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PubMed1989

Prevention of osteitis fibrosa, aluminium bone disease and soft-tissue calcification in dialysis patients: a long-term comparison of moderate doses of oral calcium +/- Mg(OH)2 vs Al(OH)3 +/- 1 alpha OH vitamin D3.

Since 1980, moderately large doses of oral calcium (80 +/- 35 mmol/day as CaCO3 +/- calcium polystyrene sulphonate), in association if necessary with Mg(OH)2 (2.5 +/- 1 g/day), with a reduction in the dialysate Mg concentrations from 0.75 to 0.375 mmol/24 h, have replaced A1(OH)3 as phosphate binders in our centre. A1(OH)3 was previously given to our haemodialysis patients in association with small doses of Ca CO3 (less than or equal to 3 g/day) and if necessary with 1 alpha OH vitamin D3. To compare the long-term efficacy of this new approach with the former one in the prevention of renal osteodystrophy and soft-tissue calcification, 32 current patients were selected on the basis of at least 24 months of treatment in our centre and availability of a yearly bone survey (profile of lumbar spine and anteroposterior view of the pelvis, shoulders and hands). A group of 30 patients treated before 1980 were then selected on the same criteria and matched for age, sex, and duration on dialysis. Linear calcifications of the anterior and posterior walls of the aorta in front of L2, L3, L4 and on the lateral walls of the iliac and femoral arteries were measured and the para-articular calcifications and subperiosteal resorptions of the hands evaluated. The initial extent and the subsequent increase of the ocular and para-articular calcification were comparable in the two groups. Plasma alkaline phosphatase was stable in the normal range in both groups, as was plasma concentration of calcium. Plasma phosphate was slightly elevated (1.7 mmol/l) but stable and comparable in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1984

Bone disease in long-term hemodialysis patients with low dialysate aluminium.

The dialysis unit in Sunderland uses softener water treatment with low Al concentration (dialysate mean Al 22 micrograms/L) but employs continuous oral Al (OH)3 to control serum phosphate. Thirty-one patients, 22 males and 9 females, with a mean age of 45 years, maintained on hemodialysis for a mean of 48 months were studied. Patients had higher Al concentrations than normal controls (p less than 0.001) and the postdialysis serum Al levels were also significantly higher than the predialysis levels. Twenty-four of 31 patients had evidence of hyperparathyroidism on radiology but only 4 of 31 had fractures. From a histopathological point of view, the patients were found to have no lesions (4 patients), osteitis fibrosa alone (17 patients), and osteitis fibrosa combined with osteomalacia (5 patients). The effect of 1-alpha(OH)D3 treatment was checked by repeated bone biopsies. One case of the last group showed no improvement of osteitis fibrosa, while osteomalacia progressed to severe. We conclude that both antacids and dialysate contribute to the serum and tissue Al accumulation in Sunderland Renal Unit, where over a period of ten years only one patient developed Al-related osteomalacia.

Adult↗
PubMed1989

Elevated bone aluminum and suppressed parathyroid hormone levels in hypercalcemic dialysis patients.

We studied 21 dialysis patients who became hypercalcemic without vitamin D or calcium therapy and compared them to 28 dialysis patients who were not hypercalcemic. In the hypercalcemic group, the mean ionized-calcium level was elevated compared to normal subjects (5.4 +/- 0.4 vs. 4.9 +/- 0.1; p less than 0.001), while the ionized-calcium level in the control dialysis patients was below normal (4.5 +/- 0.4 vs. 4.9 +/- 0.1; p less than 0.001). Bone biopsies were performed in all patients. Two thirds of the hypercalcemic patients had low-turnover osteodystrophy (LTO, predominantly osteomalacia), a fraction significantly higher than in the control dialysis patients (13/21 vs. 8/28, respectively; p less than 0.05). The hypercalcemic patients with LTO had markedly elevated surface bone aluminum (63 +/- 24% of all trabecular surfaces). In contrast, the nonhypercalcemic dialysis patients with LTO and all patients with osteitis fibrosa had minimal surface bone aluminum. Hypercalcemic patients with osteitis fibrosa had a significantly lower mean N-terminal parathyroid hormone (PTH) value than did nonhypercalcemic patients with osteitis fibrosa (149 +/- 81 vs. 278 +/- 135 pg/ml, respectively; p less than 0.005). Both mean values were markedly elevated in comparison with those obtained in normal subjects (16 +/- 5 pg/ml). In contrast, patients with LTO, irrespective of the calcium level, had mean PTH values that were not significantly different from those of normal subjects. A PTH level greater than 100 pg/ml was 95% sensitive and 87% specific for osteitis fibrosa, as demonstrated by histomorphometry in nonhypercalcemic dialysis patients. However, this level was only 62% sensitive and 77% specific for a diagnosis of osteitis fibrosa in hypercalcemic dialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1977

Histopathology of renal osteodystrophy with particular reference to the effects of 1alpha-hydroxyvitamin D3 in patients treated by long-term haemodialysis.

(1) The bone histology of 233 non-dialysed and 276 haemodialysed patients with chronic renal failure is reviewed. In non-dialysed patients osteitis fibrosa occurred in 83.7% and osteomalacia in 23.6% of patients. Osteomalacia was not found in the absence of osteitis fibrosa. In haemodialysed patients there was a more variable bone histology, sometimes resembling non-dialysed bone disease, but in general with a greater incidence of osteomalacia, especially with increasing time on dialysis. In some patients there was a predominance of osteomalacia accompanied by no or only mild osteitis fibrosa and the serum alkaline phosphatase was normal. (2) The results of treating twenty-six haemodialysed patients with 1alpha-hydroxyvitamin D3 (1alpha-OHD3) are described. Patients with osteomalacia and minimal or no osteitis fibrosa and a normal serum alkaline phosphatase (Group I) in general failed to respond and it is suggested that 1,25-dihydroxyvitamin D3 deficiency is not the sole factor responsible for the osteomalacia in these patients. In contrast, 1alpha-OHD3 therapy was effective in improving osteitis fibrosa and osteomalacia in some patients with moderate to severe degrees of osteitis fibrosa and osteomalacia (Group IIa) and in improving osteitis fibrosa where this occurred alone (Group IIb).

Adolescent↗
PubMed1976

[Collagen metabolism and mineralization of uremic bone--aspects of the molecular pathology of renal osteodystrophy].

Importance sequelae of uremia are hormonal changes in calcium homeostasis combined with chronic calcium imbalance causing structural alteration and functional insufficiency of bone. Morphological findings of the so called renal osteodystrophy are osteomalacia, osteitis fibrosa and osteoporosis. Osteitis fibrosa and abnormal skeletal metabolism (changes of collagen turnover, insufficient maturation of stable bone crystals) impair the mechanical qualities of bone. Probably the uremia per se influences the collagen metabolism; additional factors such as secondary hyperparathyroidism and deficiency of vitamin D3 are discussed.

Animals↗
PubMed1998

Can we use 99mTc-MIBI in functional studies of the parathyroid gland?

The usefulness of technetium-99m-sestamibi (99mTc-MIBI) in patients with secondary hyperparathyroidism on haemodialysis was assessed. We studied 33 patients with parathyroid scintigraphy with i.v. (99mTc-MIBI). Static images in a scintillation camera were taken at 15 and 120 min after the injection. With P x Ca<80, we performed an inhibition test with calcitriol i.v. 2 microg, three times a week, for 2 weeks. The MIBI study and assessment of intact parathyroid hormone (iPTH) were performed before (baseline study) and after inhibition. A 'focal positive study' corresponded to one or more areas of abnormal hypercaptation in relation to surrounding thyroid tissue seen in early images and persisting in later images, and a 'negative study' did not correspond to the previous image. In the baseline study, iPTH in the positive MIBI group was significantly greater than in the negative group. Eight positive MIBI patients had a bone biopsy; six corresponded to severe osteitis fibrosa and two to mild osteitis fibrosa. In the negative MIBI group, four of the six patients who had bone biopsy had mild forms of osteitis fibrosa (Fisher=0.03); the other two had low turnover forms. A positive inhibition test was defined when the basal uptake disappeared after calcitriol administration. In these patients, we observed a significant decrease of iPTH, not observed in the negative inhibition test. In 10 patients who had been parathyroidectomized, those with alpha positive basal MIBI result had a nodular parathyroid hyperplasia. We conclude that a scintigraphic parathyroid study with 99mTc-MIBI showed a good correlation with functional parathyroid status. With the same inhibition test, only some glands were inhibited, suggesting that this could be the expression of different vitamin D receptor densities in inhibited glands and/or a different kind of proliferation in those glands. This test would be of value in functional studies when a therapeutic decision must be made.

Adult↗
PubMed1999

Renal osteodystrophy in pre-dialysis patients: ethnic difference?

The purpose of the present study is to investigate whether an ethnic difference exists in the incidence of renal osteodystrophy between Asian and Western countries in end-stage renal disease (ESRD) patients. We evaluated bone histology in 58 pre-dialysis patients (28 male, 30 female; mean age: 47.7 years). All patients had bone biopsies with quantitative histomorphometry and serological parameters such as intact PTH, osteocalcin, total alkaline phosphatase, and basal and deferoxamine-stimulated serum aluminum levels. We observed that 91.4% of all evaluated patients showed renal osteodystrophy before the start of dialytic therapy. Mild osteitis fibrosa were observed in 21 patients (36.2%), severe osteitis fibrosa in 5 patients (8.6%), mixed lesions in 7 patients (12.1%), osteomalacia in 6 patients (10.3%), aplastic bone disease in 14 patients (24.1%), and normal bone in 5 patients (8.6%). Among the bone histomorphometric parameters, fibrosis area rate (%) showed the best correlation with intact PTH, and osteocalcin and osteoid area rate (%) with total alkaline phosphatase. Aluminum-related bone disease was not observed. Among patients with aplastic bone disease, only 14.3% showed aluminum deposition of any significance (5% < stainable bone surface aluminum < 25%). In the diabetic patients, aplastic bone disease was most common, but no case was related to aluminum intoxication. In conclusion, the distribution of renal osteodystrophy in our study was different from that of Western countries in pre-dialysis patients. Our patients tended to have more mild-form osteitis fibrosa and normal findings, and less severe-form osteitis fibrosa and aplastic bone disease. Aluminum-related bone disease was not observed.

Adult↗
PubMed1983

Osteomalacia in patients with chronic renal failure before dialysis or transplantation.

The case records of 327 patients who underwent bone biopsy in late or terminal renal failure, before any form of dialysis or transplantation, were examined for clues to the aetiology of renal osteomalacia and its manifestations. Fifty four per cent of the biopsies showed pure osteitis fibrosa, 34 per cent osteomalacia with osteitis fibrosa and 12 per cent showed neither abnormality. Osteomalacia was strongly associated with chronic pyelonephritis and obstructive uropathy as primary renal disease. In two matched groups of 100 each, and within the major primary diseases, it was associated with acidosis, hypocalcaemia and normophosphataemia (as opposed to hyperphosphataemia). There was no association with known length or uraemia and only a weak and inconsistent relationship with severity of uraemia. In the few patients studied, there was no relationship between osteomalacia and serum 25-hydroxycholecalciferol level. In contrast to the state of patients treated by haemodialysis, osteomalacia in this undialysed group was manifested by a higher level of serum alkaline phosphatase than pure osteitis fibrosa, serum iPTH did not differ between the groups, there was no predominance of symptoms in one group, other than proximal myopathy which had a weak association with osteomalacia, and Looser zones were more common than complete fractures. Our study shows that osteomalacia has different manifestations, and probably different causes, before and after the start of haemodialysis. These two stages of renal failure should be clearly distinguished in reports of renal bone disease.

Acidosis↗
PubMed1988

Fractures and vertebral bone mineral density in patients with renal osteodystrophy.

We investigated the relationship of CT determined vertebral bone mineral density (BMD), type of renal osteodystrophy, N terminal PTH levels and fracture history in 31 dialysis patients. BMD for patients with bone biopsy documented osteitis fibrosa was 1.6 standard deviation (SD) above the normal value for age and sex matched controls, while those patients with low turnover osteodystrophy had a mean BMD 1.2 SD below normal (p less than 0.0001). Three patients with osteitis fibrosa who had previously been treated with prednisone had a low BMD (1.8 SD below normal, different than O, p = 0.0015). There was no correlation between BMD and time on dialysis (r = 0.1). An N terminal PTH level greater than 150 pg/ml was a sensitive (94%) and specific (100%) method of separating those patients with osteitis fibrosa from those with low turnover osteodystrophy, while BMD was much less useful in this differentiation. A low BMD was not predictive of fracture history but the type of renal osteodystrophy was. Patients with low turnover osteodystrophy had a fracture rate of 0.2 fractures/dialysis year in comparison to those with osteitis fibrosis who had 0.1 fractures/dialysis year. Patients with the former bone disease fractured mainly axial rather than appendicular bones in contrast to those patients with osteitis fibrosa. In conclusion we found that patients with osteitis fibrosa had increased BMD compared to normal while those with low turnover osteodystrophy had decreased BMD, but that the N terminal PTH level was a better predictor of the type of bone disease present than was BMD.

Adult↗