No abstract

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 microg/kg BW) vis-à-vis vitamin D(3) (50-400 microg/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 D(3) at given urinary and serum Ca levels: larger doses of vitamin D(3) 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 D(3); 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 D(3), 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 D(3) in the treatment of osteoporosis.

The effects of water exercise, as a form of daily physical activity (water exercise in a warm water pool), on bone loss in healthy Japanese postmenopausal women have been cross-sectionally and longi tudinally investigated from the viewpoint of preventing osteoporosis. In the cross-sectional study, the bone mineral density (BMD) of the lumbar spine (Z-score (%)) in the Veterans group (N=27), who had been exercising for 35.2 months on average, was significantly higher than that in the Newcomers (N=40), who had only begun to exercise 3 or 4 weeks before, and that in the Non-exercisers (N=30), serving as a control group. The rate of change in the BMD of the lumbar spine was-0.92%! year in the Non-exercisers (N=30), +1.55%/year in the Veterans (N= 20), and +2.16%/year in the Newcomers (N=15) , based on BMD Z-scores. In the Exercisers groups, it was found that the rate of change in the BMD showed a slight increase rather than a decrease irrespective of the duration of menopause. On the other hand, in the Non-exercisers group, the rate of change in the BMD decreased slightly. The results of questionnaires showed that the subjects' general awareness of health and fitness in daily life was enhanced after starting the water exercise pro gram. These results suggest that consistently participating in water exercise is an important factor in preventing bone loss, and moreover , appears not only to indirectly improve awareness of daily physical activity but also to promote health and improve daily life.

There is a concern that the combination of exercise with food intake reduction has a risk of reducing bone strength and bone mass in young female athletes. We examined the influence of the interaction of voluntary running exercise and food restriction on bone in young female rats. Seven-week-old female Sprague-Dawley rats were divided into four groups: the sedentary and ad libitum feeding group (SED), voluntary running exercise and ad libitum feeding group (EX), sedentary and 30 % food restriction group (SED-FR), and voluntary running exercise and 30 % food restriction group (EX-FR). The experiment lasted 12 weeks. Statistical analysis was carried out by two-way analysis of variance with exercise and restriction as the between-subjects factors. As a result, there were significant interactions of running and restriction on energy availability, breaking force, breaking energy, and bone mineral density (BMD). Breaking force and energy in the EX group were significantly higher than in the SED group; breaking force and energy were significantly lower in the EX-FR group than in the EX group, and breaking force in the EX-FR group was significantly lower than that in the SED-FR group. BMD in the EX-FR group was significantly lower than in the EX and SED-FR groups. These results suggest that food restriction induced low bone strength in young female rats engaging in voluntary running exercise. Also, through the interaction of exercise and food restriction, voluntary running exercise combined food restriction, unlike ad libitum feeding conditions, induced low bone strength, and low BMD in young female rats.

SummaryWe have reported that soybean milk is an excellent source for increasing bone mineral density (BMD) and mechanical bone strength. However, it is not known what kind of components in soybean milk affect bone metabolism. Consequently, the purpose of this study is to fi nd the effective components in soybean milk on bone metabolism. It might be some peptide in soybean milk. Therefore, in this study the soybean milk was separated into two different preparations according to molecular weight: a high-molecular-weight soybean milk, and a low molecular-weight soybean milk. Then, the effect of the peptides in soybean milk on bone metabolism was examined. After producing the experimental osteoporotic model rats, they were divided into four groups. The BMD and the mechanical bone strength of the three experimental groups, whose diet contained a soybean milk, a high-molecular soybean milk, or a low-molecular soybean milk (soybean milk peptide) were significantly higher than those of the control group. Moreover, the intestinal Ca absorption for the three experimental groups was significant ly increased. From these results, the peptides in the soybean milk are effective for the acceleration of the intestinal Ca absorption. It is possible to assume that the mechanism for increasing the BMD and the mechan ical strength in the three experimental groups was due to increasing the intestinal Ca absorption by alimenting the soybean milk, the high molecular soybean milk or the low-molecular soybean milk. Key Words osteoporosis, soybean milk, soybean milk peptide, intestinal calcium absorption, bone mineral density, mechanical bone strength Soybean is well known as being an excellent source of protein, as well as minerals. Soybean and/or soybean products are popular in Japanese diet and particularly, many elderly Japanese people favor the taste, texture, and flavor. Calcium (Ca) intake of the ordinary Japanese had never been sufficient according to the national nutrition survey performed in 1992 (1). An inadequate intake of calcium is one of the risk factors for osteoporosis (2). Although milk is an excellent calcium source (3), some elderly Japanese are not used to drinking milk, and some have a lactase intolerance. This makes it more difficult for the elderly to have the correct amount of Ca intake. Since the soybean and the soybean products have been proved to contain Ca as high as one third of Ca in milk (4), soybean products could be a good source of Ca. We have reported that soybean milk is an excellent source for incerasing bone mineral density (BMD) and mechanical bone strength (5). However, the mechanism of increasing the BMD and the mechanical bone strength by alimenting the soybean milk is unclear. There are some reports that some peptides, such as a casein-derived phosphopeptide (CPP) (6), a peptide present in bovine bone (7), and globin preparation (8), enhance the intestinal Ca absorption and affect the bone metabolism. It is possible to assume that the mechanism for increasing the BMD and the bone strength in the...