1975, British Journal of Radiology, 48, 878-884
Bone scan in chronic dialysis patients with evidence of secondary hyperparathyroidism and renal osteodystrophy By W. M. Sy, M.D., and A. K. Mittal, M.D. Departments of Radiology and Medicine, Brooklyn-Cumberland Medical Center, Brooklyn, N.Y. 11201, U.S.A. {Submitted December, 1974 and in revised form May, 1975) ABSTRACT
Bone scans in 13 of 14 patients on chronic dialysis were found to be abnormal. Symmetrical increased activity was noted in the calvarium, mandible, sternum, shoulders, vertebrae, and the distal aspects of the femur and tibia, as well as the patella. The scan abnormality is felt to be most likely the result of secondary hyperparathyroidism because of clinical and laboratory data, and, in four, confirmatory tissue diagnoses. The scan findings support the data of some earlier investigations on bone isotopic accretion in hyperparathyroidism. However, co-existing osteomalacia giving rise to abnormal activity in some of the patients cannot be excluded. Dihydrotachysterol may have minimized the extent of osteomalacia in these patients. Osteoporosis was probably present in some patients, but it appears differently on scan. Osteosclerosis was not detected on radiographic examination. Scan manifestations, especially mandibular activity, were pronounced and appeared earlier than the radiographic changes. The degree and extent of abnormal activity correlated with the length of dialysis and the level of alkaline phosphatase.
The use of radiopharmaceuticals for radionuclide scanning for bony metastases and its advantages over radiographic detection is now well recognized and documented (Roy, Nathan and Beales, 1971; Milner, Maynard and Cowan, 1971; Galasko and Doyle, 1972; Helson, Watson and Benua, 1972; Wanken, Eyring and Samuels, 1973; Blaufox and Freeman, 1974-75; DeNardo, 1972). Bone scanning has been used to a lesser extent for non-metastatic conditions such as primary bone tumour (McNeil et al.y 1973), multiple myeloma (Charkes, Durant and Barry, 1972), myelofibrosis (Van Dyke, Anger and Parker, 1971), Paget's disease (Khari, Wellman and Robb, 1973), fractures (Illingworth and Schiss, 1971), non-union (Bekier and Cech, 1970), osteonecrosis (Crutchlow, 1970) osteoarthritis, osteomyelitis (Waxman, Bryan and Siemsen, 1973), septic arthritis (Staheli, Nelp and Marty, 1972), and tuberculous spondylitis (Fellander and Lindberg, 1966), while scanning for secondary hyperparathyroidism and renal osteodystrophy due to dialysis for chronic renal disease has not previously been reported. This report describes the 99Tcm stannous polyphosphate bone scan findings in 14 patients with *Abstract presented at the First World Congress of Nuclear Medicine, Tokyo, Japan, September 30-October 4, 1974.
end-stage chronic renal failure, with clinical and laboratory evidence of secondary hyperparathyroidism and renal osteodystrophy. These findings have been graded and then correlated with the duration of the dialysis, and the clinical and laboratory data. PATIENTS
Fourteen patients, six male and eight female, with end-stage chronic renal failure on maintenance dialysis are the subject of this report. All patients were on a therapeutic regimen of phosphate-binders, iron replacement, dihydrotachysterol, and multivitamins. Antihypertensive agents and antibiotics were administered when necessary. The age ranged from 23 to 64 years. The median duration of dialysis was 43-5 months. Pertinent clinical and biochemical data are summarized in Table I. Skeletal surveys were obtained, and in most instances, these included the calvarium, mandible, chest, shoulders, spine, pelvis, and hands. Biochemical evidence for secondary hyperparathyroidism of varying duration existed in all patients at the time of their bone scan. Four patients (Cases 1, 5, 11, and 12), had tissue diagnoses of hyperparathyroidism. Three large parathyroids and part of a fourth gland, all demonstrating chief cell hyperplasia, were removed at surgery in Cases 1, 5, and 11. A limited autopsy in one (Case 12) disclosed osteitis fibrosa cystica. METHODS
Each of the 14 patients received 15 mCi of 99Tcmlabelled stannous polyphosphate intravenously. Approximately three hours after the radionuclide administration, anterior and posterior total body scans, with 5:1 minification, were obtained using the Ohio-Nuclear 84 five-inch dual scanner. Low energy, 3^ in. focal-distance collimators were used. A speed setting of 600 (450 cm.min^1) was used based upon an information density of over 1,000 counts cm2. Three-minute photo scans of the hands using a Dyna-Pic upgraded 2-C camera with ultrafine collimator also were obtained on seven patients.
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\
A Posterior FIG. 1. Anterior and posterior 5:1 total body scans. Note the high activity in the axial as well as appendicular bones and the absence of renal outline (Case 1). B Anterior 879
1975
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FIG. 2. High activity is present in both hands while a corresponding radiograph shows some subperiosteal changes (Case 12).
Bone scans in seven areas—calvarium, mandible, sternum, acromio-clavicular region, vertebrae, pelvis, and femur-tibia—were evaluated separately. The activity in each of these areas was arbitrarily semiquantitated and scored, with a range from zero, for normal areas, to a maximum of 4-j-, for regions with greatest activity. The degree of abnormal bone activity was assessed on the total of the seven regional scores—cumulative scores of 0-3 were regarded as normal, 4-9 as mild, 10-15 moderate, 16-21 as marked, and 22-27 as severe involvement. RESULTS
Abnormal bone scans of varying degrees were observed in 13 out of 14 patients. Two were judged to have mild, four moderate, four marked and three
FIG. 3. Note the unusually heavy activity in the costochondral junctions as well as in the calvarium, mandible, shoulder areas, vertebrae and pelvis (Case 10).
