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High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats.

Kasai S, Ito A, Shindo K, Toyoshi T, Bando M - PLoS ONE (2015)

Bottom Line: Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans.The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies.In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses.

View Article: PubMed Central - PubMed

Affiliation: Vitamin E Information and Technology Section, Customer Joy Department, Eisai Co. Ltd., Tokyo, Japan.

ABSTRACT
Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of αT, we investigated the in vivo effects of αT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing αT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, αT-fed rats showed a tendency for an osteogenesis-dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, αT consumption may have beneficial effects on bone health.

No MeSH data available.


Related in: MedlinePlus

Histomorphometric analysis of secondary cancellous bones in distal femur metaphysis.(A) Representative micrographs of slices of frontal section of distal femur stained with Villanueva bone staining without decalcifying treatment are shown. (B) Histomorphometrical parameters (BV/TV, bone volume/tissue volume; ES/BS, eroded surface/bone surface; OV/OS, osteoid volume/osteoid surface; O.Th, osteoid thickness; MAR, mineral apposition rate; N.Mo.Oc/BS, number of mononuclear osteoclast/bone surface; N.Mu.Oc/BS, number of multinuclear osteoclast/bone surface; and N.Ob/BS, number of osteoblast/bone surface) of secondary cancellous bones in distal femur metaphysis are shown. Data are presented as mean ± standard error of the mean. ***P < 0.001 vs. sham rat group; †††P < 0.001 vs. normal rat control group.
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pone.0132059.g005: Histomorphometric analysis of secondary cancellous bones in distal femur metaphysis.(A) Representative micrographs of slices of frontal section of distal femur stained with Villanueva bone staining without decalcifying treatment are shown. (B) Histomorphometrical parameters (BV/TV, bone volume/tissue volume; ES/BS, eroded surface/bone surface; OV/OS, osteoid volume/osteoid surface; O.Th, osteoid thickness; MAR, mineral apposition rate; N.Mo.Oc/BS, number of mononuclear osteoclast/bone surface; N.Mu.Oc/BS, number of multinuclear osteoclast/bone surface; and N.Ob/BS, number of osteoblast/bone surface) of secondary cancellous bones in distal femur metaphysis are shown. Data are presented as mean ± standard error of the mean. ***P < 0.001 vs. sham rat group; †††P < 0.001 vs. normal rat control group.

Mentions: αT supplementation had different effects on the bone turnover of secondary cancellous bones in the vertebral body and distal femur metaphysis in normal rats. For the vertebral secondary cancellous bone, αT-supplemented normal rats had a significant increase or a trend for increase in BV/TV in comparison with control rats [low dose, +21% (P = 0.189); medium dose, +32% (P < 0.05); and high dose, +25% (P = 0.099)], which was accompanied by reduced ES/BS [medium dose, −34% (P < 0.01); high dose, −30% (P < 0.01)], increased OV/OS [medium dose, +14% (P < 0.01); high dose, +24% (P < 0.001)], increased O.Th [medium dose, +15% (P < 0.01); high dose, +25% (P < 0.001)], and increased MAR [low dose, +16% (P < 0.001); medium dose, +17% (P < 0.001); high dose, +22% (P < 0.001)]. Although the number of osteoblasts was significantly higher in αT-supplemented normal rats than in control rats [medium dose, +59% (P < 0.05); high dose, +82% (P < 0.01)], no significant changes were found in the number of osteoclasts, in the mononuclear subpopulation (N.Mo.Oc/BS) or the multinuclear subpopulation [(N.Mu.Oc/BS); Fig 4]. In contrast to the secondary cancellous bone in the vertebral body, αT supplementation did not significantly alter any of the osteogenic or bone resorption parameters in bone histomorphometry for the secondary cancellous bone of the distal femur metaphysis, except for MAR (Fig 5). These results indicate that αT supplementation in normal rats resulted in a trend for increased bone mass in the vertebral secondary cancellous bone through reducing bone resorption and enhancing osteogenesis but had virtually no effect on the secondary cancellous bone in the distal femur metaphysis.


High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats.

Kasai S, Ito A, Shindo K, Toyoshi T, Bando M - PLoS ONE (2015)

Histomorphometric analysis of secondary cancellous bones in distal femur metaphysis.(A) Representative micrographs of slices of frontal section of distal femur stained with Villanueva bone staining without decalcifying treatment are shown. (B) Histomorphometrical parameters (BV/TV, bone volume/tissue volume; ES/BS, eroded surface/bone surface; OV/OS, osteoid volume/osteoid surface; O.Th, osteoid thickness; MAR, mineral apposition rate; N.Mo.Oc/BS, number of mononuclear osteoclast/bone surface; N.Mu.Oc/BS, number of multinuclear osteoclast/bone surface; and N.Ob/BS, number of osteoblast/bone surface) of secondary cancellous bones in distal femur metaphysis are shown. Data are presented as mean ± standard error of the mean. ***P < 0.001 vs. sham rat group; †††P < 0.001 vs. normal rat control group.
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Related In: Results  -  Collection

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pone.0132059.g005: Histomorphometric analysis of secondary cancellous bones in distal femur metaphysis.(A) Representative micrographs of slices of frontal section of distal femur stained with Villanueva bone staining without decalcifying treatment are shown. (B) Histomorphometrical parameters (BV/TV, bone volume/tissue volume; ES/BS, eroded surface/bone surface; OV/OS, osteoid volume/osteoid surface; O.Th, osteoid thickness; MAR, mineral apposition rate; N.Mo.Oc/BS, number of mononuclear osteoclast/bone surface; N.Mu.Oc/BS, number of multinuclear osteoclast/bone surface; and N.Ob/BS, number of osteoblast/bone surface) of secondary cancellous bones in distal femur metaphysis are shown. Data are presented as mean ± standard error of the mean. ***P < 0.001 vs. sham rat group; †††P < 0.001 vs. normal rat control group.
Mentions: αT supplementation had different effects on the bone turnover of secondary cancellous bones in the vertebral body and distal femur metaphysis in normal rats. For the vertebral secondary cancellous bone, αT-supplemented normal rats had a significant increase or a trend for increase in BV/TV in comparison with control rats [low dose, +21% (P = 0.189); medium dose, +32% (P < 0.05); and high dose, +25% (P = 0.099)], which was accompanied by reduced ES/BS [medium dose, −34% (P < 0.01); high dose, −30% (P < 0.01)], increased OV/OS [medium dose, +14% (P < 0.01); high dose, +24% (P < 0.001)], increased O.Th [medium dose, +15% (P < 0.01); high dose, +25% (P < 0.001)], and increased MAR [low dose, +16% (P < 0.001); medium dose, +17% (P < 0.001); high dose, +22% (P < 0.001)]. Although the number of osteoblasts was significantly higher in αT-supplemented normal rats than in control rats [medium dose, +59% (P < 0.05); high dose, +82% (P < 0.01)], no significant changes were found in the number of osteoclasts, in the mononuclear subpopulation (N.Mo.Oc/BS) or the multinuclear subpopulation [(N.Mu.Oc/BS); Fig 4]. In contrast to the secondary cancellous bone in the vertebral body, αT supplementation did not significantly alter any of the osteogenic or bone resorption parameters in bone histomorphometry for the secondary cancellous bone of the distal femur metaphysis, except for MAR (Fig 5). These results indicate that αT supplementation in normal rats resulted in a trend for increased bone mass in the vertebral secondary cancellous bone through reducing bone resorption and enhancing osteogenesis but had virtually no effect on the secondary cancellous bone in the distal femur metaphysis.

Bottom Line: Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans.The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies.In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses.

View Article: PubMed Central - PubMed

Affiliation: Vitamin E Information and Technology Section, Customer Joy Department, Eisai Co. Ltd., Tokyo, Japan.

ABSTRACT
Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of αT, we investigated the in vivo effects of αT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing αT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, αT-fed rats showed a tendency for an osteogenesis-dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, αT consumption may have beneficial effects on bone health.

No MeSH data available.


Related in: MedlinePlus