No effect of growth hormone on bone graft incorporation: Titanium chamber study in the normal rat

Abstract

A recent series of publications reported greatly improved mechanical properties and increased callus size during the late stages of fracture healing in normal (not hypophysectomized) rats after twice daily injections of growth hormone (GH). We tested whether GH could enhance the incorporation of bone allografts in a new experimental model where we have demonstrated an increase in bone allograft incorporation by local application of basic fibroblast growth factor (bFGF)- Cylinders of defatted allogeneic cancellous bone were placed as grafts in titanium Bone Conduction Chambers in the tibiae of female rats. Only one end of this chamber is open for tissue ingrowth. This permits us to measure the distance into the graft that new bone penetrates after entering the chamber. We injected 10 rats with 1.5 IU per rat of subcutaneous human recombinant GH twice daily for 6 weeks and another 10 rats with similar doses of sterile normal saline. GH caused a constant increase in the rate of weight gain and in the serum concentration of Insulin-like Growth Factor 1 (IGF 1). Tibiae became longer and the ash weight of the second tail vertebra was increased. We also noted an increased joint cartilage thickness. There was no difference in the amount of new bone that had penetrated and replaced parts of the graft in GH-treated or control rats and this was also the case with TcMDP activity of bone samples from both groups. New bone forms in the grafts by membranous (metaplastic) ossification. It appears that the effects of excessive GH stimulation on endochondral and membranous ossification in this model are markedly different.