Understanding the influence of alendronate on the morphology and phase transformation of apatitic precursor nanocrystals

Bisphosphonates (BPs) are a class of synthetic pyrophosphate analogs that can prevent the loss of bone mass, given orally to treat postmenopuasal osteoporosis. It is not clear yet if the benefits of BPs include the possibility of affecting bone apatitic precursors transition for bone consolidation except for encouraging osteoclasts to undergo apoptosis. Furthermore, the complexity of the in vivo system makes it difficult to isolate and study such extracellular topographical cues that trigger bone turnover response. Herein, we proposed a wet-chemical approach employing alendronate sodium (AS) as a guide of hydroxyapatite (HA) precursor growth and conversion which was initiated from the nucleantion of octacalcium phosphate (OCP) in a cell membrane-mimicking surfactant micelle aqueous system. The nanocrystal clusters of dicalcium phosphate dihydrate (DCPD) and OCP nanocryatals were readily precipitated within a relatively narrow AS concentration range (2-8 μM). However, such low concentrations of AS seemed to stabilize the more acidic phases, and to delay the transformation into HA, to an extent which increased on increasing AS concentration. In contrast, at a slight higher concentrations (16-32 μM), AS promoted HA precipitation after ageing for 1 h. It was found that the effect of AS on the phase selectivity of apatitic precursors was concentration-dependent within a prolonged ageing time stage (0.5-168 h). The AS-assisted reactions in vitro offer an expedient way to understand the underlying implementarity between bone and BPs for bone consolidation, and to improve our understanding of benefit of BP dosages on bone turnover and trauma healing.