Bone-Graft Substitutes: Facts, Fictions, and Applications
; A. Seth Greenwald, DPhil(Oxon); Scott D. Boden, MD; Victor M. Goldberg, MD; Yusuf Khan, MS; Cato T. Laurencin, MDPhD; Randy N. Rosier, MD

The Emergence of Bone-Grafting

It is estimated that more than 500,000 bone-grafting procedures are performed annually in the United States, with approximately half of these procedures related to spine fusion. These numbers easily double on a global basis and indicate a shortage in the availability of musculoskeletal donor tissue traditionally used in these reconstructions (Fig. 1).

Fig. 1:

United States trends in musculoskeletal tissue donors. Source: United Network for Organ Sharing and the Musculoskeletal Transplant Foundation.

This reality has stimulated a proliferation of corporate interest in supplying what is seen as a growing market in bone-substitute materials (Fig. 2). These graft alternatives are subjected to varying degrees of regulatory scrutiny, and thus their true safety and effectiveness in patients may not be known prior to their use by orthopaedic surgeons. It is thus important to gain insight into this emerging class of bone-substitute alternatives.

Fig. 2:

United States sales of bone graft and bone substitutes. Source: Orthopedic Network News, industry estimates.

The Physiology of Bone-Grafting

The biology of bone grafts and their substitutes is appreciated from an understanding of the bone formation processes of osteogenesis, osteoinduction, and osteoconduction.

Graft osteogenesis: The cellular elements within a donor graft, which survive transplantation and synthesize new bone at the recipient site.

Graft osteoinduction: New bone realized through the active recruitment of host mesenchymal stem cells from the surrounding tissue, which differentiate into bone-forming osteoblasts. This process is facilitated by the presence of growth factors within the graft, principally bone morphogenetic proteins (BMPs).

Graft osteoconduction: The facilitation of blood-vessel incursion and new-bone formation into a defined passive trellis structure.

All bone graft and bone-graft-substitute materials can be described through these processes.

Bone Autografts

Fresh autogenous cancellous and, to a lesser degree, cortical bone are benchmark graft materials that allograft and bone substitutes attempt to match in in vivo performance. They incorporate all of the above properties, are …

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