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Ibaraki, Japan

The purpose of the present study was to determine whether teriparatide and monthly minodronic acid would have an additive effect on cancellous bone mass in ovariectomized rats. Seven-week-old female Sprague-Dawley rats were randomized into five groups of 10 animals each, including a sham-operation. +. vehicle group, an ovariectomy (OVX). +. vehicle group, an OVX. +. minodronic acid (6. μg/kg. s.c., every 4. weeks) group, an OVX. +. teriparatide (20. μg/kg. s.c., daily) group, and an OVX. +. minodronic acid. +. teriparatide group. After the 12-week experimental period, static and dynamic histomorphometric analyses were performed on the cancellous bone of the tibial proximal metaphysis. OVX decreased the bone volume per total volume (BV/TV) and the trabecular number (Tb.N) and increased the trabecular separation (Tb.Sp) as a result of increased bone remodeling. Minodronic acid prevented the OVX-induced decreases in BV/TV, while teriparatide increased the BV/TV and trabecular width (Tb.Wi) beyond the values of the sham controls. Minodronic acid prevented, but teriparatide only mitigated, the OVX-induced decrease in Tb.N, although both drugs similarly prevented the OVX-induced increase in Tb.Sp. A combination of teriparatide and minodronic acid further increased the BV/TV and Tb.N and decreased the Tb.Sp as a result of the suppression of bone remodeling, compared with teriparatide alone. These results suggest the differential effect of teriparatide and monthly minodronic acid on cancellous bone structure and the additive effect of the two drugs on cancellous bone mass in OVX rats. © 2014 Elsevier Inc. Source


Iwamoto J.,Keio University | Seki A.,Hamri Co. | Sato Y.,Mitate Hospital
Chinese Journal of Physiology | Year: 2014

High-dose glucocorticoids reduce cortical bone gain in rats. The aim of the present study was to examine the effect of the intermittent administration of human parathyroid hormone (1-34) (hPTH[1-34]) on cortical bone in rats treated with high-dose prednisolone (PSL). Twenty-five female Sprague-Dawley rats (6 weeks old) were randomized into the following three groups: a vehicle administration (control) group, a PSL (10 mg/kg s.c., 5 times a week) administration group, and a PSL + hPTH(1-34) (30 μg/kg s.c., 3 times a week) administration group. After 8 weeks of treatment, the bone mineral density (BMD) of the femoral diaphysis was determined using peripheral quantitative computed tomography, and a static bone histomorphometric analysis was performed on the tibial diaphysis. PSL administration induced a decrease in the BMD of the femoral diaphysis, compared with the control group, as well as decreases in the total tissue area, cortical area, percent cortical area, and periosteal perimeter and increases in the marrow area, percent marrow area, and endocortical perimeter of the tibial diaphysis, compared with the control group. The intermittent administration of hPTH(1-34) to PSL-treated rats attenuated PSL-related changes in the BMD of the femoral diaphysis and the percent cortical area, marrow area, percent marrow area, and endocortical perimeter of the tibial diaphysis. The findings of the present study suggest that the intermittent administration of hPTH(1-34) improves cortical BMD, acts on the endocortical bone surface, and improves cortical bone geometry, in rats treated with highdose PSL. © 2014 by The Chinese Physiological Society and Airiti Press Inc. Source


This study investigated the effects of combined teriparatide (an anabolic agent) and monthly risedronate (an anti-resorptive agent) therapy on cancellous bone mass in orchidectomized (ORX) rats. Fifty 14-week-old male Sprague–Dawley rats were randomized into five groups of ten animals each: sham-operation + vehicle; ORX + vehicle; ORX + risedronate (90 μg/kg subcutaneous, every 4 weeks); ORX + teriparatide (30 μg/kg subcutaneous, three times per week); and ORX + risedronate + teriparatide. After the 12-week experimental period, cancellous bone in the tibial proximal metaphysis was examined by static and dynamic histomorphometric analyses. ORX decreased bone volume per total volume (BV/TV) and trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Risedronate increased BV/TV and Tb.N above the sham control values, while teriparatide prevented the ORX-induced decrease in BV/TV and increased trabecular width (Tb.Wi) above sham control levels. Risedronate decreased Tb.Sp below control values, while teriparatide prevented the ORX-induced increase in Tb.Sp. The combination of teriparatide and risedronate further increased BV/TV and Tb.N and decreased Tb.Sp as a result of suppression of bone remodeling, compared with teriparatide alone. These results suggest that teriparatide and monthly risedronate exert different effects on cancellous bone structure and thus have additive effects on cancellous bone mass in ORX rats. © 2015, Springer Science+Business Media New York. Source


