TN has received research grants and/or consulting fees (Asahi Kasei Pharma, Astellas, Banyu, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan Ono, Takeda, Teijin Pharma); belongs to the Japan Ministry of Health, Welfare and Labor as a councilor for hospital administration and social medical insurance. MF has received a consulting fee (Astellas). MS has received consulting fees (Asahi Kasei Pharma, Astellas, Chugai, Daiichi Sankyo,
Teijin Pharma); lecture fees (Eisai, Ono). TM is a member of musculoskeletal global advisory board (Lilly); has received consulting fees (Asahi Kasei Pharma, Astellas, Chugai, Daiichi Sankyo, Eli Lilly Japan, JT, Ono, Teijin Pharma). We thank the doctors who participated in the clinical trial. This study was supported in part by a grant for the Promotion of Fundamental Studies in Health Sciences from the National Institute of Biomedical Innovation selleck chemicals llc (NIBIO) of Japan (06–31 to MI). “
“Vitamin D metabolism plays an essential role in regulation of mineral and bone homeostasis [1]. The active form of 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3),
acts through the vitamin D receptor (VDR) present in target organs such as the intestines, kidney and parathyroid glands. It stimulates calcium absorption and reabsorption while blocking both the synthesis and secretion of another essential regulator of mineral balance, the parathyroid hormone (PTH) [2]. VDR has also been found in osteoblasts and osteoclasts, suggesting that vitamin D may directly affect the skeleton [3] and [4]. In bone, the hormone is MAPK Inhibitor Library screening important in at least two different ways: first, it interacts with the VDR in osteoblastic cells and regulates osteoclastic activity via the osteoprotegerin (OPG)/receptor activator nuclear factor kB (RANK)/RANK ligand (RANKL) system [5]; second, it secures a supersaturated state of calcium–phosphorus products in the blood, which indirectly enables osteoid mineralization [6]. Vitamin D deficiency may lead to exacerbated bone resorption as a result of increases in osteoclast number and activity, and may also cause a type of bone mineralization defect known as rickets in children and osteomalacia
in adults [7]. Interestingly, 1α,25-(OH)2D3 was shown to promote osteoclastic bone resorption in culture [8] and in vivo [9] and to enhance the expression of RANKL on bone marrow stromal cells Rho [10]. Despite its good acceptance in the management of conditions like psoriasis [11] and cancers [12], the use of vitamin D in the treatment of osteoporosis has been hindered due to its calcemic activity and the notion that the hormone drives osteoclastic bone resorption [13], [14] and [15]. However, there have been reports showing that the therapeutic effect of active vitamin D can be dissociated from the one on calcium absorption [16] and that it is mostly related to suppression of bone resorption due to decreases in the pool of osteoclast precursors [17] and [18].