Menatetrenone Ameliorates Reduction in Bone Mineral Density and Bone Strength in Sciatic Neurectomized Rats

Iwasaki-Ishizuka, Yoshiko; Yamato, Hideyuki; Murayama, Hisashi; Abe, Masako; Takahashi, Kimio; Kurokawa, Kiyoshi; Fukagawa, Masafumi; Ezawa, Ikuko

doi:10.3177/jnsv.49.256

Cited by 10 publications

(4 citation statements)

References 31 publications

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“…However, vitamin K2 has also been reported to suppress bone resorption in vitro (28)(29)(30). Thus, vitamin K2 could regulate bone formation and bone resorption, which is supported by the results of numerous studies using various rat models of osteoporosis (10-13, [31][32][33][34][35][36][37][38][39][40][41].…”

Section: Discussionmentioning

confidence: 76%

Beneficial Effect of Pretreatment and Treatment Continuation with Risedronate and Vitamin K<sub>2</sub> on Cancellous Bone Loss after Ovariectomy in Rats: A Bone Histomorphometry Study

Iwamoto

Takeda

Satō

et al. 2006

J Nutr Sci Vitaminol

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The following articles have been retracted by the Editorial Board of Journal of Nutritional Science and Vitaminology, because some parts of their contents were published in other journals. 1. Iwamoto J, Yeh JK, Takeda T, Sato Y. Comparative effects of vitamin K and vitamin D supplementation on calcium balance in young rats fed normal or low calcium diets. J Nutr Sci Vitaminol 51, 211-215, 2005 2. Iwamoto J, Seki A, Takeda T, Sato Y, Yamada H, Yeh JK. Effect of risedronate on the cortical and cancellous bone mass and mechanical properties in ovariectomized rats: a comparison with the effects of a lfacalcidol. J Nutr Sci Vitaminol 52, 393-401, 2006 3. Iwamoto J, Seki A, Takeda T, Sato Y, Yamada H, Yeh JK. Comparative therapeutic effects of alendronate and alfacalcidol on cancellous and cortical bone mass and mechanical properties in ovariectomized osteopenic rats. J Nutr Sci Vitaminol 52, 1-8, 2006 4. Iwamoto J, Takeda T, Sato Y, Shen C-L, Yeh JK. Benefi cial effect of pretreatment and treatment continuation with risedronate and vitamin K2 on cancellous bone loss after ovariectomy in rats: a bone histomorophometry study. J Nutr Sci Vitaminol 52, 307-315, 2006 5. Iwamoto J, Seki A, Takeda T, Yamada H, Sato Y, Yeh JK. Effects of alfacalcidol on cancellous and cortical bone mass in rats treated with glucocorticoid: a bone histomorophometry study. SummaryThe purpose of the present study was to examine the effect of pretreatment with risedronate and/or vitamin K 2 and treatment continuation with reduced dosing frequency of the drugs on the early cancellous bone loss induced by ovariectomy (OVX) in rats. Eighty female Sprague-Dawley rats, 4 mo of age, were randomized by the stratified weight method into eight groups ( n ϭ 10 in each group); rats subjected to OVX, but not sham-operated rats, were treated with vehicle, risedronate, vitamin K 2 (menatetrenone), or risedronate ϩ vitamin K 2 for 4 wk before the surgery, and the treatment was either discontinued (pretreatment groups) or continued after the surgery (treatment continuation groups) for 2 wk. Sham-operated rats (controls) were treated with the vehicle throughout the experimental period. During the 4 wk prior to the surgery (pretreatment), risedronate and vitamin K 2 were administered five times a week either subcutaneously at a dose of 2.5 g/kg body weight (risedronate) or orally at the dose of 30 mg/kg body weight (vitamin K 2 ). During the 2 wk after the surgery (treatment continuation), the dosing frequency of the drugs was reduced to twice a week. Risedronate and vitamin K 2 had an anti-resorptive effect on the bone. Pretreatment with risedronate alone, but not vitamin K 2 alone, prevented the loss of the cancellous bone volume/total volume (BV/TV) of the proximal tibial metaphysis after OVX. Treatment continuation with vitamin K 2 alone prevented the loss of the cancellous BV/TV after OVX, while treatment continuation with risedronate alone increased the cancellous BV/TV to beyond the values in controls. Pretreatment with risedronate ϩ vitamin K 2 had a more ...

