A Comparison of Alfacalcidol and Menatetrenone for the Treatment of Bone Loss in an Ovariectomized Rat Model of Osteoporosis

Abstract

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.

Effects of Alfacalcidol on Cancellous and Cortical Bone Mass in Rats Treated with Glucocorticoid: A Bone Histomorphometry Study

“…The beneficial effects of ALF on cancellous bone mass and structure in ovariectomized rats has been well documented; ALF increased not only cancellous bone mass and the Tb Th, but also three-dimensional cancellous bone mass by reinforcing the interconnectivities and structures of the trabeculae (3,23). The beneficial effect of ALF on cancellous bone mass in ovariectomized rats was primarily due to its suppression of bone resorption and maintenance or even stimulation of bone formation (3).…”

The effect of alendronate sodium on trabecular bone structure in an osteoporotic rat model

“…Urine calcium was also observed to be significantly higher in the unsupplemented Ovx group. Contrary to Shiraishi et al, [17] who reported a decline in the mean calcium/ creatinine ratio in the Ovx animals, there was a decrease in the alendronate supplemented group, but an increase in the unsupplemented group in our study. Previously, urinary calcium was reported to decrease with varying doses of bisphosphonates; however, this decline appears not to be dose-dependent.…”

“…Similar positive effects of alendronate have been also reported in the literature. [9][10][11][12][13][14][15][16][17] In addition, plasma calcium levels decreased in the Ovx group, compared to the Shm and alendronate groups with no difference between the Shm and alendronate groups. Iwamoto et al [14] reported decreased plasma osteocalcin and urine deoxypyridinoline levels with increased plasma calcium levels in the Ovx rats.…”

Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats

“…Consistently, previous studies indicated that VK improves bone strength without necessarily increasing BMD (33). These effects of VK are considered to be due to the increase of active (carboxylated) OC and lysyl oxidase-mediated enzymatic cross-linking of collagen, thereby improving bone strength (elasticity and toughness) without significantly affecting BMD (34)(35)(36). Notably, the combination of VK and TPTD increased the BMD compared to VK alone.…”