Clmtcal Radiology (1986) 37, 63-70 0009-9260/86/583063502.00 © 1986 Royal College of Radiologists

Radiological Assessment of Aluminium-related Bone Disease PETER GARRETI ' , MARION McWADE and JOHN O 'CALLAGHAN

Department of Medicine and Nephrology, and Department of Radiology, Jervis Street Hospital, Dublin 1, Ireland

Two hundred and fifty-nine radiological skeletal surveys were reviewed in 67 cases of end-stage renal failure. Fractures were identified in 16 patients, of whom 12 (17.9% of total) had aluminium-related bone disease. Moderate or severe fracturing osteopathy with more than five fractures not explained by trauma was 100% specific for aluminium intoxication. It is sufficient to perform radiological skeletal surveys in the assessment of renal osteodystrophy annually. They should include radiographs of the fingers, a lateral view of the lumbar spine and oblique views of the ribs. The primary aim of reporting on such surveys should be to grade the severity of fracturing osteopathy and of subperiosteal erosions.

Bone disease is a well recognised complication of chronic renal failure and is divided into the five radio- logical and pathological categories of osteoporosis, osteomalacia, hyperparathyroid bone disease, osteo- sclerosis, and extraosseous calcification. Multiple fac- tors are probably involved in the pathogenesis of each of these categories and more than one type of bone disease may exist in a single patient.

Severe bone disease in renal failure is usually caused by hyperparathyroidism. However, during the late 1960s and early 1970s a new entity of severe renal bone disease without evidence of hyperparathyroidism was recognised (Siddiqui and Kerr, 1971; Parfitt et al., 1972). This new syndrome occurred only in patients established on haemodialysis and was characterised by bone pain, reduced radiological bone density and multi- ple pathological fractures. Later work showed that the histological lesion was ostedmalacia (Simpson et al., 1976; Ellis et al., 1977) and epidemiological and histo- chemical studies linked its pathogenesis with aluminium poisoning (Ward et al., 1978; Buchanan et al., 1981). The features of this syndrome are summarised in Table 1.

Development and progression of renal bone disease may be monitored clinically, biochemically, radio- logically and histologically. The study, in one active

Table 1 - Features of fracturing osteomalacic dialysis osteopathy

1. Almost exclusively limited to patients on maintenance haemodialysis

2. Incidence varies from centre to centre 3. Severe bone pain 4. Proximal myopathy 5. Multiple pathological fractures 6. Histologically, gross osteomalacla 7. Relative absence of biochemical, radiological or histological

evidence of hyperparathyroidism 8. No response to vitamin D therapy 9. Tendency to hypercalcaemia

10. Association with dialysis encephalopathy 11. Alumxnium demonstrable at calcification front

Address for correspondence: Dr Peter Garrett, l l a Clyde Lane, Dublin 4, Ireland.

renal unit, evaluated the use of radiological skeletal surveys in monitoring renal osteodystrophy, with special reference to aluminium-related bone disease.

METHODS

All radiological skeletal surveys available from 67 patients on renal dialysis were reviewed.

Each survey consisted of postero-anterior radio- graphs of the chest, hands and feet, an antero-posterior radiograph of the pelvis and lateral radiographs of the skull and the thoracic and lumbar spine.

The following features were assessed in each survey.

1. Overall decrease in bone density. Diffuse increase in bone lucency; 'ghosting' of vertebral bodies with promi- nence of end plates; predominance of vertical tra- beculae in vertebral bodies; predominance of weight- bearing trabeculae in femoral necks; thinning of cortex; loss of cortico-medullary junction; loss of medullary bone with lace-like trabecular pattern.

2. Overall increase in bone density. Localised patchy sclerosis; coarsening of trabecular structure; diffuse chalky increase in bone density.

3. Evidence of hyperparathyroid bone disease. Diffuse granularity of skull vault; subperiosteal erosion of bone along borders of phalanges of fingers and toes, terminal tufts of phalanges, lateral ends of clavicles, sacro-iliac joints, symphysis pubis; 'brown turnouts'.

4. 'Rugger-jersey spine'. 5. Fractures. Ribs; metacarpals; metatarsals; phal-

anges; pubic rami; femoral necks; crush fractures of vertebrae; elsewhere.

6. Looser's zones. Lateral margins of scapulae; pubic rami; shaft and neck of femur; ribs.

7. Extraosseous calcification. Great arteries; small vessels; chondrocalcinosis; periarticular calcification in ligaments and joint capsules; tumoral subcutaneous calcification; nephrocalcinosis; other organs.

Objective assessments of bone density such as step- wedge densitometry were not employed.

Each feature was scored on a scale of 0-5 (absent; equivocal; mild; moderate; severe; gross). For numeri- cal abnormalities such as fractures, one discernible lesion was regarded as equivocal; between two and five as mild; from six to ten, moderate; 11 to 20, severe; and over 20, gross.

Abnormalities were then analysed with respect to exposure to aluminium-rich dialysate, defined as dialy- sate made up from water containing more than 20 #g/litre aluminium. Patients were divided into three categories:

I pre-dialysis, or on haemodialysis for less than 18 months;

64 CLINICAL RADIOLOGY

II on dialysis for more than 18 months, but less than 18 months' exposure to aluminium-rich dialysate;

III on haemodialysis with exposure for longer than 18 months to aluminium-rich dialysate.

Finally, a limited follow-up study was performed on 18 patients with fractures and/or moderate changes of hyperparathyroidism, with two further patients without radiological evidence of bone disease but known to be at risk of aluminium intoxication. The follow-up study included oblique views of the ribs on both sides. Many of these patients underwent a change of treatment during the course of the study.

RESULTS

A total of 259 surveys were reviewed in 67 patients over 251 patient-years: an average of very close to one survey per patient per year.

Radiological Signs of Bone Disease

The numbers of surveys showing unequivocal evi- dence of the different types of bone disease are detailed in Table 2. Fig. 1 - Multiple pathological fractures of the metatarsals

Table 2 - Numbers of surveys (numbers of patients) showing unequivo- cal and moderate or marked radiological features of bone disease

Unequivocal Moderate/ marked

No. of surveys (No. of pattents) No. of surveys

(No. of pauents)

DEcreased density 59 (21) 52 (19) Increased density 42 (16) 21 (9) Fractures 59 (16) 31 (8) Hyperparathyroidlsm 59 (21) 35 (14) Extraosseous calcification 69 (23) 29 (12) 'Rugger-jersey spine" 59 (20) 44 (15)

Fifty-nine surveys in 21 patients demonstrated un- equivocal radiological features of hyperparathyroidism. The most useful signs here were subperiosteal erosions along the radial borders of the phalanges and erosion of the terminal tufts, both in the fingers. Changes in other bones were not seen unless finger lesions were also present.

'Rugger-jersey spine' was apparent in 59 surveys in 20 patients. When present, this lesion was always evident in the lumbar spine, although sometimes more distinct in the thoracic spine. Even though the onset of 'rugger- jersey spine' tended to parallel the appearance of sub- periosteal erosions, the spinal abnormality often per- sisted after the erosions had responded to treatment.

Sixteen patients had fractures (Figs 1-5), evident in 59 surveys. Of these, 12 patients were diagnosed as having aluminium toxicity on the basis of more than 18 months' exposure to high-aluminium dialysate with clinical evi- dence of dialysis encephalopathy (speech disturbance, myoclonus and seizures) and/or positive aluminium staining of bone (Fig. 6). All eight cases of moderate or severe fracturing osteopathy could be diagnosed confi- dently as aluminium-related bone disease. Patients with fractures due to aluminium-related bone disease always had fractures of the ribs, with or without fractures

elsewhere. Fractures not due to aluminium intoxication were seen in one patient with hyperparathyroid bone disease, in one with hyperparathyroidism with hypo- phosphataemic osteomalacia and in one with two unex- plained rib fractures but no aluminium staining of bone and only mild histological features of bone disease. Biopsy was not performed in a further patient who was an alcoholic, with fractured ribs which may have resulted from frequent physical trauma.

Ectopic calcification was common, occurring in 69 surveys in 23 patients. The sites most often affected were the great vessels, such as the abdominal aorta, visible on lateral films of the lumbar spine, and the iliac and femoral arteries, evident on pelvic films. Looser's zones (Fig. 3) were distinguished from pathological fractures mainly by the site affected and were apparent in only six surveys in two patients.

'Relative Value of Regional Radiographs

Changes in hyperparathyroidism were not seen on skull films unless lesions were also evident in the fingers. Lateral views of the thoracic spine sometimes showed more distinct features in patients with changes also apparent in the lumbar spine. Views of the thoracic spine were never abnormal, however, if the lumbar spine was normal.