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Section: Discussionmentioning

confidence: 76%

Beneficial Effect of Pretreatment and Treatment Continuation with Risedronate and Vitamin K<sub>2</sub> on Cancellous Bone Loss after Ovariectomy in Rats: A Bone Histomorphometry Study

Iwamoto

Takeda

Satō

et al. 2006

J Nutr Sci Vitaminol

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“…An additional limitation of this study is the fact that only male monkeys were studied. To our knowledge, there has been no evaluation of vitamin K treatment on osteoporosis in men; however, vitamin K2 (menatetrenone) treatment has been reported to have beneficial skeletal effects in male rats (35,36) . Despite this, it is plausible that vitamin K deficiency may not have adverse skeletal consequence in males but could impact estrogen deficiency bone loss in women.…”

Section: Discussionmentioning

confidence: 99%

Vitamin K Deficiency From Long-Term Warfarin Anticoagulation Does Not Alter Skeletal Status in Male Rhesus Monkeys

Binkley¹,

Krueger²,

Engelke³

et al. 2007

Journal of Bone and Mineral Research

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Vitamin K (K) inadequacy may cause bone loss. Thus, K deficiency induced by anticoagulants (e.g., warfarin) may be an osteoporosis risk factor. The skeletal impact of long-term warfarin anticoagulation was evaluated in male monkeys. No effect on BMD or bone markers of skeletal turnover was observed. This study suggests that warfarin-induced K deficiency does not have skeletal effects. Introduction:The skeletal role of vitamin K (K) remains unclear. It is reasonable that a potential role of vitamin K in bone health could be elucidated by study of patients receiving oral anticoagulants that act to produce vitamin K deficiency. However, some, but not all, reports find K deficiency induced by warfarin (W) anticoagulation to be associated with low bone mass. Additionally, epidemiologic studies have found W use to be associated with either increased or no change in fracture risk. Such divergent results may imply that human studies are compromised by the physical illnesses for which W was prescribed. Materials and Methods: To remove this potential confounder, we prospectively assessed skeletal status during long-term W anticoagulation of healthy nonhuman primates. Twenty adult (age, 7.4-17.9 yr, mean, 11.7 yr) male rhesus monkeys (Macaca mulatta) were randomized to daily W treatment or control groups. Bone mass of the total body, lumbar spine, and distal and central radius was determined by DXA at baseline and after 3, 6, 9, 12, 18, 24, and 30 mo of W treatment. Serum chemistries, urinary calcium excretion, bone-specific alkaline phosphatase, and total and percent unbound osteocalcin were measured at the same time-points. Prothrombin time and international normalized ratio (INR) were monitored monthly. Serum 25-hydroxyvitamin D was measured at the time of study conclusion. Results: W treatment produced skeletal K deficiency documented by elevation of circulating undercarboxylated osteocalcin (8.3% W versus 0.4% control, p < 0.0001) but did not alter serum markers of skeletal turnover, urinary calcium excretion, or BMD. Conclusions: In male rhesus monkeys, long-term W anticoagulation does not alter serum markers of bone turnover or BMD. Long-term W therapy does not have adverse skeletal consequences in primates with high intakes of calcium and vitamin D.

