In vitro effects of aluminum on bone phosphatases: A possible interaction with bPTH and vitamin D3 metabolites

Abstract

Summary. The present study was undertaken to test the in vitro action of aluminum on bone phosphatase activities and the possible interaction of this metal with parathyroid hormone (bPTH) or vitamin D3 dihydroxymetabolites [1,25-and 24,25(OH)2D3). Three-day-old rat calvaria were incubated for 24 h with one of the following: bPTH at 5 • 10-SM, 1,25-or 24,25(OH)2D3 at 2.5 • 10-9M, A1 at concentrations ranging from 3 • 10-11M to 6 • 10-6M, or their corresponding solvents. AI effects were also investigated when the medium phosphate or calcium concentrations were modified. In some experiments, A1 was added simultaneously with bPTH or one of the vitamin D3 metabolites at the beginning of the 24 h incubation. At the end of all incubations, acid and alkaline phosphatase activities were measured in bone cytoplasmic extract. The results show that: (a) When compared to the value found in half calvaria incubated in a control medium, the bone acid and alkaline phosphatase content is significantly higher in paired halves incubated with A1 (3 • 10-'IM to 1.5 • 10-6M) as well as with bPTH, 1,25-, or 24,25(OH)2D3 and sharply decreased with higher A1 concentrations (6 • 10-6M). (b) The A1 effect on phosphatase activities is modified in a free phosphate or a free calcium medium.

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

“…the induction of de novo bone formation with an increase in trabecular bone volume, trabecular number, an increase of the osteoblast number and activ ity producing a large amount of unmineralized woven bone over the whole trabecular surface even in places where resorption had not taken place. The stimulating action of high doses of aluminum and the depressing action of low doses of aluminum in the Quarles' study in the beagle are apparently in contradiction with the in vitro data of Lieberherr et al [46,47] who showed that low doses of aluminum stimulated bone alkaline phospha tase and collagen synthesis whereas the high doses had the opposite effect. A stimulating effect of aluminum on de novo bone formation has also been reported to occur at some times by Galceran et al [48] after relatively low-dose aluminum intoxication in the dog (0.75 mg/kg.…”

“…In vitro experimental data further support also the direct toxic effect of aluminum on both bone mineralization and on bone formation: not only can Al inhibit hydroxy apatite crystal formation from calcium phosphate in vitro [45] but, at least at high doses, it decreases bone alkaline phosphatase of rat cal varia [46] or of mouse osteoblasts in culture and this is associated with a decreased collagen synthesis and an inhibition of cell proliferation with a decrease of the stimulating effect of PTH on osteoblasts cAMP [47], This decrease of cAMP response to PTH by previous aluminium intoxication was also found in iso lated perfused bone studies [48]. It has recently been explained by a primary effect of aluminum on the affinity of PTH receptor which may be related to exchange of aluminum with magnesium at the G protein level [49].…”

Short-term aluminum administration in the rat. Effects on bone formation and relationship to renal osteomalacia.

“…Other investigators have reported evidence of an increase in acid and alkaline phosphatase activity in rat calvaria in tissue culture during exposure to low concentrations of aluminum (39). Further study will be required to confirm these observations and to clarify the effect of aluminum on bone resorption in general and on the cellular activity of osteoclasts in particular.…”

Prevention of Microcytic Hypochromic Anemia in Chronic Hemodialysis Patients

“…The precise mechanism of this anemia is obscure. Aluminum accumulates in the bone of hemodialysis patients [10][11][12] and it may directly interfere with erythropoiesis. The microcytic features of the anemia suggest a disturbance of normal hemoglobin synthe sis by aluminum.…”