Bue Bak

Bone repair inhibited by indomethacin: Effects on bone metabolism and strength of rabbit osteotomies

We measured mineral content, maximum bending strength, and regional blood flow after tibial osteotomy fixed with a small metal plate in 38 rabbits. Half of the animals were treated with indomethacin (10 mg/kg/day) while the other half served as controls. After 2 and 6 weeks, the bone mineral content and maximum bending strength were lower in the indomethacin group when compared with the controls. Compared with the controls, the blood flow at the osteotomy site was decreased after 2 weeks and increased after 6 weeks in the indomethacin-treated animals. Inhibition of blood flow increase by indomethacin medication in the early period following osteotomy, as well as retarded bone healing, are probably caused by inhibition of the inflammatory reaction.

The effect of aging on fracture healing in the rat

SummaryThe effect of age on the biomechanical properties of healing tibial fractures was studied by comparing the fracture healing in 2-year-old male Wistar rats with the fracture healing in 3-month-old male Wistar rats after 40 and 80 days of healing. There were no significant differences in the mechanical parameters after 40 days of healing, but after 80 days, a considerable delay in the fracture healing process was noted in the old rats compared with the young adult rats when evaluated by maximum load, maximum stress, stiffness, and energy absorption in a three-point bending procedure. In the contralateral, nonfractured bones, the tibiae from the old animals sustained higher loads and had higher stiffness than the bones from the young adult animals, but stress values, elastic modulus, and capacity for energy absorption was much lower in the old animals.

Mechanical properties and biochemical composition of rat cortical femur and tibia after long-term treatment with biosynthetic human growth hormone

The influence of biosynthetic human growth hormone (b-hGH) on female rat cortical femur and tibia was studied after administration of hormone doses of 0.16, 1.10, or 8.33 mg/kg body weight/day for 90 days. The mechanical properties, dimensions, real density, ash weight, and the mineral and collagen concentrations of the bones were measured. In both femur and tibia a positive linear relation was found between the dose of hormone and ultimate load, ultimate stiffness, energy absorption at ultimate load, load at failure, energy absorption at failure, and deflection at failure. In the femur a positive correlation between dose and deflection at ultimate load was also found. After normalizing the mechanical data for the dimensions of the bones, no differences were found in the hormone treated groups compared to placebo, except for the elastic modulus (Youngs modulus), which was decreased in the femur in the group given 8.33 mg b-hGH. The mineral and collagen concentration were unaffected in both femur and tibia, whereas the real density was decreased in the femur. The growth-hormone-induced changes in the mechanical properties seem to be caused mainly by increased dimensions of the bones.

Dose response of growth hormone on fracture healing in the rat.

The effect of different doses of biosynthetic human growth hormone on the mechanical properties of tibial fractures and intact bones was studied in a rat model; a three-point bending test was applied 40 days after fracturing. Ninety-day-old female rats received a daily dose of 0, 0.08, 0.4, 2.0, or 10 mg of growth hormone/kg body weight starting 1 week before fracture and continuing until mechanical testing. In the animals given 2.0 and 10 mg of hormone, the ultimate load sustained by the fractures, stiffness, and energy absorption at ultimate load increased, while the ultimate stress increased only in the latter groups. In the intact bones, ultimate load of the bones increased in the same groups, while stiffness and energy absorption at ultimate load increased only in the group given the highest dose of hormone.

Effect of Local Prostaglandin E2 on Fracture Callus in Rabbits

We investigated the effect of local infusion with prostaglandin E2 (PGE2) in doses of 0.0003 to 4.0 mg/hour per kg body weight for 6 weeks on a plated unilateral osteotomy in rabbits. PGE2 caused a dose-dependent stimulation of callus formation. Total bone mineral content increased, although the mineral content per volume of the callus was reduced. In another experiment, PGE2 was infused either in the first half or in the second half of the healing period. No effect of PGE2 infusion could be observed in the first half of the 6-week healing period, whereas PGE2 infusion during the second half caused callus stimulation.

Increased mechanical strength of healing rat tibial fractures treated with biosynthetic human growth hormone.

