Dr. Hendrik Delport

Orthopedisch Chirurg, Medico-Legale Expertisen

BONE SUBSTITUTES: IS ANYTHING AS GOOD AS THE REAL THING ?

Introduction

Bone grafting is one of the most common procedures performed in orthopaedic surgery.  Annually all over the world approximately 2.2 million orthopaedic operations use bone grafts in one form or the other.  Autologous bone grafts, i.e. bone harvested from the patient’s own body, has long been the “gold standard”.  The most prevalent donor site is the iliac crest.  The problems associated with it have been well documented, including donor site morbidity and restricted availability, especially if large quantities are required.  There are a few commercially available bone graft substitutes  but we still have nog found ani deal substitute for autologous bone graft.  In this article, we will have a look at the different options available along with their characteristics, and see how they match up with the “gold standard”.

Characteristics of ani deal bone graft

1.       Osteoinduction

This is the process by which mesenchymal stem cells are induced to differentiate into osteoblasts.  This is mediated by a variety of growth factors of which bone morphogenic protein (BMP) is one.

2.       Osteoconduction

This is the ability of the graft tob e a scaffold for bone to in-grow microscopically and macroscopically by allowing for vascular ingrowth.

3.       Osteogenesis

This is the actual process of bone formation from the osteoblasts.  Ideally a bone graft or a substitute should be able to combine all the above properties.  In addition they should also be histo-compatible which means they should not elicit an immunological response in the host.

 

Classification

Laurencin et al.classified bone grafts and bone graft substitutes depending on their inherent properties as follows :

A.      Harvested Bone Grafts and graft substitutes

1.       Bone Grafts

a.       Autologous bone grafts

b.      Bone marrow

c.       Allogenic bone grafts

2.       Demineralised Bone Matrix (DBM)

B.      Growth factor-based graft substitutes

1.       BMP

2.       Platelet Rich Plasma

C.      Cell-Based bone graft substitutes

1.       Stem Cell

2.       Collagen

3.       Gene Therapy

D.      Ceramic-based bone graft substitutes

1.       Calcium Hydroxyapatite

2.       Tricalcium phosphate

3.       Bioactive glass

4.       Calcium sulphate

5.       Inejctable ceramic cements

E.       Polymer-based bone graft substitutes

1.       Natural or synthtic polymers

2.       Degradable or non-degradable polymers.

F.       Miscellaneous

1.       Coralline-HA

 

Autologous bone graft

This is still considered as the ideal method for bone grafting due to the fact they are osteoinductive, osteoconductive and contain osteogenic potential.  Since they are sourced from the patient’s own body they have excellent histo-compability. The disadvantages are limited availability and donor-sit e morbidity, need for a second procedure, potential blood loss, prolonged operating time and poor aesthetic outcome. They can be in the form of cancellous, cortico-cancellous, cortical or free vascularised bone grafts. Autologous bone graft is usually sourced from the iliac crests but can be harvested from the end of long bones too.  Recently large volumes of graft have been harvested from intra-medullary reaming using the new Reamer-Irrigator-Aspirator System.

 

Bone Marrow Aspirate

Bone marrow aspirate from the iliac crest has been used as an osteoinductive and osteogenic material.  The effect of the bone marrow aspirate can be enhanced by centrifugation and producing a bone marrow aspirate concentration (BMAC).  The main advantage is the harvesting can be done percutaneously with minimal patient morbidity.  The obvious downside is lack of osteoconduction and limited availability.  The lack of osteoconduction can be offset by mixing it with demineralised bone matrix.  At the moment injecting bone marrow aspirate is used to treat delayed unions and for filling up small cystic defects in bone.

 

Bone Allografts

Allogenic bone grafts is graft obtained from human cadavers and to a lesser extent living donors.  The graft tissue is freeze-dried or irradiated, and can be used in various sizes and shapes, with an endless supply.  The disadvantages are that there is nog osteogenic property, as the cells get killed and a small risk of transmission of infections.  The other problems associated with this are histo-compatibility and rejection in the host environment and the high cost involved in sourcing and processing allograft.  It is still being used extensively, especially in revision hip and knee athroplasty, where large amounts of bone is required to fill huge defects.

 

Demineralised Bone Matrix (DBM)

This is acid extracted bone allograft where all the mineral content has been removed.  It does not provide any osteoconduction or osteogenesis and only provides osteoinduction due to the presence of growth factors like bone morphogenic protein.  It provides no structural support and can be only used in a structurally stable environment.  There is still a small riks of transmitting infectious diseases.

 

Bone Morphogenic Protein (BMP)

As mentioned previously, BMP has excellent osteoinductive potential.  With the use of recombinant DNA technology, synthetic BMP’s are now available.  They can be used in combination with a carrier matrix that releases them consistently over time.   They work by turning mesenchymal stem cells into bone forming osteoblasts.

 

Platelet-Rich Plasma (PRP)

Platelet-Rich Plasma is an ultra centrifuge of the patient’s own blood with a high concentration of platelets and several other growth factors. These have been used in the treatment of soft tissue enthesopathies like tennis elbows.  The advantages are safety, easy availability and histo-compatibility.  As far as being used as a bone graft substitue they do have some osteoinductive potential but there is still nog enough clinical evidence to warrant regular use as a bone graft substitute.

 

Mesenchymal Stem Cells (MSC)

There is currently lot of research and ethical controversy regarding the use of mesenchymal stem cells in treating a variety of medical conditions.  The idea of injecting mesenchymal stem cells which can proliferate into bone forming osteoblasts is very attractive.  At the moment the role of MSC in bone regeneration is still in its infancy.  The aim in the future with additional research would bet o find alternative sources of stem cells without destruction of human embryos and to establish cell-based bone graft substitutes in vitro.

 

 

Collagen

Collagen is an important component of an extracellular bone matrix.  Synthetic collagen has excellent osteoconductive material, but at the moment it is only used as a carrier for growth factors like BMP and not as a graft itself. 

 

Gene therapy

Transferring genetic material into a targeted cell can be done directly (in vivo) or indirectly by removing the cells from the body and manipulating them in tissue culture (in vitro) and re)implanting them back.  With this technology, we can manipulate cells to express specific growth factors like BMP.  Early results from animal studies have shown encouraging results.

 

Ceramic-based bone graft substitutes

Various ceramic products like calcium hyroxyapatite, tricalcium phosphate, bioactive glass and calcium sulphate have been extensively used in the past to stimulate bone-healing.  However, none of these have shown tob e effective for anything other than bone defect fillers with limited osteoconductive properties.

 

Polymer-based bone graft substitutes

This is usually in the form of biodegradable synthetic polymers like polylactic acid and poly lactic-co-glycolic acid.  They are used primarily fort heir osteoconductive properties where they are completely reabsorbed over a period of time and replaced by normal bone.

 

Coralline hydroxyapatite

This is based on a natural material derived from sea coral whose porous structure is similar to cancellous bone.  It’s used once again as a bone defect filler and has reasonable osteoconductive properties to allow for bone in-growth.  In addition to the naturally available sea coral, there are synthetic forms, which are converted from natural coralline to refine its properties of osteoconduction.

 

Conclusion

We have looked briefly at various natura land synthetic bone graft substitutes.  Despite the variety of materials available, autologous bone graft continues to remain as the gold standard, with excellent osteogenic, osteoinductive and osteoconductive properties.  All the commercially available bone graft substitutes lack one or two essential properties.  In the future genetic engineering and stem cell research would probably allow for growing one’s own bone if needed, but at the present moment of time, autologous bone grafting seems tob e the prevailing method of bone substitution which is used the world over.

 

                                                                                                                Sam Anand

                                                                                                                Horton General Hospital

                                                                                                                Banbury, Oxfordshire.

 

(Orthopaedic Product News – November/December 2012)