Search

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.

There are two primary types of bone disorders observed in patients with end-stage renal disease: a high-turnover osteodystrophy characterized by osteitis fibrosa, and a low-turnover osteodystrophy characterized initially by osteomalacia and, more recently, by adynamic or aplastic bone disease. This article reviews the clinical presentation, pathogenesis, and laboratory findings of patients with these two disorders. It discusses the important roles of phosphorous binding, vitamin D administration, and correction of acidosis in prevention and treatment of bone disease in patients with moderate renal insufficiency.

The effects of a very low-protein diet (VLPD) supplemented with amino acids and ketoanalogues (KA) and with 1 g of calcium carbonate and 1000 IU of vitamin D2, were studied in 17 patients with advanced renal failure (GFR < or = 20 ml/min) over a period of one year. The protein intake was 0.3 g protein/kg body wt/day. Daily phosphorus and calcium intake were respectively 1,500 mg and 300 mg. Sequential bone densitometry was performed and bone histomorphometry after double tetracycline labeling was evaluated, before and after one year of diet. Calcium and phosphate metabolism parameters were monitored every two months. In spite of a significant decrease of GFR, phosphorus, parathyroid hormone (1-84) and osteocalcin plasma levels decreased significantly, while low plasma bicarbonate normalized, and calcitriol and calcium levels remained respectively low and normal. Before the diet, histological study disclosed four cases of mixed osteopathy: osteomalacia associated with osteitis fibrosa (OM/OF), nine pure osteitis fibrosa (OF) and four with normal bone remodeling (NB). After one year of diet, the OM component of OM/OF disappeared, as evidenced by a normalization of the mineral apposition rate and osteoid thickness. In the patients presenting pure OF, a significant decrease in osteoblastic and osteoclastic surfaces, in the number of osteoclasts, and in the bone formation rate (BFR) were found. Vertebral mineral density measured by quantitative computerized tomodensitometry did not change significantly. In conclusion, this study not only confirms the beneficial effects of VLPD + KA + calcium on uremic hyperparathyroid bone disease in advanced renal failure assessed using static bone histomorphometry, but also shows a correction of histodynamic bone parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Rickets, osteomalacia, and renal osteodystrophy are disorders of the mineralization of bone that result from a lack of available calcium, phosphorus, or both. The diseases that result from numerous mechanisms present with a symptom-sign-radiographic complex with such a high degree of stereotypy that laboratory investigation is often required to distinguish one form from another. The disorders in children, known as rickets, produce bowing and other deformities of the long bones and dwarfism. These disorders are principally related to the profound effect of the deficiency states on the epiphyseal plate; whereas the same disorders in adults produce an often severe osteopenia and pathologic fractures. Because of newer developments in our understanding of the factors affecting calcium-phosphorus hemostasis and vitamin D metabolism, many of the children and adults with these disorders can now be treated effectively.

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.

Histologic bone changes of osteitis fibrosa and osteomalacia are commonly present in patients with end-stage renal disease. Although many patients are not symptomatic from these bone changes, some patients are severely disabled. Altered metabolism of vitamin D, calcium, phosphorus, and parathyroid hormone occurs in renal failure and contributes to the development of uremic bone disease. This article reviews the current theories of pathogenesis and treatment of renal osteodystrophy. In addition, the clinical presentation, pathogenesis, and treatment of the various aluminum-associated osteomalacic syndromes in uremia are discussed.

Histologic bone changes of osteitis fibrosa and osteomalacia are commonly present in patients with end-stage renal disease. Although many patients are not symptomatic from these bone changes, some patients are severely disabled. Altered metabolism of vitamin D, calcium, phosphorus, and parathyroid hormone occurs in renal failure and contributes to the development of uremic bone disease. This article reviews the current theories of pathogenesis and treatment of renal osteodystrophy. In addition, the clinical presentation, pathogenesis, and treatment of the various aluminum-associated osteomalacic syndromes in uremia are discussed.

Hyperparathyroidism is the main cause of renal bone disease. At the moment its progress can be retarded by controlling plasma calcium and phosphate. But the prevention and cure of hyperparathyroidism without surgery eludes us. There is a suggestion that the administration of some metabolite of Vitamin D may be more successful. Osteomalacia on the other hand does not appear to be an important problem and is easily prevented and cured.