Search

Background: The target for serum parathyroid (PTH) hormone level in dialysis patients is higher than that in the normal population in order to prevent adynamic bone disease (ABD) that is associated with more frequent cardiovascular and bone disease. Based on biological and clinical data, we aimed at identifying the different types of low PTH (L-PTH) in order to determine the best therapeutic strategies in these patients., Methods: Between 2004 and 2010, all haemodialysis (HD) patients were assessed. Patients with serum L-PTH (<130pg/mL) were classified into five groups as follows : 'PTX' for patients with a history of parathyroidectomy (PTX); 'HypoMed' for patients with a tendency to hypocalcemia without PTX; 'IatroMed' for patients who had undergone excessive PTH-lowering treatments (calcium, vitamin D, or cinacalcet); 'EndoG' for patients with endogenous hypercalcaemia (immobilization, cancer, or granulomatosis); and 'SponT' for patients with L-PTH without evident causes and with 'normal' biology in most cases., Results: From 520 charts, 163 (31.3 %) L-PTH cases were recorded, with 17.7% of PTX in younger patients with longer dialysis times; 2.4% of HypoMed in older women with high co-morbidities (these two groups needed calcium and vitamin D therapy to prevent hypocalcaemia); 22.6% of IatroMed in diabetic patients receiving excessive PTH-lowering treatments; 3% of EndoG in hypercalcaemic patients, more frequently in the hospitalization ward; and 54% of SponT, more frequently comprising old diabetic patients not receiving PTH-lowering treatment and without biological signs of ABD. Treatment changes were necessary only in cases of IatroMed and EndoG, requiring a lowered prescription of PTH-lowering therapies and the addition of bisphosphonates for EndoG., Conclusion: In our HD population, we could identify five types of L-PTH based on medical conditions and biological data. Only two types, i.e. approximately 25% of patients needed therapeutic modifications. For the other patients, L-PTH could be maintained without decreasing the calcium and vitamin D intake that can lead to osteomalacia or administering recombinant PTH 1-34 or calcium-receptor inhibitors that need to be assessed in HD patients., (Copyright © 2012 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

The prevalence and the clinical gravity of the various histopathological varieties of renal osteodystrophy in dialysis patients depends on the severity of both the aluminium intoxication and that of hyperparathyroidism. The prevalence of bone pains, fractures and hypercalcemias are the highest in adynamic bone diseases (ABD) with severe aluminium intoxication, then in osteitis fibrosa and mixed osteopathy, in the ABD with moderate aluminium intoxication and rare in the mild lesion in spite of similar moderate aluminium intoxication. In the absence of aluminium intoxication, hypercalcemia and hyperphosphatemia prevalence is higher only when intact PTH is more that 4 times the upper limit of normal. When PTH is between 1 and 2 folds the ULN this prevalence is null and bone mineral density is the highest. 2. The low turnover aluminic bone diseases (osteomalacic or adynamic) will be cured by long term deferoxamine treatment. The hazards of such treatment justify the performance of a bone biopsy to ensure the diagnosis. Their prevention relies on adequate treatment of tapwater and definitive exclusion of long term administration of aluminum phosphate binders. 3. Non aluminic osteomalacia will be treated according to the same guidelines given for the uremic patients before dialysis. 4. Non aluminic adynamic bone disease will be cured by means aiming at stimulating PTH secretion as discontinuing 1 alpha hydroxylated vitamin D derivatives, and, if there is no hyperphosphatemia by discontinuation of calcium supplement. In case of hyperphosphatemia in dialysis patients CaCO3 doses have to be nevertheless increased after the dialysate calcium concentration (DCa) has been decreased in order to induce a negative perdialytic calcium balance for PTH secretion stimulation. In the near future substitution of CaCO3 by non calcemic non aluminic phosphate binders will suffice. 5. Osteitis fibrosa due to hyperparathyroidism will be treated first by securing an optimal vitamin D repletion (bringing plasma 25OH vitamin D around 30 and 60 ng/ml or 75-150 nmol/l) and by correcting hypocalcemia and hyperphosphatemia by CaCO3 at high doses (3-12 g/day) taken with the meals. In case of hypercalcemia dialysate calcium concentration will be decreased to correct it or, in a near future, CaCO3 will be decreased to 3 g/day and hyperphosphatemia will be controlled by non calcemic, non aluminic phosphate binders. When hyperphosphatemia is controlled whereas plasma calcium is normal or low, 1 alpha hydroxylated vitamin D derivatives can be administered. 6. Instrumental parathyroidectomy should be considered when plasma levels of intact PTH remain above 7 folds the upper limit of normal whereas hyperphosphatemia persists and hypercalcemia occurs in order to prevent thining of the corticals and subsequent fracture risk. In case of previous exposition to aluminum, a deferoxamine test and/or a bone biopsy will be performed to decide a long term DFO treatment before the parathyroidectomy in order to prevent the transformation of a mixed osteopathy into an aluminic adynamic bone disease. 7. The difficulty of hyperparathyroidism control in dialysis patients is due to poor compliance to phosphate binders and to irreversible parathyroid hyperplasia with occured before the dialysis stage. This stress the primary importance if its early prevention without iatrogenia by first CaCO3 and vitamin D repletion, as soon as the creatinine clearance decreases below 60 ml/min/1.73 m2.

