Application of bone morphogenetic proteins in orthopaedic practice: their efficacy and side effects.

Bone morphogenetic proteins (BMPs) have been extensively studied since the discovery of agents within bone that could induce bone formation at ectopic sites by Urist in the 1960s. Extensive preclinical research has been carried out showing the efficacy of these products in promoting bone healing. Clinical trials are encouraging, with meta-analysis of results revealing better rates of healing than treatment with autologous bone grafting (risk ratio [RR]: 0.845; 95% confidence interval [CI]: 0.772 - 0.924; p < 0.001 for clinical outcome and RR: 0.884; 95% CI: 0.825 - 0.948; p < 0.001 for radiological outcome). Preclinical and clinical safety assessments have revealed little evidence of toxic effects and there have been few reports of adverse events related to their use. A small rate of immunological reaction following administration, resulting in antibody formation, has been observed in some patients, without clinical consequence, although the long-term implications of this are unknown. Ongoing research is revealing that BMPs act on an extremely wide range of body tissues in a variety of manners and this is far from fully understood. It should be noted, however, that given the role of BMP as a differentiation factor, the production of undifferentiated neoplastic tissue seems unlikely. It has also been shown in an animal model that artificially administered BMP can cross the placenta and subsequently be detected in the growing embryo. As this area has been little investigated, use in pregnancy is currently contraindicated. Until the long-term safety profile is more fully documented it would seem sensible to continue to carefully control use and monitor patients closely. However, the current evidence is very promising.