Lars B. Engesaeter

Mechanical Properties of Fractured and Intact Rat Femora Evaluated by Bending, Torsional and Tensile Tests

Mechanical properties of healing fractures and growing, intact bones were studied in male rats aged 8 weeks at the beginning of the study period. A standardized, closed fracture was produced in the middle of the left femur. The fracture was not immobilized. At various intervals after the fracture, the healing fractured femora and the contralateral, intact femora were subjected to bending, torsional and tensile tests. The fractured femora regained the strength and the ultimate deformation of the contralateral, intact femora after about 8 weeks when tested in bending, and after about 13 weeks when tested in torsion. In the first phases of fracture repair, the healing fractures could resist more torsional moments increased with increase in age and weight of the animals, whereas the ultimate angular deformation remained constant. The ultimate bending and torsional stresses (bone material strength) increased to reach a plateau when the rats were about 14 weeks old. No significant differences were observed between the bending, torsional and tensile application.

INFLUENCE OF AGE ON MECHANICAL PROPERTIES OF HEALING FRACTURES AND INTACT BONES IN RATS

Mechanical properties of fractured and intact femora have been studied in young and adult, male rats. A standardized, closed, mid-diaphyseal fracture was produced in the left femur, the right femur serving as control. The fracture was left to heal without immobilization. At various intervals, both fractured and intact femora were loaded in torsion until failure. The fractured femora regained the mechanical properties of the contralateral, intact bones after about 4 weeks in young and after about 12 weeks in adult rats. For intact bones, both the ultimate torsional moment (strength) and the torsional stiffness increased with age of the animals, whereas the ultimate torsional angle remained unchanged. For bone as a material, however, the ultimate torsional stress (strength) and the modulus of rigidity (stiffness) increased with age only in young rats, being almost constant in the adult animals. The various biomechanical parameters of the healing fractures did not reach those of the contralateral, intact bones simultaneously. The torsional moment required to twist a healing femoral fracture 20 degrees (0.35 radians), a deformation close to what an intact femur can resist, proved to be a functional and simple measure of the degree of fracture repair in rats.

Effects of Oxytetracycline on Mineralization of Bone in Young Rats

The metabolism of minerals and collagen in young rats receiving oxytetracycline was studied by employing double-isotope techniques. The dosage of the antibiotic was adjusted to obtain plasma concentrations comparable with human therapeutic levels. Reduced mineralization and possibly increased resorption of bone were observed after oxytetracycline administration, whereas no effect on the rate of collagen synthesis could be detected.

Effects of Oxytetracycline on Solubility and Synthesis of Collagen in Young Rats

In a recent study we demonstrated that the antibiotic oxytetracycline reduces both growth and mechanical strength of bone and skin in young rats. The present study deals with the effects of 14 days of oxytetracycline medication on salt solubility of collagen (cross-linking) and conversion of 14C-proline to 14C-hydroxyproline in collagen (synthesis). At the end of the medication period, significantly higher solubility of collagen was found in the femurs and skin of rats receiving oxytetracycline than in controls. No effect of the antibiotic on the rate of collagen synthesis could be demonstrated. These findings may indicate that oxytetracycline in young rats causes reduced mechanical strength of bone and skin by interfering with the cross-linking of collagen.

Effects of Cyclophosphamide on Mechanical Properties of Bone and Skin in Rats

The effects of several different doses of cyclophosphamide on weight increase, longitudinal bone growth and mechanical properties of bone, intact skin and skin wounds, were studied in 30 young, male rats. The cystostatic effect was evaluated by counting white blood cells (WBC) in arterial blood at the end of the medication period. Compared with the control animals, the longitudinal bond growth, the mechanical properties of the distal femoral metaphysis and the skin wounds were most noticeably affected by the drug. Diaphyseal torsional strength of the femoral bone and tensile strength of intact skin were less affected.

Effects of oxytetracycline on the mechanical properties of bone and skin in young rats.

