Beneficial Effect of Pretreatment and Treatment Continuation with Risedronate and Vitamin K₂ on Cancellous Bone Loss after Ovariectomy in Rats: A Bone Histomorphometry Study

Abstract

The following articles have been retracted by the Editorial Board of Journal of Nutritional Science and Vitaminology, because some parts of their contents were published in other journals. 1.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 ...

Vitamin K and Bone Metabolism: A Review of the Latest Evidence in Preclinical Studies

“…Effect of combined use of vitamin K2 and bisphosphonate on osteoporosis was evaluated in rat models. It was recommended that vitamin K2 could ameliorate the suppressive effect of bisphosphonates on bone turnover and increase the bone volume as well as the bone formation parameters [ 68 , 74 ]. Other reviews emphasized the potentially positive effect of combined treatment with bisphosphonate and vitamin K2 for preventing the fractures in postmenopausal osteoporotic women [ 75 , 76 ].…”

The Effect of Risedronate on Posterior Lateral Spinal Fusion in a Rat Model

“…Among bisphosphonates (risedronate, alendronate, pamidronate, etidronate) risedronate (RIS) shows a higher antiresorptive effect 3,7,18,34) . It affects bone remodeling and increase bone mass through the inhibition of osteoclasts 23,24) . Its effect on osteoblasts, and the balance between osteoblastic and osteoclastic activity on bone turnover and healing, is not completely understood.…”

Prior treatment with vitamin K2 significantly improves the efficacy of risedronate

“…In the animal studies, a much higher dosage of 30–50 mg MK-4/kg/day has been used, thus resulting in a significantly higher mineral content in cortical bone without bisphosphonate [ 31 ]. However, the results are inconsistent among different animals or strains [ 16 – 18 , 32 – 34 ]. In the present study, we did not observe significant increase in BMD or BMC at the lower level of ~100 μg/kg/day unless MK-4 was followed by risedronate.…”

“…The lack of such prevention as well as the lack of other beneficial effects found in K to R cortex, such as the higher/larger BMD, BMC, and thickness, would explain why no significant effect was detectable in K to WO by the three-point bending test. In the MK-4 treated pre-OVX rats, Iwamoto et al reported the elevated eroded surface as well as the bone formation rate that remained high after the MK-4 withdrawal [ 16 ]. The cellular mechanisms of the elevated collagen degradation therefore have to be confirmed in the future.…”

“…Such an entirely different pharmacological action of vitamin K 2 from other drugs would make it worth studying combinatory administration with bisphosphonate. Limited reports of trabecular bone implied that the combined treatment is more efficacious in osteoporotic rats [ 15 , 16 ], while others have reported otherwise [ 17 , 18 ]. Therefore, the efficacy of their combinatory use was further investigated in ovariectomized (OVX) ICR mice to clarify the effect on the cortical bone and strength.…”