Density and structural changes in the bone of growing rats after weekly alendronate administration with and without a methotrexate challenge.

Alendronate (ALN) and other bisphosphonates have been used successfully in pediatric patients with osteopenia secondary to connective tissue diseases. Loss of growth in height has not been reported, but concerns remain regarding the effect of these potent antiresorptive agents when used in children and adolescents. High-dose methotrexate (MTX) and other chemotherapy drugs have been implicated in osteoporosis and a high fracture incidence in survivors of childhood cancers and are also associated with osteopenia in adult animals. The effect of high dose MTX on bone density during rapid skeletal growth, however, has not been widely studied, nor has the potentially therapeutic effect of bisphosphonates in this setting. We examined the effects of ALN and MTX administration, alone and in combination, on bone density, morphology, mechanical strength, and longitudinal growth in normal growing rats. Sprague-Dawley rats were given ALN once weekly (0.3 mg/kg) from 5 to 11 weeks of age, with and without a course of methotrexate (MTX) given daily in weeks 1 and 3 (0.75 mg/kg/day). Twenty-four animals were randomly divided into four groups: Control (vehicle), ALN alone, ALN + MTX, and MTX alone. After 6 weeks, the femora, tibiae, and lumbar spine were studied by dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, mechanical strength testing, microradiography, light microscopy, and by determination of ash weights and bone lengths. ALN treatment increased bone mineral density (BMD) by 23% to 68%. The largest increases in the femur occurred in the distal third where endochondral bone growth was greatest and included large increases in trabecular bone and total cross-sectional area. ALN + MTX produced similar effects to ALN alone. MTX only reduced BMD by 8% in the vertebrae, but not significantly at other sites. MTX also led to femoral length reductions of 2.9%. The small reductions in BMD due to MTX were overwhelmed by the increases due to ALN, whereas the length loss was unaffected. Transverse density banding corresponding to weekly ALN administrations were clearly evident radiographically throughout the growing skeleton, likely due to decreased resorption and possibly increased mineralization in the bands. ALN or ALN + MTX treatment also led to increases in mechanical strength in the femora. Although MTX administration during growth leads to some BMD reduction, ALN given with MTX eliminates this reduction and in fact bone density and strength increase above control levels.

Novel radioprotectant drugs for sparing radiation-induced damage to the physis.

PURPOSE: To determine if pentoxifylline, interleukin 1alpha, selenium and misoprostol can minimize damage to physeal longitudinal growth during single radiation dose exposure in an animal model. MATERIALS AND METHODS: Eighty-seven weanling Sprague-Dawley rats were randomized into 15 drug/dose groups. All groups received a single 17.5-Gy gamma-irradiation exposure to the right knee, the left limb serving as an internal control. Pentoxifylline was injected 30 min before exposure, sodium selenite and interleukin 1alpha 24 h before exposure and misoprostol 2 h before exposure. Positive controls received 17.5 Gy. At 6 weeks, animals were sacrificed, the hind limb lengths were measured and detailed histomorphometric analysis was performed. RESULTS: Statistically significant reductions (p < or = 0.03) in mean limb length discrepancy compared with irradiation alone were seen following administration of pentoxifylline (50 mg kg(-1)), interleukin 1alpha (15 mcg kg(-1)), selenium (5 mg kg(-1)) and misoprostol (20 mg kg(-1)). Histomorphometric endpoints and growth rate remained altered at 6 weeks despite treatment, but length discrepancy reduction was highly correlated with the appearance of regenerative clones. CONCLUSIONS: Each drug reduced the amount of anticipated growth arrest in the animal model and some compared favourably in magnitude with that previously demonstrated for the established radioprotectant drug amifostine. Restoration of growth appears related to appearance of regenerative clones.

Silver anode treatment of chronic osteomyelitis.

Twenty-five patients with active, chronic osteomyelitis, resistant to conventional management, were treated with surgical debridement and daily application of electrically activated silver dressings. Sixteen (64%) cases resulted in closed, stable, pain-free wounds, with the remainder resulting in persistent drainage or amputation. Nine of 12 cases complicated by nonunion achieved union. In 13 patients an open-bone graft was performed and silver treatment continued: these tended to remain free of purulent drainage but fared no better than average in the long-term follow-up. The silver anode dressing seems to be an effective aid in the treatment of chronic bone infection when combined with adequate surgical debridement, thereby reducing the need for prolonged systemic antibiotics.

Clinical experiences with low intensity direct current stimulation of bone growth.

Low intensity direct current stimulation of bone growth involves the continuous application of cathodic currents in the nanoampere range. The technique has been applied to 13 patients with a variety of non-unions and pseudarthroses with a success rate of 77 per cent. Preliminary data indicate that a range of total energy, from 0.6 to 2.5 Joules, is maximally effective. The technique has been combined with anodic control of local bacterial infection with promising results. Both the osteogenic stimulation and the bacterial suppression techniques as described in this paper, appear to be safe and effective.

Antibacterial effects of silver electrodes with weak direct current.

Silver, platinum, gold, stainless-steel, and copper electrodes were used with low currents (0.02 to 20 muA/mm(2)) to explore their electrochemical effects on the growth of four bacterial species. In the higher current ranges, all electrodes inhibited growth at both poles, usually in conjunction with electrolytic break-down of the medium and severe corrosion of the metal. Silver, however, was extremely bacteriostatic, even at the lowest current, when used as the anode. Quantitative studies showed that most of this inhibition takes place in a few hours and is not accompanied by changes in pH. Electrochemically injected silver from the anode is probably the instrumental agent, being effective in concentrations of about 5 mug/ml. This is the equivalent concentration of silver sulfadiazine that has been shown to give complete inhibition of bacteria, but without the sulfonamide moiety.