Clinical trial: comparison of alendronate and alfacalcidol in glucocorticoid-associated osteoporosis in patients with ulcerative colitis.

BACKGROUND: Bone loss is often observed in patients with ulcerative colitis, particularly if they require glucocorticoids. AIM: To determine whether the bisphosphonate, alendronate, is safe and effective in preserving bone mass compared to the active vitamin D3, alfacalcidol, in ulcerative colitis patients receiving glucocorticoids. METHODS: Thirty-nine patients with ulcerative colitis and treated with glucocorticoids were randomized to receive alendronate (5 mg/day) or alfacalcidol (1 microg/day) daily for 12 months. Loss of bone mass was evaluated by bone mineral density, bone resorption by urinary N-telopeptide for type I collagen, and bone formation by serum bone alkaline phosphatase. RESULTS: Alendronate, but not alfacalcidol, significantly increased bone mineral density in the lumbar spine. Alendronate decreased serum bone alkaline phosphatase levels, but alfacalcidol did not. Urinary N-telopeptide for type I collagen levels decreased in both groups, but were significantly lower in the alendronate group. There were no significant differences in the adverse events in the two groups. CONCLUSION: Our study indicates that alendronate is a safe, well-tolerated and more effective therapy than alfacalcidol for preventing glucocorticoid-associated bone loss in patients with ulcerative colitis.

Development of granulocyte and monocyte adsorptive apheresis in the rat dextran sodium sulfate-induced colitis model.

Granulocytapheresis (GCAP) selectively removes large numbers of granulocytes and monocytes from peripheral blood by adsorptive apheresis, and in patients with ulcerative colitis GCAP has been associated with significant efficacy. However, the mechanism(s) of efficacy of this strategy is poorly understood. This rat model of dextran sodium sulfate (DSS)-induced colitis was to investigate the effect of GCAP on tumor necrosis factor (TNF)-alpha release by peripheral leukocytes. By using mini columns, an experimental GCAP setting was developed and applied to the DSS-induced colitis model. The production of TNF-alpha by lipopolysaccharide-activated leukocytes in whole blood was measured by enzyme-linked immunosorbent assay. In rats that received GCAP with columns containing leukocytapheresis carriers, TNF-alpha release by leukocytes was significantly (p < 0.05) suppressed, while no change in TNF-alpha production was seen in rats that received GCAP with sham columns. This first experimental setting in the rat colitis model suggests that GCAP is feasible in animals and should shed light on the mechanism(s) of GCAP in clinical settings. Given that TNF-alpha is a major inflammatory cytokine, down-modulation of TNF-alpha might represent one mechanism of antiinflammatory effects of GCAP.

Resonance behaviour of the seated human body and effects of posture.

Understanding of the resonance behaviour of the human body is important in the identification of vibration frequencies and body postures associated with back problems. In this study, experimental modal analysis was applied to whole-body vibration. Eight subjects were exposed to vertical random vibration while adopting three different postures on a rigid seat without a backrest. Motions of the spine, pelvis and viscera in the mid-sagittal plane were derived from skin-mounted accelerometers; head responses were measured using a bite-bar. Eight modes of vibration response were extracted below 10 Hz. A principal resonance of the human body at about 5 Hz consisted of an entire body mode, in which the skeleton moved vertically due to axial and shear deformations of buttocks tissue, in phase with a vertical visceral mode, and a bending mode of the upper thoracic and cervical spine. A bending mode of the lumbar and lower thoracic spine was found with a pitching mode of the head in the next higher mode located close to the principal mode. The second principal resonance at about 8 Hz corresponded to pitching modes of the pelvis and a second visceral mode. When subjects changed posture from erect to slouched, the natural frequency of the entire body mode decreased, resulting in a decrease in the principal resonance frequency. Shear deformation of buttocks tissue increased in the entire body mode due to the same change of posture. The complex body motions suggest that any forces causing injury from whole-body vibration will not be well-predicted by biodynamic models incapable of representing the appropriate body motions and the effects of body posture. It seems likely that the greatest risk of back problems will arise from the bending deformations of the spine.

A data correction method for surface measurement of vibration on the human body.

A data correction method to eliminate the effect of local tissue-accelerometer vibration from surface measurements of vibration over the spine has been developed and compared with previous direct measurements. A single degree-of-freedom linear model for the local tissue-accelerometer system in the vertical and the fore-and-aft axes is assumed. The natural frequency and the damping ratio of the local system are estimated so as to form a correction frequency function, using spectral analysis of the free vibration response of the local system caused by transient displacements of the accelerometer attached to the body surface. Accelerometers were attached to the skin over the spinous process of the vertebra L3 and on the abdominal wall. For four different masses and each site, correction frequency functions were computed. Seated subjects were then exposed to vertical random vibration (0.5-35 Hz) and acceleration transfer functions from the seat to each accelerometer were calculated. Different transfer functions were obtained with different additional masses but the differences were eliminated by the correction method so as to indicate the transfer functions to the spine and the viscera. For vertical responses, the correction method was effective at frequencies below the estimated natural frequencies of the local system. Fore-and-aft response over the spine did not require correction at frequencies below 35 Hz.