The influence of the tetracycline antibiotics on growing bones has been disputed. In the present study 58 young male rats were given intraperitoneal injections twice a day for 2 weeks; half of the rats received oxytetracycline and the other half placebo. The concentration of oxytetracycline in plasma was comparable with therapeutic levels in man. Compared with the control animals the oxytetracycline rats had, at the end of the medication period, a significantly lower weight (7 per cent), shorter bones (1--2 per cent), lower bending strength of both the tibia diaphysis (9 per cent) and the distal femur metaphysis (22 per cent) and even lower tensile strength of intact (17 per cent ) and sutured (27 per cent) skin. The effect oxytetracycline seems to be reversible as no differences between the two groups could be detected 1--3 weeks after the end of medication.

Mechanical Properties of Bone and Skin During Recovery after Cyclophosphamide Administration

SummaryThe effects of cyclophosphamide were studied 2, 5 and 9 days after terminating a two-week every-second-day intraperitoneal medication in young, male rats. The cytostatic effect was assessed by counting white blood cells (WBC) in arterial blood.WBC counts were reduced by 72% of control values at 2 days and regained normal values at 9 days after an overshooting leucocytosis at 5 days.Compared to control animals, the treated rats had significantly reduced body weights, metaphyseal bending strength and longitudinal growth of the femur at all time intervals observed. The torsional strength of the femur diaphysis and the strength of wounded skin were not affected at 2 days, but significantly reduced at 5 and 9 days. The tensile strength of intact skin was not found to be affected by the drug.From the 5th to the 9th day after ending medication, the curves for control and treated animals were assuming parallel slopes regarding metaphyseal bone strength, longitudinal bone growth and tensile strength of wounds. This may indicate reversion of the drug effects approximately one week after terminating medication.ZusammenfassungDie Auswirkungen von Cyclophosphamid wurden bei jungen männlichen Ratten untersucht, 2, 5 und 9 Tage nach Beendigung einer zweiwöchigen Verabreichung, die alle 2 Tage intraperitoneal erfolgte. Die cytostatische Wirkung wurde durch die Leukozytenzählung im arteriellen Blut bestimmt.Die Leukozytenwerte waren am zweiten Tage um 72% reduziert und erreichten wieder eine normale Höhe am 9. Tag nach einer überschießenden Leukozytose am 5. Tag.Verglichen mit Kontrolltieren hatten die behandelten Ratten ein signifikant reduziertes Körpergewicht, eine herabgesetzte Biegefestigkeit der Metaphysen und ein verringertes Längenwachstum des Femur. Die Torsionsfestigkeit der Femurdiaphyse und die Festigkeit der verletzten Haut waren nach 2 Tagen nicht verändert, aber nach 5 und 9 Tagen signifikant herabgesetzt. Die Dehnungsfestigkeit der unverletzten Haut zeigte keine Verānderung durch das Medikament.Vom 5. bis zum 9. Tag nach Absetzen der Medikation zeigten die Kurven der Kontrollgruppe und der behandelten Tiere parallele Verläufe bezüglich der metaphysären Knochenfestigkeit, des Knochenlängenwachstums und der Zugfestigkeit der Hautwunden. Dies kann als Hinweis dafür gewertet werden, daß die Auswirkungen des Medikamentes sich etwa 1 Woche nach Beendigung der Verabreichung zurückbilden.

Effects of Cloxacillin, Doxycycline, Fusidic Acid and Lincomycin on Mineralization and Solubility of Collagen in Young Rats

The antibiotics doxycycline, fusidic acid and lincoymcin have recently been shown to reduce growth of bones and tensile strength of skin in young rats. Such adverse effects were not found in rats receiving cloxacillin. The present investigation deals with the influences of these four antibiotics on the mineralization of bones and on the solubility of collagen in skin. In rats receiving doxycycline the content of calcium and phosphorus in bones and the concentration of albumin in serum were reduced. None of the antibiotics had a detectable effect on the solubility of collagen.