with severe bone involvement. Abnormally increased activity was consistently noted in the calvarium, mandible, acromio-clavicular areas, sternum, vertebrae, and distal thirds of the long bones (Fig. 1). Photoscans of the hands in seven patients also demonstrated abnormally increased activity in the distal and proximal phalanges, metacarpals, and sometimes in the carpal bones (Fig. 2A and B). Bilaterally increased activity was also generally noted in the iliac crests and symphysis pubis, and moderately increased activity was usually present in the ischio-acetabular regions. A few scans also disclosed
880
NOVEMBER
1975
Bone scan in chronic dialysis patients TABLE I CLINICAL AND LABORATORY DATA
Creatinine Age and sex
Renal disease
mg%
1 2 3 4 5 6 7 8 9
48 m
15-6
10 11 12 13 14
23 f 40 f 59 m 47 f 50 f
Glomerulonephritis Pyelonephritis Pyelonephritis Glomerulonephritis Glomerulonephritis Glomerulonephritis Glomerulonephritis Pyelonephritis Accelerated hypertension Glomerulonephritis Glomerulonephritis Polycystic kidneys Diabetic nephropathy Glomerulonephritis
Patient
51m 61m
37 m 40 f 64 m 38 f 47 f 38 f
9-4
19-5 20-5 18-5 12-5 19-5 121 160
22-0 18-0 19-8 15-6 18-5
Ca. mg%
Phosphorus
9-3 7-9 90 9-3
8-0 6-4 7-9 5-9 7-4 5-0 6-4 8-1 7-9
10-4 8-2 8-8
10-4 9-8
9-0
10-5 8-2 7-5 9-2
mg%
6-4 8-6 7-1 41 5-2
Note: Patients 1,3,4, 5, 10,11, and 14 experienced bone pains while patients 2, 5, 10, 11 and 14 had pruritus. Except for patients 2, 9, and 13, who were on peritoneal dialysis, the remainder of the patients were on haemodialysis.
prominent rib-cage activity, and in one particular scan (Case 10), heavy activity in the costochondral junctions was demonstrated giving rise to a "rosary bead" pattern (Fig. 3) similar in localization to that observed in rickets on X ray. There was no activity in the urinary tract in all patients because of the underlying renal disease. Normally, the kidneys and the urinary bladder are well outlined on a "Tc m -labelled stannous polyphosphate scan since 40-50 per cent of the administered dose is already eliminated through this route by three hours (Subramanian, McAfee and Bell, 1972). The generalized abnormal activity in the axial and appendicular bones found in most of the dialyzed patients does not appear to be due to their medically anephric state since a gradation of abnormality was found on the scans; likewise, some anuric patients not on dialysis failed to manifest findings comparable to the more severe cases (Sy, 1974a). DISCUSSION
The association of bone abnormalities and chronic renal disease has been known almost a century (Lucas, 1883). The increase in longevity of patients with end-stage renal disease because of dialysis has resulted in higher and more overt incidence of bone morbidity (Standbury, 1966; Kaye et al, 1960; and Kaye, 1969). Both typical osteomalacia and osteoporosis have been described, but the commonest bone pathology is that resulting from secondary hyperparathyroidism (Black, 1972; Bricker et al., 1969) is typified by osteitis fibrosa cystica pathologically, and subperiosteal resorption
and demineralization on X ray. Rarely, there is osteoscierosis, particularly of the lumbar spine (Kaye et al, 1960; Black, 1972). Most of the abnormal bone scan findings in our patients are likely to be due to the effects of secondary hyperparathyroidism. Co-existing osteomalacia, accounting for some scan findings in some patients, cannot be completely discarded, however. The fact that all 14 patients were on a regimen of dihydrotachysterol concurrent with dialysis, probably minimized the extent of osteomalacia (Kaye et al., 1970). Osteoporosis is a less common complication of chronic renal disease (Standbury, 1968) and it may also have been present in some patients. Except in instances of vertebral collapse, osteoporosis is, however, manifested on scan as an area of diminished activity (Sy, 1975). Osteoscierosis was not observed radiographically in any of our patients. The scan abnormalities due to secondary hyperparathyroidism support the findings of some earlier investigations. Dymling (1964), for instance, has demonstrated that a marked increased accretion rate with 47Ca and 85 Sr exists in patients with hyperparathyroidism and similar findings have been reported by other workers (Fraser, Harrison and Ibbertson, 1960; Rich, 1957). Costeas, Woodward and Laughlin (1971) have shown that the administration of parathyroid hormone resulted in 60 per cent increased uptake of 18 F in rabbit tibias. Recently, Sy (1974b) described patients with proved primary hyperparathyroidism showing comparable bone abnormalities on scan. Furthermore, our follow-up studies of post-parathyroidectomized patients
881
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B
4. Photoscan showing severe activity in the calvarium and mandible, but only minimal changes shown in the radiograph (Case 1). FIG.