Radiological evidence of hyperparathyroid bone dis- ease in any single patient included involvement of the fingers. Pathological fractures of the metatarsals (Figs 1, 5) or metacarpals were seen in several patients, all of whom also had pathological rib fractures. Views of the pelvis (Fig. 2) were often the best method of demonstrating patchy sclerosis of the femoral heads. Pelvic films also revealed Looser's zones in one subject and 'brown tumours' in two.

Chest radiographs were valuable for the demonstra- tion of rib fractures (Figs 3, 4). These could be revealed

ALUMINIUM-RELATED BONE DISEASE 65

v

v~, v v

Fig. 2 - Pathological fractures of the pubic rami.

earlier and in greater numbers by oblique views of the ribs. Erosion of the lateral ends of the clavicles was seen in a few patients, all of whom also had hyperparathyroid finger lesions. In one case with severe radiological changes of hyperparathyroidism, a pathological fracture developed through a markedly eroded area of the shaft of the clavicle. Looser 's zones at the lateral margins of the scapulae (Fig. 3) and a 'brown tumour ' of the shaft of

the humerus were each evident in a single patient. Coar- sening of the trabecular pattern of the ribs and patchy sclerosis of the head of the humerus were often per- ceived but were difficult to evaluate objectively. In addi-

v

Fig. 3 - Multiple pathological rib fractures with Looser 's zones Fig. 4 - Multiple rib fractures showing healing with callus formation (arrowed) at the lateral margins of the scapulae, after successful renal transplantation.

66 CLINICAL RADIOLOGY

(a) (b) Fig. 5 (a, b) - Rapid healing of metatarsal fractures after successful renal transplantation.

tion, chest radiographs showed evidence of cardio- respiratory disease and fluid overload.

Aluminium Risk Category

Similar numbers of surveys were reviewed in each category (Fig. 7). Radiological evidence of bone disease was less often found in Category I patients, although gross examples of hyperparathyroidism did occur in this group. The great majority of fractures were seen in Category III patients. Decreased bone density was also much commoner in this group.

Increased bone density, hyperparathyroid bone dis- ease, ectopic calcification, and 'rugger-jersey spine' were all most frequently seen in Category II patients.

Prevalence of Severe or Moderate Disease

Moderate or severe radiological changes of bone dis- ease of any type were observed in 40 of the 67 patients studied. Moderate or severe fracturing osteopathy was identified in 31 surveys in eight patients, all with aluminium-related bone disease, and moderate or severe hyperparathyroidism in 35 surveys in 14 patients (Table 2).

Correlations Between Different Types of Bone Disease

Overall correlations between different types of dis- ease are summarised in Table 3. Fractures showed sig- nificant negative correlations with subperiosteal erosions, 'rugger-jersey spine' and increased bone den- sity. Although there was no overall correlation between fracturing osteopathy and diminished bone density, where fractures were present the grade of severity cor- related with the degree of reduction in bone density (r=0.264; p<0.05). There was no relationship between fractures and extraosseous calcification.

Follow-up Study

The cases followed included eight cases of fracturing osteopathy due to aluminium-related bone disease with- out radiological evidence of hyperparathyroidism, one patient with fractures due to aluminium intoxication plus residual evidence of hyperparathyroid bone dis- ease, one alcoholic patient with fractures, one patient with mild fracturing osteopathy and mild histological bone disease, two cases of mild fracturing osteopathy together with radiological changes of hyperparathyroid- ism, five patients with moderate or severe hyper- parathyroid lesions without fractures and two patients

ALUMINIUM-RELATED BONE DISEASE 67

• 3

Ost

MB

~ J

j*

l

Fig. 6 - Alumlnmm stain of undecalclfled bone section: alumlmum demonstrable as dark hne (arrows) at interface between mlneralised bone (MB) and osteoid (Ost).

with normal skeletal surveys but known to be at risk ot aluminium intoxication.

Changes of hyperparathyroid bone disease tended to progress with time, but progression could be modified by transplantation, vitamin D therapy and aluminium intoxication. Numbers of fractures tended to increase with continuing exposure to high-aluminium dialysate. Rib fractures, demonstrated on oblique rib radiographs, appeared in two patients with previously normal skeletal surveys but known to be at risk of aluminium poisoning. Numbers of fractures usually did not progress in patients who had been switched to low-aluminium dialysate.

Three patients with hyperparathyroid bone disease received functioning renal grafts during the course of the study. Radiological changes of hyperparathyroidism persisted in one case in a survey performed 3 months after transplantation. In a second patient, hyper- parathyroid changes had resolved in the skull but not in the fingers 6 months after the onset of graft function. Biochemical hyperparathyroidism, with high plasma calcium, plasma alkaline phosphatase activity and serum parathyroid hormone, persisted in this patient who later required parathyroidectomy. Resolution of the changes in both the skull and the fingers had occur- red in the third patient 12 months after transplantation. Rib and metatarsal fractures in patients with aluminium- related bone disease showed rapid healing with abun- dant callus formation after successful renal transplanta- tion (Figs 4, 5).

Vitamin D analogues as 1-a-hydroxycholecalciferol were introduced in one patient during the course of the study without improvement in the radiological features of hyperparathyroidism. In another case, hyper- parathyroid changes in the skull resolved following introduction of vitamin D, but recurred when the drug was withdrawn.

Oblique radiographs of the ribs demonstrated frac- tures for the first time in two patients with known dialysis encephalopathy or continuing exposure to high- aluminium dialysate. Oblique rib views revealed addi- tional healed fractures in another patient with aluminium-related bone disease and in a further case of fracturing osteopathy without histological data. Marked changes of hyperparathyroidism persisted in one case and progressed in another without appearance of rib fractures, despite continued exposure to dialysate with a very high aluminium concentration•

Rib fractures which had not healed over the previous 6 years showed healing with callus formation 4 months after the introduction of desferrioxamine chelation therapy in one patient. In another case, however, frac- tures were shown for the first time by oblique rib views during a course of desferrioxamine.

One patient displayed a steady progression from increased bone density, hyperparathyroid bone disease and 'rugger-jersey spine', to severely decreased bone density, disappearance of hyperparathyroid changes and the spinal changes and development of fracturing osteopathy with progressive exposure to aluminium-rich dialysate. Subtotal parathyroidectomy had been carried out more than 12 months before the bone disease began to alter, but may have played a part nevertheless. 'Rug- ger-jersey spine' vanished with the onset of aluminium intoxication in another patient who had never under- gone neck exploration. These two cases were the only examples seen of resolution of 'rugger-jersey spine'. Mild or equivocal hyperparathyroid changes disap- peared in another two patients with progressive aluminium intoxication, both of whom had undergone parathyroidectomy. 'Rugger-jersey spine' and hyper- parathyroid bone disease persisted, however, in one further patient, despite the onset of severe aluminium- related bone disease.

Interval between Skeletal Surveys

Alterations in radiological bone abnormalities did not occur at less than 12-monthly intervals, except after successful renal transplantation.

DISCUSSION

The radiological features of the specific bone disease of renal dialysis patients have been described by Simp- son et al. (1973) and Platts et al. (1973). These authors drew attention to multiple pathological fractures and overall reduction in bone density. Simpson and his col- leagues (1976) correlated these radiological findings with histological osteomalacia. Subsequent work (Ward et al., 1978) linked the syndrome with high aluminium concentrations in dialysis water supplies. Recently, however, little attention has been paid to the radiologi- cal aspects of this disease.

68 CLINICAL R A D I O L O G Y

40

( / 3 >- 30 LU

r~

u~

" 20 o

W

z

I Normal

I H y p e r p a r a - thyroid Bone Disease

I I I I I ' R u g g e r E x t r a Increased Decreased F r a c t u r e s Jersey Osseous Density Density Sp ine ' Calcification

(a)

40-

i/1 >- LU 30" ee'

20" e¢

m

~ 10- z

0- i

Normal

1 I I I i

Hyperpara - t hy ro i d Bone Disease

'Rugger Decreased Fractures Jersey Density Spine '

I . . . . . . . . . i i . . . . . . . . . . 1

Ex t ra Osseous Calci f icat ion

(b)

II Increased Density

40-

30-

20" 0

Normal Hyperpa ra - thyroid Bone Disease

'Rugger Ex t ra Increased Decreased Fractures Jersey Osseous Densi ty Densi ty Spine ' Calcification

(c) Fig. 7 (a, b, c) - Preva lence of r ad io log ica l b o n e d isease r e l a t ed to a l u m i n l u m r isk ca tegor i e s I, I I , and III .

