Evidence that serum calcium increases with the dose of vitamin D administered but calcium absorption reaches a plateau once normalized by a small dose of vitamin D [21] suggests the existence of a safer, side effect-free therapeutic window for vitamin D and its analogs. Many attempts have been made to synthesize Ruxolitinib nmr a compound that would retain only the differentiation and anti-proliferative effects of 1α,25-(OH)2D3, thus allowing for safer usage and less side effects [22] and [23]. Eldecalcitol, formerly known as ED-71, is an analog of 1α,25-(OH)2D3 bearing a hydroxypropyloxy residue at the 2β position that was developed

in the early 80s and is currently awaiting approval as a drug for treatment of osteoporosis in Japan [24] and [25]. It has been reported that eldecacitol lowered biochemical

and histological parameters of bone resorption in a rat ovariectomized (OVX) model of osteoporosis [26] and that its effects on bone were observed without sustained hypercalcemia or hypercalciuria [27]. Examinations focusing on the effects of vitamin D analogs at the tissue level have been relatively neglected despite the therapeutic potential of these compounds for the treatment of bone diseases. A recent report involving bone marrow ablation showed that eldecalcitol may promote bone formation and angiogenesis in addition to inhibiting bone resorption [23]. Further data on the histological subtleties and on the interplay among bone cells CTLA-4 inhibiton after eldecalcitol treatment are not yet available. In the present study, we used histological, histochemical, histomorphometrical and ultrastructural analyses as tools for investigating the tissue events following the administration of eldecalcitol in OVX rats. All animal experiments were approved by the Institutional Animal Care and Use Committee of Chugai Pharmaceutical Co., Ltd., Niigata University and Hokkaido University, and were conducted in accordance with Florfenicol accepted standards of humane animal care. Eight-months old Crl:CD(SD)(IGS)

rats were obtained from Charles River Laboratories Japan, Inc., and acclimated until 11 months of age under standard laboratory conditions (23 ± 3 °C, humidity 35%–75%, light–dark cycle 12 h), with ad libitum access to food (1.25% calcium, 1.06% phosphate, CE-2, Clea Japan, Inc., Tokyo, Japan) and water. Rats were then divided in three groups: 1) the Sham group, whose animals were sham-ovariectomized and received only vehicle (medium chain triglyceride, MCT) after the procedure (n = 8), 2) the OVX group, where animals underwent standard ovariectomy but received only MCT after the surgical procedure (n = 8), and 3) the eldecalcitol group, where animals underwent standard ovariectomy and were given eldecalcitol by gavage (n = 8, 30 ng/kg, 5 times per week, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan).