The impact of ovariectomy and hyperglycemia on graft consolidation in rat calvaria.

OBJECTIVE: Implant placement frequently depends on bone augmentation. However, the impact of systemic metabolic diseases on the consolidation of bone substitutes remains poorly understood. Our goal is to study the impact of ovariectomy and hyperglycemia on graft consolidation in rat calvaria. MATERIAL AND METHODS: We determined a rat model in which methacrylate hemispheres filled with deproteinized bovine bone mineral were fixed on the calvaria. The first group received streptozotocin (STZ) to induce diabetes. The second group of animals underwent ovariectomy (OVX), causing osteoporosis. Control animals remained untreated, only receiving vehicle injections (STZ-control) but not sham operation, respectively. Specimens were assessed by histomorphometry and µCT. RESULTS: Graft consolidation was similar between the two groups. The rate of new bone formation after 4 weeks was 0.61±0.53% in the STZ group (n=10) and 0.69±0.91% in the control group (n=8). After 8 weeks, the rates of new bone formation were 4.98±3.16% in the OVX group (n=7) and 2.35±1.30% in the control group (n=10). The volume occupied by the bone substitute was not affected by STZ or OVX treatment. The low amount of newly formed bone could not be quantified by µCT. CONCLUSION: We conclude that neither STZ nor OVX altered the early phase of graft consolidation. Our findings are limited by the weak osteogenic potential of the rat calvaria in this augmentation model.

Combined L-arginine and antioxidative vitamin treatment mollifies ischemia-reperfusion injury of skeletal muscle.

Enhanced production of superoxide in L-arginine-depleted environments and concomitant reduction of nitric oxide (NO) concentration are involved in ischemia-reperfusion (I/R) injury. Treatment with L-arginine or antioxidative vitamins alone and in combination was used to mollify I/R injury in skeletal muscle. Untreated rabbits were compared with those treated with L-arginine/antioxidative vitamin cocktail Omnibionta only, or a combination of L-arginine/ antioxidative vitamins during hind limb I/R (2.5 hours/2 hours). NO was continuously measured in vivo. Plasma malondialdehyde (MDA) served as the measure of oxygen free radical formation. Interstitial edema formation, microvessel diameter alterations, microvessel plugging, and blood flow changes were used as indicators of I/R injury. The MDA level in untreated animals 2 hours after reperfusion was significantly higher than in control animals (0.81 micromol/L +/- 0.14 micromol/L vs 0.57 micromol/L +/- 0.11 micromol/L; P<.05), indicating enhanced production of oxygen free radicals. This sequela paralleled the decreasing concentration of NO, which dropped below the detection limit (1 nmol/L) after reperfusion. Microvascular changes during I/R injury were expressed as a 40% decrease in microvessel diameter and adhesion of neutrophils in 20% of microvessels, which led to a consequent 60% reduction in blood flow, demonstrating "no reflow" (reperfusion failure after restoration of blood flow). The increase in the fraction of muscle interfiber area by 85% indicated prominent edema formation. Treatment with antioxidative vitamins alone had a minimally positive effect on edema formation and microvascular plugging, possibly by suppression of oxygen free radical production, as expressed by the reduction in plasma MDA levels. However, this therapy failed to preserve basal NO production and to protect from microvascular constriction and no reflow. Treatment with L-arginine alone had a stronger protective effect, maintaining basal NO production, further reduction of neutrophil plugging, abolition of microvascular constriction, and no reflow. The combination of antioxidative vitamins and L-arginine was the best treatment against I/R injury, expressed not only by the protection of microvessel constriction, but also by abolition of microvascular plugging, increase in NO production (68 nmol/L +/- 5 nmol/L) over the basal level (52 nmol/L +/- 7 nmol/L), and higher blood flow, as compared with treatment with L-arginine or antioxidative vitamins alone.