Inhibition of bone repair in a rat model for chronic and excessive alcohol consumption.

Alcohol abuse is associated with increases in both the incidence of fractures and complications in fracture healing. The purpose of this study was to determine the dose-dependent effects of ethanol on bone repair in a rat model. Three-month-old male Wistar rats were continuously fed liquid diets containing ethanol as either 36% or 26% of total calories or control diets for 6 weeks. Then, a bone repair model was created in all rats. Bone healing and liver metabolism were evaluated 7 weeks after bone injury. For each dose, there were three ethanol-feeding groups receiving (1) ethanol for 13 weeks, (2) control diet for 13 weeks (pair-fed), and (3) ethanol before bone injury and control diet (pair-fed) after injury. Another group was fed ethanol (36%) before injury and given control diet ad libitum after injury. There were also two nutritional controls consuming control diet and standard rat chow ad libitum for 13 weeks. Abnormal liver metabolism was evident at the higher ethanol dose - increases in cytochrome P4502E1 specific activity (5-fold; P < .01), triglyceride content (4-fold; P < .02), and liver weight (25%; P = .05) - compared with pair-fed controls. The higher dose of ethanol resulted in deficient bone repair when compared with rats receiving ethanol-free control diet by pair-feeding: 26% less (P = .02) rigidity of the repaired bone, 41% less (P = .02) intrinsic stiffness, 24% less intrinsic strength (P = .05), and 14% less (P = .001) ash density of the repair tissue. The reduced food consumption of ethanol-fed rats compared with that in the nutritional controls did not contribute to this deficiency. Furthermore, removal of ethanol (as 36% of calories) from the diet after bone injury completely restored normal bone healing and nearly normalized the liver metabolism. The lower ethanol dose (26% of calories) had a minimal effect on liver metabolism and bone repair. We conclude that ethanol (as 36% of calories) in the rat diet, especially during the postinjury period, was solely responsible for the observed inhibition of bone repair.

Chronic ethanol consumption results in deficient bone repair in rats.

There is evidence that ethanol inhibits osteoblast function and that chronic ethanol consumption induces systemic bone loss and increases the risk of fracture in humans. The purpose of the present study was to determine whether chronic ethanol consumption also compromises the healing of injured bone. Male Sprague-Dawley rats, 8-10 weeks old, were placed into four feeding groups: group A received ethanol (36% of calories) as part of a liquid diet; group B was pair-fed to group A and received an isocaloric control diet containing maltodextrin; group C was fed the AIN-93M standard semi-purified liquid diet ad libitum; group D was fed the same ethanol diet as group A before bone injury, but after surgery (see below) these rats were given isocaloric control diet ad libitum. After 6 weeks on their respective diets, a bone repair model was surgically created at the midshaft in both fibulae of each rat. Seven weeks after injury the animals were euthanized and bone healing was evaluated by determining rigidity of the fibula by three-point bending, flexural modulus of the repair tissue and mineral content of the repair tissue. Rigidity of fibula in ethanol-fed rats and their pair-fed controls (groups A and B) were respectively 48 and 47% lower than in group C. Flexural modulus of the repair tissue in ethanol-fed rats had a 55% (P = 0.046) deficiency compared with their pair-fed controls. The mineral contents in groups A and B were respectively 16 and 13% lower than in group C. There were no significant differences in the results between groups C and D. Thus, the outcome of bone repair in ethanol-fed rats was deficient compared with rats receiving a standard maintenance diet. The repair tissue in ethanol-fed rats was mechanically inferior to that in pair-fed controls. This deficiency could not be attributed to the reduced food consumption of these animals. On the other hand, the restoration of normal bone healing in group D cannot be attributed solely to the cessation of ethanol feeding after bone injury because of the increased food consumption during this period.