THE EFFECTS OF GROWTH-HORMONE ON FRACTURE-HEALING IN RATS - A HISTOLOGICAL DESCRIPTION

Previous biomechanical studies have indicated that growth hormone has a stimulatory effect on fracture healing. This study was designed to give a histological description of the long-term effects of growth hormone on fracture healing in rats. Sixty-four female rats were divided into two groups and were given either biosynthetic human growth hormone (2.7 mg/kg body weight/day) or saline s.c. in two daily injections. This treatment was given for 20 days after a closed tibial fracture with medullary nailing had been performed. Five or six rats were killed from each group after 10, 20, 30, 40, 50, and 80 days of healing. The fracture site was embedded undecalcified in methylmethacrylate, cut into 8 mum thick, midfrontal sections, and investigated in a normal light microscope after staining with Masson Trichrome and in polarized light after staining with Sirius red. The results revealed that growth hormone had an initially stimulatory effect on external callus formation. However, the callus formed was loosely structured and was not removed by the normal modeling and remodeling process. The callus therefore persisted even after 80 days of healing. In contrast, after only 40 days the saline treated rats showed healing, with a resumption of the normal size and shape of the fractured tibial bone, leaving only a small amount of dense callus tissue. The study also revealed that the hemopoietic system was stimulated by growth hormone, with massive invasion of marrow cells into the external fracture callus. Bone marrow cells dominated the intratrabecular space in growth-hormone treated animals, even after 80 days of healing. On the basis of this study, it is concluded that although there is an initially stimulatory effect of growth hormone on callus formation, the callus formed during growth hormone treatment is abnormal with an extremely loose structure, and modeling and remodeling of this callus are delayed. It seems that the bone marrow cells grow at the expense of the mineralized callus tissue, or that the normal architecture of the callus tissue is disrupted.