A comparison of alfacalcidol and menatetrenone for the treatment of bone loss in an ovariectomized rat model of osteoporosis.
We conducted this study to evaluate the characteristic effects of alfacalcidol (ALF) and menatetrenone (VK) in preventing bone loss using an ovariectomized rat model of osteoporosis. Bilateral ovariectomy (OVX) or sham operation was performed on 10-month-old female Wistar rats. OVX caused a significant decrease in the bone mass and the mechanical strength of the lumbar vertebra as well as the femur 6 months after surgery. VK treatment (30 mg/kg, food intake) required a 6-month period to prevent the bone loss induced by estrogen deficiency, whereas ALF (0.1 or 0.2 mg/kg, p.o.) increased the bone mass and the mechanical strength of the lumbar vertebra as well as the femur in a 3-month treatment period, far above the level in the sham-operated rats. Neither ALF or VK caused hypercalcemia, despite administration for as long as 6 months. By doing a micro-CT analysis of the vertebral trabecular microstructure, it was revealed that ALF treatment increased the interconnections and the plate-like structures and that VK significantly increased the trabecular number. It was also indicated that the increase in spinal strength by ALF treatment was closely associated with improvement of the microstructure, but not VK. The results of histomorphometric analysis showed that ALF caused a significant suppression of bone resorption yet maintained formation in the endocortical perimeter, and also stimulated bone formation in the periosteal perimeter, thereby causing an increase in cortical area. No marked effect of VK on histomorphometric parameters was observed, whereas VK as well as ALF maintained the material strength at femoral midshaft of the normal level, suggesting that VK affected bone quality and thereby prevented the decrease in mechanical strength of femur caused by OVX. In conclusion, it was demonstrated that the two drugs, ALF and VK, differed markedly in their potency and mechanisms for improving bone strength. These results have important implications in understanding the characteristic actions of vitamin K and active vitamin D on bone metabolism.
Shiraishi
A
A
Product Research Laboratory, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Higashi
S
S
Masaki
T
T
Saito
M
M
Ito
M
M
Ikeda
S
S
Nakamura
T
T
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000503:physiopathology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000502:physiology / Q000503:physiopathology; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000502:physiology / Q000503:physiopathology*; D010024:Osteoporosis / Q000503:physiopathology* / Q000517:prevention & control*; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D006887:Hydroxycholecalciferols; D024482:Vitamin K 2; C030814:menatetrenone; C008088:alfacalcidol