The only specific sign of aluminium-related bone dis- ease in our series was rib fractures; all patients with more than five fractured ribs had aluminium intoxica- tion. Reduction in bone density was difficult to assess. Medullary resorption of bone with a lace-like trabecular pattern (Simpson et al., 1976) was seen in a small num- ber of our aluminium-toxic patients but, again, was

difficult to define. More recently, Chambers and Win- ney (1985) have suggested that periosteal new bone formation may be an early sign of aluminium-related bone disease. This feature, affecting the metatarsals and pubic rami, was seen in only two of our patients with fractures.

In this study, aluminium-related bone disease was

ALUMINIUM-RELATED BONE DISEASE

Table 3 - Correlation between different types of bone disease

69

Fracturing osteopathy r= - 0.37 Hyperparathyrotd p<0.001 bone disease

r= -0 .53 r = - 0 . 2 6 Increased p<0.001 p<0.02 density

r=0.08 r - - 0 . 4 4 NS p<0.001

r= -0 .20 r = - 0 . 3 2 NS p<0.001

r=-0 .51 r=0.01 r= -0 .39 p<0.001 NS p<0.001

Decreased density

Extra-osseous calctficatton

r = - 0 . 4 0 r = - 0 40 'Rugger-jersey p<0.001 p<0.001 spine'

equally remarkable for the relative absence of certain radiological signs. In particular, subperiosteal erosions showed a negative correlation with fractures. Several possible reasons for a dissociation between aluminium poisoning and hyperparathyroidism have been sug- gested: a direct toxic action of aluminium on the para- thyroid gland (Cann etal . , 1979), reversible inhibition of secretion of parathyroid hormone by circulating aluminium (Morrissey et al., 1983), inhibition of the effects of parathyroid hormone at tissue level (Lieberherr et al., 1982), a protective effect of hyper- parathyroidism against aluminium poisoning (Cournot- Witmer et al., 1981) and suppression of parathyroid hormone secretion by hypercalcaemia associated with aluminium intoxication (Cannata et al., 1983). In addi- tion, many patients with chronic aluminium poisoning may have previously undergone subtotal parathyroidec- tomy. Nevertheless the two disorders are not mutually exclusive and, indeed, two of our cases with radiological and histological changes of severe hyperparathyroidism displayed positive staining of bone for aluminium. One model of dialysis-related bone disease would, therefore, be a spectrum with, at one end, low-turnover fracturing osteomalacia with positive aluminium staining and, at the other, increased osteoblastic and osteoclastic activity with marrow fibrosis and negative aluminium histochemistry.

Aluminium intoxication and hyperparathyroidism are the likeliest aspects of dialysis osteodystrophy which will influence patient management. We suggest that the primary function of reporting radiological skele- tal surveys in chronic renal failure should be to grade the severity of hyperparathryroid bone disease (i.e. sub- periosteal erosions) and aluminium-related bone dis- ease (i.e. fractures). Severity of extraosseous calcification should also be graded, whereas features such as 'rugger-jersey spine' and patchy sclerosis of bone, which are of uncertain significance, only require mention.

Abnormalities on skeletal radiographs are unlikely to become apparent until osteopathy is advanced and a skeletal survey is, therefore, an insensitive method of assessing bone disease. Radiological skeletal surveys do, however, represent a convenient and non-invasive method of evaluating the type and severity of symp- tomatic bone disease and of identifying asymptomatic cases of osteopathy. The survey must, of course, be interpreted in the light of the clinical and biochemical profile and cannot replace bone histology in the exact diagnosis of renal osteodystrophy.

A study based on radiologically apparent lesions is, therefore, likely to underestimate the true incidence of

6

bone disease. Even so, radiological changes of aluminium intoxication were present in 17.9% of the group studied, which included the great majority of the dialysis patients at the time of the project. Aluminium- related bone disease also accounted for 20% of all cases of moderate or severe bone disease, as opposed to 35% due to hyperparathyroidism. These figures illustrate the continuing importance of aluminium poisoning as a cause of morbidity in dialysis patients nowadays.

In this series, fractures were demonstrated more readily by oblique views of the ribs than by the standard components of a skeletal survey. This finding is in accord with a recent large review of traumatic rib frac- tures (Danher et al., 1984), in which 33% of all cases of fractures were apparent only on oblique views. Sub- periosteal erosions were most easily seen in the fingers, and ectopic calcification as well as 'rugger-jersey spine' were best illustrated by lateral radiographs of the lum- bar spine. Except in patients with transplants, altera- tions in radiological findings did not occur at less than yearly intervals.

Radiological skeletal surveys in the assessment of renal osteodystrophy should, therefore, consist of radio- graphs of the fingers, lateral radiographs of the lumbar spine and oblique views of the ribs, and need not be carried out more often than once a year.

Acknowledgements. Our thanks are due to Dr M. Carmody and Dr J. F. Donohoe for permission to review their cases. We are also indebted to Herma Boyle at Woodview Hospital, Michael Foley at Belfield Hospital and George Scully, Denise Olin and John Bourke at Mater Hospital for assistance with illustrations.

REFERENCES

Buchanan, M. R., Ihle, B. U. & Dunn, C. M. (1981). Haemodialysis related osteomalacia: a staining method to demonstrate aluminlum. Journal of Clinical Pathology, 34, 1352-1354.

Cann, C. E., Prussln, S. G. & Gordan, G. S. (1979). Aluminium uptake by the parathyroid glands. Journal of Clintcal Endocrinol- ogy and Metabohsm, 49, 543-545

Cannata, J. B., Briggs, J. D., Junor, B. J., Fell, G. S. & Beastall, G. (1983). Effect of acute aluminium overload on calcium and para- thyroid hormone metabolism. Lancet, i, 501-503.

Chambers, S. E. & Wlnney, R. J. (1985). Perlosteal new bone in patients on intermittent haemodialysis: an early indicator of aluminium-induced osteomalacia 9 Clinical Radiology, 36, 163- 168.

Cournot-Witmer, G., Zingraff, J., Plachot, J. J., Escaig, F., LeFevre, R., Boumati, P. et al. (1981). Alfiminium localisation in bone from haemodialysed patients: relationship to matrix mineralisatxon. Kidney International, 20, 375-378.

Danher, J., Eyes, B. E. & Kumar, K. (1984). Oblique rib views after blunt chest trauma: an unnecessary routine? British Medical Jour- nal, 289, 1271.

70 CLINICAL RADIOLOGY

Ellis, H. A., Pierides, A. M., Feest, T. G., Ward, M. K. & Kerr, D. N. (1977). Histopathology of renal osteodystrophy with particular reference to the effects of one alpha hydroxyvitamin D3 In patients treated by long-term haemodialysls. Clinical Endocrinology (Suppl.), 7, 31S 38S.

Lleberherr, M., Grosse, B , Cournot-Wltmer, G., Thll, C. L & Balsan, S. (1982). In vitro effects of aluminium on bone phos- phatases: a possible interaction with bPTH and vitamin D 3 metabolltes. Calcified Ttssue International, 34, 280--284.

Morrissey, J., Rothsteln, M , Mayor, G. & Slatopolsky, E. (1983). Suppression of parathyroid hormone secretion by aluminlum. Kidney International, 23, 699-704.

Parfitt, A M., Massry, S G. & Winfield, A. C (1972). Ostoepenia and fractures occurring during maintenance haemodialysis: a new form of renal osteodystrophy. Clintcal Orthopedzcs and Related Research, 87, 287-302.

Platts, M. M., Grech, P., McManners, T. & Cochran, M. (1973). Skeletal changes in patients treated by regular haemodialysls in the Sheffield area. Brittsh Journal of Radiology, 46, 585 593.

Siddlqui, J. & Kerr, D. N. (1971). Complications of renal failure and their response to dialysis. Brmsh Medical Bulletin, 27, 153-159

Simpson, W., Ellis, H. A., Kerr, D. N , McElroy, M., McNay, R. A. & Peart, K. N (1976). Bone disease in long-term haemodialysls: the association of radlological with histological abnormalities. Br> tish Journal of Radtology, 49, 105-110.

Simpson, W., Kerr, D N., Hill, A V. & Siddiqui, J. Y (1973). Skeletal changes in patients on regular haemodialysis Ra&ology, 107, 313-320.

Ward, M K., Feest, T. G., Ellis, H. A., Parkinson, I. S., Kerr, D. N., Herrlngton, J. et al., (1978). Osteomalacic dialysis osteodystrophy: evidenced for a water-borne aetiological agent, probably aluminlum. Lancet, i, 841-845.