抗てんかん剤長期服用におけるくる病発症要因に関する臨床的研究
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概要
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Rickets or osteomalacia has shown to be associated with long-term anticonvulsant therapy. lt was the purpose of this study to elucidate the factor which lead to rachitic changes and to determine the effect of 1α-Hydoxyvitamin D (1α-OH-D_3) on patients suffering from slight osteomalacia found out from epileptic patients. The authers measured the serum concentrations of calcium (Ca), phosphorus (P), alkaline-phosphatase (Al-p), 25-Hydroxyvitamin D (25-OH-D), and evaluated ΣGS/D (index of bone density) and MCI (metacarpal index) using microdensitometry method. The patients were 92 epileptic children aged 3 to 22 yrs (mean 10.5 yrs old) who had been recieving various combinations of anticonvulsants for at least 3 yrs (mean 5.8 yrs). 1α-OH-D_3 was given to 16 of the above mentioned patients showed low levels of serum 25-OH-D (below -2SD) or low ΣGS/D values for metacarpal bone (below -1.65SD). The obtained results are as follows. 1) Serum Ca levels decreased with a duration of therapy and were lower in 21 patients (22.8%) compared with age matched controls. Serum Al-p levels were higher in 5 patients (6.5%) aged 6 to 14 yrs. Serum 25-OH-D levels decreased with a duration of therapy and with age and were low in 17 patients (18.5%). 2) In 11 patients (13.4%), the ΣGS/D values were low and almost all cases were 9 to 14 years old, who were recieved PB or PB with other anticonvulsant drugs for more than 7 yrs and had been medicated from earlier age than other patients. In 8 (72.7%) of 11 patients had showed low levels of serum 25-OH-D. 3) Serum Ca levels had significantly increased from 9.0 mg/dl to 9.3 mg/dl at 3 mos after taking 1α-OH-D_3. Serum levels of P and Al-p did not vary before or after treatment with 1α-OH-D_3. 4) Serum 25-OH-D levels significantly increased from 15.8 ng/ml to 26.7 ng/ml, similar to the levels in controls. 5) The ΣGS/D values of patients on treatment with 1α-OH-D_3 for 18 mos were higher than those of controls and healthy children. There was no difference in the MCI values between patients with 1α-OH-D_3 and controls. These results suggest that long-term treatment with PB or PB with other anticonvulsant drugs and patient's age are the factors leading to rachitic changes and evaluations of ΣGS/D together with those of Ca, Al-p and 25-OH-D are useful for early detection of rachitic changes, Treatment with 1α-OH-D_3 improves the bone density in epileptic children undergoing long-term anticonvulsant therapy.
- 神戸大学の論文