Injectable calcium phosphate cements for bone graft substitution: where do we stand and where do we go?

摘要

The first calcium phosphate cements (CPCs) were discovered in the early 1980's. A decade later, the first commercial formulations were launched. At that time, the most optimistic CPCs supporters believed that these materials would eventually replace metallic internal fixation. Nowadays, the reality is very much different. Despite some positive effects on the healing time of tibia plateau fractures, CPCs cannot be used for load-bearing applications. Also, CPCs have some important drawbacks compared to calcium phosphate granules and blocks, such as (ⅰ) high cost, (ⅱ) low resorption rate, and (ⅲ) poor handling. As a result, CPCs have only a small share of the bone graft substitute market. To change this fact, the main drawbacks of CPCs should be solved or at least reduced. This is the reason why various researchers have tried to improve CPCs handling or to produce macroporous CPCs. In both cases, the use of additives is required, which increases even more the high production costs. Also, the incorporation of macropores in CPC pastes increase CPCs resorption rate, but reduces their injectability and mechanical properties. As a result, the difference between an injectable macroporous CPC and a non-setting injectable calcium phosphate bone graft substitute ("putty") becomes negligeable. Since the latter products have generally lower production costs and better biological properties than CPCs, CPCs are currently loosing the race against calcium phosphate putties. Ten years ago, many researchers thought that CPCs would be the ideal candidates for bone augmentation procedures. Compared to PMMA, CPCs have excellent biological properties. Also, most bone augmentation procedures require fairly low mechanical properties. However, there are reports suggesting that CPCs are still too weak for most bone augmentation procedures. Also, recent results raised concerns about CPCs safety. Finally, CPCs cost five to ten times more than PMMA cements. So, it appears that the only possibility to generalize the use of CPCs for bone augmentation properties is to make them tougher, for example with the use of fiber-reinforcement. Another potential application is the enhancement of screw fixation, particularly for osteoporotic patients. However, the introduction of locking screws for osteosynthesis plates has greatly reduced this need. So, at the moment, it appears likely that CPC products will remain a niche product. However, an increase of the relevance of CPCs is expected due to their interesting features for the production of calcium phosphate granules and blocks. Indeed, CPCs can be used to produce solids of any form without the need of sintering. This feature can be used to pre-fill metallic spine fusion cages with a macroporous calcium-deficient hydroxyapatite scaffold. Similarly, complex bone graft substitute forms can be produced by means of solid free-form fabrication. This could potentially enable the production of cosrumer-made implants within minutes, directly in the operating theatre. Last but not least, there is evidence that low-temperature calcium phosphates, such as monetite, brushite, octacalcium phosphate, or calcium-deficient hydroxyapatite, may provide advantageous biological properties, such as a fast resorption, fast bone formation and a fair amount of osteoinductivity. To summarize, it appears quite unlikely that CPCs will ever play a dominant role among bone graft substitutes. However, CPCs offer exciting possibilities for the (biomimetic) synthesis of advanced calcium phosphate bone graft substitutes. So, it is likely that the fraction of calcium phosphate bone graft substitutes produced via CPC reactions / chemistry will increase in coming years. The extent of this increase will depend on our ability to go beyond the frontiers set by the high production costs and the relatively low amount of scientific evidence showing the great potential of biomimetic calcium phosphates such as monetite, brushite or octacalcium phosphate.