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	Fig. 1 Factors contributing to the success of bone substitutes. As only living cells can produce new bone, the success of any bone-grafting procedure is dependent on having enough bone-forming or ‘osteogenic‘ cells in the area. An ideal bone substitute should be able to provide a framework for bone deposition (osteoconductivity). Osteoinductive growth factors, many of which are present in normal human bone, induce bone formation locally by stimulating stem cells or immature bone cells to grow and mature, thus forming healthy bone.		printable version
			Bone Grafts The global use of bone grafts in 2000 has been calculated to be about 1 million yearly, less than 15% being with synthetic material. The contributing factors for bone substitute incorporation are shown in figure 1. The gold standard is the autograft. For allografts (bone transplanted from another human) there is good evidence today for use mainly in joint prosthetic surgery. Xenografts (taken from animals) are mainly bovine apatite, sintered from cattle, collagen originating both from cattle or pigs, digested and then cross-linked, and sea coralline which is thermally converted into calcium carbonate. For these substances, evidence for use in humans is scarce, with definite drawbacks such as weak, unpredictable mechanical strength and structure, and a risk of transmisson of infection. An upcoming European regulation may even restrict their use.   Osteoinductive Factors Of the osteoinductive (bone-forming) substances, the growth factor family is the largest. Most important are the bone morphogenic proteins, BMPs. Good overviews on the subject have been presented in the last years by Lane et al. [1], and Keating and McQueen [2]. The drawbacks are that they are expensive and difficult to administer. For stem cell transplantation, immediate transfer after harvesting from the iliac crest (pelvic bone) is optimal. It has been shown that multiplying the stem cells by up to five times improves graft incorporation. Recently, systemic drug treatment with bisphosphonates has been reported to increase bone ingrowth in the early healing period, in joint prosthetic surgery. Animal studies have shown a similar positive effect of parathyroid hormone and BMPs in grafting procedures. The future strategy might be to combine synthetic grafts with systemic short-term osteoinductive drug treatment.
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