Effect of diphosphonates on hydroxyapatite formation induced by calcium-phospholipid-phosphate complexes

The diphosphonates disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) and disodium dichloromethylene diphosphonate (Cl2MDP) prevent hydroxyapatite (HA) formation in metastable calcium phosphate solutions, induced by calcium-phospholipid-phosphate complexes and by the acidic phospholipids phosphatidyl serine and phosphatidyl inositol. The diphosphonates appear to act not only as HA crystal poisons but also as surfactants which probably change the nature of the lipid micelle and the charge and conformational properties of the lipid molecules. The surfactants sodium dodecyl sulfate (SDS) and Non-Idet P-40 (NP-40), like the diphosphonates, prevent HA formation by the acidic phospholipids and complexed lipids, but do not act as HA surface poisons. The lipid surfactant lyso-phosphatidyl serine did not induce HA formation from solution. The relevance of the ability of the diphosphonates to act as lipid surfactants to the in vivo use of these agents is discussed.