have manifested significant regression of the abnormal bone activity observed prior to surgery. The initial radiographic changes in hyperparathyroidism occur in the spongy bones and the subperiosteum of long bones. These components of the bone are the most active metabohcally and the most responsive to changes in the level of parathyroid hormone (Williams, 1968). The distribution of abnormal activity on the scan in our patients closely follows this pattern. The bone effects of secondary hyperparathyroidism which appear as generalized abnormal activity are detected much earlier on scan, than on radiographs. The extent and degree of these bone changes also appear to be more pronounced on scan. Generalized demineralization of the spine, moderate to overt was noted on radiographs only in Cases 1,11,12, and 5, and yet all patients except for Case 2 manifested varying gradations of increased activity on scan. Spotty demineralization of the calvarium was present in Cases 1 and 12, but marked to severe involvement is apparent on imaging in these and five other cases (Fig. 4). We observed no radiographic changes in the mandibles of our patients, as was the experience of Katz, Hampers and Merrill (1969) in 195 patients with secondary hyperparathyroidism and renal osteodystrophy. On the other hand, the scans showed early, diffuse and consistent activity throughout the body and rami of the mandibles. Cases 9 and 13, which were mild forms, also demonstrated some increased mandibular activity. The photoscans of the hands (Cases 1, 3, 4, 11, 12, 13, and 14) demonstrated abnormal findings ranging from localized periarticular activity to more extensive involvement of all phalanges, metacarpals, and carpals. The radiographs in Cases 1, 11, and 13 showed some subperiosteal bone resorption mostly in the ungual tufts and trabeculations in some phalanges. A majority of the patients showed heavy activity in the acromioclavicular regions while only Cases 1 and 12 showed definite subperiosteal resorption of the distal thirds of the clavicles. Similarly, the distal ends of long bones manifested increased activity in most instances, and only limited demineralization and resorption were present on radiographs in the three severe cases. The "rosary beaded" pattern activity observed in Case 10 had no corresponding detectable costochondral changes on chest radiograph. Thus, whenever demonstrable demineralization, bone resorption or subperiosteal changes are apparent in the X rays of the calvarium clavicles, spine, pelvis, or hands, the corresponding scans disclosed a more striking degree of abnormal activity. The dif-
882
NOVEMBER 1975
Bone scan in chronic dialysis patients
25
15-
12
60
36 DIALYSIS
D U R A T I O N
FIG.
84 ALKALINE
( M O N T H S )
5.
PHOSPHATASE FIG.
( IU)
6.
Correlation of the duration of dialysis and the severity of bone scan changes.
Correlation of alkaline phosphatase level and the severity of bone morbidity.
ference in the ability of these two modalities to detect bone morbidity in this group of patients is not unexpected. More than 50 per cent demineralization of bone is needed before it is detected on X ray (Blaufox and Freeman, 1974-75; Denardo, 1972), whereas abnormal bone activity on scan is dependent on enhanced bone turnover and increased vascularity, an occurrence likely to happen early in the skeletal system of end-stage renal disease patients. Fifty per cent of patients on haemodialysis for two years or more manifest evidence of increased bone resorption and serum alkaline phosphatase (Katz et al, 1969; Fournier et al., 1971). In our patients, those who had been on haemodialysis for more than 30 months, all manifested severe, marked, or moderate forms of abnormality on scan. A correlation of the bone scan cumulative scores and the duration of dialysis is shown in Fig. 5. Case 2 had a negative scan and Cases 13 and 9 manifested mild changes. Cases 2 and 13 had been on dialysis for only four months duration while Case 9 had been on dialysis for 12 months. It should also be noted that these last three patients were treated with peritoneal dialysis and not with haemodialysis like the others. The degree of scan abnormality correlates with the serum alkaline phosphatase activity (Fig. 6). Two of three patients with the severest changes on scan also demonstrated the highest level of alkaline phosphatase, over 650 I.U. All four patients with marked changes, a majority of the moderate form and another severe form, are clustered in the 200-500 I.U. range level. Two patients that showed the least changes and another with moderate form
are in the 100-150 I.U. range level. This is in accord with the findings of Katz et al. (1969), who demonstrated that in the absence of concomitant liver disease, the serum alkaline phosphatase activity correlates well with the extent of bone involvement in chronic dialysis patients. ACKNOWLEDGMENTS
The authors wish to express their thanks to P. Scaglione, M.D., and J. Meyer, M.D. for reviewing the manuscript; to M. Malach, M.D. for his encouragement; and also to Mrs. M. D. Harris for her secretarial effort. REFERENCES BEKIER, A., and CECH, O., 1970. 85Strontium uptake study in nonunion in man. European Surgical Research, 2, 226-232. BLACK, D., 1972. In Renal Disease, 3rd edn., pp. 506, 473 (Blackwell Scientific Publications, Oxford and London). BLAUFOX, M. D., and FREEMAN, L. M., 1974-75. PDR for
Radiology and Nuclear Medicine. In The Skeletal System, pp. 31-33 (Oradell, New Jersey, Medical Economics Company). BRICKER, N. S., SLATOPOLSKY, E., REISS, E., and AVIOLI,
L. V., 1969. Calcium, phosphorus and bone in renal disease and transplantation. Archives of Internal Medicine, 123, 543-553. CHARKES, N. D., DURANT, J., and BARRY, W. E., 1972.
Bone pain in multiple myeloma: studies with radioactive 87m Sr. Archives of Internal Medicine, 130, 53-58. COSTEAS, A., WOODWARD, H. Q., and LAUGHLIN, J. S., 1971.
Comparative kinetics of calcium and fluoride in rabbit bone. Radiation Research,8546, 317-333. CRUTCHLOW, W. P., 1970. Strontium scintimetry of the hip in osteoarthritis and osteonecrosis. American Journal ofRoentgenology, 109, 803-812. DENARDO, G. L., 1972. The 85Sr scintiscan in bone disease. Seminars of Nuclear Medicine, 2, 18-20. DYMLING, J. F., 1964. Calcium kinetics in osteopenia and parathyroid disease. Acta Medica Scandinavica Supplement, 408,175, 6-56. FELLANDER, M., and LINDBERG, L., 1966. Clinical use of
883
radiostrontium in evaluation of spondylitis. Journal of Bone and Joint Surgery, 48A, 1585-1606.
VOL.
r
48, No. 575
W. M. Sy and A. K. Mittal with albuminuria, rickets of adolescents. Lancet, 1, 993-994.
FOURNIER, A. E., JOHNSON, W. J., TAVES, D. R., et al.,
1971. Etiology of hyperparathyroidism and bone disease with potentially ethilogic factors. Journal of Clinical Investigation, 50, 592-598.
MCNEIL, B. J., CASSADY, R. J., and GEISER, C. F., JAFFE, N., TRAGGIS, D., and TREVES, S., 1973. Fluorine-18
bone scintigraphy in children with osteosarcoma or Ewing's sarcoma. Radiology, 109, 627-631.
FRASER, R., HARRISON, M., and IBBERTSON, K., 1960. The
rate of calcium turnover in bone. Quarterly Journal of Medicine, 29, 85-111. GALASKO, C. S. B., and DOYLE, F. H., 1972. Response to
therapy of skeletal metastases from mammary cancer: assessment by scintigraphy. British Journal of Surgery, 59, 85-88. HELSON, L., WATSON, R. C , and BENUA, R. S., 1972.
18 Fluorine radioisotope scanning of metastatic bone lesions in children with neuroblastoma. American Journal ofRoentgenology, 115, 191-199.
ILLINGWORTH, G. I., and SCHIESS, F. A., 1971.
87m
Strontium
MILNER, T. H., MAYNARD, C. D., and COWAN, R. J., 1971.
Evaluation of 85Sr bone scans and roentgenograms in 100 patients. Archives of Surgery, 103, 371-372. RICH, C , 1957. The calcium metabolism of a patient with renal insufficiency before and after partial parathyroidectomy. Metabolis, 6, 574-582. ROY, R. R., NATHAN, B. E., and BEALES, J. S. M., 1971.
18 Fluorine total body scans in patients with sarcoma of the prostate. British Journal of Urology, 43, 58-64. STAHELI, L. T., NELP, W. B., and MARTY, R., 1972.
87m in prognosis of fractures of tibia. Proceedings of the Strontium scanning: early diagnosis of bone and joint Royal Society of Medicine, 64, 633-634. infections in children. Journal of American Medical KAYE, M., 1969. Concepts of therapy: Prevention and Association, 221, 1159-1160. management of osteodystrophy in patients with long STANDBURY, S. W., 1968. Bone disease in uremia. American term hemodialysis. Archives of Internal Medicine, 124, Journal of Medicine, 44, 714-724. 656-662. SUBRAMANIAN, G., MCAFEE, J. G., and BELL, E. G., 1972. KAYE, M., CHATTERJEE, G., COHEN, G. B., and SAGAR, S., Technetium 99m-labeled polyphosphate as skeletal 1970. Arrest of hyperparathyroid bone disease with diimaging agent. Radiology, 102, 701-704. hydrotachysterol in patients undergoing chronic dialysis. SY, W. M., 1974a. Unpublished data. Annals of Internal Medicine, 73, 225-233. 1974b. Bone scan in primary hyperparathyroidism. KAYE, M., PRITCHARD, J. E., HALPENNY, G. W., and LIGHT, Journal of Nuclear Medicine, 15, 189-191. W., 1960. Bone disease in chronic renal failure with 1975. Unpublished observations. particular reference to osteosclerosis. Medicine, 39, 157- VAN DYKE, D., ANGER, H. O., and PARKER, H., 1971. 190. Markedly increased bone blood flow in myelofibrosis. KATZ, A. I., HAMPERS, C. L., and MERRILL, J. P., 1969. Journal of Nuclear Medicine, 12, 506-512. Secondary hyperparathyroidism and renal osteodystrophy WANKEN, J. J., EYRING, E. J., and SAMUELS, L. D., 1973. in chronic renal failure: Analysis of 195 patients with Diagnosis of pediatric lesions: correlation of clinical, observations on the effects of chronic dialysis, kidney roentgenographic, 87mSr scan and pathologic diagnosis. transplantation and subtotal parathyroidectomy. Medicine Journal of Nuclear Medicine, 14, 803-806. {Baltimore), 48, 333-374. WAXMAN, A. D., BRYAN, D., and SIEMSEN, J. K., 1973. KHARI, M. R. A., WELLMAN, H. N., and ROBB, J. A., 1973. Bone scanning in the drug abuse patient: Early detection Paget's disease of bone (osteitis deformans): symptomatic of hematogenous osteomyelitis. Journal of Nuclear lesions and bone scan. Annals of Internal Medicine, 79, Medicine, 14, 647-650. 348-351. WILLIAMS, R. H., 1968. Textbook of Endocrinology, 4th edn., LUCAS, R. C , 1883. On a form of late rickets associated Rasmussen, H.: The Parathyroids, p. 866 (W. B. Saunders Co., Philadelphia, Pennsylvania).
Book review Diseases of the Esophagus. By G. Vantrappen and J. Hellemans, pp. 877, 358 illus. (some in colour), 1974 (Berlin, Heidelberg, New York, Springer-Verlag), DM 390, $159.20. This book is one of a series under the title Handbuch der inneren Medizin and is Part I of the third series on the digestive organs. Professor Vantrappen and Professor Hellemans are not only editors, but also major contributors. Most of the other contributors come from the University of Leuven, but the editors have enlisted much talent from other countries including Professor Monges from France, Dr. Heitmann from Germany and Dr. D. A. W. Edwards from this country. The radiologists are Professor Bonette and Professor Pringot of the University of Leuven and Professor Bernard Wolf of the Mount Sinai Hospital, New York. There is one chapter devoted to the radiology of the oesophagus but there are also many interesting references to radiology throughout the book. This is the most complete and informative book on the oesophagus that the reviewer has ever seen. The whole field of the oesophagus has been covered and in addition to chapters on such obvious subject as anatomy, embryology,
physiology, diagnostic procedures, etc. there are contributions on manometry, pH measurements, exfoliative cytology, PD measurements and electromyography. The standard is level throughout and of the highest. To the radiologist the book is of considerable value in providing a good background on anatomy, physiology, manometry, etc. and also as a reference book for the rarer diseases of the oesophagus, for example, those complicating cutaneous diseases. The account of the radiology of the oesophagus is excellent and includes sections on cinefluorography and video recording. This is a work which should certainly find its way into every hospital library and also into the departmental libraries of the X-ray departments of larger hospitals. The only possible reason against this is the high cost of the book. Considering the amount of work which has gone into its production, the vast knowledge of the contributors, the faultless format, and the high quality of the reproductions, the price is not really excessive. The editors especially, but also the contributors, are to be congratulated on the production of a superb text-book on the oesophagus and the reviewer hopes that, expensive or not, it will have the success it deserves.
884
F. R. BERRIDGE.
Bone scan in chronic dialysis patients with evidence of secondary hyperparathyroidism and renal osteodystrophy By W. M. Sy, M.D., and A. K. Mittal, M.D. Departments of Radiology and Medicine, Brooklyn-Cumberland Medical Center, Brooklyn, N.Y. 11201, U.S.A. {Submitted December, 1974 and in revised form May, 1975) ABSTRACT
Bone scans in 13 of 14 patients on chronic dialysis were found to be abnormal. Symmetrical increased activity was noted in the calvarium, mandible, sternum, shoulders, vertebrae, and the distal aspects of the femur and tibia, as well as the patella. The scan abnormality is felt to be most likely the result of secondary hyperparathyroidism because of clinical and laboratory data, and, in four, confirmatory tissue diagnoses. The scan findings support the data of some earlier investigations on bone isotopic accretion in hyperparathyroidism. However, co-existing osteomalacia giving rise to abnormal activity in some of the patients cannot be excluded. Dihydrotachysterol may have minimized the extent of osteomalacia in these patients. Osteoporosis was probably present in some patients, but it appears differently on scan. Osteosclerosis was not detected on radiographic examination. Scan manifestations, especially mandibular activity, were pronounced and appeared earlier than the radiographic changes. The degree and extent of abnormal activity correlated with the length of dialysis and the level of alkaline phosphatase.
The use of radiopharmaceuticals for radionuclide scanning for bony metastases and its advantages over radiographic detection is now well recognized and documented (Roy, Nathan and Beales, 1971; Milner, Maynard and Cowan, 1971; Galasko and Doyle, 1972; Helson, Watson and Benua, 1972; Wanken, Eyring and Samuels, 1973; Blaufox and Freeman, 1974-75; DeNardo, 1972). Bone scanning has been used to a lesser extent for non-metastatic conditions such as primary bone tumour (McNeil et al.y 1973), multiple myeloma (Charkes, Durant and Barry, 1972), myelofibrosis (Van Dyke, Anger and Parker, 1971), Paget's disease (Khari, Wellman and Robb, 1973), fractures (Illingworth and Schiss, 1971), non-union (Bekier and Cech, 1970), osteonecrosis (Crutchlow, 1970) osteoarthritis, osteomyelitis (Waxman, Bryan and Siemsen, 1973), septic arthritis (Staheli, Nelp and Marty, 1972), and tuberculous spondylitis (Fellander and Lindberg, 1966), while scanning for secondary hyperparathyroidism and renal osteodystrophy due to dialysis for chronic renal disease has not previously been reported. This report describes the 99Tcm stannous polyphosphate bone scan findings in 14 patients with *Abstract presented at the First World Congress of Nuclear Medicine, Tokyo, Japan, September 30-October 4, 1974.
end-stage chronic renal failure, with clinical and laboratory evidence of secondary hyperparathyroidism and renal osteodystrophy. These findings have been graded and then correlated with the duration of the dialysis, and the clinical and laboratory data. PATIENTS
Fourteen patients, six male and eight female, with end-stage chronic renal failure on maintenance dialysis are the subject of this report. All patients were on a therapeutic regimen of phosphate-binders, iron replacement, dihydrotachysterol, and multivitamins. Antihypertensive agents and antibiotics were administered when necessary. The age ranged from 23 to 64 years. The median duration of dialysis was 43-5 months. Pertinent clinical and biochemical data are summarized in Table I. Skeletal surveys were obtained, and in most instances, these included the calvarium, mandible, chest, shoulders, spine, pelvis, and hands. Biochemical evidence for secondary hyperparathyroidism of varying duration existed in all patients at the time of their bone scan. Four patients (Cases 1, 5, 11, and 12), had tissue diagnoses of hyperparathyroidism. Three large parathyroids and part of a fourth gland, all demonstrating chief cell hyperplasia, were removed at surgery in Cases 1, 5, and 11. A limited autopsy in one (Case 12) disclosed osteitis fibrosa cystica. METHODS
Each of the 14 patients received 15 mCi of 99Tcmlabelled stannous polyphosphate intravenously. Approximately three hours after the radionuclide administration, anterior and posterior total body scans, with 5:1 minification, were obtained using the Ohio-Nuclear 84 five-inch dual scanner. Low energy, 3^ in. focal-distance collimators were used. A speed setting of 600 (450 cm.min^1) was used based upon an information density of over 1,000 counts cm2. Three-minute photo scans of the hands using a Dyna-Pic upgraded 2-C camera with ultrafine collimator also were obtained on seven patients.
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\
A Posterior FIG. 1. Anterior and posterior 5:1 total body scans. Note the high activity in the axial as well as appendicular bones and the absence of renal outline (Case 1). B Anterior 879
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FIG. 2. High activity is present in both hands while a corresponding radiograph shows some subperiosteal changes (Case 12).
Bone scans in seven areas—calvarium, mandible, sternum, acromio-clavicular region, vertebrae, pelvis, and femur-tibia—were evaluated separately. The activity in each of these areas was arbitrarily semiquantitated and scored, with a range from zero, for normal areas, to a maximum of 4-j-, for regions with greatest activity. The degree of abnormal bone activity was assessed on the total of the seven regional scores—cumulative scores of 0-3 were regarded as normal, 4-9 as mild, 10-15 moderate, 16-21 as marked, and 22-27 as severe involvement. RESULTS
Abnormal bone scans of varying degrees were observed in 13 out of 14 patients. Two were judged to have mild, four moderate, four marked and three
FIG. 3. Note the unusually heavy activity in the costochondral junctions as well as in the calvarium, mandible, shoulder areas, vertebrae and pelvis (Case 10).
