著者

Junkichi Kanda Nobuo Izumo Yoshiko Kobayashi Kenji Onodera Taketoshi Shimakura Noriaki Yamamoto Hideaki E. Takahashi Hiroyuki Wakabayashi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.11, pp.1934-1940, 2017-11-01 (Released:2017-11-01)

参考文献数

35

被引用文献数

1 24

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Long-term treatment with antiepileptic drugs (AEDs) is accompanied by reduced bone mass that is associated with an increased risk of bone fractures. Although phenytoin has been reported to adversely influence bone metabolism, little is known pertaining to more recent AEDs. The aim of this study was to evaluate the effects of gabapentin or levetiracetam on bone strength, bone mass, and bone turnover in rats. Male Sprague-Dawley rats were orally administered phenytoin (20 mg/kg), gabapentin (30 or 150 mg/kg), or levetiracetam (50 or 200 mg/kg) daily for 12 weeks. Bone histomorphometric analysis of the tibia was performed and femoral bone strength was evaluated using a three-point bending method. Bone mineral density (BMD) of the femur and tibia was measured using quantitative computed tomography. Administration of phenytoin significantly decreased bone strength and BMD, which was associated with enhanced bone resorption. In contrast, treatment with gabapentin (150 mg/kg) significantly decreased bone volume and increased trabecular separation, as shown by bone histomorphometric analysis. Moreover, the bone formation parameters, osteoid volume and mineralizing surface, decreased after gabapentin treatment, whereas the bone resorption parameters, osteoclast surface and number, increased. Levetiracetam treatment did not affect bone strength, bone mass, and bone turnover. Our data suggested that gabapentin induced the rarefaction of cancellous bone, which was associated with decreased bone formation and enhanced bone resorption, and may affect bone strength and BMD after chronic exposure. To prevent the risk of bone fractures, patients prescribed a long-term administration of gabapentin should be regularly monitored for changes in bone mass.

著者

Yukiko Ishibashi Nobuo Izumo Keiko Iwata Tomomi Morikawa Toshiki Kameyama Yasuo Watanabe Takayuki Manabe Hideo Matsuzaki

出版者

Japan Brain Science society

雑誌

脳科学誌 (ISSN:13415301)

巻号頁・発行日

vol.46, pp.5-19, 2016 (Released:2017-05-09)

参考文献数

20

著者

Junkichi Kanda Megumi Furukawa Nobuo Izumo Taketoshi Shimakura Noriaki Yamamoto Hideaki E. Takahashi Hiroyuki Wakabayashi

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.14, no.2, pp.77-83, 2020-04-30 (Released:2020-05-06)

参考文献数

39

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Tacrolimus, a calcineurin inhibitor, affects bone metabolism and increases the risk of fracture due to marked bone loss. Bisphosphonates increase the bone mineral density (BMD) in osteoporosis patients. Menatetrenone has less positive effects on BMD but reduces the risk of fracture by improving bone quality. In this study, we investigated the effectiveness of the combined administration of risedronate and menatetrenone against bone loss induced by tacrolimus. Wistar rats were divided into four groups: [1] control, [2] tacrolimus at 1.5 mg/kg, [3] tacrolimus + risedronate at 1.0 mg/kg, and [4] tacrolimus + risedronate + menatetrenone at 20 mg/kg. After the drugs were administered for 4 weeks, bone histomorphometric analysis was performed and bone strength was evaluated using a three point bending method. BMD was measured using quantitative computed tomography. Tacrolimus significantly reduced the BMD and strength properties of the lower limb bones. These tacrolimusinduced decreases were suppressed by risedronate treatment. The combined administration of risedronate and menatetrenone more significantly improved bone strength properties than risedronate alone. Bone histomorphometric analysis revealed a significant increase in bone resorption with tacrolimus. Risedronate alone significantly suppressed the tacrolimus-induced increase in bone resorption but simultaneously reduced bone formation. On the other hand, the combined administration of risedronate and menatetrenone suppressed the tacrolimus-induced increase in bone resorption, in addition to the significant risedronate-induced decrease in bone formation. This study suggests that the combined administration of risedronate and menatetrenone improves bone strength in tacrolimus-treated rats by preventing and ameliorating the risedronate-induced suppression of bone formation.

著者

Atsushi Kiuchi Satoshi Shimegi Ippei Tanaka Nobuo Izumo Ryo Fukuyama Hiromichi Nakamuta Masao Koida

出版者

Japan Society of Physical Education, Health and Sport Sciences

雑誌

International Journal of Sport and Health Science (ISSN:13481509)

巻号頁・発行日

vol.4, pp.10-18, 2006 (Released:2008-01-25)

参考文献数

26

被引用文献数

1 3

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The purpose of this study was to investigate the effects of different intensities of resistance exercise training on established bone loss in ovariectomized (ovx-ed) rats by densitometry and histomorphometry. Thirty Female Wistar rats were ovx-ed or sham-operated (SHM) at 3 months of age and maintained untreated for 5 months after surgery to establish osteopenia. When they reached 8 months, the ovx-ed rats were divided into four groups in accordance with varying weights applied to a squat-training device: The weight classifications were 1) kept sedentary (OVX); 2) lifted 0 g (LOW); 3) 750 g (MID); and 1500 g (HIGH). The rats in the three training groups performed weight-lifting of 10 reps, performing 2 sets per day, 3 days a week for a ten week period. The Femora and tibiae were removed from each rat and were used for analyses. Ovx induced a significant loss of total BMC in all the bones tested. The ovx-induced femoral BMC loss was observed at all locations tested on the bone (proximal, shaft, and distal), and exercise-intensity dependent restoration was found at the proximal and the distal sites, but not at the shaft. In the tibia, ovx-induced significant bone loss occurred only at the proximal metaphyseal site. The training increased the tibial BMC of all sites in an exercise-intensity dependently, irrespective of the degree of ovx effect. At the tibial shaft, the training increased the cortical bone mass significantly above sham level by the bone apposition at the periosteum. At the proximal tibial metaphysis, exercise had no effect on the cancellous bone volume after ovx-induced bone loss. This finding suggests that the exercise induced bone increase in the ovx-ed rats was from cortical bone, not from cancellous bone, at least in the proximal tibia. These findings indicate that the weight-lifting exercise in rats reversed the ovx-induced bone loss in an exercise-intensity dependent and site-specific manner, even in established osteopenic skeleton 5 mon after ovx.