Iwamoto J.,Keio University | Seki A.,Hamri Co. | Sato Y.,Mitate Hospital | Matsumoto H.,Keio University | And 2 more authors.
Calcified Tissue International | Year: 2010

The purpose of the present preclinical study was to determine whether vitamin K2 would promote bone healing in a rat femoral osteotomy model with or without glucocorticoid (GC) treatment. Thirty-eight 6 week-old female Sprague-Dawley rats underwent a unilateral osteotomy of the femoral diaphysis followed by intramedullary wire fixation and then were randomized into four groups that received the following treatment schedules: vehicle, vitamin K2, GC + vehicle, and GC + vitamin K2. GC (prednisolone, 2.5 mg/kg) was administered subcutaneously twice a week. Vitamin K2 (menatetrenone, 30 mg/ kg) was administered orally five times a week. After 8 weeks of treatment, the wires were removed and a bone histomorphometric analysis was performed on the bone tissue inside the callus. Vitamin K2 administration to GCuntreated rats decreased the osteoclast surface/bone surface (OcS/BS), osteoblast surface (ObS)/BS, eroded surface (ES)/BS, and bone formation rate (BFR)/BS and increased the lamellar area/bone area. Although GC treatment increased the ES/BS and decreased the ObS/BS, BFR/BS, and lamellar area/bone area, vitamin K2 administration to GC-treated rats decreased the OcS/BS and prevented an increase in the ES/BS and a decrease in the lamellar area/ bone area. These results suggested that vitamin K2 downregulated bone turnover and stimulated lamellar bone formation in GC-untreated rats and prevented an increase in bone resorption while maintaining bone formation and prevented a decrease in lamellar bone formation in GCtreated rats. Thus, vitamin K2 appears to be effective for promoting bone healing in a rat femoral osteotomy model with or without GC treatment. © Springer Science+Business Media, LLC 2010. Source


Iwamoto J.,Keio University | Seki A.,Hamri Co. | Sato Y.,Mitate Hospital | Matsumoto H.,Keio University | And 2 more authors.
Calcified Tissue International | Year: 2011

The purpose of the present study was to examine the effect of vitamin K2 on cancellous and cortical bone mass in rats with streptozotocin (STZ)-induced type 1 diabetes. Twenty-seven male Sprague-Dawley rats aged 12 weeks were randomized by the weight-stratified method into the following three groups: age-matched control group, STZ + vehicle group, and STZ + vitamin K 2 group. STZ (40 + 50 mg/kg) was administered intravenously twice during the initial 1-week period. Vitamin K2 (menatetrenone, 30 mg/kg) was administered orally 5 days a week. After 12 weeks of treatment, the serum glucose concentration and femoral length and weight were measured and histomorphometric analysis was performed on the cancellous and cortical bone of the distal femoral metaphysis and femoral diaphysis, respectively. STZ administration induced hyperglycemia and a decrease in femoral weight. The STZ + vehicle group also showed cancellous osteopenia due to a decrease in the number of osteoblasts/bone surface (N.Ob/BS) and the osteoblast surface (ObS)/BS without any significant changes in boneresorption parameters, but it did not have a significant decrease in cortical bone mass. Administration of vitamin K2 to STZ-treated rats prevented the development of hyperglycemia and a decrease in femoral weight. Vitamin K2 also prevented cancellous osteopenia by inhibiting the decrease in N.Ob/BS and ObS/BS without significantly affecting bone-resorption parameters, but it did not significantly increase cortical bone mass. These results suggest that vitamin K2 has beneficial effects on glucose concentration and cancellous bone mass in rats with STZ-induced type 1 diabetes. © Springer Science+Business Media, LLC 2010. Source

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