Assessment of the aluminum overload and of its possible toxicity in asymptomatic uremic patients: Evidence for a depressive effect on bone formation

Sébert, J. L.; Mariè, A.; Guéris, J; Hervé, M A; Leflon, P.; Garabédian, M; Smadja, A; Fournier, A

doi:10.1016/8756-3282(85)90335-7

Cited by 13 publications

(8 citation statements)

References 5 publications

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“…This was not the case with our 1991 study (10) 10 in which aluminum‐phosphate binders had been excluded in 1980 (11), an important point since, independent of the PTH level, aluminum overload per se suppresses bone remodeling (12). This lack of aluminum intoxication is one explanation why our optimal PTH range (based on normal bone formation rate assessed by double tetracycline labeled bone biopsies) was lower (one to two times the upper limit of normal).…”

Section: What Is the Optimal Target Pth Range With Calcimimetic Use?mentioning

confidence: 89%

Viewpoint: How Do Calcimimetics Fit Into the Management of Parathyroid Hormone, Calcium, and Phosphate Disturbances in Dialysis Patients?

Shahapuni

Mansour

Harbouche

et al. 2005

Seminars in Dialysis

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As suggested by its American brand name (Sensipar), the calcimimetic cinacalcet sensitizes the parathyroid cells to the extracellular calcium signal, suppressing parathyroid hormone (PTH) release and synthesis and preventing parathyroid cell proliferation. This primary PTH suppression decreases the release of calcium and phosphate from bone without increasing intestinal absorption of calcium and phosphate. Therefore cinacalcet decreases the risk of hypercalcemia and hyperphosphatemia in contrast to 1alpha-OH vitamin D derivatives. Compared with calcium-containing oral phosphate binder (OPB), it increases the risk of hypocalcemia and may decrease the PTH-mediated phosphaturia in predialysis patients. This justifies its combined use with calcium-containing OPB in order to prevent hypocalcemia and enhance the hypophosphatemic effect of the latter, while improving PTH suppression. The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) has recommended restriction of supplemental elemental calcium to 1.5 g/day, a recommendation that we believe should be revised. No pathophysiologic or randomized trial data have yet evidenced the absolute necessity for systematically using 1alpha-OH vitamin D derivatives and noncalcium-containing OPB rather than higher doses of calcium-containing OPB alone in uremic patients without vitamin D insufficiency. In patients with hyperparathyroidism as severe as in the "Treat to Goal Study," the Durham study showed that a calcium carbonate dose more than three times the K/DOQI limit could decrease PTH into the recommended range, with the advantage of a lower calcium-phosphate product compared with the combination of calcitriol and noncalcium OPB. Besides the efficient PTH suppression associated with lower calcium-phosphate product and a good gastrointestinal tolerance, long-term data suggest that cinacalcet may decrease the risk of parathyroidectomy and fracture, while high bone turnover lesions are improved. However, no long-term data on bone mineral density and cardiovascular calcification and complications are yet available. Such studies, along with those comparing cinacalcet and 1alpha-OH vitamin D-based approaches to hyperparathyroidism, are needed.

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Section: What Is the Optimal Target Pth Range With Calcimimetic Use?mentioning

confidence: 89%

Viewpoint: How Do Calcimimetics Fit Into the Management of Parathyroid Hormone, Calcium, and Phosphate Disturbances in Dialysis Patients?

Shahapuni

Mansour

Harbouche

et al. 2005

Seminars in Dialysis

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“…The latter could have positive aluminum staining on their cement lines demonstrating that aluminum deposited at this initially mineralised osteoid bone interface had not prevented subsequent bone formation and mineralization. Sebert et al [13] in patients with mild aluminum overload (i.e. without posi tive aluminum staining of their bone biopsy) found the same increase of plasma aluminum after DFO and the same bone aluminum content (measured by inductively plasma emission spectrometry) in their patients with OF or ABD so that no linear correlation was found between BFR and the aluminum parameters.…”

Section: Evidences That Aluminum Cannot Be the Sole Culprit In The Pamentioning

confidence: 97%

“…The absence of aluminum overload in these observations has however been excluded only on the negativity of the histological staining for aluminum (<5% of positive surface with aluminon) in patients who have been exposed routinely to aluminum phosphate binders and who may neverthe less have high bone aluminon content [13]: Hercz et al [82] have reported this pattern in 36% of 80 patients with ABD; Dunlay et al [83] have reported 8 such patients, 5, however, being diabetics, and shown that they had com parable PTH plasma levels for various levels of plasma calcium when compared with 17 patients with ABD and positive aluminon stainings. Marie et al [53] reported also 3 nonparathyroidectomized dialysis patients with ABD and negative aluminon staining.…”

Section: Evidence That Uremic Adynamic Bone Disease May Be Idiopathicmentioning

confidence: 99%

“…However, a significant positive corre lation between BFR and PTH was found in these studies by the least-squares method. In order to evaluate the role of aluminum independently of PTH, Sebert et al [13] used a multidimensional analysis and showed that a signifi cant negative link could beestabished between BFR and the bone aluminum content. These data point to the critical role of PTH suppression as cofactor in the mani festation of ABD found in association with aluminum overload.…”

Section: Evidences That Aluminum Cannot Be the Sole Culprit In The Pamentioning

confidence: 99%

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Adynamic Bone Disease in Uremia: May It Be Idiopathic? Is It an Actual Disease?

Fournier¹,

Morinière²,

Solal

et al. 1991

Nephron

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“…[14][15][16][17] This may be due to parenteral exposure to inadequately treated water for dialysis solutions and/or the use of large amounts of aluminum-containing phosphate binding agents for prolonged periods. 5,[18][19][20] In the last decade, the use of adequate water purification methods for the preparation of dialysis solutions and the avoidance of aluminum-containing gels for the control of hyperphosphatemia have significantly decreased the incidence of aluminum intoxication in dialyzed patients.…”

Section: Discussionmentioning

confidence: 99%

The spectrum of bone disease in 200 chronic hemodialysis patients: a correlation between clinical, biochemical and histological findings

et al. 1998

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Introduction:Renal osteodystrophy includes the complete range of mineral metabolism disorders that affect the skeleton in patients with chronic renal failure. Patients and Methods: 200 patients with end-stage renal disease and on dialysis were investigated regarding the clinical, biochemical and histological findings of bone disease. Results: The spectrum of renal osteodystrophy consisted mainly of high turnover bone lesions (74.5%), including osteitis fibrosa in 57.5%. Patients with mild bone disease were on dialysis for shorter periods of time and were mostly asymptomatic. Patients with aluminum-related bone disease (16.5%) had the greatest aluminum exposure, either orally or parenterally, and together with patients with high turnover mixed disease, were the most symptomatic. Although on a non-regular basis, the vast majority of the patients (82.5%) had been receiving vitamin D. The incidence of adynamic bone disease was high (n=8) among parathyroidectomized patients (n=12). Significantly higher serum levels of alkaline phosphatase were observed in osteitis fibrosa. Conclusions: The use of calcitriol and phosphate-binding agents on a non-regular basis seems to be the reason for the apparent reduced response to the treatment of secondary hyperparathyroidism. Alkaline phosphatase has been shown to be a fair marker for bone turnover in patients with osteitis fibrosa. The severity of the clinical manifestations of bone disease correlates with the histological features of bone lesion and to the time spent on dialysis.Uniterms: Renal osteodystrophy. Chronic renal failure. Hemodialysis. Aluminum intoxication. Bone metabolism.

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Assessment of the aluminum overload and of its possible toxicity in asymptomatic uremic patients: Evidence for a depressive effect on bone formation

Cited by 13 publications

References 5 publications

Viewpoint: How Do Calcimimetics Fit Into the Management of Parathyroid Hormone, Calcium, and Phosphate Disturbances in Dialysis Patients?

Viewpoint: How Do Calcimimetics Fit Into the Management of Parathyroid Hormone, Calcium, and Phosphate Disturbances in Dialysis Patients?

Adynamic Bone Disease in Uremia: May It Be Idiopathic? Is It an Actual Disease?

The spectrum of bone disease in 200 chronic hemodialysis patients: a correlation between clinical, biochemical and histological findings

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