Alfacalcidol-Stimulated Focal Bone Formation on the Cancellous Surface and Increased Bone Formation on the Periosteal Surface of the Lumbar Vertebrae of Adult Female Rats

Purpose To investigate the skeletal effects of alfacalcidol alone or in combination with exercise in intact adult female rats. Methods Seventy-four 8.5-month-old rats were orally administered 0, 0.005, 0.025, 0.05 or 0.1 μg/kg of alfacalcidol for 12 weeks, alone or in combination with exercise. Cancellous bone histomorphometric measurements were performed on the second lumbar vertebra. Results At 0.05 and 0.1 μg/kg, alfacalcidol caused a significant increase in cancellous bone volume, accompanied by an increase in trabecular architecture. Percent eroded surface, bone resorption and formation were suppressed by alfacalcidol treatment. However, mineral apposition rate was significantly increased, indicating osteoblast activity was increased. A positive balance between bone formation and resorption was observed in the rats treated with the highest dose of alfacalcidol. Alfacalcidol induced a unique bone formation site (“bouton”) on the cancellous surface. These boutons connected adjacent trabeculae and increased trabecular thickness. They exhibited both smooth and scalloped cement lines, suggesting that they were formed by minimodeling- and remodeling-based bone formation. Furthermore, alfacalcidol at 0.1 μg/kg increased periosteal bone formation of the lumbar transverse processes. Bipedal stance exercise alone did not have an effect on bone balance and bone turnover. There were no interactions between alfacalcidol and bipedal stance exercise except for a decrease in bone resorption. Conclusion Alfacalcidol exhibited both anti-catabolic and anabolic effects on bone in intact female rats. The effect of combined treatment with alfacalcidol and bipedal stance exercise was no better than that of alfacalcidol alone.     

The Advantage of Alfacalcidol Over Vitamin D in the Treatment of Osteoporosis

Although alfacalcidol is widely used in the treatment of osteoporosis, its mechanism of action in bone is not fully understood. Alfacalcidol stimulates intestinal calcium (Ca) absorption, increases urinary Ca excretion and serum Ca levels, and suppresses parathyroid hormone (PTH) secretion. It remains to be clarified, especially under vitamin D-replete conditions, whether alfacalcidol exerts skeletal effects solely via these Ca-related effects, whether the resultant suppression of PTH is a prerequisite for the skeletal actions of alfacalcidol, and, by inference, whether alfacalcidol has an advantage over vitamin D in the treatment of osteoporosis. To address these issues, we (1) compared the effects of alfacalcidol p.o. (0.025–0.1 μg/kg BW) vis-à-vis vitamin D₃ (50–400 μg/kg BW) on bone loss in 8-month-old, ovariectomized (OVX) rats as a function of their Ca-related effects, and (2) examined whether the skeletal effects of alfacalcidol occur independently of suppression of PTH, using parathyroidectomized (PTX) rats continuously infused with hPTH(1–34). The results indicate that (1) in OVX rats, alfacalcidol increases BMD and bone strength more effectively than vitamin D₃ at given urinary and serum Ca levels: larger doses of vitamin D₃ are required to produce a similar BMD-increasing effect, in the face of hypercalcemia and compromised bone quality; (2) at doses that maintain serum Ca below 10 mg/dl, alfacalcidol suppresses urinary deoxypyridinoline excretion more effectively than vitamin D₃; and (3) alfacalcidol is capable of increasing bone mass in PTX rats with continuous infusion of PTH, and therefore acts independently of PTH levels. It is suggested that alfacalcidol exerts bone-protective effects independently of its Ca-related effects, and is in this respect superior to vitamin D₃, and that the skeletal actions of alfacalcidol take place, at least in part, independently of suppression of PTH. Together, these results provide a rationale for the clinical utility of alfacalcidol and its advantage over vitamin D₃ in the treatment of osteoporosis.     

Treatment of Glucocorticoid-Induced Osteoporosis with Alfacalcidol/Calcium Versus Vitamin D/Calcium

Vitamin D/calcium substitution is generally regarded as an effective first step treatment for glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to evaluate the efficacy of the active vitamin D metabolite alfacalcidol (1α) compared with the native vitamin D₃ in patients with established GIOP with or without vertebral fractures. Patients on long-term corticoid therapy were given either 1 μg alfacalcidol plus 500 mg calcium per day (group A, n = 43) or 1000 IU vitamin D₃ plus 500 mg calcium (group B, n = 42). The two groups were alike in age range, sex ratio, percentages of underlying diseases, average initial bone density values (lumbar spine: mean T-score −3.28 and −3.25, respectively), and rates of vertebral and nonvertebral fractures. During the 3-year study we found a small but significant increase of lumbar spine density in group 1α (+2.0%, P < 0.0001) and no significant changes at the femoral neck. In the D₃ group, there were no significant changes at both sites. At the end of the study, 12 new vertebral fractures had occurred in 10 patients of the group 1α and 21 in 17 patients of the D₃ group. In accordance with the observed fracture rates, the alfacalcidol group showed a significant decrease in back pain (P < 0.0001) whereas no change was seen in the vitamin D group. We conclude that with the doses used in this trial, alfacalcidol is superior to vitamin D in the treatment of established GIOP.     

阿法骨化醇对肾移植受者血脂的影响

回顾性比较发现,12例肾移植受者服用阿法骨化醇6周后,甘油三酯(TG)、总胆固醇(CH)、低密度脂蛋白(LDL-C)明显降低,高密度脂蛋白(HDL-C)明显升高。提示阿法骨化醇可能对血脂有一定调节作用。