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“…Iwasaki et al48 showed that the cancellous bone mass of the proximal tibial metaphysis was reduced, with a decrease in bone formation and resorption (bone turnover) in sciatic neurectomized rats, and that the administration of vitamin K 2 to these rats increased the cancellous bone mass by preventing the reduction in bone formation and further reducing bone resorption. Iwasaki-Ishizuka et al49 also showed that sciatic neurectomy in rats was associated with a transient increase in bone resorption and a sustained reduction in bone formation, resulting in a reduction in the BMD of the femoral distal metaphysis and diaphysis and also a reduction in the bone strength of the femoral diaphysis, and that vitamin K 2 ameliorated these abnormalities. Iwamoto et al45 showed that sciatic neurectomy in rats increased bone resorption and decreased bone formation in the cancellous bone.…”

Section: Effects Of Vitamin K2 On the Development Of Osteopenia In Ratsmentioning

confidence: 96%

“…Hind-limb immobilization by sciatic neurectomy increased bone resorption and decreased bone formation, resulting in cancellous and cortical osteopenia in the hind-limb of rats 45,48,49. Several studies have reported the effects of vitamin K 2 on the cancellous and/or cortical bone mass in sciatic neurectomized rats.…”

Section: Effects Of Vitamin K2 On the Development Of Osteopenia In Ratsmentioning

confidence: 99%

Effects of Vitamin K2 on the Development of Osteopenia in Rats as the Models of Osteoporosis

2006

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Vitamin K2 is widely used for the treatment of osteoporosis in Japan. To understand the effects of vitamin K2 on bone mass and bone metabolism, we reviewed its effects on the development of osteopenia in rats, which characterizes models of osteoporosis. Vitamin K2 was found to attenuate the increase in bone resorption and/or maintain bone formation, reduce bone loss, protect against the loss of trabecular bone mass and its connectivity, and prevent the decrease in strength of the long bone in ovariectomized rats. However, combined treatment of bisphosphonates and vitamin K2 had an additive effect in preventing the deterioration of the trabecular bone architecture in ovariectomized rats, while the combined treatment of raloxifene and vitamin K2 improved the bone strength of the femoral neck. The use of vitamin K2 alone suppressed the increase in trabecular bone turnover and endocortical bone resorption, which attenuated the development of cancellous and cortical osteopenia in orchidectomized rats. In addition, vitamin K2 inhibited the decrease in bone formation in prednisolone-treated rats, thereby preventing cancellous and cortical osteopenia. In sciatic neurectomized rats, vitamin K2 suppressed endocortical bone resorption and stimulated bone formation, delaying the reduction of the trabecular thickness and retarding the development of cortical osteopenia. Vitamin K2 also prevented the acceleration of bone resorption and the reduction in bone formation in tail-suspended rats, which counteracted cancellous bone loss. Concomitant use of vitamin K2 with a bisphosphonate ameliorated the suppression of bone formation and more effectively prevented cancellous bone loss in tail-suspended rats. Vitamin K2 stimulated renal calcium reabsorption, retarded the increase in serum parathyroid hormone levels, and attenuated cortical bone loss primarily by suppressing bone resorption in calcium-deficient rats while maintaining the strength of the long bone in rats with magnesium deficiency. These findings suggest that vitamin K2 may not only stimulate bone formation, but may also suppress bone resorption. Thus, vitamin K2 could regulate bone metabolism in rats, which represented the various models of osteoporosis. However, the effects of vitamin K2 on bone mass and bone metabolism seem to be modest.

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Menatetrenone Ameliorates Reduction in Bone Mineral Density and Bone Strength in Sciatic Neurectomized Rats

Cited by 10 publications

References 31 publications

Beneficial Effect of Pretreatment and Treatment Continuation with Risedronate and Vitamin K<sub>2</sub> on Cancellous Bone Loss after Ovariectomy in Rats: A Bone Histomorphometry Study

Beneficial Effect of Pretreatment and Treatment Continuation with Risedronate and Vitamin K<sub>2</sub> on Cancellous Bone Loss after Ovariectomy in Rats: A Bone Histomorphometry Study

Vitamin K Deficiency From Long-Term Warfarin Anticoagulation Does Not Alter Skeletal Status in Male Rhesus Monkeys

Effects of Vitamin K2 on the Development of Osteopenia in Rats as the Models of Osteoporosis

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