calcium phosphate cements

Calcium Phosphate Cements (CPCs)

1. Properties

• The introduction of an external component in the human body brings up the general problem of biocompatibilty.  Bone cements also need to be bioactive and stimulate  bone formation.  Calcium phosphate cements (CPCs) are now injectable and are used in vertebroplasties.
• CPC are made of one or several calcium phosphate (CaP) powders and an aqueous solution.  CPCs belong to the category of the low-temperature CaPs that  are obtained by precipitation from an aqueous solution at or around room temperature.
• Low temperature CaPs are made of precipitated hydroxyapatite (PHA) and are very similar to the mineral part of bone.  They have also a very large specific surface area (100m²/g) which makes CaP biologically much more reactive.  Two broad categories of CPCs exist, depending on the end product obtained: apatite (PHA) and brushite (DCPD).
• Considering their properties, CPCs might potentially be used in vertebroplasty to reinforce osteoporotic vertebral bodies and thoracolumbar burst fractures.
• The compressive strength is always greater than the tensile strength because of the fragility of the CaP; nevertheless, the mechanical properties of CPC are lower than those of PMMA.

• These initial mechanical properties may vary with implantation time and animal studies have shown that mechanical properties of apatite CPCs tend to increase continually, in contrast to those of brushite CPCs, which initially decrease and then increase when bone grows.   This is the result of different porosity and bioresorption between apatite and brushite CPCs.
• Furthermore, in comparision with PMMAs, CPCs have longer cure times and maximum compressive strength is achieved over a 24-hours period.
• Concerning the bioresorption, apatite CPC is less bioresorbable than brushite CPC. Moreover, when the crystal size increases or the porosity decreases, the bioresorption will be longer.  Norian® SRS (Norian) and a-BSM® (Etex-Merck) are therefore expected to bioresorb faster than BoneSource® (Orthofix-Howmedica), Biopex® (Mitsubishi) and Cementek® (Teknimed).  A study reported a 30% decrease in the amount of Norian® SRS in a rabbit femur after 24 months.
• Another calcium phosphate cement is also now available on the market in Europe: Calcibon® (Biomet-Merck).  This cement is injectable and both animal and clinical studies have shown that it has appropriate mechanical properties which allow good results in the filling of cancellous bone defects.

Figure 19: Presentation of Calcibon®.

Figure 20 : Lateral radiographic view. Filling with Calcibon of a cancellous bone defect in a calcaneum. Better radio-opacity than Norian®.

• This cement hardens at body temperature in about 10 minutes and reaches its final compressive strength after 3 days (about 60MPa).  This strength exceeds the compressive strength of cancellous bone (5-20 MPa) and is as strong as some cortical bone (25-100 MPa).
• The biocompatibility of Calcibon® is due to its chemical composition and its crystalline structure that mimic the chemical composition of natural bone mineral. The histological evaluation after 2 weeks shows an abundant bone apposition on the Calcibon® surface without any inflammatory reaction or fibrous encapsulation. Osteoclast-like cells were resorbing the bone substitute.
• The mechanical and rheological properties of Calcibon® should permit its indication in vertebroplasty.  It appears more radio-opaque than Norian® and its injection under radiologic guidance would be easier and safer in comparision with others CPC.  Further studies have to evaluate its efficiency in terms of pain relief and technique of injection.

Figure 21: Rheological property of Calcibon®.

• Moreover, the mechanical properties of the different CPC depend on the composition of the cement.  The main factor is the ratio between the amount of cement powder (P) and the mixing liquid (L).
• If the P/L ratio is large, the porosity of the cement is low.  In addition, the mechanical properties of a CPC increase when the porosity is low.  However, the less porous the cements are, the less bioresorbable they are. So, there is a balance to find between the porosity and the mechanical properties of CPC to obtain a cement with good resorption, with sufficient compressive and tensile strengths as well as good rheological properties in order to inject them into bones.

2. Modalities of use

a) Preparation of the cement

• Calcium phosphates hqve been known as bone repair materials for the last 80 years but they have only been used in spinal surgery more recently as granules or blocks in interbody fusion and scoliosis surgery.  CPCs, due to their biocompatibility, represent a new and interesting product which can be used as injectable cement for vertebroplasties.
• However, to be injected in the vertebral bodies, those cements must have two features: injectability and cohesion.
• To avoid the demixing (separation of the mixing liquid and the cement powders), manufacturers have adapted the composition of the cements in order to obtain good cohesion, always keeping the best porosity, fluidity and mechanical properties as possible.
• Concerning the radio-opacity, CPCs are intrinsically radio-opaque. Their radio-opacity should depend on the porosity of each cement and in practice they are often not radio-opaque enough .  The addition of radiopacifers in bioresorbable cement is not recommended due to the unknown biological outcome of these small radio-opaque particles.
• The preparation of the cement needs to be mixed well and there are mixing devices or instructions provided with the cement in order to obtain a paste ready for injection.

 Figure 22: Presentation of Norian® SRS.

 Figure 23: The mixing device for Norian® SRS.

 Figure 24: Introduction of Norian® SRS in the injection set (Cemento®).

b) Injection of the cement

• When the paste is ready, the cement can be injected, but it is always very difficult to inject these cements in the vertebrae.  This is due to the cements that are more viscous in order to maintain their cohesion and also to the hydrophilic property of CPC. They tend, therefore, to mix with body fluids and lose their cohesion.
• Concerning their injectability, they are the opposite of the PMMA cements, which are hydrophobic and tend to stay compact within the vertebral bodies.
• In order to prevent this problem, two solutions exist:
• creation of a cavity in the vertebral body with an expandable balloon and filling of the new cavity with CPC.
• removal of bone marrow from the vertebrae using a suction device and injection of the CPC.
• In our department, we use CPC in the treatment of recent burst fractures of thoracolumbar vertebral bodies in young patients.  In such cases, the use of a bioresorbable cement is justified.  Most of time, the consolidation of these fractures requires a complementary kyphoplasty.
• Therefore, the use of an expandable balloon has two indications:
• correction of the kyphosis
• creation of the cavity for an easier injection of the cement

Figure 25: Position of the patient before percutaneous vertebroplasty. Burst vertebral fracture stabilised by brace.

Figure 26: Axial CT. Introduction of the spinal needle inside the vertebral body through an intercosto-transverse approach.

Figure 27: Lateral fluoroscopic view. Definitive positioning of the needle.

Figure 28: CT. Final result after injection of Norian® SRS.