Results The results of the variety of biochemical determinations performed on our patients were consistent with the post JI Bypass state (Table 1).1o Only one of the eight had mildly elevated circulating iPTH levels and, as selection for inclusion in the study was the presence of hypovitaminosis D, serum 25-OHD levels were less than 10 ng/ml in all patients. Six of the eight patients had abnormal bone biopsies as assessed by standard nonfluorescent microscopy (Table 2). As a group, the biopsies demonstrated osteopenia and contained an excess of osteoid (hyperosteoidosis). In three patients the percentage of total bone volume was decreased, and the relative osteoid volume was increased. Moreover, there was an inverse correlation between these two parameters within the group as a whole which failed to exist within the normal biopsies (Fig. 1). The biopsy of one of the five nonosteopenic bypass patients also contained an increased percentage of relative osteoid volume, and two patients had an increased percentage of total osteoid surface. The percentage of trabecular surface covered by osteoblasts was increased in four biopsies, being the only abnormality in one. Moreover, two bopsies contained an excess of osteoclasts and the mean number of these cells within the group was more than three times the normal mean. The biopsies of two patients failed to exhibit any
Vol. 189 . No. 6
SKELETAL ABNORMALITIES AFTER BYPASS
787
TABLE 2. Histological Data from Vitamin D Deficient Patients
Patient
C.W. N.R. M.B. D.J. H.S. G.G. V.P. M.H. Mean ± S.D. Normal mean ± S.D. *
Per Cent Total Bone Volume
Per Cent Relative Osteoid Volume
Per Cent Total Osteoid Surface
Per Cent Osteoblastic Osteoid Surface
Per Cent Surface Fibrosis
Osteoclasts/ mm2
Cellular Rate of Bone Mineralization (um/Day)
26.1 15.9 21.9 19.2 16.4 9.3* 7.8 5.7* 15.3 ± 7.It
0.2 0.4 1.6 2.0 4.2* 4.4* 7.1* 8.2* 3.5 ± 5.1
1.1 4.2 9.1 16.6 24.5 21.1 26.6* 25.1* 16.0 ± 9.6t
0 0.5 4.0* 2.7 16.3* 1.3 18.0* 8.6* 6.4 ± 7.1
0 0 0 0 0 0 0 0 0
0.231 0.347 0.248 1.029* 0 0.452* 0.318 0 0.33 ± 0.31
0* 0* 1.15* 0.89 0.83 0.73 0.66 0.73 0.62 ± 0.42
24.8 ± 5.1
1.1 ± 1.4
7.6 ± 8.7
1.0 ± 1.4
0
0.10 ± 0.14
0.70 ± 0.16
+2 s.d. from normal mean. tDifference from normal mean
(p < 0.01).
tetracycline fluorescence, and in one, the cellular rate of bone mineralization was increased. All eight patients had metacarpal cortical thickness measurements within two standard deviations of the age-sex norm. Densitometric osteopenia (below 95% confidence limits) was documented in two patients with hyperosteoidosis and in two patients with normal histomorphology (Table 3). Early intracortical resorption was found only in two patients with excess osteoid, only one of whom had densitometric osteopenia. Regression analysis was performed between all morphometric and clinical and biochemical parameters,
and no significant relationships were demonstrated. Furthermore, when the patients were divided into I) those with normal quantities of osteoid and II) those with excess osteoid, there were no clinical (Table 4) or biochemical (Table 1) differences between the groups. In short, no biochemical or radiographic measurements made in this group of vitamin D deficient patients were of value in predicting bone histology.
Discussion JI bypass has become widely accepted as a means of treating morbidly obese patients who are intractable
10r 9 w 0 0
81 7
a
FIG. 1. Relationship of percentage of relative osteoid volume and percentage total C,) bone volume in bone biop- 0 sies of eight postjejunoileal w bypass patients with low circulating 25-OHD (R = .88, p= .~~~~
-T'h.
FIGS. 2a and b. (a, top) Bone biopsy 07M
markedly shortened small intestinal segment in our patients therefore represents a continuing threat to their vitamin D economy, in spite of the previously reported adaptive response.21 Furthermore, there is evidence that, aside from its effect on intestinal calcium transport, vitamin D is necessary for normal bone mineralization to occur.5'21'22 Whether 25-OHD is a/the metabolite responsible for this event remains to be determined. However, post-JI bypass patients have low serum 25-OHD concentrations and ineffectively absorb a challenge oral dose of 25-OHD.20'21 Consequently, the threat of continuing vitamin D depletion and clinically significant bone
9,.
:.
disease appears strong enough to warrant judicious vitamin D prophylaxis. References 1. Arnaud, S., Goldsmith, R. S., Lambert, P. W., et al.: 25-OHD: Evidence of an Enterohepatic Circulation in Man. Proc. Soc. Exp. Biol. Med., 149:590, 1975. 2. Avioli, L. V., Lee, S. W., McDonald, J. E., et al.: Metabolism of Vitamin D3-3H in Human Subjects: Distribution in Blood, Bile, Feces and Urine. J. Clin. Invest., 49:983. 1967. 3. Compston, J. E., Laker, M. F., Woodhead, J. S.. et al.: Bone Disease after Jejunoileal Bypass for Obesity. Lancet. ii: 1. 1978. 4. DeWind, L. T. and Payne, J. H.: Intestinal Bypass Surgery for Morbid Obesity: Long-Term Results. JAMA. 236:2298. 1976.
790
HALVERSON AND OTHERS
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