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KMID : 0360419710070010053
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Korean Journal of Pharmacology
1971 Volume.7 No. 1 p.53 ~ p.65
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Studies on the Fracture Healing in the Alloxan Treated Rabbits
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Abstract
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It is well known that diabetes mellitus is associated with metabolic derangements, such as hyperglycemia, ketosis, glycosuria, and also widespread alterations in the blood vessels, kidneys, eyes, peripheral nerves and heart. It is also recognized that healing of skin wound is delayed in diabetics. In bone, according to Aegerter, osteopenia develops in diabetes mellitus and it is chiefly ascribed to overutilization of protein. Shim claims that total blood flow to the entire skeletal system is approximately 4 to 8 percent of resting cardiac output and blood supply to the skeletal system would be decreased on account of secondary arteriosclerotic changes in the diabetics.
An adequate blood supply is an essential factor in the healing process of fracture, and disturbed blood flow, either local or systemic, will invariably delay union of the fragments or the fragments from being fused.
As the author has encountered several cases of diabetics in whom healing of fracture was delayed or incomplete, this experimental study was undertaken to elucidate the effects of hyperglycemia and diabetes mellitus on the healing process of fracture.
In this experiment adult albino rabbits, weighing about 2 kg were used and divided into 6 groups. The femur of each animal was fractured surgically, and then the healing process of fracture was periodically checked by radiography at an iaterval of one week for a period of 6 weeks. Thereafter, all the rabbits were killed to obtain tissue preparation of the femur. The experimental groups were as follows;
1) Control group: Six rabbits sustained a surgical fracture to the femur, without being given any other treatment or drug.
2) Alloxan-treated group: For inducing diabetes, alloxan was given intravenously to 17 rabbits in various dose as follows; to 7 of them 40 mg/kg, to 6 rabbits 80 mg/kg and to 4 rabbits 120 mg/kg of body weight, respectively.
3) Insulin-treated groop: Protamine-zinc insulin was injected subcutaneously to each of 6 rabbits in a daily dose of 1 unit per kilogram of body weight.
4) Group treated with insulin after alloxan: Four rabbits were given 80 mg of alloxan once and then 1 unit of insulin per kilogram of body weight daily. Another 5 rabbits were injected 1 unit of insulin per kg of body weight daily following administration of alloxan in a dose of 120 mg/kg.
5) Homotransplantation group: Following intravenous injection of alloxan in a dose of 120 mg/kg, 10 rabbits underwent homotransplantation of a short bone segment to the femur. Five of them were subsequently given 1 unit/kg of insulin daily.
6) Sugar-treated group: six rabbits were fed 15~20 gm of sugar daily throughout the period of experiment.
The results obtained are summarized as follows;
1. Blood sugar level and damage to the pancreatic islet increased proportionately when alloxan was given to the rabbits in various doses. No appreciable change could be observed in the islets when the blood sugar level was altered by either oral administration of sugar or subcutaneous injection of insulin.
2. Comparing with the control group, healing of fracture was delayed in the alloxan-treated group, while callus formation and periosteal reaction were shown to be more prominent in this group and subsequently, the ultimate osseous tissue formed at the fracture site was significantly smaller in amount and less compact. These findings were more marked as the amount of alloxan increased.
3. Administration of insulin prevented the delay in healing process of fracture in the rabbits with alloxan-induced hyperglycemia. In this case, the course and progression of fracture healing were almost similar to those of control group.
4. Union between the host bone and the fragment transplanted from other rabbit of the same species was more delayed in the group treated with alloxan alone than in the group to which insulin was administered after development of alloxan-induced diabetes. In both groups periosteal new bone developed from the ends of the host bone, above and below the transplanted fragment, and directly fused with failure of periosteal callus to bridge the adjacent ends of the host bone and the transplanted fragment.
5. The healing process of fracture Iras not inhibited by alteration in blood sugar level when the blood sugar was abnormally increased by eacessive sugar intake or lowered by administration of insulin alone. The healing of fracture in these groups progressed similarly as in the control group.
In brief summary, it appears that the healing process of fracture would be definitely disturbed in diabetic state brought about by damage to the pancreatic islet. As such an inhibition could be overcome with insulin, it seems that insulin plays an improtant role in healing of fracture, but alteration in blood sugar level alone does not modify healing process of fracture to significant degree.
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