Calcium Phosphate

Definition

„Calcium phosphate cement” (CPC) is the generic term to describe chemical formulations in the chemical system CaO-H 3PO 4-H 2O that can experience a transformation from a liquid or pasty state to a solid state, and in which the end-product of the reaction is a calcium phosphate. CPCs consist generally of a concentrated mixture of one or several calcium phosphate powders and an aqueous solution (e.g. water), but it may also consist of a mixture of two or more solutions.

Use

CPCs are used as bone substitute. Indications vary from filling congenital defects in bone, for example filling bone after cyst removal, to trauma indications in all bones[1-3]. CPCs act as spacer favouring bone ingrowth. CPCs can be implanted mini-invasively, but have relatively low resorption- and bone ingrowth rates (compared to calcium phosphate granules) due to the absence of interconnected pores of sufficient dimension to allow cell and blood vessel ingrowth (typically Ø > 0.05mm). One promising field of application for CPCs is in bone augmentation, i.e. the reinforcement of osteoporotic bone through CPC injection [4-6]. Such procedures ease the fixation of screws in mechanically poor bone (for example for osteosynthesis) and decrease pains associated with unstable vertebrae (e.g. vertebroplasty [7]). The long-term outcomes is however poorly-documented and questionable considering the brittleness of CPCs. CPCs can also be used as drug carrier [8, 9] or for the synthesis of calcium phosphate scaffolds [10-12].

History

The discovery of CPCs has been ascribed to Brown and Chow for an abstract published in 1983 [13]. However, several authors worked with similar reactions before 1983. For example, Kingery looked at formulations based on CaO and phosphoric acid in 1950 [14]. In the 1970’s and early 1980’s, Monma described the hydraulic properties of α-TCP [15, 16]. In 1982, R. LeGeros et al. published an abstract on apatitic compounds setting in physiological conditions [17]. The first reports on the clinical use of CPCs came out in the mid 1990’s

Types of reaction

Numerous CPC formulations have been proposed in the last 25 years, but they can all be classified into two types of reactions: an acid-base reaction (called here “two-component” CPC to simplify) or the transformation of a metastable phase into a more stable phase (“one-component” CPC) [19-22]. In 1983, Brown and Chow proposed two-component CPCs based on mixtures of tetracalcium phosphate (TetCP - see acronym list at the end for chemical formula) and dicalcium phosphate (DCP [13]. The end-product of the reaction was an apatite whose stoichiometry depended on the ratio between TetCP and DCP: hydroxyapatite (HA) for TetCP/DCP = 1 (x = 0 in reaction (1) - see reactions (1) and (1a) hereafter) to tricalcium phosphate (TCP) for TetCP/DCP = 0.5 (x = 1; reaction (1b)): Another two-component CPC was disclosed by Lemaître et al in 1987 [23]: mixtures of β-tricalcium phosphate (β-TCP), monocalcium phosphate (MCPM) and water form dicalcium phosphate dihydrate (DCPD) according to reaction (2). The use of phosphoric acid was proposed in the same year by Bajpai [24] (Reaction (3)). One component CPCs are based on α-tricalcium phosphate [15, 16] or amorphous (tri)calcium phosphate [25, 26] (reactions (4) and (5). To summarize, the end product of CPC formulations can be either an apatite or DCPD. As the mineral name of DCPD is brushite, CPCs are often referred to apatite CPC or brushite CPC. The main difference between apatite and brushite CPC is the pH during the reaction: neutral or basic pH for apatite CPC and acidic pH (<6) for brushite CPC. 

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