"Even though bone tissue has fantastic regenerative properties, all conventional bone grafting techniques are doomed to failure in the case of defects in excess of five centimetres. That is why it is important for us to identify more innovative forms of treatment," Prof Peter Giannoudis of the University of Leeds told the 15th EFORT Congress in London.
Gold standard - bone grafting and distraction osteogenesis
"Vascularised bone grafting is a good option for defects measuring up to 25 centimetres," Prof Giannoudis added. The fibula, iliac crest and ribs are among the donor sites for the procedure. "This treatment does have its limitations: it calls for special skills and is less suitable for patients with concomitant disorders or those of advanced age." Distraction osteogenesis continues to deliver satisfactory treatment outcomes. While vascularised bone grafting and distraction osteogenesis today still provide the gold standard, new techniques have been emerging.
New strategies - osteoinductive substances and cellular therapies
New ways to combat impaired fracture healing are also being made possible by osteoinductive substances such as morphogenetic proteins. "It is still unclear exactly how much locally-produced bone volume is in fact attributable to the osteoinductive properties of the substances used, but based on the clinical evidence available and personal experience, it is thought that one vial of morphogenetic proteins is enough to promote healing in bone defects measuring up to two centimetres," noted the expert. Recently developed treatment strategies include cellular therapies which involve implanting stem cells, or osteoprogenitor cells, taken from the bone marrow in the pelvis. "Although clinical experiences to date have been largely confined to slow-healing fractures rather than the treatment of large bone defects, this method could prove viable," Prof Giannoudis concluded.
Bioactive membranes kick-start bone regeneration
Bioactive membranes have also emerged as an attractive option, guiding bone regeneration with or without the additional implantation of bone graft or osteoinductive agents. "But this method is still very much at the experimental stage, with examples of clinical experience few and far between," Prof Giannoudis cautioned. While the 'induced membrane technique' has lately emerged as a popular treatment for large bone defects, it requires two bouts of surgery. A second procedure is needed to remove the cement spacer added during the first, and to simultaneously graft the defect with allograft or autograft, or a combination of the two. The use of scaffolds populated with osteoprogenitor cells or growth factors that stimulate regeneration (or both) has also generated considerable interest. "Possible ways to optimise this method are currently the subject of heated debate. The majority of experiences are based on experimental procedures, and moves towards the transition to clinical settings are still in their infancy," reported Prof Giannoudis.
Diamond concept increasingly used as treatment standard
The recently developed 'diamond concept' is fêted for its optimal treatment of bone defects and is gaining ground in terms of popularity. The concept is a tissue engineering strategy whereby all the key components of bone repair are implanted during surgery: a growth factor, a scaffold and osteoprogenitor cells. At the same time particular attention is paid to successful osteosynthesis, i.e. optimisation of the mechanical environment. "This approach appears to be very attractive and preliminary clinical data indicate favourable outcomes," Prof Giannoudis confirmed.
Therapy option of the future - biological chambers, local bioreactors
"Future research portfolios will be dominated by therapeutic approaches that are based on tissue engineering. In my view, the basic tenets of the diamond concept will be applied using a range of innovative combinations of materials, doses and techniques. The concept of 'biological chamber' and 'local bioreactor' - which represents a clearly defined and regulated molecular environment - will be further developed and tested," the expert said. According to Prof Giannoudis, another area ripe for exploration is simultaneous administration of systemic pharmacological agents containing anabolic properties with the implantation of local factors. But here, too, a large number of studies are required. Research will be dominated by combination therapies.
"Tried-and-tested methods will continue to be used, owing to their proven reliability. However, our aim is to achieve a breakthrough that will put us in a position to treat bone loss, non-union and very large fractures more efficiently and reliably, and hopefully, more quickly too, while minimising the risks for patients," explained Prof Giannoudis.