Differential Effect of Vitamin K and Vitamin D Supplementation on Bone Mass in Young Rats Fed Normal or Low Calcium Diet

Jun Iwamoto,Tsuyoshi Takeda,Shoichi Ichimura,Yoshihiro Sato,James K. Yeh 연세대학교의과대학 2004 Yonsei medical journal Vol.45 No.2

The purpose of this study was to clarify the differential effect of vitamin K and vitamin D supplementation on bone mass in young rats fed a normal or low calcium diet. Ninety female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into nine groups with 10 rats in each group: baseline control, and 0.5% (normal) or 0.1% (low) calcium diet, either alone, or with vitamin K (30 mg/100g, food intake), vitamin D (25μg/100g, food intake), or vitamin K+ vitamin D. After 10 weeks of feeding, bone histomorphometric analyses were performed on cortical bone of the tibial shaft and cancellous bone of the proximal tibia. Vitamin K supplementation increased the maturation-related cancellous bone gain and retarded the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation-related cortical bone gain in rats fed a normal calcium diet. Vitamin D supplementation reduced the maturation-related cancellous bone gain, prevented the reduction in periosteal bone gain, and enhanced the enlargement of the marrow cavity, with no significant effect on the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation- related cancellous and cortical bone gains with increased periosteal bone gain in rats fed a normal calcium diet. An additive effect of vitamin K and vitamin D on the maturation- related cortical bone gain was found in rats fed a normal calcium diet. This study shows the differential effects of vitamin K and vitamin D supplementation on cancellous and cortical bone mass in young rats fed a normal or low calcium diet, as well as the additive effect on cortical bone under calcium sufficient condition.

Comparison of the Effect of Vitamin K2 and Risedronate on Trabecular Bone in Glucocorticoid-Treated Rats: A Bone Histomorphometry Study

Jun Iwamoto,Hideo Matsumoto,Tsuyoshi Tadeda,Yoshihiro Sato,James K. Yeh 연세대학교의과대학 2009 Yonsei medical journal Vol.50 No.2

Purpose: To compare the effect of vitamin K2 and risedronate on trabecular bone in glucocorticoid (GC)-treated rats. Materials and Methods: Forty-eight Sprague-Dawley female rats, 3 months of age, were randomized by the stratified weight method into 5 groups according to the following treatment schedule: age-matched control, GC administration, and GC administration with concomitant administration of vitamin K2, risedronate, or vitamin K2 + risedronate. GC (methylprednisolone sodium succinate, 5.0 mg/kg) and risedronate (10 μg/kg) were administered subcutaneously three and five times a week, respectively. Vitamin K2 (menatetrenone, 30 mg/kg) was administered orally three times a week. At the end of the 8-week experiment, bone histomorphometric analysis was performed on trabecular bone of the tibial proximal metaphysis. Results: GC administration decreased trabecular bone mass compared with age-matched controls because of decreased bone formation (mineralizing surface, mineral apposition rate, and bone formation rate) and increased bone erosion. Vitamin K2 attenuated GC-induced trabecular bone loss by preventing GC-induced decrease in bone formation (mineralizing surface) and subsequently reducing GC-induced increase in bone erosion. Risedronate prevented GC-induced trabecular bone loss by preventing GC-induced increase in bone erosion although it also suppressed bone formation (mineralizing surface, mineral apposition rate, and bone formation rate). Vitamin K2 mildly attenuated suppression of bone formation (mineralizing surface) and bone erosion caused by risedronate without affecting trabecular bone mass when administered in combination. Conclusion: The present study showed differential effect of vitamin K2 and risedronate on trabecular bone in GC-treated rats. Purpose: To compare the effect of vitamin K2 and risedronate on trabecular bone in glucocorticoid (GC)-treated rats. Materials and Methods: Forty-eight Sprague-Dawley female rats, 3 months of age, were randomized by the stratified weight method into 5 groups according to the following treatment schedule: age-matched control, GC administration, and GC administration with concomitant administration of vitamin K2, risedronate, or vitamin K2 + risedronate. GC (methylprednisolone sodium succinate, 5.0 mg/kg) and risedronate (10 μg/kg) were administered subcutaneously three and five times a week, respectively. Vitamin K2 (menatetrenone, 30 mg/kg) was administered orally three times a week. At the end of the 8-week experiment, bone histomorphometric analysis was performed on trabecular bone of the tibial proximal metaphysis. Results: GC administration decreased trabecular bone mass compared with age-matched controls because of decreased bone formation (mineralizing surface, mineral apposition rate, and bone formation rate) and increased bone erosion. Vitamin K2 attenuated GC-induced trabecular bone loss by preventing GC-induced decrease in bone formation (mineralizing surface) and subsequently reducing GC-induced increase in bone erosion. Risedronate prevented GC-induced trabecular bone loss by preventing GC-induced increase in bone erosion although it also suppressed bone formation (mineralizing surface, mineral apposition rate, and bone formation rate). Vitamin K2 mildly attenuated suppression of bone formation (mineralizing surface) and bone erosion caused by risedronate without affecting trabecular bone mass when administered in combination. Conclusion: The present study showed differential effect of vitamin K2 and risedronate on trabecular bone in GC-treated rats.

Green Tea Polyphenols Improve Bone Microarchitecture in High-Fat-Diet–Induced Obese Female Rats Through Suppressing Bone Formation and Erosion

Chwan-Li Shen,Ming-Chien Chyu,Jay J. Cao,James K. Yeh 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.5

This study evaluates the effects of green tea polyphenols (GTPs) on bone microarchitecture in high-fat-diet (HFD)–induced obese female rats. Thirty-six 3-month-old female rats were fed either a control diet or a HFD for 4 months. Animals in the control group continued on the control diet for another 4 months. Animals in the HFD group were divided into two groups, with 0.5 g/100 mL GTP (the HFD+GTP group) or without GTP (the HFD group) in drinking water, in addition to the HFD for another 4 months. Compared to the control group, the HFD group increased bone formation and erosion rates at the tibia, decreased trabecular volume and thickness, but had no impact on bone mineral density (BMD), trabecular number (Tb.N), and separation. Compared to the control group, the HFD+GTP group demonstrates a greater Tb.N at the proximal tibia, and a greater trabecular thickness at the femur and the lumbar vertebrae, but a smaller trabecular separation (Tb.Sp) and mineralizing surface at the proximal tibia, and a reduced endocortical mineral apposition rate (MAR) at the tibia shaft. Relative to the HFD group, the HFD+GTP group demonstrates (1) a higher BMD at the femur, a greater trabecular volume, thickness, and number at the proximal tibia, a larger cortical area and thickness at the tibial shaft, and a greater trabecular volume and thickness at the femur and the lumbar vertebrae, (2) a smaller Tb.Sp, MAR, bone formation rate, and eroded surface at the tibia. We concluded that GTP supplementation in drinking water improves bone microarchitecture in the HFD-induced obese female rats, possibly through suppressing bone turnover, resulting in a larger net bone volume.

Influence of Ovariectomy on Bone Turnover and Trabecular Bone Mass in Mature Cynomolgus Monkeys

Jun Iwamoto,Azusa Seki,Masao Matsuura,Yoshihiro Sato,Tsuyoshi Takeda,Hideo Matsumoto,James K. Yeh 연세대학교의과대학 2009 Yonsei medical journal Vol.50 No.3

Purpose: To examine the influence of ovariectomy (OVX) on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites in mature cynomolgus monkeys. Materials and Methods: Six female cynomolgus monkeys, aged 17-21 years, were randomized into 2 groups by the stratified weight: the OVX and sham-operation groups (n = 3 in each group). The experimental period was 16 months. Lumbar bone mineral density (BMD) in vivo and serum and urinary bone turnover markers were longitudinally measured, and peripheral quantitative computed tomographic and bone histomorphometric analyses were performed on trabecular bone of the lumbar vertebra, femoral neck, and distal radius at the end of the experiment. Results: OVX induced in a reduction in lumbar BMD compared with the sham controls and the baseline, as a result of increased serum levels of bonespecific alkaline phosphatase and urinary levels of cross-lined N- and C-terminal telopeptides of type I collagen. Furthermore, OVX induced reductions in trabecular volumetric BMD and trabecular bone mass compared with the sham controls, with increased bone formation rate at the lumbar vertebra, femoral neck, and distal radius. Conclusion: The results indicated that OVX in mature cynomolgus monkeys (17-21 years of age) increased bone turnover and induced trabecular bone loss at the three skeletal sites compared with the sham controls. Thus, mature cynomolgus monkeys could be utilized for preclinical studies to examine the effects of interventions on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites. Purpose: To examine the influence of ovariectomy (OVX) on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites in mature cynomolgus monkeys. Materials and Methods: Six female cynomolgus monkeys, aged 17-21 years, were randomized into 2 groups by the stratified weight: the OVX and sham-operation groups (n = 3 in each group). The experimental period was 16 months. Lumbar bone mineral density (BMD) in vivo and serum and urinary bone turnover markers were longitudinally measured, and peripheral quantitative computed tomographic and bone histomorphometric analyses were performed on trabecular bone of the lumbar vertebra, femoral neck, and distal radius at the end of the experiment. Results: OVX induced in a reduction in lumbar BMD compared with the sham controls and the baseline, as a result of increased serum levels of bonespecific alkaline phosphatase and urinary levels of cross-lined N- and C-terminal telopeptides of type I collagen. Furthermore, OVX induced reductions in trabecular volumetric BMD and trabecular bone mass compared with the sham controls, with increased bone formation rate at the lumbar vertebra, femoral neck, and distal radius. Conclusion: The results indicated that OVX in mature cynomolgus monkeys (17-21 years of age) increased bone turnover and induced trabecular bone loss at the three skeletal sites compared with the sham controls. Thus, mature cynomolgus monkeys could be utilized for preclinical studies to examine the effects of interventions on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites.