The bisphosphonates HEBP and AHPrBP but not AHBP inhibit mineral mobilization and lysosomal enzyme release from mouse calvarial bones in tissue culture.
The effect of 3 bisphosphonates, 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP), 3-amino-1-hydroxy-propylidene-1, 1-bisphosphonate (AHPrBP) and azacycloheptylidene-2, 2-bisphosphonate (AHBP), on the release of minerals (40Ca, 45Ca, Pi) and enzymes from cultured mouse calvaria was investigated in an organ culture system. HEBP and AHPrBP reduced PTH-stimulated mobilization of calcium and inorganic phosphate without affecting the release of lactate dehydrogenase. In contrast, no significant effect by AHBP on mineral mobilization and lysosomal enzyme release could be registered. In parallel with inhibited mineral mobilization, HEBP and AHPrBP inhibited the release of the lysosomal enzyme beta-glucuronidase. A possible cellular mechanism of action of bisphosphonates is discussed in the light of these data.
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D005966:Glucuronidase / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D008903:Minerals / Q000378:metabolism*; D009924:Organ Culture Techniques; D000077268:Pamidronate; D010281:Parathyroid Hormone / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism
D004164:Diphosphonates; D008903:Minerals; D010281:Parathyroid Hormone; D010710:Phosphates; D005966:Glucuronidase; D000077268:Pamidronate; D002118:Calcium