with severe bone involvement. Abnormally increased activity was consistently noted in the calvarium, mandible, acromio-clavicular areas, sternum, vertebrae, and distal thirds of the long bones (Fig. 1). Photoscans of the hands in seven patients also demonstrated abnormally increased activity in the distal and proximal phalanges, metacarpals, and sometimes in the carpal bones (Fig. 2A and B). Bilaterally increased activity was also generally noted in the iliac crests and symphysis pubis, and moderately increased activity was usually present in the ischio-acetabular regions. A few scans also disclosed
880
NOVEMBER
1975
Bone scan in chronic dialysis patients TABLE I CLINICAL AND LABORATORY DATA
Creatinine Age and sex
Renal disease
mg%
1 2 3 4 5 6 7 8 9
48 m
15-6
10 11 12 13 14
23 f 40 f 59 m 47 f 50 f
Glomerulonephritis Pyelonephritis Pyelonephritis Glomerulonephritis Glomerulonephritis Glomerulonephritis Glomerulonephritis Pyelonephritis Accelerated hypertension Glomerulonephritis Glomerulonephritis Polycystic kidneys Diabetic nephropathy Glomerulonephritis
Patient
51m 61m
37 m 40 f 64 m 38 f 47 f 38 f
9-4
19-5 20-5 18-5 12-5 19-5 121 160
22-0 18-0 19-8 15-6 18-5
Ca. mg%
Phosphorus
9-3 7-9 90 9-3
8-0 6-4 7-9 5-9 7-4 5-0 6-4 8-1 7-9
10-4 8-2 8-8
10-4 9-8
9-0
10-5 8-2 7-5 9-2
mg%
6-4 8-6 7-1 41 5-2
Note: Patients 1,3,4, 5, 10,11, and 14 experienced bone pains while patients 2, 5, 10, 11 and 14 had pruritus. Except for patients 2, 9, and 13, who were on peritoneal dialysis, the remainder of the patients were on haemodialysis.
prominent rib-cage activity, and in one particular scan (Case 10), heavy activity in the costochondral junctions was demonstrated giving rise to a "rosary bead" pattern (Fig. 3) similar in localization to that observed in rickets on X ray. There was no activity in the urinary tract in all patients because of the underlying renal disease. Normally, the kidneys and the urinary bladder are well outlined on a "Tc m -labelled stannous polyphosphate scan since 40-50 per cent of the administered dose is already eliminated through this route by three hours (Subramanian, McAfee and Bell, 1972). The generalized abnormal activity in the axial and appendicular bones found in most of the dialyzed patients does not appear to be due to their medically anephric state since a gradation of abnormality was found on the scans; likewise, some anuric patients not on dialysis failed to manifest findings comparable to the more severe cases (Sy, 1974a). DISCUSSION
The association of bone abnormalities and chronic renal disease has been known almost a century (Lucas, 1883). The increase in longevity of patients with end-stage renal disease because of dialysis has resulted in higher and more overt incidence of bone morbidity (Standbury, 1966; Kaye et al, 1960; and Kaye, 1969). Both typical osteomalacia and osteoporosis have been described, but the commonest bone pathology is that resulting from secondary hyperparathyroidism (Black, 1972; Bricker et al., 1969) is typified by osteitis fibrosa cystica pathologically, and subperiosteal resorption
and demineralization on X ray. Rarely, there is osteoscierosis, particularly of the lumbar spine (Kaye et al, 1960; Black, 1972). Most of the abnormal bone scan findings in our patients are likely to be due to the effects of secondary hyperparathyroidism. Co-existing osteomalacia, accounting for some scan findings in some patients, cannot be completely discarded, however. The fact that all 14 patients were on a regimen of dihydrotachysterol concurrent with dialysis, probably minimized the extent of osteomalacia (Kaye et al., 1970). Osteoporosis is a less common complication of chronic renal disease (Standbury, 1968) and it may also have been present in some patients. Except in instances of vertebral collapse, osteoporosis is, however, manifested on scan as an area of diminished activity (Sy, 1975). Osteoscierosis was not observed radiographically in any of our patients. The scan abnormalities due to secondary hyperparathyroidism support the findings of some earlier investigations. Dymling (1964), for instance, has demonstrated that a marked increased accretion rate with 47Ca and 85 Sr exists in patients with hyperparathyroidism and similar findings have been reported by other workers (Fraser, Harrison and Ibbertson, 1960; Rich, 1957). Costeas, Woodward and Laughlin (1971) have shown that the administration of parathyroid hormone resulted in 60 per cent increased uptake of 18 F in rabbit tibias. Recently, Sy (1974b) described patients with proved primary hyperparathyroidism showing comparable bone abnormalities on scan. Furthermore, our follow-up studies of post-parathyroidectomized patients
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4. Photoscan showing severe activity in the calvarium and mandible, but only minimal changes shown in the radiograph (Case 1). FIG.
