Bone Grafting and Bone Graft Substitutes
Drew R. Engles
Andrew J. Schoenfeld
While the majority of osseous injuries can be treated with either immobilization or surgical stabilization, there is a specific subset of injuries or conditions that require supplemental bone grafting. These include instances where there is actual bone loss (i.e., open fractures), relative bone loss (i.e., impacted distal radius fractures), or loss of sufficient bone quality (i.e., osteonecrosis). Bone resection for tumors or osteomyelitis can also result in significant actual bone loss with varying degrees of structural compromise. In order to address these insufficiencies, bone graft or bone graft substitutes are employed. Initially, simple techniques relying on cortical and cancellous autografts were employed. Today, the field has now expanded to encompass the use of allografts, synthetic ceramic-based and collagen-based matrices, demineralized bone matrix (DBM) and even vascularized bone grafts. Recently, the use of purified recombinantly manufactured human osteoinductive growth factors, known as bone morphogenetic proteins (BMPs), has also become common in the clinical realm. The science and rationale behind the utilization of the various types of bone graft and bone graft substitutes commonly employed in hand surgery will be discussed.
I. Basic Science
Basic properties. All bone grafts and bone graft substitutes have inherent properties vital to their performance and function in the clinical realm. These include osteoconductivity, osteoinductivity, osteogenic potential as well as individual structural properties.
Osteoinduction. Proteins signal local mesenchymal stem cells to differentiate into cells capable of producing bone. Recruitment and differentiation of cells are controlled by matrix-derived growth factors.
BMP-2, -4 and -7 are members of the transforming growth factor (TGF)-β superfamily. Undifferentiated perivascular mesenchymal cells are the targets for BMP.
Fibroblast growth factors are angiogenic factors important in neovascularization and wound healing.
Platelet-derived growth factor.
Insulinlike growth factor II stimulates type I collagen production, cartilage matrix and osseous formation.
Osteoconduction. A substance’s three-dimensional structure facilitates the ingrowth of perivascular tissue, capillaries, and osteoprogenitor cells, ultimately enabling bone ingrowth/ongrowth.
Osteoconduction is a property of cancellous bone grafts, DBM, and synthetic bone graft substitutes.
Pore size of osteoconductive grafts plays a vital role in facilitating bone ingrowth. Optimal pore size is 150 to 500 µm.
Osteogenic potential includes the ability to synthesize new bone through cells present in the graft or derived from the host.
Osteoblasts, osteocytes, and undifferentiated mesenchymal stem cells.
Cortical and cancellous grafts both possess cells that can survive transplantation and form new bone at the graft site.
Structural properties include the ability of the graft to confer initial strength and/or immediately resist tensile/compressive forces at the graft site.
Free vascularized cortical grafts are biomechanically superior to nonvascularized cortical grafts for 6 months after transplantation.
Autologous cortical bone provides structural support initially; this becomes more limited during the resorption phase.
Calcium phosphate cement provides structural support and remodels according to Wolff law.
Cancellous bone graft and DBM provide minimal structural integrity.
Ceramics must be shielded from loading forces due to their brittle nature.
Types of graft
Autograft harvested from the patient
Can be vascularized, nonvascularized, cortical, cancellous, corticocancellous, or osteochondral.
Allograft—harvested from a human donor
Can be cortical, cancellous, corticocancellous, or osteochondral.
Xenograft is harvested from another species (usually porcine or bovine).
Autografts are harvested from the same patient in whom they will be used. Harvesting autografts involves a risk of infection and fracture at the donor site. There is increased operative time and surgical cost. In addition, there is a potential for increased surgical blood loss, postoperative pain, and lengthier or requisite hospital stay.
Allografts are harvested from cadaveric donors.
Frozen or freeze-dried (lyophilization) tissue decreases antigenicity and limits the risk of disease transmission. Frozen bone retains the greatest biomechanical strength. Freeze-dried bone grafts are weak in torsion and bending.
Osteoprogenitor cells are destroyed but osteoconductive properties remain. Disease transmission (HIV and HCV) remains a potential risk, although with a statistically low likelihood. Due to strict donor screening, tissue testing, and preparation techniques, there are only two documented cases of HIV transmission in more than 3 million tissue transplants. Both cases occurred with the transplantation of unprocessed, fresh-frozen allografts.
Most studies regarding the efficacy of bone graft and bone graft substitutes are nonrandomized in which efficacy cannot be proven.
There are no studies directly comparing the performance of osteoconductive bone graft substitutes.
The method of allogeneic graft preparation influences clinical performance.
Expense—All bone graft substitutes incur an expense and indiscriminate use, without proper indications, can result in gratuitous health care expenditures.
Bone graft impairment
Smoking inhibits cellular proliferation and causes vasoconstriction, which inhibits bone healing and graft consilidation. Several studies have indicated that smoking increases the risk of tibial pseudoarthrosis by as much as 40%. It also increases time to union, and incidence of infection.
Systemic steroids inhibit progenitor cell differentiation down the osteoblastic pathway.
NSAIDs inhibit prostaglandin formation, decreasing blood flow, and delaying graft resorption.
Malnutrition. Calcium and phosphorous deficiencies are associated with delayed formation of new bone.
Autologous cancellous bone
Commonly harvested from the iliac crest, distal radius, olecranon, tibial metaphysis (proximal or distal), and calcaneus.
Indicated for nonunions with less than 5 to 6 cm of bone loss or as filler for bone cysts or bone voids.
Contraindicated in situations where structural integrity of the graft is required.
Iliac crest provides twice the volume of bone graft as either the distal radius or the olecranon.
Does not provide significant structural support, but acts mainly as an osteoconductive graft with some (theoretical) osteoinductive potential, achieving optimal strength at 6 to 12 months.
Easily revascularized and rapidly incorporated at the graft site. The process occurs through osteointegration, whereby the graft unites with pre-existing osseous structures and is remodeled along lines of stress.
Autologous cortical bone
Sources include the iliac crest, rib, and fibula.
Provides immediate structural support.
Incorporated by a process of creeping substitution.
Demonstrated most significantly at the graft-host bone interface.
Process leads to an initial loss of biomechanical strength at 6 weeks of implantation.
No difference in the biomechanical strength of vascularized and nonvascularized cortical grafts at 6 months.