This article reviews the clinical, biological, radiological, and pathological procedures and their respective indications for the practical diagnosis of the following various histological patterns of renal osteodystrophy: osteitis fibrosa due to parathyroid hormone (PTH) hypersecretion: osteomalacia or rickets due to native vitamin D deficiency and/or aluminum overload; and adynamic bone disease (ABD) due to aluminum overload and/or PTH secretion oversuppression. Our advice regarding bone biopsy is to restrict it to patients with symptoms and hypercalcemia, especially those who have been previously exposed to aluminum. In other cases, we propose relying merely on the determination of the plasma concentrations of calcium, protide, phosphate, bicarbonate, intact PTH, aluminum, 25(OH)D3, and alkaline phosphatase (total and bony if hepatic disease is associated) to choose the appropriate treatment. Because of the danger of the desferrioxamine treatment necessary to chelate and remove aluminum, the suspicion of aluminic bone disease (osteomalacia or ABD) will always be confirmed by a bone biopsy. In the case of nonaluminic osteomalacia, correction of the vitamin D deficiency by native vitamin D or 25(OH)D3, and of the calcium deficiency and acidosis by alkaline salts of calcium and if necessary sodium bicarbonate are sufficient to cure the disease. In the case of nonaluminic ABD, the stimulation of PTH secretion by the discontinuation of 1alpha hydroxylated vitamin D and the induction of a negative calcium balance during dialysis by decreasing the calcium concentration in the dialysate will allow an increase of the CaCO3 dose to correct for hyperphosphatemia without inducing hypercalcemia. For hyperparathyroidism, i.e., plasma intact PTH levels greater than two- or four-fold the upper limit of normal levels (according to the absence or presence of previous aluminum exposure), the treatment will consist in increasing the CaCO3 dose to correct for hyperphosphatemia together with a decrease of the calcium concentration in the dialysate if the dose of CaCO3 is so high that it induces hypercalcemia. When the hyperphosphatemia has been corrected and there is still a low or normal corrected plasma calcium level, 1alpha(OH)D3 in an oral bolus 2 or 3 times a week should be given at the minimal dose of 1 microg. When the PTH level stays above 400 pg while hypercalcemia occurs and hyperphosphatemia persists, surgical subtotal parathyroidectomy is recommended or the injection of calcitriol into the big nodular hyperplastic parathyroid glands under sonography control in high surgical risk patients. Special recommendations are given for children.

In patients maintained on regular haemodialysis in Newcastle upon Tyne the development of osteomalacia is substantially reduced when water used to prepare dialysate is deionised. After 1--4 years of dialysis, osteomalacia was evident in 15% of patients on deionised water in 70% of patients on softened water from the same source. The close association of dialysis encephalopathy and osteomalacia suggests a common aetiology. Both diseases occur in centres with a high tap-water aluminium content. Serum-aluminium concentrations were raised in patients undergoing regular haemodialysis in the Northern Region of England. Those using softened water had higher concentrations than those using deionised water. Patients on softened water who had encephalopathy or dementia had serum-aluminium concentrations similar to those of patients using the same water-supplies without symptoms of these diseases, but they had been treated for longer. The evidence that aluminium absorption from dialysate causes osteomalacia and encephalopathy is strong enough to justify the expense of treating water by deionisation, reverse osmosis, or both in centres where tap-water aluminium is high.

Four chronic haemodialysis patients suffering from osteomalacia were treated by increasing their dialysate calcium concentration from 1-40 to 2-15 mM/I. Bone biopsies were taken before and after 22 weeks of this treatment and a further biopsy was taken in one patient after 52 weeks. Symptomatic cure occurred in one patient with mild osteomalacia and some improvement osteomalacia and hyperparathyroidism. Bone biopsies showed slight improvement in the patient with mild osteomalacia after 22 weeks, and considerable improvement after 25 weeks. In the patient with mixed histology, the osteitis fibrosa subsided and the osteomalacia became a little worse after 22 weeks. There was no histologic improvement in the two patients with severe osteomalacia after 22 weeks. It is concluded that high calcium dialysis is not an effective treatment for renal osteomalacia.

Results of diagnosis and treatment of renal osteodystrophy are discussed concerning 162 patients with chronic renal failure treated by hemodialysis. In most cases (15%) osteopenia and hyperparathyroidism were revealed. Roentgenologic investigation revealed metastatic calcification mostly in foot vessels, whereas microscopic study of internal organs in the lungs. The increase of calcium concentration in dialysate from 1.75 to 2.5 Mmol/l was not followed by greater calcinosis in patients with hyperphosphatemia. Uremic pruritus was treated by ultraviolet irradiation and administration of prednisolone for 3-5 days. The effect of I alpha-hydroxy-vitamin D3 was studied in 30 patients. Improvement of clinical status and, principally, relief of muscular pains in the extremities was observed as well as positive changes in blood serum biochemical indices.

It is generally accepted that aluminium induces osteomalacia in chronic hemodialysis patients by binding to the calcification front, thereby inhibiting mineralization of osteoid. Because this form of osteomalacia is vitamin D resistant, the condition has often been assumed to be irreversible, although promising results have been achieved recently by using a chelating agent for removal of aluminium from the skeleton. In this paper we present four chronic hemodialysis patients with aluminium toxicity and histologic osteomalacia in whom the mineralization defect greatly regressed after the use of reverse osmosis treated-water for dialysis, but without further treatment. In three other patients, also with aluminium toxicity and histologic osteomalacia, similarly treated, the histological severity of the osteomalacia remained static. Those patients in whom bone mineralization status improved developed hyperparathyroidism after reverse osmosis water-treatment, whereas the static patients remained euparathyroid. The results suggest that resolution of aluminium related osteomalacia may occur with reduction in dialysis fluid aluminium, and that parathyroid hormone plays a role in the healing of aluminium related osteomalacia. The therapeutic implications are twofold: attempts to remove all traces of hyperparathyroidism may be detrimental to the bone mineralization status; and stimulation of the parathyroid glands by means of a mild reduction in dialysis fluid calcium may be of value in the management of those cases with persistent osteomalacia and low bone turnover.

A 61-year-old male hemodialysis patient developed the syndrome of aluminum intoxication including bone pain, fractures, proximal myopathy, progressive anemia and expressive aphasia. Serum aluminum was 130 micrograms/l and rose to 445 micrograms/l after the administration of 2 grams of desferrioxamine. Bone biopsy of the iliac crest revealed severe osteomalacia, heavy staining for aluminum and a bone aluminum content of 229 mg/kg dry bone. Treatment with combined hemofiltration and desferrioxamine administration led to a marked clinical improvement and a repeat bone biopsy striking healing of the osteomalacia with a bone aluminum content of 11 mg/kg dry bone.