Delayed union of femoral fractures in older rats:decreased gene expression.

BACKGROUND: Fracture healing slows with age. While 6-week-old rats regain normal bone biomechanics at 4 weeks after fracture, one-year-old rats require more than 26 weeks. The possible role of altered mRNA gene expression in this delayed union was studied. Closed mid-shaft femoral fractures were induced followed by euthanasia at 0 time (unfractured) or at 1, 2, 4 or 6 weeks after fracture in 6-week-old and 12-15-month-old Sprague-Dawley female rats. mRNA levels were measured for osteocalcin, type I collagen alpha1, type II collagen, bone morphogenetic protein (BMP)-2, BMP-4 and the type IA BMP receptor. RESULTS: For all of the genes studied, the mRNA levels increased in both age groups to a peak at one to two weeks after fracture. All gene expression levels decreased to very low or undetectable levels at four and six weeks after fracture for both age groups. At four weeks after fracture, the younger rats were healed radiographically, but not the older rats. CONCLUSIONS: (1) All genes studied were up-regulated by fracture in both age groups. Thus, the failure of the older rats to heal promptly was not due to the lack of expression of any of the studied genes. (2) The return of the mRNA gene expression to baseline values in the older rats prior to healing may contribute to their delayed union. (3) No genes were overly up-regulated in the older rats. The slower healing response of the older rats did not stimulate a negative-feedback increase in the mRNA expression of stimulatory cytokines.

Age and ovariectomy impair both the normalization of mechanical properties and the accretion of mineral by the fracture callus in rats.

The impact of age and ovariectomy on the healing of femoral fractures was studied in three groups of female rats at 8, 32 and 50 weeks of age at fracture. In the two older groups, the rats had been subjected to ovariectomy or sham surgery at random at 26 weeks of age. At fracture, all rats received unilateral intramedullary pinning of one femur and a middiaphyseal fracture. Rigidity and breaking load of the femora were evaluated at varying times up to 24 weeks after fracture induction by three-point bending to failure. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. In the youngest group, 8-week-old female rats regained normal femoral rigidity and breaking load by 4 weeks after fracture. They exceeded normal contralateral values by 8 weeks after fracture. In the middle group, at 32 weeks of age, fractures were induced, and the femora were harvested at 6 and 12 weeks after fracture. At 6 weeks after fracture there was partial restoration of rigidity and breaking load. At 12 weeks after fracture, only the sham-operated rats had regained normal biomechanical values in their fractured femora, while the fractured femora of the ovariectomized rats remained significantly lower in both rigidity and breaking load. In contrast, for the oldest group of rats, 50 weeks old at fracture, neither sham-operated nor ovariectomized rats regained normal rigidity or breaking load in their fractured femora within the 24 weeks in which they were studied. In all fractured bones, there was a significant increase in BMD over the contralateral intact femora due to the increased bone tissue and bone mineral in the fracture callus. Ovariectomy significantly reduced the BMD of the intact femora and also reduced the gain in BMD by the fractured femora. In conclusion, age and ovariectomy significantly impair the process of fracture healing in female rats as judged by measurements of rigidity and breaking load in three-point bending and by accretion of mineral into the fracture callus.

Evaluation of standard surgical preparation performed on superficial dermal abrasions.

OBJECTIVES: To determine the difference, if any, between the reduction of bacteria on contaminated normal skin and contaminated superficially abraded skin following standard surgical preparations at clinically relevant time points after injury. DESIGN: Prospective animal study. SETTING: Laboratory. SUBJECTS: Thirty-two New Zealand white rabbits. INTERVENTION: Two sites, two by two centimeters, one abraded and one nonabraded (control), were studied on each rabbit. Both were inoculated with encapsulated Staphylococcus aureus strain Wood 46. Four six-millimeter punch biopsies were obtained after inoculation, immediately before surgical scrub, and five minutes and then two hours after completion of the surgical scrub. The rabbits were divided into four cohort groups with surgical scrubs performed at six, twelve, twenty-four, and forty-eight hours after inoculation. Bacterial counts were determined. MAIN OUTCOME MEASUREMENTS: Numbers of bacteria on surgical sites. RESULTS: Before surgical preparation, the amount of bacteria on the normal skin (control sites) dropped significantly (p<0.02) except in the six-hour group (p<0.20). At the abraded skin sites, the bacteria flourished. The surgical scrub dropped bacterial counts at both the abraded and nonabraded skin sites significantly (p<0.05) except for the abraded site in the twenty-four-hour group (p<0.08). However in the twelve-, twenty-four-, and forty-eight-hour groups, the bacterial counts (colony-forming units) were still markedly elevated (>1x10(5) at abraded sites) when compared with the nonabraded skin sites (p<0.008) at the respective time intervals. Only at the six-hour interval were the bacterial counts reduced similarly at both the abraded and nonabraded skin sites. CONCLUSIONS: In a rabbit model the standard surgical preparation using povidone-iodine at six hours after inoculation is effective in reducing the bacterial count on abraded skin to that of surgically prepared nonabraded skin. Beyond that time, the standard surgical preparation is ineffective in reducing counts to those of nonabraded skin at similar time intervals.

Comparison of mechanical loads produced by current intramedullary reamer systems.

OBJECTIVE: This study evaluated the mechanical loading experienced by four clinically used intramedullary reamer cutter designs to evaluate the effects of variations in speed and feed rate on reamer system performance. DESIGN: Biomechanical laboratory study. SETTING: Research laboratory. MAIN OUTCOME MEASURE: Four clinically used reamer systems with detachable cutters were tested using a computer-controlled machining system at representative reaming and drilling speeds of 250 and 750 revolutions per minute (RPM), respectively. Hard oak blocks with mechanical properties similar to cortical bone were reamed using cutter heads with diameters from nine to fourteen millimeters (in 0.5-millimeter increments) at feed rates of 1.0 and 7.6 centimeters per second. Reactive axial loads and torques were recorded and analyzed. RESULTS: All systems demonstrated reduced maximal loads/torques for small reamer sizes (9 to 10.5 millimeters) at drilling speeds rather than reaming speeds. Individual systems demonstrated measurable differences in sensitivity to alterations in operating speed, indicating that some designs are not amenable to operation at increased speeds. In tests where reamer head cutting characteristics were isolated by using identical solid drive shafts, the deeply fluted design with a long lead taper and a rounded, burrlike body consistently produced significantly lower mechanical loading at all speeds and feed rates. In addition, two of the four systems tested use a larger flex shaft diameter for reamer head sizes of thirteen millimeters or greater. There was no indication of a need to use larger flex shafts for the larger reamers, based on mechanical load/torque data for those systems. CONCLUSIONS: The tests performed demonstrate that appropriate control of reaming speeds (RPM) can be used to minimize mechanical loading for all systems. Caution should be exercised, however, so that any operational changes that reduce resistive loads and torques do not lead the surgeon to increased feed rates. Additional study is required to investigate the variable effects of increasing the operating speed of each system on localized thermal changes.