Importance of the field: Bone is one of the most transplanted tissues worldwide. Autograft is the ideal bone graft but is not widely used because of donor site morbidity and restricted availability. Allograft is easily accessible but can transmit infections and elicit an immune response.

Areas covered in this review: This review identifies all in vitro and in vivo evidence of immune responses following bone transplantation and highlights methods of improving host tolerance to bone allotransplantation.

What the reader will gain: In humans, the presence of anti-HLA specific antibodies against freeze-dried and fresh-frozen bone allografts has been demonstrated. Fresh-frozen bone allograft can still generate immune reactions whilst freeze-dried bone allografts present with less immunogenicity but have less structural integrity. This immune response can have an adverse effect on the graft's incorporation and increase the incidence of rejection. Decreasing the immune reaction against the allograft by lowering the immunogenic load of the graft or lowering the host immune response, would result in improved bone incorporation.

Take home message: It is essential that the complex biological processes related to bone immunogenicity are understood, since this may allow the development of safer and more successful ways of controlling the outcome of bone allografting.