The deposition of amyloid beta (Abeta) protein is a neuropathological change that characterizes Alzheimer's disease. Animals with the osteopetrosis (op/op) mutation suffer from a general skeletal sclerosis, a significantly reduced number of macrophages and osteoclasts in various tissues, and have no systemic macrophage colony stimulating factor (M-CSF). This study examined the effect that M-CSF injections had on Abeta deposition and microglial cell distribution in the brains of normal and op/op mice. Abeta-positive plaques were detected in the cerebral cortex of op/op mice, but not in normal mice. M-CSF reduced the numbers of Abeta-positive plaques in op/op mice. The microglial cell population was reduced in op/op mice compared with normal mice, and M-CSF increased the numbers to 65.8% of that observed in normal mice. Our results suggest that a clearer understanding of the role that microglial cells play in Abeta deposition may help determine the mechanisms involved in the pathogenesis of Alzheimer's disease.

Alendronate, one of the bisphosphonates, is known to have an inhibitory effect on bone resorption. The purpose of this study was to investigate the effects of alendronate on ectopic bone graft resorption and to determine the optimal dose in the mouse. The grafted bone in the control group disappeared due to resorption by osteoclasts within 5 weeks. In the experimental groups, the area of bone tissue decreased by only 20-40% at 5 weeks post-operatively. At 8 and 9 weeks after surgery, the decreased area of bone structure was significantly less in all the 10 -4 M injected alendronate-immersed groups than in the 10 -4 M non-injected alendronate-immersed. At 9 weeks after surgery, the number of osteoclasts were significantly less in the 10 -4 M injected alendronate-treated groups than in the 10 -4 M non-injected alendronate-treated groups. These results suggest that alendronate inhibits resorption of ectopic bone graft at concentrations of 10 -4 and 10 -6 M.

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Alendronate, one of the bisphosphonates, is known to have an inhibitory effect on bone resorption.

It is well accepted that reduced masticatoiy function resulted from a soft diet with low physical consistency causes motphologic and histologic alterations in the craniofacial skeleton in growing animals. It is also assumed that these alterations are associated with reduced proliferative activity of osteoblasts on the bone surface, indicating a significant role of mechanical stimuli mediated by various local growth factors such as insulin-like growth factor-I (IGF-I) and parathyroid hormone (PTH). A previous study demonstrated that PTH accelerated the effect of IGF-I on bone formation. This study was thus conducted to examine the effect of PTH on the induction of osteoclasts and osteoblasts and the subsequent nasopremaxillaiy growth under different mechanical loading conditions from mastication. In animals treated with PTH, the nasal bone length increased significantly in the solid-diet group. No significant differences in these dimensions were found between the solid-diet mice injected with physiological saline and the granulated-diet group injected with PTH. It is shown that PTH induces nasal and premaxillaiy growth, and the effects may be exerted if mechanical loading from mastication is sufficient. it is also demonstrated that the effects of PTH are more potent in the ostcogenic activity than in the osteoclastic one, in terms of more significant expression of osteoblasts than osteoclasts.It is indicated that physical exercise or the related mechanical loading has a positive effect on bone remodeling to increase bone mass, and contrarily defect of mechanical stress during space flight decreases bone mass. Dehority er oi. reported that unloading decreased the number of osteoblasts, the rates of mineral apposition and bone formation and inhibited periosteal and cancellous bone formation (6). In our previous study, different masticatory loadAbbreviufioris: PTH; parathyroid hormone, IGF-I; insulin-like growth factor-I, GH; growth hormone, bFGF; basic fibroblast growth factor. *Corresponding author to Dr Chiyoko Tokimasa, at the above address. Japan. Tel: +81-82-257-5686; Fax: +81-82-25'?-5687; E-meil: tokichi@hiroshima-u.ac.jp ings induced by varying physical consistencies of diet caused morphologic and histologic alterations in the nasopremaxillaiy complex in growing mice (31). Furthermore, morphometric analyses demonstrated that changes in masticatoiy function affected not only the local bone morphology in the vicinity of muscle attachments but also the overall morphology of the upper viscerocranium (23, l4). The zygomatic width was significantly smaller with a significantly larger gonial angle of the mandible in rats fed a soft diet (1, 27, 23, 22). In addition, reduced masticatoiy function significantly affected the dimension of facial sutures (17, 21) and morphology of the nasopreniaxillary skeleton and cortical bone formation (1 l).it is well accepted that mechanical loading inhibits bone resorption and increases in vivo bone forma-