Bone-graft substitutes in orthopedic surgery

Of the more than 3 million musculoskeletal procedures done annually in the United States, about half involve bone grafting with either an autograft or an allograft.

Autograft bone usage is limited by donor-site morbidity and supply.

Limitations of using allografts include immunogenic response by the host to the foreign tissue of the graft and the potential for disease transmission.

Bone morphogenic protein (BMP) has osteoinductive potential.

There is, at least, 20 BMPs are identified that are part of the larger transforming growth factor-beta (TGF-β) family.

Bone-graft substitutes provide scaffolding for osteoconduction, growth factors for osteoinduction, and progenitor cells for osteogenesis.

The gold standard for autogenous bone graft contains osteoblasts, endosteal osteoprogenitor cells capable of synthesizing new bone, and a structural matrix that acts as a scaffold.

The donor-site morbidity of autograft can be as high as 25 percent.

Nearly one third of all bone grafts used are allografts.

Allografts have osteoconductive proprieties and can serve as substitutes for autografts but carry the risk of disease transmission.

Allograft risk for transmission of human immunodeficiency virus (HIV) is 1:1,500,000; for hepatitis C, the risk is 1:60,000; and for hepatitis B, it is 1:100,000.

Allograft tissue is treated to minimize the risk of disease transmission by tissue freezing, freeze drying, and sterilization with gamma radiation, electron-beam radiation, and ethylene oxide.

The above sterilization process leaves allograft tissue void of its osteoinductive potential, and thus, allograft material serves primarily as an osteoconductive scaffold during bone grafting.

Demineralized bone matrix (DBM) is produced by acid extraction of allograft cortical bone, and contains noncollagenous proteins: type 1 collagen, which provides the osteoconductive scaffold for osseous in-growth; and osteoinductive growth factors that include BMPs, fibroblast growth factor, insulin-like growth factor, platelet-derived growth factor, and TGF-β.

Demineralized bone matrix (DBM) is both osteoconductive and osteoinductive, and is available as freeze-dried powder, granules, gel, putty, and strips.

Bone morphogenic proteins (BMP) 2-7 and 9 possess independent osteoinductive activity, and proteins bind to receptors on the membrane of mesenchymal stem cells.

Receptors on the membrane of mesenchymal stem cells trigger an intracellular signaling pathway transforming stem cells into tissue-specific progenitor cells that participate in the synthesis of extracellular matrix, musculoskeletal tissue formation, and growth.

BMP use contraindicated with pregnancy, history of cancer, skeletal immaturity, and history of bone tumors.

Other osteoconductive bone-graft substitutes include coralline hydroxyapatite, collagen-based matrices, calcium phosphate, calcium sulfate, and bioactive glass have no osteoinductive properties.

Coralline hydroxyapatite is produced from marine coral exoskeleton that have pore structures resembling cancellous bone, and is effective for managing metaphyseal defects.

Collagen-based matrices are xenografts consisting of spongelike strips of bovine collagen combined with hydroxyapatite, and act primarily as osteoconductive bone-graft substitutes.

Calcium phosphate, an injectable calcium paste, has 4 to 10 times the compressive strength of cancellous bone.

Calcium phosphate cement has the highest mechanical compression strength of any of the oseteoconductive bone-graft substitutes.

95 percent of calcium phosphate is resorbed in 26 to 86 weeks.

Calcium sulfate is the quickest of any of the osteoconductive products.

Calcium sulfate resorbs in 4 to 12 weeks, and is better used as a bone-graft extender rather than for structural support.

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