have manifested significant regression of the abnormal bone activity observed prior to surgery. The initial radiographic changes in hyperparathyroidism occur in the spongy bones and the subperiosteum of long bones. These components of the bone are the most active metabohcally and the most responsive to changes in the level of parathyroid hormone (Williams, 1968). The distribution of abnormal activity on the scan in our patients closely follows this pattern. The bone effects of secondary hyperparathyroidism which appear as generalized abnormal activity are detected much earlier on scan, than on radiographs. The extent and degree of these bone changes also appear to be more pronounced on scan. Generalized demineralization of the spine, moderate to overt was noted on radiographs only in Cases 1,11,12, and 5, and yet all patients except for Case 2 manifested varying gradations of increased activity on scan. Spotty demineralization of the calvarium was present in Cases 1 and 12, but marked to severe involvement is apparent on imaging in these and five other cases (Fig. 4). We observed no radiographic changes in the mandibles of our patients, as was the experience of Katz, Hampers and Merrill (1969) in 195 patients with secondary hyperparathyroidism and renal osteodystrophy. On the other hand, the scans showed early, diffuse and consistent activity throughout the body and rami of the mandibles. Cases 9 and 13, which were mild forms, also demonstrated some increased mandibular activity. The photoscans of the hands (Cases 1, 3, 4, 11, 12, 13, and 14) demonstrated abnormal findings ranging from localized periarticular activity to more extensive involvement of all phalanges, metacarpals, and carpals. The radiographs in Cases 1, 11, and 13 showed some subperiosteal bone resorption mostly in the ungual tufts and trabeculations in some phalanges. A majority of the patients showed heavy activity in the acromioclavicular regions while only Cases 1 and 12 showed definite subperiosteal resorption of the distal thirds of the clavicles. Similarly, the distal ends of long bones manifested increased activity in most instances, and only limited demineralization and resorption were present on radiographs in the three severe cases. The "rosary beaded" pattern activity observed in Case 10 had no corresponding detectable costochondral changes on chest radiograph. Thus, whenever demonstrable demineralization, bone resorption or subperiosteal changes are apparent in the X rays of the calvarium clavicles, spine, pelvis, or hands, the corresponding scans disclosed a more striking degree of abnormal activity. The dif-
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Bone scan in chronic dialysis patients
25
15-
12
60
36 DIALYSIS
D U R A T I O N
FIG.
84 ALKALINE
( M O N T H S )
5.
PHOSPHATASE FIG.
( IU)
6.
Correlation of the duration of dialysis and the severity of bone scan changes.
Correlation of alkaline phosphatase level and the severity of bone morbidity.
ference in the ability of these two modalities to detect bone morbidity in this group of patients is not unexpected. More than 50 per cent demineralization of bone is needed before it is detected on X ray (Blaufox and Freeman, 1974-75; Denardo, 1972), whereas abnormal bone activity on scan is dependent on enhanced bone turnover and increased vascularity, an occurrence likely to happen early in the skeletal system of end-stage renal disease patients. Fifty per cent of patients on haemodialysis for two years or more manifest evidence of increased bone resorption and serum alkaline phosphatase (Katz et al, 1969; Fournier et al., 1971). In our patients, those who had been on haemodialysis for more than 30 months, all manifested severe, marked, or moderate forms of abnormality on scan. A correlation of the bone scan cumulative scores and the duration of dialysis is shown in Fig. 5. Case 2 had a negative scan and Cases 13 and 9 manifested mild changes. Cases 2 and 13 had been on dialysis for only four months duration while Case 9 had been on dialysis for 12 months. It should also be noted that these last three patients were treated with peritoneal dialysis and not with haemodialysis like the others. The degree of scan abnormality correlates with the serum alkaline phosphatase activity (Fig. 6). Two of three patients with the severest changes on scan also demonstrated the highest level of alkaline phosphatase, over 650 I.U. All four patients with marked changes, a majority of the moderate form and another severe form, are clustered in the 200-500 I.U. range level. Two patients that showed the least changes and another with moderate form
are in the 100-150 I.U. range level. This is in accord with the findings of Katz et al. (1969), who demonstrated that in the absence of concomitant liver disease, the serum alkaline phosphatase activity correlates well with the extent of bone involvement in chronic dialysis patients. ACKNOWLEDGMENTS
The authors wish to express their thanks to P. Scaglione, M.D., and J. Meyer, M.D. for reviewing the manuscript; to M. Malach, M.D. for his encouragement; and also to Mrs. M. D. Harris for her secretarial effort. REFERENCES BEKIER, A., and CECH, O., 1970. 85Strontium uptake study in nonunion in man. European Surgical Research, 2, 226-232. BLACK, D., 1972. In Renal Disease, 3rd edn., pp. 506, 473 (Blackwell Scientific Publications, Oxford and London). BLAUFOX, M. D., and FREEMAN, L. M., 1974-75. PDR for
Radiology and Nuclear Medicine. In The Skeletal System, pp. 31-33 (Oradell, New Jersey, Medical Economics Company). BRICKER, N. S., SLATOPOLSKY, E., REISS, E., and AVIOLI,
L. V., 1969. Calcium, phosphorus and bone in renal disease and transplantation. Archives of Internal Medicine, 123, 543-553. CHARKES, N. D., DURANT, J., and BARRY, W. E., 1972.
Bone pain in multiple myeloma: studies with radioactive 87m Sr. Archives of Internal Medicine, 130, 53-58. COSTEAS, A., WOODWARD, H. Q., and LAUGHLIN, J. S., 1971.
Comparative kinetics of calcium and fluoride in rabbit bone. Radiation Research,8546, 317-333. CRUTCHLOW, W. P., 1970. Strontium scintimetry of the hip in osteoarthritis and osteonecrosis. American Journal ofRoentgenology, 109, 803-812. DENARDO, G. L., 1972. The 85Sr scintiscan in bone disease. Seminars of Nuclear Medicine, 2, 18-20. DYMLING, J. F., 1964. Calcium kinetics in osteopenia and parathyroid disease. Acta Medica Scandinavica Supplement, 408,175, 6-56. FELLANDER, M., and LINDBERG, L., 1966. Clinical use of
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W. M. Sy and A. K. Mittal with albuminuria, rickets of adolescents. Lancet, 1, 993-994.
FOURNIER, A. E., JOHNSON, W. J., TAVES, D. R., et al.,
1971. Etiology of hyperparathyroidism and bone disease with potentially ethilogic factors. Journal of Clinical Investigation, 50, 592-598.
MCNEIL, B. J., CASSADY, R. J., and GEISER, C. F., JAFFE, N., TRAGGIS, D., and TREVES, S., 1973. Fluorine-18
bone scintigraphy in children with osteosarcoma or Ewing's sarcoma. Radiology, 109, 627-631.
