The pleiotropic effects of vitamin D in bone. 2013

Paul H Anderson, and Nga N Lam, and Andrew G Turner, and Rachel A Davey, and Masakazu Kogawa, and Gerald J Atkins, and Howard A Morris
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide 5000, Australia. paul.anderson@health.sa.gov.au

A current controversial question related to vitamin D supplementation is what level of serum 25-hydroxyvitamin D3 (25(OH)D3) is required to reduce the incidence of osteoporotic fractures. The reasoning behind vitamin D supplementation has been mostly derived from the role of vitamin D to promote intestinal calcium absorption and reduce bone resorption. While minimum 25(OH)D3 levels of 20nmol/L are required for sufficient intestinal calcium absorption to prevent osteomalacia, the mechanistic details of how higher 25(OH)D3 levels, well beyond that required for optimal calcium absorption, are able to prevent fractures and increase bone mineral density is unclear. Substantial evidence has arisen over the past decade that conversion of 25(OH)D3 to 1,25(OH)2D3via the 1-alpha hydroxylase (CYP27B1) enzyme in osteoblasts, osteocytes, chondrocytes and osteoclasts regulates processes such as cell proliferation, maturation and mineralization as well as bone resorption, which are all dependent on the presence the of the vitamin D receptor (VDR). We and others have also shown that increased vitamin D activity in mature osteoblasts by increasing levels of VDR or CYP27B1 leads to improved bone mineral volume using two separate transgenic mouse models. While questions remain regarding activities of vitamin D in bone to influence the anabolic and catabolic processes, the biological importance of vitamin D activity within the bone is unquestioned. However, a clearer understanding of the varied mechanisms by which vitamin D directly and indirectly influences mineral bone status are required to support evidence-based recommendations for vitamin D supplementation to reduce the risk of fractures. This article is part of a Special Issue entitled 'Vitamin D workshop'.

UI MeSH Term Description Entries
D010024 Osteoporosis Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis. Age-Related Osteoporosis,Bone Loss, Age-Related,Osteoporosis, Age-Related,Osteoporosis, Post-Traumatic,Osteoporosis, Senile,Senile Osteoporosis,Osteoporosis, Involutional,Age Related Osteoporosis,Age-Related Bone Loss,Age-Related Bone Losses,Age-Related Osteoporoses,Bone Loss, Age Related,Bone Losses, Age-Related,Osteoporoses,Osteoporoses, Age-Related,Osteoporoses, Senile,Osteoporosis, Age Related,Osteoporosis, Post Traumatic,Post-Traumatic Osteoporoses,Post-Traumatic Osteoporosis,Senile Osteoporoses
D001842 Bone and Bones A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principal cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX. Bone Tissue,Bone and Bone,Bone,Bones,Bones and Bone,Bones and Bone Tissue,Bony Apophyses,Bony Apophysis,Condyle,Apophyses, Bony,Apophysis, Bony,Bone Tissues,Condyles,Tissue, Bone,Tissues, Bone
D002112 Calcifediol The major circulating metabolite of VITAMIN D3. It is produced in the LIVER and is the best indicator of the body's vitamin D stores. It is effective in the treatment of RICKETS and OSTEOMALACIA, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. 25-Hydroxycholecalciferol,25-Hydroxyvitamin D 3,25-Hydroxycholecalciferol Monohydrate,25-Hydroxyvitamin D3,Calcidiol,Calcifediol Anhydrous,Calcifediol, (3 alpha,5Z,7E)-Isomer,Calcifediol, (3 beta,5E,7E)-Isomer,Calderol,Dedrogyl,Hidroferol,25 Hydroxycholecalciferol,25 Hydroxycholecalciferol Monohydrate,25 Hydroxyvitamin D 3,25 Hydroxyvitamin D3,Anhydrous, Calcifediol,Monohydrate, 25-Hydroxycholecalciferol
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014807 Vitamin D A vitamin that includes both CHOLECALCIFEROLS and ERGOCALCIFEROLS, which have the common effect of preventing or curing RICKETS in animals. It can also be viewed as a hormone since it can be formed in SKIN by action of ULTRAVIOLET RAYS upon the precursors, 7-dehydrocholesterol and ERGOSTEROL, and acts on VITAMIN D RECEPTORS to regulate CALCIUM in opposition to PARATHYROID HORMONE.
D015519 Bone Density The amount of mineral per square centimeter of BONE. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by X-RAY ABSORPTIOMETRY or TOMOGRAPHY, X RAY COMPUTED. Bone density is an important predictor for OSTEOPOROSIS. Bone Mineral Content,Bone Mineral Density,Bone Densities,Bone Mineral Contents,Bone Mineral Densities,Density, Bone,Density, Bone Mineral
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018167 Receptors, Calcitriol Proteins, usually found in the cytoplasm, that specifically bind calcitriol, migrate to the nucleus, and regulate transcription of specific segments of DNA with the participation of D receptor interacting proteins (called DRIP). Vitamin D is converted in the liver and kidney to calcitriol and ultimately acts through these receptors. Calcitriol Receptors,Cholecalciferol Receptors,Receptors, Vitamin D,Vitamin D 3 Receptors,Vitamin D Receptors,1,25-Dihydroxycholecalciferol Receptor,1,25-Dihydroxycholecalciferol Receptors,1,25-Dihydroxyvitamin D 3 Receptor,1,25-Dihydroxyvitamin D3 Receptor,1,25-Dihydroxyvitamin D3 Receptors,Calcitriol Receptor,Receptors, 1,25-Dihydroxyvitamin D 3,Receptors, Cholecalciferol,Receptors, Vitamin D 3,Receptors, Vitamin D3,Vitamin D 3 Receptor,Vitamin D Receptor,Vitamin D3 Receptor,Vitamin D3 Receptors,1,25 Dihydroxycholecalciferol Receptor,1,25 Dihydroxycholecalciferol Receptors,1,25 Dihydroxyvitamin D 3 Receptor,1,25 Dihydroxyvitamin D3 Receptor,1,25 Dihydroxyvitamin D3 Receptors,D Receptor, Vitamin,D Receptors, Vitamin,D3 Receptor, 1,25-Dihydroxyvitamin,D3 Receptor, Vitamin,D3 Receptors, 1,25-Dihydroxyvitamin,D3 Receptors, Vitamin,Receptor, 1,25-Dihydroxycholecalciferol,Receptor, 1,25-Dihydroxyvitamin D3,Receptor, Calcitriol,Receptor, Vitamin D,Receptor, Vitamin D3,Receptors, 1,25-Dihydroxycholecalciferol,Receptors, 1,25-Dihydroxyvitamin D3

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