The effects of biosynthetic human growth hormone on the biomechanical properties of healing tibial fractures and intact bones in the rat were studied after 20 and 40 days of healing. Growth hormone, 2.0 mg per kg per day, was given subcutaneously in two daily doses. Control animals were injected with a corresponding volume of saline. After 20 days of fracture healing, there were no differences in mechanical properties between the healing fractures and intact bones. After 40 days, the ultimate load and maximum stiffness of the fractures of the b-hGH injected animals had increased to more than 400% of the corresponding values of the saline injected animals, and ultimate stress and energy absorption at ultimate load had increased to 270% compared with the saline injected animals. Ultimate load, stiffness, and energy absorption of the intact bones increased in the b-hGH injected animals, but no differences were found in ultimate stress values or normalized energy, indicating that the changes in the intact bones were quantitative phenomena.

The effect of growth hormone on fracture healing in old rats.

The healing of fractures is known to decrease with age. Several mechanisms have been identified that might explain this age-related decrease in capacity for fracture repair, one of them being a decrease in growth hormone secretion. In the present experiment, two-year-old male rats with a standardized tibial fracture were given biosynthetic human growth hormone (b-hGH, 2.7 mg/kg/day in two daily injections) during the first 40 days of fracture healing and the controls were injected with saline. After 40 or 80 days of healing, the mechanical properties of the healing fractures were evaluated by three-point bending. At day 40, no differences were found in mechanical properties of fractured and intact tibiae between b-hGH injected rats and saline injected controls. At day 80, ultimate load, stiffness, and ultimate stress of the fractures had increased by 78%, 63%, and 58%, respectively, compared with the controls. In the contralateral, intact tibiae, ultimate load and energy absorption had increased by 12% and 17%, respectively, compared with the controls.

Standardization of tibial fractures in the rat

The influence of the fracture level on the biomechanical properties of healing rat tibial fractures has not been investigated so far, despite the widespread use of rats in fracture healing studies. Fractures were produced in four different zones in the right rat tibia and immobilized with a K-wire. A fifth group of rats was not fractured. After 40 days of healing the fractures and the non-fractured bones were tested in three-point bending. A distinct correlation was found between fracture level and mechanical parameters: maximum load, maximum stiffness, and maximum stress decreased the more distal the fracture was located. In the non-fractured bones, maximum load and maximum stress were constant in all four zones tested, whereas energy absorption increased in the distal part of the tibia. No influence of the healing fracture was found on the contralateral, non-fractured tibia, compared with the animals left undisturbed, and the mechanical properties of the right and the left tibia were found to be symmetrical in terms of mean values. Four different methods of determining the area moment of inertia were investigated, and the simple method of approximating the cross section to an elliptical annulus was found to correlate well with the area moment of inertia, determined from computer tracings of bone slices prepared from the test specimens after the bending test. The computer tracings were corrected for the compression of the specimens caused by the mechanical test.

Growth hormone promotes healing of tibial fractures in the rat.

The effect of administering growth hormone for different periods of time on the mechanical properties of healing rat tibial fractures was investigated after 40 days of healing. Biosynthetic human growth hormone, 2.7 mg/kg body weight/day, was administered to three groups of rats for 1, 2, or 3 weeks following fracture, whereas isotonic saline was administered to a control group for 3 weeks. The ultimate load values and maximum stiffness of the fractures increased in the groups injected with growth hormone for 2 or 3 weeks; linear regression analysis revealed a high probability of a positive linear relationship. In the intact bones an increase in ultimate load, maximum stiffness, and energy absorption at ultimate load was found in the group injected with growth hormone for 3 weeks, with linear regression analysis again showing a high probability of a positive linear relationship.

Reduced energy absorption of healed fracture in the rat

Mechanical testing of closed tibial fractures in rat fixed with a medullary nail was performed after 10-80 days of healing. In the three-point bending test, the maximum load at fracture and maximum stiffness of the fracture gradually increased, reaching 81 and 118 percent, respectively, of intact bone values after 80 days. The fracture failed immediately after the maximum load had been reached in contrast to intact bone, where further bending resulted in gradually decreasing load values until failure occurred at 73-85 percent of the maximum load values. Therefore, the resulting energy absorption until load at fracture and until failure of the healing bone was only 33 and 13 percent, respectively, of intact values after 80 days of healing, and thus markedly reduced even though the maximum stiffness and the load at fracture (maximum load) approximated the values of intact bone.