FRASER, R., HARRISON, M., and IBBERTSON, K., 1960. The
rate of calcium turnover in bone. Quarterly Journal of Medicine, 29, 85-111. GALASKO, C. S. B., and DOYLE, F. H., 1972. Response to
therapy of skeletal metastases from mammary cancer: assessment by scintigraphy. British Journal of Surgery, 59, 85-88. HELSON, L., WATSON, R. C , and BENUA, R. S., 1972.
18 Fluorine radioisotope scanning of metastatic bone lesions in children with neuroblastoma. American Journal ofRoentgenology, 115, 191-199.
ILLINGWORTH, G. I., and SCHIESS, F. A., 1971.
87m
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MILNER, T. H., MAYNARD, C. D., and COWAN, R. J., 1971.
Evaluation of 85Sr bone scans and roentgenograms in 100 patients. Archives of Surgery, 103, 371-372. RICH, C , 1957. The calcium metabolism of a patient with renal insufficiency before and after partial parathyroidectomy. Metabolis, 6, 574-582. ROY, R. R., NATHAN, B. E., and BEALES, J. S. M., 1971.
18 Fluorine total body scans in patients with sarcoma of the prostate. British Journal of Urology, 43, 58-64. STAHELI, L. T., NELP, W. B., and MARTY, R., 1972.
87m in prognosis of fractures of tibia. Proceedings of the Strontium scanning: early diagnosis of bone and joint Royal Society of Medicine, 64, 633-634. infections in children. Journal of American Medical KAYE, M., 1969. Concepts of therapy: Prevention and Association, 221, 1159-1160. management of osteodystrophy in patients with long STANDBURY, S. W., 1968. Bone disease in uremia. American term hemodialysis. Archives of Internal Medicine, 124, Journal of Medicine, 44, 714-724. 656-662. SUBRAMANIAN, G., MCAFEE, J. G., and BELL, E. G., 1972. KAYE, M., CHATTERJEE, G., COHEN, G. B., and SAGAR, S., Technetium 99m-labeled polyphosphate as skeletal 1970. Arrest of hyperparathyroid bone disease with diimaging agent. Radiology, 102, 701-704. hydrotachysterol in patients undergoing chronic dialysis. SY, W. M., 1974a. Unpublished data. Annals of Internal Medicine, 73, 225-233. 1974b. Bone scan in primary hyperparathyroidism. KAYE, M., PRITCHARD, J. E., HALPENNY, G. W., and LIGHT, Journal of Nuclear Medicine, 15, 189-191. W., 1960. Bone disease in chronic renal failure with 1975. Unpublished observations. particular reference to osteosclerosis. Medicine, 39, 157- VAN DYKE, D., ANGER, H. O., and PARKER, H., 1971. 190. Markedly increased bone blood flow in myelofibrosis. KATZ, A. I., HAMPERS, C. L., and MERRILL, J. P., 1969. Journal of Nuclear Medicine, 12, 506-512. Secondary hyperparathyroidism and renal osteodystrophy WANKEN, J. J., EYRING, E. J., and SAMUELS, L. D., 1973. in chronic renal failure: Analysis of 195 patients with Diagnosis of pediatric lesions: correlation of clinical, observations on the effects of chronic dialysis, kidney roentgenographic, 87mSr scan and pathologic diagnosis. transplantation and subtotal parathyroidectomy. Medicine Journal of Nuclear Medicine, 14, 803-806. {Baltimore), 48, 333-374. WAXMAN, A. D., BRYAN, D., and SIEMSEN, J. K., 1973. KHARI, M. R. A., WELLMAN, H. N., and ROBB, J. A., 1973. Bone scanning in the drug abuse patient: Early detection Paget's disease of bone (osteitis deformans): symptomatic of hematogenous osteomyelitis. Journal of Nuclear lesions and bone scan. Annals of Internal Medicine, 79, Medicine, 14, 647-650. 348-351. WILLIAMS, R. H., 1968. Textbook of Endocrinology, 4th edn., LUCAS, R. C , 1883. On a form of late rickets associated Rasmussen, H.: The Parathyroids, p. 866 (W. B. Saunders Co., Philadelphia, Pennsylvania).
Book review Diseases of the Esophagus. By G. Vantrappen and J. Hellemans, pp. 877, 358 illus. (some in colour), 1974 (Berlin, Heidelberg, New York, Springer-Verlag), DM 390, $159.20. This book is one of a series under the title Handbuch der inneren Medizin and is Part I of the third series on the digestive organs. Professor Vantrappen and Professor Hellemans are not only editors, but also major contributors. Most of the other contributors come from the University of Leuven, but the editors have enlisted much talent from other countries including Professor Monges from France, Dr. Heitmann from Germany and Dr. D. A. W. Edwards from this country. The radiologists are Professor Bonette and Professor Pringot of the University of Leuven and Professor Bernard Wolf of the Mount Sinai Hospital, New York. There is one chapter devoted to the radiology of the oesophagus but there are also many interesting references to radiology throughout the book. This is the most complete and informative book on the oesophagus that the reviewer has ever seen. The whole field of the oesophagus has been covered and in addition to chapters on such obvious subject as anatomy, embryology,
physiology, diagnostic procedures, etc. there are contributions on manometry, pH measurements, exfoliative cytology, PD measurements and electromyography. The standard is level throughout and of the highest. To the radiologist the book is of considerable value in providing a good background on anatomy, physiology, manometry, etc. and also as a reference book for the rarer diseases of the oesophagus, for example, those complicating cutaneous diseases. The account of the radiology of the oesophagus is excellent and includes sections on cinefluorography and video recording. This is a work which should certainly find its way into every hospital library and also into the departmental libraries of the X-ray departments of larger hospitals. The only possible reason against this is the high cost of the book. Considering the amount of work which has gone into its production, the vast knowledge of the contributors, the faultless format, and the high quality of the reproductions, the price is not really excessive. The editors especially, but also the contributors, are to be congratulated on the production of a superb text-book on the oesophagus and the reviewer hopes that, expensive or not, it will have the success it deserves.
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