Calcium phosphate cements (CPCs) are applied for bone repair. Modification of CPCs with bisphosphonates (BPs) for the treatment of osteoporosis is a promising approach for the delivery of the BPs at the place where they are needed, reducing systemic side effects [1].

In this study, a CPC composed of 61 wt.% α-tricalcium phosphate (α-TCP), 26 wt.% monetite, 10 wt.% CaCO₃ and 3 wt.% precipitated hydroxyapatite was modified with either alendronate or risedronate in concentrations of 0.5, 1 and 2 wt.%. A 30 wt.% Na₂HPO₄/NaH₂PO₄ solution was used as mixing liquid with a L/P of 0.4 ml/g. The setting reaction was studied by isothermal calorimetry, in-situ X-ray diffraction (XRD) and Imeter measurements (automated Gillmore needle). The set cements were characterized by XRD and Rietveld refinement after defined time periods.

Addition of alendronate or risedronate resulted in pronounced retardation of the setting reaction, whereas the retarding effect increased with increasing BP content. A liquefying effect of the BPs on the cement pastes was qualitatively observed and confirmed by Imeter measurements. In the BP-modified cements, dissolution of a major fraction of α-TCP was followed by slower dissolution of monetite and calcite. The fraction of dissolved α-TCP was increased by the BPs, resulting in an increased formation of calcium-deficient hydroxyapatite (CDHA). BPs significantly reduced the crystallite size of CDHA and affected the lattice parameters: Increase of the a-parameter and decrease of the c-parameter was observed, while this effect was more evident for shorter setting times (1 d compared to 3 d). This indicates initial incorporation of the BPs into the crystal structure of CDHA.

In conclusion, both alendronate and risedronate strongly affect the setting kinetics of the cement investigated, while the effect of both BPs is very comparable. This retarding effect supposedly results from the measured adsorption of the BPs on the surface of the cement particles, impeding their dissolution. Complexation of Ca²⁺ by the BPs can be another factor [2]. However, cement setting within reasonable time can be achieved by application of a highly concentrated phosphate solution as accelerator.

[1] MP Ginebra, C Canal, M Espanol, D Pastorino, EB Montufar. Adv Drug Deliv Rev 2012;64(12):1090-110.

[2] V Schnitzler et al., Acta Biomater 2011;7:759-770.