Abstract: Inhibitors of bone calcium resorption are administered, and calcium intake in the subject's diet is restricted, to allow high doses of vitamin D compounds or mimetics to be given with the intent of treating diseases such as metabolic bone diseases, hyperparathyroidism, cancer, psoriasis, and autoimmune diseases without the dangers of calcification of kidney, heart, and aorta. Inhibitors of bone calcium resorption include the bis-phosphonates, OPG (osteoprotegerin) or the soluble RANKL (receptor activator of NF-?B ligand) receptor known as sRANK (soluble RANK which is the protein expressed by the NF-?B gene), and function to block the availability of calcium from bone thereby preventing hypercalcemia and the resulting calcification of soft tissues. Thus, high doses of 1?,25-dihydroxyvitamin D3 (1,25-(OH)2D3), its analogs, prodrugs, or mimetics can be utilized to treat the target disease with minimal risk to a patient.

Abstract: Inhibitors of bone calcium resorption are administered to allow high doses of vitamin D compounds or mimetics to be given with the intent of treating non-calcium related diseases such as cancer, psoriasis, and autoimmune disease without the dangers of calcification of kidney, heart, and aorta. Inhibitors of bone calcium resorption include the bis-phosphonates, OPG (osteoprotegerin) or the soluble RANKL (receptor activator of NF-?B ligand) receptor known as sRANK (soluble RANK which is the protein expressed by the NF-?B gene), and function to block the availability of calcium from bone thereby preventing hypercalcemia and the resulting calcification of soft tissues. Thus, high doses of 1?,25-dihydroxyvitamin D3 (1,25-(OH)2D3), its analogs, prodrugs, or mimetics can be utilized with minimal risk to a patient. Specifically, alendronate is shown to block the bone calcium mobilization activity of both 1,25-(OH)2D3 and its very potent analog, 2-methylene -19-nor-(20S)-1?,25-dihydroxyvitamin D3.

Abstract: The present invention provides isolated nucleic acids containing functional polynucleotide sequences from the upstream region of the RANKL gene useful in conferring transcriptional responsiveness (e.g., vitamin D3 receptor complex responsiveness) on associated promoters and methods of using same to identify chemical entities capable of affecting transcriptional activity of the RANKL gene.

Abstract: This invention relates to methods of producing a substantially homogenous population of mesenchymal stem cells derived from embryonic stem cells. Also, disclosed is a homogenous population of mesenchymal stem cells capable of further differentiating into a variety of specific cell types, characterized by various morphological factors and cell-specific markers. The compositions and methods described in this disclosure are useful for a variety of commercially important diagnostic, drug screening, and therapeutic applications.

Abstract: It has been discovered that the 2-carbon-modified derivatives of 1?,25-dihydroxyvitamin D3 specifically stimulate osteoblasts to form new bone. The ability of the 2-carbon-modified vitamin D analogs to stimulate new bone formation suggest that these compounds can be used where synthesis of new bone is required. Thus, these compounds can be used either systemically or locally to stimulate the growth of bone transplants, to increase the rate of fracture healing and thereby reduce the time required for the healing of fractures, the stimulation of bone growth when required for replacement surgery, and also for the growth of bone to implants or other devices required to maintain the skeleton or teeth in the proper positions.

Abstract: Inhibitors of bone calcium resorption are administered to allow high doses of vitamin D compounds or mimetics to be given with the intent of treating non-calcium related diseases such as cancer, psoriasis, and autoimmune disease without the dangers of calcification of kidney, heart, and aorta. Inhibitors of bone calcium resorption include the bis-phosphonates, OPG or the soluble RANKL receptor known as sRANK, and function to block the availability of calcium from bone thereby preventing hypercalcemia and the resulting calcification of soft tissues. Thus, high doses of 1&agr;,25-dihydroxyvitamin D3 (1,25-(OH)2D3), its analogs, prodrugs, or mimetics can be utilized with minimal risk to a patient. Specifically, alendronate is shown to block the bone calcium mobilization activity of both 1,25-(OH)2D3 and its very potent analog, 2-methylene-19-nor-(20S)-1&agr;,25-dihydroxyvitamin D3.